Podcasts about ctdna

What matters most to patients with non-muscle invasive bladder cancer (NMIBC)? In this episode of BackTable Urology, Dr. Kelly Bree, Dr. Saum Ghodoussipour, and Meredith Donahue, N.P., join host Dr. Vignesh Packiam to discuss the power of shared decision-making across the NMIBC spectrum. They explore risk-adapted treatment selection, when to escalate or de-escalate therapy, and how to navigate conversations about recurrence risk, treatment burden, quality of life, and the possibility of cystectomy. --- Get the BackTable apphttps://www.backtable.com/app --- This podcast is supported by an educational grant from Johnson & Johnson. --- Timestamps 00:00 - Introduction01:55 - Second Opinions and Patient Counseling06:08 - Intermediate Risk Stratification12:13 - Treatment Options for Intermediate Risk NMIBC16:20 - BCG and Alternative Treatments for High Risk NMIBC26:49 - Options for BCG-Unresponsive NMIBC31:42 - Sequencing and Cystectomy37:03 - Financial and Time Toxicity41:08 - Biomarkers and ctDNA44:04 - Future Trials and NMIBC Innovations --- More about this episode They also review emerging therapies such as ZUSDURI, the evolving role of intravesical treatments, and the promise of biomarkers and ctDNA for personalized care. The discussion covers practical strategies for patient counseling, key updates to clinical guidelines, and a preview of innovations shaping the future of NMIBC management. --- Resources Active Surveillance Versus Intravesical Bacillus Calmette-Guérin for High-grade T1 Bladder Cancer with Negative Second Transurethral Resection: The Randomized Noninferiority Phase 3 JCOG1019 Trial:https://pubmed.ncbi.nlm.nih.gov/41571573/ Twelve-Month Results From the CISTO Study Comparing Radical Cystectomy Versus Bladder-Sparing Therapy for Recurrent High-Grade Non–Muscle-Invasive Bladder Cancerhttps://ascopubs.org/doi/10.1200/JCO-25-01324 CIRCULATING TUMOR DNA AS A BIOMARKER FOR UPSTAGING AND ADVERSE PATHOLOGY IN HIGH-RISK NON–MUSCLE-INVASIVE BLADDER CANCER:https://www.auajournals.org/doi/abs/10.1097/01.JU.0001191388.74345.c9.09 Preoperative Circulating Tumor DNA Predicts Upstaging and Recurrence in High-Risk Nonmuscle-Invasive Bladder Cancer Undergoing Radical Cystectomyhttps://pubmed.ncbi.nlm.nih.gov/41843048/ --- BackTable Urology is the go-to podcast for urologists, urologic oncologists, and urogynecologists. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

Featuring perspectives from Prof Thomas Powles, including the following topics: Circulating tumor DNA (ctDNA) analyses with adjuvant nivolumab for MIBC in the CheckMate 274 study (0:00) Use of ctDNA to guide response-adapted bladder preservation for patients with MIBC (2:27) ctDNA response-adapted treatment de-escalation for patients with metastatic urothelial carcinoma: The CT-READ trial (10:26) Emerging data and studies regarding urinary tumor DNA (18:04) CME information and select publications

Harald Müller-Huesmann, Kerstin Milicic-Ouakili und David Liesenfeld ziehen Bilanz aus Chicago: Im Fokus stehen die KRAS-Inhibition, ctDNA, Präzisionsmedizin, Prävention und die Frage, wie neue Erkenntnisse schneller in die Versorgung gelangen.

Harald Müller-Huesmann spricht mit Maggie Banys-Paluchowski über aktuelle ASCO-Daten zum Mammakarzinom: neue Erkenntnisse zur axillären Chirurgie nach neoadjuvanter Therapie, Genexpressionstests zur Chemotherapieentscheidung, ctDNA-basiertes Therapiemonitoring und neue endokrine Strategien.

Harald Müller-Huesmann spricht mit Ralf-Dieter Hofheinz über GI-Highlights vom Amerikanischen Krebskongress: ctDNA-gesteuerte Adjuvanz beim Stadium-II-Kolonkarzinom, Daraxonrasib beim vorbehandelten metastasierten Pankreaskarzinom und HER2-gerichtete ADC-Daten beim fortgeschrittenen CRC im Fokus.

Harald Müller-Huesmann spricht mit Claas Wesseler über die wichtigsten Neuigkeiten zum Lungenkarzinom. Im Fokus stehen Langzeitüberleben unter zielgerichteten Therapien, neue molekulare Behandlungsansätze und die Frage, wie ctDNA die Thoraxonkologie künftig verändern könnte.

Welche Entwicklungen prägen die Onkologie? Harald Müller-Huesmann und Uwe Martens ziehen Bilanz zum Amerikanischen Krebskongress 2026. Gemeinsam sprechen sie über Präzisionsmedizin, ctDNA, neue zielgerichtete Therapien und die Frage, wie Innovationen schneller in die klinische Praxis gelangen.

En este primer RECAP de la Reunión Anual de la Sociedad Americana de Oncología Clínica, el Dr. Fabián Martínez, oncólogo médico adscrito al Centro Médico ABC, y el Dr. Raúl Mellado Orellana, oncólogo médico adscrito al Instituto Nacional de Neurología y Neurocirugía, analizan de manera crítica los hallazgos más relevantes presentados durante los primero dos días en Chicago, IL. La discusión abre con el análisis del estudio fase III lidERA, el cual evalúa el uso de giredestrant —un degradador selectivo del receptor de estrógenos por vía oral— en comparación con la terapia endocrina estándar como adyuvancia durante 5 años en pacientes con cáncer de mama RE+/HER2- temprano.En el ámbito del CPCNP, se revisan múltiples investigaciones de alto impacto clínico. En primer lugar, se evalúa el estudio fase III WU-KONG28, que demuestra la eficacia de sunvozertinib frente a la quimioterapia convencional en la primera línea de tratamiento para pacientes con inserción del exón 20 de EGFR. Posteriormente, se examina el estudio fase III OptiTROP-Lung05, que demuestra la superioridad de la combinación sacituzumab tirumotecan más pembrolizumab frente a la monoterapia con pembrolizumab en pacientes con CPCNP PD-L1. Finalmente, se analizan los datos actualizados de supervivencia global del estudio CHRYSALIS-2 (cohorte C, amivantamab con o sin lazertinib), así como el seguimiento a 7 años del estudio CROWN (lorlatinib frente a crizotinib en primera línea CPCNP ALK+).Por último, los ponentes discuten los avances en tumores genitourinarios. Se profundiza en el estudio EV-302/KEYNOTE-A39, que evalúa la combinación de enfortumab vedotin junto a pembrolizumab en carcinoma urotelial metastásico no tratado previamente y cómo continúa obteniendo respuestas completas con la continuidad del tratamiento. En el escenario del cáncer renal de células claras, se revisa el análisis del ensayo fase III KEYNOTE-564 enfocado en el valor del ctDNA como biomarcador posterior a la nefrectomía. Referencia:Este contenido se basa en la interpretación crítica de la evidencia científica disponible, así como en la experiencia clínica del o los ponentes como profesionales de la salud en instituciones de referencia.Para profundizar en los conceptos discutidos, se recomienda al profesional de la salud consultar literatura científica vigente, guías clínicas internacionales y la normatividad aplicable en su país.

Harald Müller-Huesmann und David Liesenfeld eröffnen die Berichterstattung aus Chicago. Im Mittelpunkt stehen erwartete Kongresshighlights: RAS-Inhibition beim Pankreaskarzinom, neue Lungenkrebsdaten, ctDNA-gesteuerte Therapieansätze, orale SERDs und die wachsende Rolle von KI in der Onkologie.

In a recent interview with CancerNetwork®, Nicholas Hornstein, MD, PhD, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health, discussed emerging data and clinical shifts in the care of patients with gastrointestinal (GI) cancers ahead of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.Advancements in Colorectal CancerHornstein highlighted the increasing integration of targeted therapies into the first-line setting for patients with colorectal cancer (CRC). For those with BRAF V600E-mutated metastatic disease, data from the phase 3 BREAKWATER trial (NCT04607421) support moving targeted therapy into the first line.1 He noted that initiating these therapies early is critical, as a significant percentage of patients may experience rapid clinical decline and lose the opportunity for second-line treatment if targeted options are delayed.In the HER2-positive space, clinicians currently utilize tucatinib (Tukysa)-based regimens or fam-trastuzumab deruxtecan-nxki (Enhertu). Hornstein also anticipated the arrival of bispecific antibodies, such as zanidatamab-hrii (Ziihera), which are expected to gain approval in upper GI cancers before moving into the CRC landscape.The Role of ctDNA and Pancreatic CancerRegarding localized disease, Hornstein discussed the potential for circulating tumor DNA (ctDNA) to guide adjuvant therapy for patients with stage II colon cancer. Data from trials like CIRCULATE (NCT05174169) are expected to further clarify how ctDNA can assist in the escalation or de-escalation of treatment.2 In pancreatic cancer, the phase 3 RASolute 302 trial (NCT06625320) investigating daraxonrasib is poised to change the standard of care for patients with second-line pancreatic cancer immediately upon an anticipated regulatory approval.3Barriers to Precision MedicineA primary unmet need that Hornstein identified was the low rate of biomarker testing; currently, only about half of patients with metastatic disease receive necessary sequencing or microsatellite instability testing. Hornstein emphasized that multidisciplinary cooperation and improved systems are essential to ensure all patients with targetable mutations receive appropriate care. Finally, he highlighted the development of large language model tools to assist clinicians with data ingestion and clinical trial matching.References1.        Kopetz S, Wasan HS, Yoshino T, et al. BREAKWATER: primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). J Clin Oncol. 2026;44(suppl 2):13. doi:10.1200/JCO.2026.44.2_suppl.132.        Dasari A, Yu G, Kopetz S, et al. NRG-GI008: colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA). J Clin Oncol. 2026;44(suppl 16):TPS3686. doi:10.1200/JCO.2026.44.16_suppl.TPS36863.        Wolpin B, Wainberg ZA, Hendifar A, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA5. doi:10.1200/JCO.2026.44.17_suppl.LBA5

Interview conducted on March 11, 2026, by Dr Neil Love, including the following topics: Circulating tumor DNA (ctDNA)-guided adjuvant therapy with atezolizumab for muscle-invasive bladder cancer (MIBC) (0:00) Use of ctDNA in guiding systemic treatment selection for patients with urothelial bladder cancer (10:03) ctDNA analyses with perioperative durvalumab for MIBC in the Phase III NIAGARA study (16:51) New research advances in the monitoring and management of urothelial bladder cancer (22:21) CME information and select publications  

The FDA has been a bunch of busy bees with new approvals: 1. Sonrotoclax, an exciting new BCL2 inhibitor approved for 3rd-line Mantle Cell Lymphoma 2. An all PO regimen of decitabine/cedazuridine + venetoclax is approved for AML. 3. Zenoctuzumab gets an FDA approval for cholangiocarcinoma with an efficacy patient population = 19 4. T-DXd is a good drug and continues to pile on FDA approvals 5. Adjuvant atezolizumab in bladder cancer is approved in conjunction with ctDNA serial monitoring to determine who gets treatment Check out the Oncology Insights Newsletter: www.kelleycpharmd.com/newsletter-oncopharm

A high-functioning HCC tumor board can turn complex transplant decisions into coordinated treatment plans that account for liver reserve, tumor biology, and evolving biomarkers. In this episode of the BackTable Podcast 2026 HCC Creator Weekend™, abdominal transplant surgeon Dr. Ari Cohen (Ochsner Health) and transplant hepatologist Dr. Neil Mehta (UCSF) join host Dr. Kavi Krishnasamy to map out strategies for effective multidisciplinary treatment and transplantation planning in HCC. --- Get the BackTable apphttps://www.backtable.com/app --- This podcast is supported by an educational grant from Sirtex and Boston Scientific. --- Timestamps 00:00 - Introduction00:51 - Starting a Tumor Board06:39 - Building Referral Streams09:03 - Academic and Community Practice Integration14:31 - Treatment Selection Criteria20:38 - Modern HCC Biomarkers25:24 - Role of ctDNA and Biopsy29:37 - Bridging Therapy on Transplant Waitlist32:34 - Downstaging Strategy and Risks39:25 - Final Thoughts and Closing Remarks --- More about this episode The physicians discuss what it takes to build a robust tumor board, from fostering hospital buy-in to engaging leaders across specialties and utilizing virtual formats for consistent participation. The conversation explores clinical decision-making, emphasizing the integration of AFP-L3 and DCP biomarkers alongside AFP to better understand tumor biology and predict post-transplant recurrence. Dr. Mehta and Dr. Cohen also share their patient selection criteria, discussing how bilirubin, liver disease etiology, and INR influence decisions. While radiographic guidance remains central to HCC management, they highlight the growing potential of reliable ctDNA analysis and other biomarkers. The specialists conclude by emphasizing that an integrated, communicative tumor board is the most effective way to navigate the nuances of liver reserve and HCC biology to achieve the best possible patient outcomes. --- Resources Sustained AFP-L3 or DCP expression is associated with progression risk and inferior outcomes in unresectable hepatocellular carcinoma.https://doi.org/10.1007/s10238-025-01877-8 --- BackTable Vascular & Interventional (VI) is the go-to podcast for interventional radiologists, vascular surgeons, and interventional cardiologists. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

In this episode of the Eye Believe Podcast, we're joined by Wendy Carpenter, a metastatic ocular melanoma patient who is currently NED (No Evidence of Disease). Wendy shares her personal experience using ctDNA (circulating tumor DNA) testing as part of her ongoing surveillance and care. She discusses how this blood-based testing helps monitor disease activity, informs conversations with her medical team, and provides another tool for navigating life after treatment. In this conversation, Wendy opens up about: What ctDNA testing is and how it works How she incorporates ctDNA into her surveillance plan The emotional realities of monitoring after metastatic disease Living with hope, uncertainty, and gratitude as an NED survivor Register for Eye on ctDNA Webinar on May 22! https://events.zoom.us/ev/AvuhW89ZCjUP5wdMLqfUIHZv66yDDvXNS4Cws4X9M9okF1pnf-ax~AsOT8AphEb5PJVQjLmAyI6LsBZCgLhHe0tWYJREvI-AbmKVVmO-VUGyvCA   Hear more of Wendy's story:    Enucleation 101 Panel: https://youtu.be/fmzI_QeB5mM   Eye on Mental Health 2026 - patient panel participant (omit this if you can't find the recording or its not up)    Information on Signatera: https://www.natera.com/info/monitor-cancer/?utm_source=goog_na_sem&utm_medium=cpc&utm_campaign=4440280632&utm_keyword=bladder-cancer-check&utm_content=natesign_ubr_bladder_na&utm_id=natesign86421&gclsrc=aw.ds&gad_source=1&gad_campaignid=23805042236&gclid=Cj0KCQjwh-HPBhCIARIsAC0p3cdRcVraC3zQMJmLaetu_jgIX2Bt12wY5vs5I6sd8YB13rK8GI-VBnMaAuDVEALw_wcB   This episode offers a patient-centered perspective on an evolving area of cancer care and highlights how new technologies are helping empower patients in their journeys.

Welcome to OncLive On Air®! I'm your host today, Courtney Flaherty.OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions. In today's episode, Michael J. Pishvaian, MD, PhD, sat down to discuss the evolving role of biomarker-directed strategies in gastrointestinal (GI) oncology, as well as the importance of early comprehensive testing to identify molecular drivers and resistance mechanisms when approaching frontline treatment selection and sequencing. Pishvaian serves as director of the Gastrointestinal, Developmental Therapeutics, and Clinical Research Programs for the Johns Hopkins Kimmel Cancer Center in the National Capital Region.Pishvaian began the discussion by highlighting the shift from a disease-site-specific approach to a molecularly defined paradigm, noting that microsatellite instability–high status and NTRK fusions now dictate therapy regardless of tumor origin. He reviewed the transformational data from the phase 3 HERIZON-GE-01 trial (NCT04276493), positing that zanidatamab (Ziihera) could become the new standard of care for HER2-positive upper GI cancers due to unprecedented survival outcomes. He also emphasized the emergence of Claudin 18.2-directed therapies, noting that data from the phase 2 ILUSTRO study (NCT03505320) demonstrates remarkable progression-free survival when adding zolbetuximab (Vyloy) to mFOLFOX6 and nivolumab (Opdivo) for high-expressing subgroups.The conversation then shifted to colorectal cancer, where Dr. Pishvaian detailed how data from the phase 3 BREAKWATER trial (NCT03845036) has "locked in" a paradigm requiring frontline testing for BRAF V600E mutations to guide the use of encorafenib (Braftovi) plus cetuximab (Erbitux). He also discussed the "care revolution" in KRAS inhibition, spotlighting the significant survival benefits seen with daraxonrasib in pancreatic cancer and the potential for novel allele-specific inhibitors to combat disease resistance.Finally, Pishvaian addressed the practicalities of implementation, noting that testing rates in the community remain low. He advocated for prioritizing testing, including liquid biopsies and ctDNA, at the time of initial diagnosis to ensure no patient is left behind.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Petros Grivas, MD, PhD Could emerging biomarkers redefine how we assess response and recurrence risk in muscle-invasive bladder cancer? To find out, Dr. Charles Turck speaks with Dr. Petros Grivas about the key findings from the phase 3 NIAGARA trial. Together, they explore how perioperative durvalumab impacts circulating tumor DNA (ctDNA) clearance and clinical outcomes, including event-free and overall survival. Their conversation also highlights the prognostic value of ctDNA and the potential for urinary tumor DNA to more closely correlate with pathologic complete response. Dr. Grivas is a Professor in the Division of Hematology and Oncology at the University of Washington School of Medicine, as well as the Clinical Research Division at the Fred Hutchinson Cancer Center, where he's also the Medical Director of the International Program and of local and regional outreach.

Featuring perspectives from Dr Stacey A Cohen, Dr Christopher Lieu and Dr Jenny Seligmann, moderated by Dr Lieu, including the following topics: Role of circulating tumor DNA (ctDNA) testing in the escalation of treatment for Stage II and deescalation for Stage III colon cancer (0:00) Impact of timing on the clinical relevance of ctDNA minimal residual disease test results in localized colorectal cancer (8:58) Approach to managing Stage III colon cancer with ctDNA-positive results after adjuvant treatment (13:35) CME information and select publications

In this podcast, experts Neil Iyengar, MD; Kelly Elizabeth McCann, MD, PhD; and Wassim Mchayleh, MD, MBA, FACP, discuss the clinical applications and current evidence for using circulating tumor DNA (ctDNA) testing in early-stage and metastatic breast cancer.

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Guru P. Sonpavde, MD What if molecular relapse in muscle-invasive bladder cancer (MIBC) could be detected early enough to better inform treatment decisions? To find out, Dr. Charles Turck speaks with Dr. Guru Sonpavde to explore new IMvigor011 findings presented at the 2026 ASCO Genitourinary Cancers Symposium. Their discussion highlights how ctDNA monitoring identifies early recurrence risk, captures real-time immunotherapy activity, and positions ctDNA clearance as a powerful prognostic marker. Dr. Sonpavde is the Medical Director of Genitourinary Oncology and the Phase I Clinical Research Unit, and the Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute in Orlando.

In this episode, Dr. Aly-Khan Lalani, Dr. Christopher Wallis, and Dr. Alex Wyatt walk through the fundamentals of clinical genomics and why it matters for routine practice. They discuss which alterations matter in prostate cancer, germline vs. somatic testing, ctDNA test use cases and limits, and more.Dr. Alex Wyatt is an Associate Professor in Urologic Sciences and holds the President's Excellence Chair in Precision Oncology at the University of British Columbia. He is also a Senior Scientist at the Vancouver Prostate Centre and BC Cancer, where his work focuses on advancing clinical genomics and precision oncology in prostate cancer.This podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.ca

In this episode of the Oncology Brothers podcast, we kicked off a three-part series on colorectal cancer, starting with the current treatment algorithm. They are joined by Dr. Smitha Krishnamurthi, a GI medical oncologist from the Cleveland Clinic, who walks through the evolving standard of care from early-stage disease all the way to refractory metastatic settings. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Apple Podcast: https://podcasts.apple.com/us/podcast/oncology-brothers-practice-changing-cancer-discussions/id1653340966 Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Key topics discussed included: • The evolving role of ctDNA as both a prognostic and predictive tool in stage two and three colon cancer, including its utility in oligometastatic disease surveillance. • Neoadjuvant versus adjuvant immunotherapy in MSI-high resectable colon cancer, comparing the NICHE-2 and ATOMIC trial approaches and when to use each. • Single-agent versus dual checkpoint inhibition with Nivo-Ipi for MSI-high metastatic disease, based on CHECKMATE-8HW data showing a PFS hazard ratio of 0.21. • Sequencing strategies in RAS-mutant and RAS wild-type metastatic colorectal cancer, including the role of sidedness, anti-EGFR therapy, and refractory options like fruquintinib, TAS-102, and regorafenib. Join us for this comprehensive discussion on colorectal cancer management in 2026. Don't forget to like, subscribe, and check out our other episodes for more insights on oncology! #ColorectalCancer, #MSIHigh, #BRAFV600E, #ctDNA, #GIOncology, #OncologyBrothers

Featuring an interview with Dr Natalie Vokes, including the following topics: Perioperative minimal residual disease (MRD) detected by circulating tumor DNA (ctDNA) testing in patients with lung cancer (0:00) Ohara S et al. Clinical significance of perioperative MRD detected by ctDNA in patients with lung cancer with a long follow-up data: An exploratory study. JTO Clin Res Rep 2024;6(3):100762. Abstract Masuda K et al. MRDSEEKER (JCOG2111A): A prospective study to evaluate MRD and its association with prognosis in curative-intent NSCLC. World Conference on Lung Cancer 2025;Abstract P3.18.04.  Zhou C et al. IMpower010: Biomarkers of disease-free survival in a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC. ESMO IO 2021;Abstract 2O. MRD analysis of adjuvant therapy with osimertinib for resected EGFR-mutated Stage IB to IIIA non-small cell lung cancer (NSCLC) (8:28) Herbst RS et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med 2025;31(6):1958-68. Abstract MRD analyses of perioperative chemoimmunotherapy for resected NSCLC (15:12) Forde PM et al. Overall survival with neoadjuvant nivolumab plus chemotherapy in lung cancer. N Engl J Med 2025;393(8):741-52. Abstract  ctDNA dynamics in advanced NSCLC treated with immunotherapy (20:56) Vokes NI et al. Circulating tumor DNA (ctDNA) dynamics and survival outcomes in patients (pts) with advanced non-small cell lung cancer (aNSCLC) and high (>50%) programmed cell death ligand 1 (PD-L1) expression, randomized to cemiplimab (cemi) vs chemotherapy (chemo). ASCO 2023;Abstract 9022. Anagnostou V et al. ctDNA response after pembrolizumab in non-small cell lung cancer: Phase 2 adaptive trial results. Nat Med 2023;29(10):2559-69. Abstract Anagnostou V et al. A biomarker-directed, multi-center phase II/III study of ctDNA molecular response adaptive immuno-chemotherapy in patients with non-small cell lung cancer (BR.36). ASCO 2025;Abstract TPS8669. CME information and select publications

Featuring perspectives from Dr Stacey A Cohen, Dr Christopher Lieu and Dr Jenny Seligmann, moderated by Dr Lieu, including the following topics: Adjuvant treatment planning for Stage II or III microsatellite instability-high colon cancer (0:00) Roles of circulating tumor DNA (ctDNA), POLE mutations and advanced age in adjuvant treatment planning (6:08) Role of ctDNA in adjuvant treatment planning for Stage III colon cancer (12:31) CME information and select publications

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Pooja Ghatalia, MD Emerging evidence is redefining bladder preservation strategies in muscle-invasive bladder cancer, with circulating tumor DNA (ctDNA) offering a novel approach to response-adapted care. Joining Dr. Charles Turck to review findings from the phase II RETAIN trials, which highlight how ctDNA clearance correlates with improved metastasis-free survival and informs risk stratification, is Dr. Pooja Ghatalia. She also examines the strengths and limitations of ctDNA, including its prognostic value for systemic recurrence and its inability to reliably detect localized disease. Dr. Ghatalia is an Associate Professor in the Department of Hematology and Oncology at Fox Chase Cancer Center at Temple University Hospital in Philadelphia, and she presented this research at the 2026 ASCO Genitourinary Cancers Symposium.

This podcast features Dr. Mike Glover from MDACC discussing recent advances in germ cell tumor research, focusing on novel biomarkers like microRNA and ctDNA, and emerging therapies targeting Claudin-6. The conversation explores how these innovations could transform diagnosis, prognosis, and treatment strategies.

Welcome to the Oncology Brothers podcast! In this episode, we dived into the evolving treatment algorithms for bladder cancer following the latest data presented at GU ASCO 2026. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Apple Podcast: https://podcasts.apple.com/us/podcast/oncology-brothers-practice-changing-cancer-discussions/id1653340966 Follow us on social media: X/Twitter: https://twitter.com/oncbrothers ⁠Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Join us as we explore: The role of immunotherapy in non-muscle invasive bladder cancer, highlighting the recent positive trials: CREST with Sasanlimab and POTOMAC with Durvalumab. Insights on the current standard of care and the implications of combining BCG with immunotherapy. The shift in treatment strategies for muscle-invasive bladder cancer, including the new standard of care with the EV-Pembro combination and its impact on pathologic complete response rates. The challenges and considerations in managing side effects associated with new therapies, as well as the importance of patient selection and coordination between urologists and medical oncologists. The emerging role of ctDNA in guiding treatment decisions and the ongoing discussions around the sequencing of therapies in refractory settings. Hope you enjoy this informative discussion that aims to keep you up to date in the world of cancer treatment, here focusing on bladder cancer. Subscribe to our channel for more episodes and discussions on the latest in oncology! #BladderCancer, #NMIBC, #MIBC, #Immunotherapy, #GU26, #OncologyBrothers

In this episode of JCO Article Insights, host Dr.  Ash Gurumurthi summarizes JCO articles, "Phased Variant–Supported Circulating Tumor DNA as a Prognostic Biomarker After First-Line Treatment in Large B-Cell Lymphoma: Findings From the DIRECT Study" and " Prospective Validation of Circulating Tumor DNA Measurable Residual Disease After First-Line Therapy in Large B-Cell Lymphoma" TRANSCRIPT Ash Gurumurthi: Hi and welcome to JCO Article Insights. I'm your host, Ash Gurumurthi, and today we will be discussing two articles, both published in the Journal of Clinical Oncology, on the real-world utility of circulating tumor DNA (ctDNA) MRD in newly diagnosed large B-cell lymphoma. The first study is the article "Phased-Variant-Supported Circulating Tumor DNA as a Prognostic Biomarker After First-Line Treatment in Large B-Cell Lymphoma: Findings From the DIRECT Study" by Dr. Joanna Krupka and colleagues in the United Kingdom. For the sake of convenience, I'll refer to this as the DIRECT study. The second study is "The Prospective Validation of Circulating Tumor DNA Measurable Residual Disease After First-Line Therapy in Large B-Cell Lymphoma" by Dr. Steven Wang and colleagues in the Netherlands, referred to as the HOVON 902 study. By way of background, I wanted to talk about MRD in hematolymphoid malignancies. Nodal diseases have lacked a robust biomarker for end-of-treatment response. They have relied historically on PET scans interpreted using the semiquantitative Deauville 5-point scale, which has a high negative predictive value but a limited positive predictive value. The poor positive predictive value for survival results in extended follow-up with serial imaging for risk stratification with unnecessary and invasive biopsies. There have been recent revolutionary advancements in ctDNA MRD in B-cell lymphoma. The use of ctDNA in lymphoma began with CAPP-seq, which tracked single nucleotide variants that were tumor specific but was limited by excessive background sequencing noise with false negatives. To overcome this, Dr. Kurtz and colleagues developed the proprietary PhasED-seq assay. This tracks well-recognized phased mutations on the same DNA strand in cis configuration within hypermutated regions that are unique to B-cell lymphoma. Using this method, they pushed their limit of detection at 95%, the so-called LOD95, to 0.7 parts per million under optimal circumstances with 120 nanograms of input cell-free DNA from plasma. Based on the use of the PhasED-seq assay in trials of newly diagnosed large B-cell lymphoma with the use of investigational agents, the NCCN currently recommends consideration of ctDNA MRD assay with a detection limit of less than 1 part per million if biopsy is not feasible for a positive end-of-treatment PET. However, I believe this threshold needs reconsideration given it is based on an ideal assay LOD95 under optimal circumstances rather than sample-specific LOD95. Real-world validation of the role of end-of-treatment ctDNA and appropriate thresholds for sample-specific LOD95 were lacking until the publication of these two studies. The DIRECT and the HOVON 902 studies were multicenter, prospective trials using real-world cohorts of newly diagnosed large B-cell lymphoma treated with standard anthracycline immunochemotherapy, ie, R-CHOP chemotherapy. They validated end-of-treatment ctDNA MRD response measured on a phased-variant platform and found them to be strongly prognostic for relapse and survival. This was independent of PET imaging or baseline clinical prognostication like the International Prognostication Index, the IPI. They also demonstrated a threshold with an LOD95 of approximately 1 in 100,000 is necessary for clinical utility. Both trials recruited over a similar period between 2020 to 2023, with the DIRECT study conducted within the National Health Service in the United Kingdom and the HOVON 902 as a national study in the Netherlands. For survival analysis, only patients who reached the landmark event of end of treatment with an available ctDNA MRD sample without progressive disease or death at that time point were included. These studies evaluated similar-sized cohorts with 134 patients for HOVON 902 and 151 patients for the DIRECT study. As expected, their baseline demographics are reflective of a real-world population of newly diagnosed cases with large B-cell lymphoma. Although both used comparable statistical methodologies with time-to-event analysis, the primary outcomes vary, making headline comparisons quite challenging. The DIRECT study utilized the time to tumor progression, censoring death unrelated to disease. This was done to isolate the molecular impact of detectable ctDNA at the end of treatment. In contrast, the HOVON 902 study used progression-free survival, which counts all-cause mortality as an event. This naturally results in lower event-free rates for PFS compared to TTP in the DIRECT study. The trials differed in their choice of phased-variant platforms, with the DIRECT study developing an independent, fully open-source phased-variant ctDNA assay. This has been released on GitHub. In contrast, the HOVON 902 study utilized PhasED-seq by Foresight Diagnostics, which is currently the only proprietary and commercially available phased-variant assay for lymphoid malignancies. Interestingly, despite the differences in platforms and the primary end points, the results were remarkably consistent. The DIRECT study found a highly significant difference in the 2-year TTP rate of 96% in those with undetectable ctDNA MRD at the end of treatment compared to 45% in those with detectable ctDNA, with a hazard ratio of 15. Similarly, the HOVON 902 study found a significantly superior 3-year PFS of 85% in those with undetectable ctDNA compared to 17% with detectable ctDNA, with a hazard ratio of 10. Crucially, both studies found end-of-treatment ctDNA MRD significantly outperformed PET response assessment for long-term PFS. In fact, for the end point of PFS in both trials, the baseline IPI lost all statistical significance in both univariate and multivariable analysis when accounting for ctDNA MRD and PET status at the end of treatment. While both studies demonstrate the superiority of ctDNA MRD compared to PET in predicting survival, interestingly, the combination of both tests appeared to be complementary in identifying the highest-risk group. The HOVON 902 study identified 13 patients who were double positive, ie, they were positive with end-of-treatment PET and detectable ctDNA MRD. Every single one of these patients progressed over a 3-year period with a dismal overall survival of 17%. The DIRECT study mirrored these findings with the same double-positive group having a 2-year time to progression rate of 23%. Given consistency in identifying the poor outcome of this double-positive population in both studies, this is clearly a group that would benefit from trial-based approaches like consolidation or, alternatively, frequent surveillance for clinical relapse. On the other hand, the best-performing group was the double negative, ie, those who had achieved PET negative and ctDNA undetectable at the end of treatment. The double-negative group had a 2-year time to progression of 97% in the DIRECT study and a 3-year PFS of 88% in the HOVON 902 trial. This is quite impressive. Based on these findings, we can anticipate that ctDNA may complement rather than wholly replace PET at the end of treatment for response assessment. Perhaps the most critical finding from both studies challenged current NCCN-recommended ctDNA MRD sensitivity threshold of achieving less than one part per million. While phased-variant assays can theoretically detect this, this is under optimal conditions, specifically 120 nanograms of input cell-free DNA. In both trials, only 3% of samples could achieve this sensitivity, with the vast majority limited to a sample-specific LOD95 of approximately 1 in 100,000 informative reads. The primary constraint was simply limited plasma volume collected, a denominator problem of input cell-free DNA. For example, the HOVON 902 study had a median plasma volume of 5 mL, yielding 20 nanograms of input DNA. The DIRECT study elegantly demonstrated bridging the gap to attain the NCCN standard of LOD95 of less than 1 part per million is practically impossible. This would require greater input DNA, attained through a 20- to 30-milliliter collection of plasma rather than the standard 10 milliliters, and a massive 20- to 40-fold increase in sequencing depth. With the current real-world sensitivity of roughly 1 in 100,000 in both these studies, the negative predictive value is already nearly at 90%. There is going to be diminishing returns for further analytical sensitivity. This strongly suggests that the NCCN guidelines should be updated to prioritize achievable sample-specific LOD95 rather than assay-specific theoretical limits. Collectively, these studies validate the real-world utility of ctDNA MRD as an independent predictor of long-term outcomes following first-line therapy of large B-cell lymphoma. Finally, after two decades of the default R-CHOP for all, the field of aggressive large B-cell lymphoma is taking leaps and bounds by integrating ctDNA MRD with the current wave of bispecific and cellular therapies. I want to now leave you with my five key clinical takeaways from both these studies. ●        Firstly, ctDNA MRD is a more potent independent predictor of outcome than end-of-treatment PET/CT and baseline IPI. ●        Second, ctDNA MRD in first-line large B-cell lymphoma is already reshaping clinical trial space with therapeutic escalation and de-escalation strategies based on ctDNA kinetics during treatment, as well as identifying candidates with persistent ctDNA at the end of treatment for consolidation approaches. ●        Thirdly, this technology is ready for prime time. Whether this is through Foresight's PhasED-seq assays or the open-source method released by the DIRECT group, academic centers can now operationalize this in routine clinical care. ●        Fourth, biology clearly provides a ceiling. Current sensitivity goals of less than one part per million as recommended by the NCCN are limited by the actual amount of cell-free DNA we can extract from a patient's blood, not just the assay's technology. I believe these two studies will inform the NCCN's next revision to move away from theoretical assay limits to a more realistic sample-specific LOD95 of approximately 1 in 100,000. ●        Finally, it appears that the end-of-treatment ctDNA MRD test may be complementary to PET/CT rather than a replacement. Clearly, the best outcomes are seen in double-negative patients, while double-positive results, ie, positive end-of-treatment PET and detectable ctDNA at the end of treatment, identify a group with an extremely high risk of early progression who may need early intervention. Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries, and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Welcome to OncLive On Air®! I'm your host today, Ashling Wahner.OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.In today's episode, Marina Baretti, MD, discussed the real-world utilization of tissue-free circulating tumor DNA (ctDNA) monitoring in cholangiocarcinoma (CCA). Baretti is an assistant professor and the Jiasheng Chair in Hepato-Biliary Cancer Research at Johns Hopkins University School of Medicine, as well as co-director of the Liver and Biliary Cancer Multidisciplinary Clinic at the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland. In the exclusive interview, Dr Baretti discussed multiple potential roles for ctDNA testing in CCA management, including the detection of minimal residual disease following curative-intent surgery, longitudinal monitoring of treatment response in advanced disease, and identification of emergent resistance mechanisms with targeted therapy.Baretti also reviewed findings from a small real-world observational analysis of 44 patients, in which a tissue-free ctDNA assay demonstrated high sensitivity, detecting variant allele frequencies as low as 0.2% and identifying actionable alterations in most patients; ctDNA dynamics also correlated with response and enabled early detection of resistance alterations, including secondary FGFR2 mutations, prior to radiographic progression in select cases.Lastly, Baretti contextualized these findings within the broader treatment landscape by reviewing data from the phase 2 FIGHT-202 trial (NCT02924376), which supported the FDA approval of pemigatinib (Pemazyre) in patients with previously treated CCA harboring FGFR2 fusions or rearrangements. Real-world data have confirmed the efficacy and safety of this agent observed in clinical trials, reinforcing the importance of comprehensive molecular profiling._____That's all we have for today! Thank you for listening to this episode of OncLive On Air. Check back throughout the week for exclusive interviews with leading experts in the oncology field.For more updates in oncology, be sure to visit www.OncLive.com and sign up for our e-newsletters.OncLive is also on social media. On X and BlueSky, follow us at @OncLive. On Facebook, like us at OncLive, and follow our OncLive page on LinkedIn.If you liked today's episode of OncLive On Air, please consider subscribing to our podcast on Apple Podcasts, Spotify, and many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!Thanks again for listening to OncLive On Air.*OncLive On Air is available on: Apple Podcasts, Spotify, CastBox, Podcast Addict, Podchaser, RadioPublic, and TuneIn.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

In this JCO PO Article Insights episode, host Jordan Goldstein summarizes the article, "Generic Protocols for Analytical Validation of Tumor-Informed Circulating Tumor DNA Assays for Molecular Residual Disease: The Blood Profiling Atlas in Cancer's Molecular Residual Disease Analytical Validation Working Group Consensus Recommendation" by Baden et al. TRANSCRIPT

In this episode of the Eye Believe Podcast, Danet sits down with Dr. Vincent Ma to discuss an emerging and exciting tool in cancer monitoring: ctDNA (circulating tumor DNA)—or as Dr. Ma memorably calls it, “cancer poop.”   Dr. Ma breaks down this complex topic in a way that's easy to understand, explaining: What ctDNA is and how it works How it can be tested and monitored over time How he's using ctDNA in his practice to better track disease and guide care for his patients   This conversation offers a unique look at how innovative science is becoming more accessible—and how tools like ctDNA may help improve early detection, monitoring, and personalized treatment strategies.   Whether you're a patient, caregiver, or simply curious about the future of cancer care, this episode provides valuable insight into a rapidly evolving area of research.   Tune in to learn how something as unexpected as “cancer poop” could play an important role in advancing cancer care.

In this episode, Sam S. Chang, MD, MBA, and Matthew D. Galsky, MD, discuss the rapidly evolving treatment landscape in bladder cancer, highlighting new therapeutic options, emerging clinical trial data, including the latest results presented at ASCO GU 2026, and the growing role of biomarkers and multidisciplinary care, including: New treatment options for BCG-unresponsive non–muscle-invasive bladder cancer Intravesical therapies such as nadofaragene and N-803 The role of ctDNA in measurable residual disease detection Presenters: Sam S. Chang, MD, MBA Patricia and Rodes Hart Chair of Urologic Surgery Chief Surgical Officer Vanderbilt Ingram Cancer Center Nashville, Tennessee Matthew D. Galsky, MD Lillian and Howard Stratton Professor of Medicine Icahn School of Medicine at Mount Sinai Director, Genitourinary Medical Oncology Co-Leader, Cancer Clinical Investigation Program Associate Director for Translational Research Tisch Cancer Institute New York, New York Link to full program: https://bit.ly/479RgQn Get access to all of our new podcasts by subscribing to the Decera Clinical Education Oncology Podcast on Apple Podcasts, YouTube Music, or Spotify. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

In today's episode of OncLive On Air®, Jonathan Trent, MD, PhD, and Neeta Somaiah, MD, sat down to discuss the evolving role of circulating tumor DNA (ctDNA) testing in gastrointestinal stromal tumors (GIST), as well as the importance of identifying both initial drivers of disease and secondary resistance mechanisms when approaching frontline treatment selection and overall therapeutic sequencing.Trent is a professor of medicine, associate director of Clinical Research, and director of the Sarcoma Medical Research Program at the University of Miami Miller School of Medicine, in Florida. Somaiah is a professor and chair of the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.Drs Trent and Somaiah began their discussion by highlighting the rarity of GIST, underscoring the importance of evaluation at specialized sarcoma centers and comprehensive molecular testing to identify driver alterations.Somaiah then reviewed the molecular landscape of GIST, noting that approximately 70% to 80% of tumors harbor activating mutations in the KIT gene, while additional cases involve rarer alterations such as BRAF or NTRK fusions. Of note, resistance to imatinib (Gleevec) frequently emerges through secondary mutations in KIT exons 13 or 17, which can influence sensitivity to subsequent TKIs.ctDNA testing may help detect these resistance mechanisms, particularly at progression or when tissue is limited, enabling clinicians to refine sequencing strategies, both experts explained. They also discussed how mutation-informed approaches may guide treatment selection, including emerging strategies such as combining sunitinib (Sutent) with bezuclastinib to address resistant clones involving KIT exon 13 or 17 alterations.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

Dr. Monty Pal and Dr. Vamsi Velcheti discuss the evolving treatment landscape in EGFR-mutated non-small cell lung cancer, including landmark trials like FLAURA2, novel drug therapies, and the growing importance of ctDNA and MRD testing. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, I'm truly delighted to introduce Dr. Vamsi Velcheti, who's a professor of medicine and the chief of hematology-oncology at the Mayo Clinic in Jacksonville, Florida. We'll be discussing the expanding treatment landscape in EGFR-positive lung cancer and how to navigate the challenges of balancing treatment efficacy, toxicity, and patient quality of life in the EGFR-positive space.  Just FYI, our full disclosures are available in the transcript of this episode.  Vamsi, it's so great to have you on the podcast. Thank you so much for being here. Dr. Vamsi Velcheti: Thank you, Monty. It's a pleasure to be here with you. It's a really exciting topic and there are a lot of updates in the EGFR space. Dr. Monty Pal: So, I'm going to need your help with this because I'll be honest with you, I see very little lung cancer, if any, in my practice. I'm pretty much exclusively kidney cancer these days. I'm coming on 20 years at City of Hope now, and I still remember when trials like ECOG 1599 were presented with, you know, platinum doublets. And, of course, the field has changed a lot since then. But tell us a little bit about the first-line landscape, and I think just for the sake of time, we're going to stick with EGFR-positive disease here. What does it look like these days? Dr. Vamsi Velcheti: Monty, the foundation of care remains the third-generation EGFR inhibitors. These are selective EGFR inhibitors, like osimertinib. We've had an evolution of the development of these TKIs. Like, you know, we had the first-generation, second-generation, not-so-selective EGFR inhibitors. Now we have mutant-selective EGFR inhibitors in the clinic, and they're doing a really good job. And these are quite effective in patients who have classical activating mutations. But the reality is that these have not been transformative. These agents have fundamentally changed the response patterns, excellent CNS penetration, and very good tolerability profile. However, we don't see a lot of durability in terms of the response. So, what's different today is now there have been several trials in combination with these third-generation EGFR inhibitors that have really laid the foundation of how we kind of think about EGFR-positive disease. At the high level, there are a lot of challenges to selecting the patients for these combination-based modalities. I'm assuming we'll be talking more about these different trials and different approaches. Some of these combination-based strategies have really moved the needle in terms of improving overall survival and really improving long-term outcomes and durability in our patients. Dr. Monty Pal: And we are going to get into the weeds on this in just a moment. But I did kick off this podcast talking about chemotherapy, ECOG 1599. It does seem as though chemotherapy is still a component of management in advanced non-small cell lung cancer. So, can you tell us about, perhaps first, you mentioned osimertinib, you know, some of these next-generation EGFR inhibitors. Tell us about the role of chemo plus osimertinib. Dr. Vamsi Velcheti: That's exactly where I was going with the combination-based strategies. You know, we first started off with our earlier trials in the EGFR space evaluating the question of, are targeted therapies, are these highly effective, third-generation, EGFR-selective inhibitors, superior to platinum-doublet chemotherapy? And we've had multiple trials demonstrating that, like the FLAURA trial and in the past with second-generation EGFR inhibitors like erlotinib and gefitinib and afatinib. So, we know that these TKIs actually perform better than platinum-doublet chemotherapy. Now, we have a large, global, phase 3 trial data from the FLAURA2 trial, which looks at the question, "Hey, you know, osimertinib is better than chemotherapy, platinum-doublet chemotherapy. Can we do even better by combining osimertinib with platinum-doublet chemotherapy?" So, FLAURA2 answered that question. This is a large, phase 3 trial, and it's a positive trial with improved durability of disease control and improving overall survival with combination with chemotherapy. So, it's a very important and landmark trial, and essentially combining osimertinib with a platinum-based chemotherapy improved responses, deepened responses, and improved overall survival and really changing the disease trajectory. And this strategy is definitely compelling, especially in patients who have certain clinical high-risk features like, you know, patients who have high disease burden or patients who are sometimes having rapid disease progression early on osimertinib, especially with patients who have a lot of visceral disease burden. So, intensifying treatments up front could alter the natural trajectory of the disease. Dr. Monty Pal: So, you sort of alluded to this in that last part there, but is that kind of how you in clinical practice select? Is it based on, you know, visceral involvement? Is it based on rapidity of disease where you think about adding chemotherapy to osimertinib? Maybe you can give us the corollary. Which patients do you just use osimertinib alone in, for instance? Dr. Vamsi Velcheti: Definitely, there are some patients who have low disease burden and they have the classical mutations, like an exon 19 deletion. And these patients, especially if they don't have a lot of disease burden, they don't have CNS involvement, there may be a subset of patients who could just do fine on osimertinib of course, with close monitoring of the disease. I guess we'll get into that later, how do we do that with either ctDNA or like closer imaging or both. So, there may be some opportunity to kind of escalate patients' treatments based on certain clinical characteristics or radiographic characteristics or certain biological characteristics informed by ctDNA or other approaches. Dr. Monty Pal: No, that's interesting. And you're right, we will chat about ctDNA in just a bit. But before we get there, I think one of the big agents that has really sort of come to the fore in advanced non-small cell lung cancer is amivantamab. I've heard a lot about this in the context of even kidney cancer because in certain subsets, I'm interested in MET-directed therapies and so forth, right? So maybe tell us a little bit about the mechanism of amivantamab first, and then maybe tell us about this pivotal MARIPOSA trial where it's combined with lazertinib. Dr. Vamsi Velcheti: So, the MARIPOSA trial compared lazertinib alone with amivantamab plus lazertinib. And this trial demonstrated overall survival advantage, and there were key differences in terms of tolerability and the safety of amivantamab, which is an EGFR and MET bispecific, and there were certain kind of unique toxicity profiles that make it a little different than the intensification approach with chemotherapy through the FLAURA2 trial. So, there's a trade-off in terms of the toxicity profile. It's a different agent and a different management protocol in terms of dermatological toxicity management that clinicians need to be comfortable with. And also, there are certain unique issues in terms of amivantamab; there's a higher rate of infusion-related reactions, there's an increased risk for edema and VTEs because of amivantamab. Certainly a different toxicity profile, different management paradigm there in terms of longitudinal care of these patients requiring dermatological care and like, you know, close monitoring and prophylaxis VTEs. But having said that, definitely it's a different strategy, and it kind of changes the biology and the natural history of the cancers, and we do see some durability of responses that we see with the MARIPOSA. So, it's certainly a great alternative, at least for some patients. Dr. Monty Pal: That was a great overview of MARIPOSA. Now comes the really difficult question, which is, how do you choose between the two? You have these two great options, right, for EGFR-positive patients. You've already highlighted some of the distinctions in terms of toxicity. I think the audience is well aware of the side effects of chemo-doublet, perhaps even the EGFR-based therapies. Amivantamab is quite new. Give us a sense of how you in clinical practice decide between the two potential options here. Dr. Vamsi Velcheti: Yeah, I think that's the big challenge. I think these are two independent strategies that have evolved through the phase 3, and both of them have demonstrated overall survival benefit. So, the way I think about this is in three dimensions, right? Like, the disease biology, the patient priorities, and feasibility of care delivery. So, when I talk about the disease biology, you know, the mechanism is very different, and MET is a very dominant driver of disease in EGFR-altered patients and it's a significant mechanism of resistance, acquired resistance to TKIs. So, certainly I think there's a patient population that could benefit from a MET-directed therapy up front. However, we don't have great data to kind of really demonstrate how using amivantamab in the front line is going to change that. And are there like perhaps like some patients who we could identify who would benefit from such a strategy? Very recently, there have been some approvals in the second-line setting in lung cancer, not in the EGFR space, but like in generally in lung cancer, with the MET ADCs, and those drugs are approved with a companion diagnostic, which requires MET IHC testing. So, what has happened, at least in large academic practices and also I think in the community now, they have been checking for MET IHC expression more routinely in lung cancer. What we have been doing in our institution is we have been doing MET IHC as a reflex for all patients with EGFR, not just EGFR, but all non-small cell lung cancer patients. What that has done is now, like, we have been increasingly testing patients with EGFR for MET. And there's clearly a subset of patients who have de novo MET expression and a high MET expression. And those patients, I've been kind of like preferentially treating them with the MARIPOSA regimen. But again, I have to caution the audience that we still don't have data that MET IHC is going to help us make those decisions, whether it's better than like a FLAURA2 regimen. But however, in the second-line setting in the CHRYSALIS trial, we know that MET is a very powerful predictor of response to amivantamab. We really need more data there, but that's what I have been doing in my practice. But also, there's a lot of patient preference here. Like, there are some patients who don't want chemotherapy, and they want a non-chemotherapy approach. So, certainly there are some patients who prefer to have amivantamab. And now with the amivantamab, the subcutaneous version, the infusion reactions and the logistics of actual administration of amivantamab are more favorable with the subcutaneous approval. So, those are some of the elements that we need to take into account. Dr. Monty Pal: Well, I want to hone in on that because this subcutaneous administration route has been a big debate that I've seen on social media. Tell us, how much easier does it actually make the amivantamab experience? Does it cut down on the rash? Is it just infusion reactions? What's been your clinical experience? Vamsi Velcheti, MD: So, the subcutaneous administration of amivantamab has definitely improved the infusion reaction issue. Very rarely patients have infusion reaction now with the subcutaneous injections. And also, the infusion time is much, much shorter. Like we don't need a lot of infusion time, which is sometimes a challenge in busy infusion clinics. We need to take that into account. As far as the impact of the subcutaneous formulation on dermatological toxicity, we haven't really seen significant difference in terms of the intensity or rates of dermatological toxicity with subcutaneous. The benefits are really with the infusion reaction, the ease of administration. And interestingly, in the PALOMA trial, it also seems to be, even though this was not the primary endpoint of the study, there seems to be some suggestion that the subcutaneous amivantamab seems to have improved OS compared to the IV amivantamab. We don't really understand why, but that's a finding from the trial that's very intriguing. Dr. Monty Pal: That is really fascinating. I'm kind of curious to see how that's going to pan out. I'm going to shift gears a little bit here. And, you know, as we sort of close, I wanted to talk a little bit about biomarkers. I mean, this is obviously not a lung cancer-specific issue. It's something we think about across the board. But what I will say is that there are certain commonalities, and in bladder cancer, we think a lot now about ctDNA. But you've been way ahead of the game in lung cancer. Tell us how you guys use ctDNA, maybe both from the standpoint of monitoring for mutational status, but if you can, maybe offer some insights into some of these new MRD tests that are available too. Dr. Vamsi Velcheti: Yeah, it's rapidly evolving. Certainly, I think in the lung cancer space, you know, this has really kicked off in the lung cancer space with incorporating ctDNA into the workflow. Of course, you know, like baseline evaluation, we still kind of heavily rely on tissue genomic sequencing. But as you know, with targeted therapy, a lot of these patients have disease that evolves over time, and changes in terms of mutational pattern driving acquired resistance is a major issue across different molecular subtypes. And especially so in EGFR, when there are certain actionable opportunities associated with that transformation. So, we need to kind of have like a longitudinal snapshot of how we monitor these patients. So, the ctDNA has come to be like a tool that has now come to the forefront of clinical workflow, and almost all my patients who are having disease progression have ctDNA for kind of evaluating for resistance and informing treatment decisions, especially in EGFR. But having said that, there are a lot of challenges in terms of using ctDNA as a tool for monitoring. There are a lot of different types of assays and different platforms, and being able to use this as a quantitative tool that would be used along with the CT scans that we routinely use in clinical practice has been a challenge. And I think I would love to hear your perspectives as well, Monty, about how you're thinking about that in bladder and other disease contexts. But having said that, I think there's a lot of opportunity to incorporate ctDNA and MRD assays into clinical decision-making. Right now, in terms of clinical trials and clinical development, there have been some very interesting trials that are currently ongoing, especially in the EGFR space. We know that patients who clear ctDNA, based on some retrospective data and also like some retrospective-prospective data from trials that have already read out, that patients who clear ctDNA early with target therapy tend to do much better. They have a longer durability of response. There may be a subset of patients who have, even though they're having radiographic response, they have persistent ctDNA after a certain time point of initiation of targeted therapy. Those patients may require escalation of therapy. We don't yet know. I can't recommend that as a standard right now because we don't have clinical evidence to support that. But however, some of the clinical trials, like the ELIOS trial that's being done right now, that's actually completed enrollment, we'll hopefully see the results very soon. So, there is an emerging thought that instead of intensifying treatment for all patients with EGFR, there may be a population that may be just fine with frontline osimertinib monotherapy and introducing the intensification strategy at the time of emergence of MRD or progression on ctDNA before radiographic progression. So, there are a lot of adaptive molecular response criteria that we are kind of exploring in clinical trials that could inform how the future is going to look like for EGFR and other perhaps targeted therapies as well. So, it's fascinating, and I think there's a lot of opportunity there. Dr. Monty Pal: You know, you asked for my perspective. I actually think that what you highlighted there is the most interesting opportunity for ctDNA: the ability to de-escalate therapy. In terms of drug development, we've done so much to bring new therapies to patients, and now it's a bit of an embarrassment of riches, but the downside is that I feel like we tend to overtreat a lot of patients in the clinic. So, I definitely view MRD, you know, some of these other ctDNA techniques with methylation and so forth that may not be sort of tumor-dependent or bespoke could be incredibly, incredibly helpful. You touched on sort of the future, right, in this last section here with biomarkers. But give us a sense now in terms of novel drug therapies in the EGFR space. What are you most excited about moving forward in 2026 and beyond? Dr. Vamsi Velcheti: Yeah, I think there's a lot going on in this space, and not just this space, but across lung cancer and others as well. Like looking at the next generation of targets for ADCs. And I think a lot of these have to do with…so far in the drug development space, as you know, the improvements in clinical outcomes has been very incremental. So, we really need to make that big leap. And I think the big leap is not going to come from, in my opinion, from the next ADC, but it's going to come from how we tailor treatments and how we monitor disease better and how do we kind of incorporate the next treatment earlier and not wait for the radiographic progression. So, there's a lot of opportunity there to integrate biomarkers and dynamic biomarkers into clinical trial design and incorporating the recent advances in terms of drug design. You know, we have a lot of assets in the EGFR space, the next-generation EGFR inhibitors that are kind of designed with resistance in mind and rational combination, knowing when to introduce those combinations is also equally important. So, there's a lot going on, really exciting times to be in drug development. The one thing that I really hope will come to the forefront in drug development, not just for lung cancer, but all disease groups, is to kind of really be thoughtful about how we incorporate these really cool molecular monitoring tools and creating a composite score with imaging to be able to like really design the next generation of clinical trials. Dr. Monty Pal: You're so spot-on with that. I definitely think that we're getting to this point where, you know, we could think about the next BiTE, the next CAR-T, the next ADC. But, you know, maybe it's time for us to start really honing in on appropriate applications of these drugs, honing in on the right dose and what have you, because I definitely see some issues there.  Vamsi, this has just been terrific. I really want to thank you so much for sharing your fantastic insights with us today on the ASCO Daily News Podcast, and I really appreciate all your efforts to move the field of lung cancer forward. Dr. Vamsi Velcheti: Thanks, Monty. I really enjoyed the conversation. Dr. Monty Pal: Yeah, this was terrific.  And thanks to our listeners as well. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:     Dr. Monty Pal   @montypal  Dr. Vamsi Velcheti @VamsiVelcheti Follow ASCO on social media:          ASCO on X    ASCO on Bluesky         ASCO on Facebook          ASCO on LinkedIn          Disclosures:       Dr. Monty Pal:      Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview     Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical     Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Vamsi Velcheti:   Honoraria: Galvanize Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, AstraZeneca/MedImmune, GSK, Amgen, Taiho Oncology, Novocure, Regeneron, Takeda, Janssen Oncology, Picture Health Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline

During a visit to Columbia University Irving Cancer Research Center, experts across hematologic oncology shared their perspectives on key trends and developments in their respective fields. These conversations explored novel therapeutic approaches and translational research that may advance the paradigm across different leukemia, multiple myeloma, and lymphoma populations.First, Nicole Lamanna, MD, an associate clinical professor of medicine in the Hematologic Malignancies Section of the Hematology/Oncology Division at Irving Medical Center, discussed relevant advancements in the management of chronic lymphocytic leukemia (CLL). She described how the FDA approval of fixed-duration acalabrutinib (Calquence) plus venetoclax (Venclexta) may affirm a shift away from standard chemoimmunotherapy in the field. Her discussion also emphasized evaluating the adverse effects and benefit/risk profiles of drug classes such as BTK inhibitors and BCL-2 inhibitors during the treatment decision-making process.Next, Rajshekhar Chakraborty, MD, an assistant professor of medicine in the Division of Hematology/Oncology at Irving Medical Center, touched upon critical themes related to the use of bispecific antibodies for patients with multiple myeloma and other plasma cell disorders. Educating providers on the utility of bispecific antibodies in earlier treatment settings, he noted, is one of the important challenges that the field must address to expand usage of these therapies in community practices. He also highlighted findings from the phase 3 MajesTEC-3 trial (NCT05083169) and how they support the clinical utility of teclistamab-cqyv (Tecvayli) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) for patients with relapsed/refractory disease.Finally, Hua-Jay “Jeff” Cherng, MD, an assistant professor of medicine in the Lymphoma Program in the Division of Hematology and Oncology at Irving Medical Center, detailed translational work that may shape clinical practice in the lymphoma space. He spoke about research aiming to move markers like ctDNA and minimal residual disease from “the bench to the bedside” as part of clinical decision-making for patients with diffuse large B-cell lymphoma (DLBCL). Other future focuses, Cherng said, include leveraging molecular genotyping to improve outcomes for higher-risk subgroups or even replacing chemotherapy with less toxic targeted agents.References CALQUENCE® plus venetoclax approved in the US as first all-oral, fixed-duration combination for patients with chronic lymphocytic leukemia in the 1st-line setting. News release. AstraZeneca. February 20, 2026. Accessed March 11, 2026. https://tinyurl.com/38zbx96s Mateos MV, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator's choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients (pts) with relapsed refractory multiple myeloma (RRMM): results of MajesTEC-3. Blood. 2025;146(suppl 2):LBA-6. doi:10.1182/blood-2025-LBA-6

En este episodio, Brian, Tom y Matt Galsky analizan los datos del estudio B15 sobre terapia neoadyuvante para el cáncer de vejiga músculo-invasivo cisplatino-elegible, centrándose en la eficacia de EV-Pembro en comparación con cisplatino-gemcitabina. Exploran la SLE, SG y las implicaciones de la duración del tratamiento así como su individualización. La conversación también aborda el papel del ctDNA en las decisiones terapéuticas, las histologías alternativas y la importancia de la terapia sistémica neoadyuvante. El episodio concluye con reflexiones sobre las futuras direcciones en el tratamiento del cáncer de vejiga y la relevancia de los estudios en curso.

The DYNAMIC duo are back, with Michael climbing the "Everest" of oncology and exploring the role of CTDNA in stage two colorectal cancer. Josh has the easier job of exploring neoadjuvant immunotherapy (ipilimumab and nivolumab) in dMMR advanced colorectal cancer.Both are excellent trials, and a worthy addition to your reading list.Don't forget to check us out on YouTube if that's your thing!Studies discussed in this episode:DYNAMIC-IINICHE-2For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

Featuring an interview with Dr Christopher Lieu, including the following topics: Historical approach to the adjuvant treatment of localized colorectal cancer (CRC) (0:00) Perspectives on earlier-onset colorectal cancer and potential drivers; management of oligometastatic disease (13:16) Overview of cell-free DNA (circulating tumor DNA [ctDNA]) and techniques for its measurement (17:03) Reliability and prognostic capability of ctDNA as a biomarker for clinical status in patients with localized colorectal cancer (21:10) ctDNA assessment and treatment decision-making for patients with Stage II colon cancer (26:38) Potential incorporation of ctDNA assays into the management of metastatic colorectal cancer or microsatellite instability-high disease (34:29) Available clinical data with ctDNA assessment in localized rectal cancer (38:54) Current practice patterns with ctDNA assays for patients with localized colorectal cancer (41:17) Case: A woman in her early 40s with resected lower risk Stage III colon cancer requests ctDNA testing (45:47) Case: A man in his early 50s with Stage IIIB colon cancer wants to avoid adjuvant chemotherapy (50:39) Case: A man in his early 60s with Stage IV colon cancer receives a positive postoperative ctDNA assessment result (53:24) NCPD information and select publications

summaryThis episode explores the latest advances in circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) in bladder cancer management. Experts discuss how these biomarkers are transforming perioperative decision-making, prognosis, and personalized treatment strategies.

In this podcast , Brian, Tom and Matt Galsky discuss the B15 study data on neoadjuvant therapy for muscle invasive bladder cancer, focusing on the efficacy of EV Pembro compared to gem-cis. They explore event-free survival, overall survival, and the implications of treatment duration and individualization. The conversation also touches on the role of ctDNA in treatment decisions, alternative histologies, and the importance of neoadjuvant systemic therapy. The hosts conclude with reflections on future directions in bladder cancer treatment and the significance of ongoing studies.

Gilead is acquiring Arcellx for $7.8 billion up front three years after forging a partnership with the biotech around a cell therapy for multiple myeloma. On the latest BioCentury This Week podcast, BioCentury's analysts assess what the deal does for the Foster City, Calif.-based biotech's pipeline.The analysts also discuss the case for using ctDNA as a surrogate endpoint for early cancer trials. Turning to Washington, Steve Usdin offers his takeaways from last week's PhRMA Forum, which focused on China and the Trump administration's most favored nation (MFN) drug pricing policy, and on the lessons that can be drawn from FDA's about-face on the recent vaccine application from Moderna.View full story: https://www.biocentury.com/article/658516#BiotechMA #MultipleMyeloma #ctDNA #DrugPricingPolicy #FDA00:00 - Introduction02:34 - Gilead's Arcellx Buy11:14 - ctDNA Surrogate Endpoints21:59 - PhRMA Forum Takeaways29:19 - FDA Moderna U-turnTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

Editor's Choice: Circulating tumor DNA monitoring in ovarian cancer patients receiving PARPi maintenance therapy: Can we further personalize treatment?

Dr. Monty Pal and Dr. Ari Rosenberg discuss the evolution of treatment strategies in head and neck cancers, including the challenges of treating both HPV-positive and HPV-negative disease and the emergence of blood-based biomarkers to advance personalized therapy across different subtypes. TRANSCRIPT Dr. Monty Pal: Hello and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, we're going to explore the evolving landscape of treatment strategies in head and neck cancer management, including locoregionally advanced head and neck squamous cell carcinoma, which happens to be on the rise in United States, in part due to spike in HPV-mediated oropharyngeal cancers. We're also going to discuss the emerging strategies of using blood-based biomarkers to really advance personalized therapy. Joining me for this discussion is Dr. Ari Rosenberg. He's a medical oncologist focused on head and neck cancer, and he's an associate professor – congratulations on the recent promotion – at the University of Chicago. The University of Chicago has really produced luminaries in this field, Dr. Rosenberg included. I've had the pleasure of getting to know Dr. Ezra Cohen over the years, who really had his grounding there, and of course Everett Vokes, former ASCO President. I'm really looking forward to this conversation, Ari. Thanks so much for joining us. Dr. Ari Rosenberg: Thanks, Monty. Thanks for the invitation. Dr. Monty Pal: You got it. And just a quick note for our listeners, our full disclosures are going to be in the transcript at the end of this episode. So let's start with the basics, if you don't mind. So, head and neck cancers are very diverse and they're challenging, right? In the sense that they're near vital organs, the treatments, you know, as we all saw during fellowship, if not now in clinical practice. They can really have such a major impact on vital organ function, speech, swallowing, et cetera. Can you just comment on head and neck cancers that are on the rise in the U.S.? I alluded to this briefly. Particularly, we've heard this in the context of colorectal cancer and so forth. Are you actually seeing younger adults being affected by this? Dr. Ari Rosenberg: Yeah, thanks for that. The vast majority of head and neck cancers are head and neck squamous cell carcinomas, as I'm sure many of the listeners recall as well from fellowship or their current training. And as you alluded to, the organ function, long-term and functional quality of life outcomes are quite important, particularly in the context that these develop in high value real estate, parts of our head and neck area that we use for speaking, swallowing, all sorts of other essential functions as well. As you also alluded to, we think of this in two different particular subtypes of head and neck cancer. The historical head and neck cancer from 50, 60 years ago was almost exclusively related to carcinogen exposure, tobacco, alcohol use, and that subtype of carcinogen-induced head and neck cancer has been slowly declining. However, over the last now several decades, we've been seeing an increase in primary oropharyngeal squamous cell carcinoma, mostly tonsil, base of tongue. These are attributable to HPV, human papillomavirus exposure. And that's now the majority of the head and neck cancers that we tend to see in our clinic. As you also alluded to, these have very different prognoses as well. HPV-related head and neck cancer has a much more favorable prognosis where much of the interest has been in can we de-intensify to optimize long-term function? But then the non-HPV-related head and neck cancer, or what we call HPV-negative head and neck cancer, continue to be very, very challenging. We only managed to cure about half of these folks, with many of these patients developing the current disease. These patients, in addition to being difficult to treat, also have major impacts both in terms of the treatments they undergo as well as their disease that can impact their function and quality of life. And you hinted at this a little bit, but we have been seeing an increase in younger patients with HPV-negative head and neck cancer as well, which is quite concerning. Younger patients, oftentimes never smokers, never drinkers, who are developing non-HPV-negative head and neck cancer. And that's been a little bit of a more recent trend that we've been seeing as well. So, definitely a lot of work to be done to optimize and improve outcomes across all of these different head and neck cancer subtypes. Dr. Monty Pal: I mean, I'm just curious, you know, in the context of colorectal cancer, one of the things that we talk about is the potential role of the microbiome driving some of these young-onset cancers with, you know, perhaps there being an impact on, for instance, inflammation and the gut and what have you. Tell me about head and neck cancer. Is this anything known as to why younger patients might be getting diagnosed with non-HPV type cancers? It's odd to me. Dr. Ari Rosenberg: Yeah, it's a great question. A lot of people are working on it. I think we folks have hypotheses, but it hasn't totally panned out exactly what's going on there. It does have a little bit more of a tendency towards women, whereas historically head and neck cancer is much more common in men than it is in women. But lots of people working on that, whether it's related to chronic inflammation, whether it's related to the microbiome. Whether it's related to dental exposure, dental work. So, a lot of folks trying to parse that out because I agree with you, it needs to be identified alongside improving treatment paradigms for these patients, the young ones and the older patients as well. Dr. Monty Pal: Interesting, interesting. You know, one of the phenomena that was sort of coming around when I was in training 25 years ago was this role of sort of induction therapy for head and neck cancers. And of course, it's really come full circle now to include checkpoint inhibitors and so forth. Tell me a little bit about this and how you apply it, maybe in an HPV-mediated context, maybe in a non-HPV context. Dr. Ari Rosenberg: Yeah, absolutely. Induction chemotherapy, as you alluded to, or neoadjuvant chemotherapy, depending on what the locoregional treatment approach is. Similar to other cancer types where systemic control early on has many potential advantages in this setting. Now, in head and neck cancer, even though induction chemotherapy is quite active in head and neck cancer, both HPV-positive and HPV-negative with pretty good response rates. A survival advantage for all comers with local regionally advanced disease remains unproven. There's been two randomized trials, both underpowered, but essentially did not show a survival advantage, showing that induction chemotherapy for all patients with locoregionally advanced and neck cancer can't be justified for a survival advantage. That being said though, there remains a number of potential advantages of giving induction or neoadjuvant chemotherapy, of course, improving systemic control and debulking the disease early on has potential advantages, and predicting the responsiveness to subsequent radiation treatment. We know for some time in head and neck cancer that the percentage of shrinkage or the response to induction chemotherapy actually predicts outcome related to radiation as a dynamic biomarker where response can be used to select patients, for example, for de-escalated radiation has been an area of active investigation, active research. And it also remains a key opportunity to evaluate predictive biomarkers and understanding pre and post treatment to better understand the biology. I'll just add to your question that recently over this past year, we also saw phase 3 data for neoadjuvant immunotherapy for a subset of head and neck cancer that is surgically resectable. And so that's reintroducing the potential benefit in the immunotherapy era of incorporating immunotherapy in the neoadjuvant or the induction setting as part of the evolving treatment paradigm for these diseases. Dr. Monty Pal: That's really interesting. And you kind of alluded to already several topics that I plan to hit on, you know, for instance, the role of immune checkpoint inhibitors, induction, chemotherapy, and so forth. And you started to touch on biomarkers. And of course, I think that's something near and dear to many of us in academic oncology. One thing that we've started talking a lot about in the context of colorectal cancer is circulating tumor DNA. How do you think this might fit in the context of head and neck cancer? Can you give us a flavor for that? Dr. Ari Rosenberg: Yeah, absolutely. In head and neck cancer, the current landscape is most developed for circulating tumor DNA for HPV-related head and neck cancer. The advantage of HPV-related head neck cancer is that you have a distinctive HPV DNA that does tend to spill out into the peripheral blood and can be detected using various different blood-based assays. And because of that advantage as a tissue agnostic approach, it turns out that a number of HPV DNA plasma assays are actually quite sensitive and quite specific. And a number of them have indeed been commercialized. Of course, not only for detecting a baseline, but also grading responsiveness during treatment and probably most importantly in the post-treatment surveillance setting, the detection of HPV DNA in the plasma remains a very important and substantial predictor of developing recurrent disease. There's been a number of trials that have been emerging looking at ctDNA and HPV-related head and neck cancer, using it, for example, as a strategy to deescalate patients. That was something we saw this past ASCO from the Dana-Farber group, and also using it to early detect recurrence and potentially intervene earlier for patients with minimal residual disease positivity. So, that remains evolving and as many folks are, I think, already using it in the clinic. But ctDNA also has a lot of potential for HPV-negative head and neck cancer. This is actually a bit more challenging to develop because you don't have that HPV DNA that you can track predictably because the tumor is an HPV- negative disease are much more heterogeneous, but there are a number of data that are coming out both for personalized assays such as Signatera or some of the other assays that require tumor. Unlike colon cancer, which you referenced, where most patients get surgery upfront, in head and neck cancer, many of the patients receive non-surgical pre-chemoradiation. So sometimes the amount of tumor available to generate a personalized assay is more limited and can be one of the challenges that we see in head neck cancer. But certainly that also seems to be emerging. And there's also further assays that are being developed for HPV-negative head neck cancers, such as methylomic signatures and others that may be tissue informed or tissue agnostic. And these are also emerging, particularly in the post-treatment surveillance setting as strong predictors of recurrent disease. So while we're certainly behind some of these other more common tumor types, colon cancer, lung cancer, we're right there with them and more and more trials are going report out, including a number of trials in our upcoming [University of Chicago] Head and Neck Cancer Symposium where I'll be presenting some data and others in the field will be presenting some data looking at ctDNA both for HPV-positive and for HPV- negative to try to improve outcomes for these patients. Dr. Monty Pal: That's so interesting. I've got to tell you that in kidney cancer, what I deal with day to day is a very low shedding disease, right? So techniques as opposed to ctDNA looking for tumor-informed information, that might be less preferred to something like methylomics where you might not necessarily be so contingent on what's happening in the primary tumor. I'm really interested in you mentioning that. Just a point of clarification, this is something I'm trying to wrap my head around. You'd mentioned circulating tumor HPV DNA, right? I assume this is markedly different from just looking for HPV titers in the patient, right? So is this actually incorporated elements of HPV within, you know, essentially host genome, if you will? Dr. Ari Rosenberg: Yeah, correct. This is circulating tumor HPV DNA. And we think of it biologically as a plasma-based tumor DNA biomarker that's specific for HPV-related head and neck cancers. Dr. Monty Pal: Got it, got it. It makes me wonder whether or not this might be applicable to diseases like cervical cancer and so forth where there's also extensively, you know, biology driven by HPV. Is that fair? Dr. Ari Rosenberg: Yes, definitely. And in the head and neck cancer field, much of this ctDNA actually was derived from a different viral mediated head neck cancer, is less common in the U.S., but nasopharyngeal cancer, which is oftentimes associated with EBV. That has been a biomarker for quite some time in nasopharyngeal cancer. Of course, in places where EBV-associated nasopharyngeal cancer, is endemic, such as East Asia, this has been around for quite some time, but we've been using that in the U.S., and there's been trials that have used EBV DNA plasma to predict recurrence and stratify for adjuvant treatment, for example. And so now with HPV, it's much more applicable to our US population because the vast majority of our head and neck cancer patients that we see in the US that are viral mediated in the US tend to be HPV-related. So having assays that we can use to improve outcomes for that biological subset remains of particular interest for us. Dr. Monty Pal: Yeah, that's fascinating. By the way, for the fellows listening, there's tons of boards pearls here that Dr. Rosenberg shared, EBV-associated cancers, the role of HPV and treatment association. So if you're recertifying anytime soon, I definitely think there's notes to take from this conversation indeed. I wanted to shift gears a little bit. And obviously, you're a prolific researcher. I don't think anyone goes through their fellowship in medical oncology without recounting these experiences of our head and neck patients really suffering from treatment-related toxicities. It's a real challenge. And I'm just wondering, I know a big body of work that you're focused on is really using multimodality treatment paradigms to perhaps reduce the cumulative treatment burden of patients with head and neck cancers. Can you talk about that a little bit? Dr. Ari Rosenberg: Yeah, definitely. Thanks for the question. And before I start going into some of the strategies, I'll just say that head and neck cancer, this is particularly for the fellows that are listening as well, just in reference to your prior comment, that this is really a multidisciplinary disease. At our center, all head and neck cancer patients are seen upfront at that first visit by all three specialties, med onc, rad onc, and surgery, because the choice and sequencing of modalities to optimize not only survival, but also functional quality of life outcome is so critical. And I think that's probably the biggest takeaway for anyone who treats a lot of head and neck cancer or will be treating a lot of head and neck cancer in the clinic. But in terms of more specific attempts at trying to optimize some of those parameters that you described, we really think about these separately in terms of HPV-positive and HPV-negative head and neck cancer. For HPV-positive head and neck cancer, the cure rates are quite high with chemo radiation, although not for everyone. There's still about 15, 10 to 15 % of folks that will develop a recurrence. But for the vast majority of patients, standard chemoradiation is quite a cure to therapy, but the toxicity associated with that can be quite substantial. And so there's been a number of attempts to try to deescalate treatment. It turns out that deescalating everyone with locoregionally advanced HPV-positive head and neck cancer is not a good strategy because it's not able to select out the patients that really do need full dose treatment. And we have seen some negative trials that show inferior outcomes when everyone is deescalated. But what does remain promising is again, trying to select out who the best candidates are for deescalated treatment. The folks at MSK have hypoxia imaging that they're using in trials that looks quite promising to select for the more favorable deescalatable biology. At our center, we've been interested in using induction chemotherapy to stratify response and select patients for deescalated treatment with excellent survival outcomes and reduce toxicity with deescalated treatment. And more recently, ctDNA that us and other groups, such as the Dana-Farber group, is using. And that also looks quite promising. Again, how do you select the patient who will do well with less radiation versus the ones that really need the full doses and volumes of radiation? And then for HPV-negative head and neck cancer, this is a much trickier disease because already the survival outcomes are not like we want it to be. Trying to figure out how to improve survival outcomes remains an important thing. Using immunotherapy seems to be one of the key cornerstones to that. But these are patients that also suffer from a lot of toxicity related to their treatment. We completed a trial not too long ago that we published this past year where we, in HPV-negative head and neck cancer patients, de-intensified the radiation for responders to neoadjuvant chemoimmunotherapy. And those patients did similar, if not even a little bit better, than the non-responders who got full dose treatment. So something that does warrant further investigation as well. How do we not only improve survival for those patients, but also reduce some of the long-term toxicities? Dr. Monty Pal: This is brilliant. I'm taking so many notes as you were mentioning these items. There are so many areas where I think the research crosses over. I already mentioned, know, ctDNA, for instance, and metabolomics and the places where that might apply to kidney cancer. The hypoxia imaging really caught my ear too. Obviously, kidney cancer is disease highly predicated on hypoxia. So thank you for all of this. We've got about a minute or so. So, I'm going to ask you for a really tall task here. Can you tell us what you foresee being some of the biggest challenges that sort of lie ahead and head and neck cancer. You've already kind of alluded to it with ongoing research, but if you had to pick maybe 2, 3 problems, the very most that we really need to get to and head and neck cancer, what would that be? Dr. Ari Rosenberg: Yeah, that's a great question. Obviously, lots of things to be done, but if I'm going to limit it to just a couple, I would say number one is really trying to improve the survival for HPV negative local regionally advanced head and neck cancer. We talked early on about how we are seeing, you know, of course we see many of these people that were smokers and drinkers, but also seeing these in younger patients, in patients without a history of tobacco use. Some of these are very biologically aggressive and we need better treatments beyond surgery, beyond chemo radiation, beyond immunotherapy to improve outcomes for these patients and cure more of them. So, I would say that's one big area. And the other is, which we didn't speak about so much in this talk, but remains one of the biggest challenges that we see in the clinic is the recurrent metastatic head and neck cancer patients. This is an incredibly challenging disease to treat, not only with poor survival, but also with substantial impacts on quality of life and function. mean, these are bad recurrences that cause a lot of pain, functional deficits, really impacts quality of life as well. So developing novel therapies, many of which are currently in clinical trials and many of which are currently continuing to be developed, remains so critical. How do we develop better systemic therapies, better targeted therapies, better biomarkers for recurrent metastatic head neck cancer to improve their survival and quality of life and functional outcomes. Those are the two big areas that require the most work at this time within the head and neck cancer field. Dr. Monty Pal: That's brilliant. I mean, I have to tell you I could probably talk to you all day about this, such a fascinating topic. It's a very exciting time in the field. Thank you, Dr. Rosenberg, for all your incredible contributions and thanks for sharing with us your insights on the ASCO Daily News Podcast. Dr. Ari Rosenberg: Yeah, and thanks for the introduction. Hope to do it again soon. Dr. Monty Pal: And many thanks to our listeners for your time today. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. More on today's speakers:      Dr. Monty Pal   @montypal  Dr. Ari Rosenberg @AriRosenbergMD Follow ASCO on social media:           ASCO on X     ASCO on Bluesky          ASCO on Facebook           ASCO on LinkedIn           Disclosures:        Dr. Monty Pal:       Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview      Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical      Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Ari Rosenberg:     Stock and Other Ownership Interests: Privo Technologies Consulting or Advisory Role: Nanobiotix, EMD Serono, Vaccitech, Novartis, Eisai, Astellas Pharma, Regeneron, RAPT Therapeutics, Geovax Labs, Janssen, Summit Therapeutics Speakers' Bureau: Coherus Biosciences Research Funding (Inst.): Hookipa Biotech, EMD Serono, Purple Biotech, Bristol-Myers Squibb/Celgene, BeiGene, Abbvie, Astellas Pharma, Pfizer, Janux Therapeutics

Send a textA drop of blood can change the course of cancer care. Speaking of Women's Health Podcast host Holly Thacker, MD sits down with variant curator Stetson Thacker, PhD to unpack how circulating tumor DNA and tumor‑informed minimal residual disease testing help clinicians see recurrence months before imaging, tailor adjuvant therapy, and track response in real time. Together, they translate complex genomics into clear choices: when a negative MRD result supports de‑escalation, when a persistent positive argues for chemotherapy and how colorectal and breast cancers have led the way in clinical validation.They also cover the guardrails. Not everyone has banked tissue for a tumor‑informed assay, and sensitivity and specificity vary by platform and cancer type. Early multi‑cancer detection tests promise a lot but risk overdiagnosis and anxiety if used without clear indications. The smarter path is matching the right test to the right person at the right time, ideally within guidelines and with an oncologist who can synthesize genomics, imaging, pathology, and patient goals. From colorectal screening shifts to balancing overtreatment in prostate and thyroid cancers, we focus on practical decisions that protect both survival and quality of life.If this deep dive helped you make sense of liquid biopsies and MRD, subscribe, share the episode with someone navigating cancer decisions and leave a review so more listeners can find the show.Support the show

JCO PO author Dr. Foldi at UPMC Hillman Cancer Center and University of Pittsburgh School of Medicine shares insights into the JCO PO article, "Personalized Circulating Tumor DNA Testing for Detection of Progression and Treatment Response Monitoring in Patients With Metastatic Invasive Lobular Carcinoma of the Breast." Host Dr. Rafeh Naqash and Dr. Foldi discuss how serial ctDNA testing in patients with mILC is feasible and may enable personalized surveillance and real-time therapeutic monitoring. TRANSCRIPT Dr. Rafeh Naqash: Hello, and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I am your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, we are thrilled to be joined by Dr. Julia Foldi, Assistant Professor of Medicine in the Division of Hematology-Oncology at University of Pittsburgh School of Medicine and the Magee-Womens Hospital of the UPMC. She is also the lead and corresponding author of the JCO Precision Oncology article entitled "Personalized Circulating Tumor DNA Testing for Detection of Progression and Treatment Response Monitoring in Patients with Metastatic Invasive Lobular Carcinoma of the Breast." At the time of this recording, our guest's disclosures will be linked in the transcript. Julia, welcome to our podcast, and thank you for joining us today. Dr. Julia Foldi: Thank you so much for having me. It is a pleasure. Dr. Rafeh Naqash: Again, your manuscript and project address a few interesting things, so we will start with the basics, since we have a broad audience that comprises trainees, community oncologists, and obviously precision medicine experts as well. So, let us start with invasive lobular breast carcinoma. I have been out of fellowship for several years now, and I do not know much about invasive lobular carcinoma. Could you tell us what it is, what some of the genomic characteristics are, why it is different, and why it is important to have a different way to understand disease biology and track disease status with this type of breast cancer? Dr. Julia Foldi: Yes, thank you for that question. It is really important to frame this study. So, lobular breast cancers, which we shorten to ILC, are the second most common histologic subtype of breast cancer after ductal breast cancers. ILC makes up about 10 to 15 percent of all breast cancers, so it is relatively rare, but in the big scheme of things, because breast cancer is so common, this represents actually over 40,000 new diagnoses a year in the US of lobular breast cancers. What is unique about ILC is it is characterized by loss of an adhesion molecule, E-cadherin. It is encoded by the CDH1 gene. What it does is these tumors tend to form discohesive, single-file patterns and infiltrate into the tumor stroma, as opposed to ductal cancers, which generally form more cohesive masses. As we generally explain to patients, ductal cancers tend to form lumps, while lobular cancers often are not palpable because they infiltrate into the stroma. This creates several challenges, particularly when it comes to imaging. In the diagnostic setting, we know that mammograms and ultrasounds have less sensitivity to detect lobular versus ductal breast cancer. When it comes to the metastatic setting, conventional imaging techniques like CT scans have less sensitivity to detect lobular lesions often. One other unique characteristic of ILC is that these tumors tend to have lower proliferation rates. Because our glucose-based PET scans depend on glucose uptake of proliferating cells, often these tumors also are not avid on conventional FDG-PET scans. It is a challenge for us to monitor these patients as they go through treatment. If you think about the metastatic setting, we start a new treatment, we image people every three to four cycles, about every three months, and we combine the imaging results with clinical assessment and tumor markers to decide if the treatment is working. But if your imaging is not reliable, sometimes even at diagnosis, to really detect these tumors, then really, how are we following these patients? This is really the unique challenge in the metastatic setting in patients with lobular breast cancer: we cannot rely on the imaging to tell if patients are responding to treatment. This is where liquid biopsies are really, really important, and as the field is growing up and we have better and better technologies, lobular breast cancer is going to be a field where they are going to play an important role. Dr. Rafeh Naqash: Thank you for that easy-to-understand background. The second aspect that I would like to have some context on, to help the audience understand why you did what you did, is ctDNA, tumor informed and non-informed. Could you tell us what these subtypes of liquid biopsies are and why you chose a tumor informed assay for your study? Dr. Julia Foldi: Yes, it is really important to understand these differences. As you mentioned, there are two main platforms for liquid biopsy assays, circulating tumor DNA assays. I think what is more commonly used in the metastatic setting are non-tumor informed assays, or agnostic assays. These are generally next-generation sequencing-based assays that a lot of companies offer, like Guardant, Tempus, Caris, and FoundationOne. These do not require tumor tissue; they just require a blood sample, a plasma sample, essentially. The next-generation sequencing is done on cell-free DNA that is extracted from the plasma, and it is looking for any cell-free DNA and essentially, figuring out what part of the cell-free DNA comes from the tumor is done through a bioinformatics approach. Most of these assays are panel tests for cancer-associated mutations that we know either have therapeutic significance or biologic significance. So, the results we receive from these tests generally read out specific mutations in oncogenic genes, or sometimes things like fusions where we have specific targeted drugs. Some of the newer assays can also read out tumor fraction; for example, the newest generation Guardant assay that is methylation-based, they can also quantify tumor fraction. But the disadvantage of the tumor agnostic approach is that it is a little bit less sensitive. Opposed to that, we have our tumor informed tests, and these require tumor tissue. Essentially, the tumor is sequenced; this can either be whole exome or whole genome sequencing. The newer generation assays are now using whole genome sequencing of the tumor tissue, and a personalized, patient-specific panel of alterations is essentially barcoded on that tumor tissue. This can be either structural variants or it can be mutations, but generally, these are not driver mutations, but sort of things that are present in the tumor tissue that tend to stay unchanged over time. For each particular patient, a personalized assay, if you want to call it a fingerprint or barcode, is created, and then that is what then is used to test the plasma sample. Essentially, you are looking for that specific cancer in the blood, that barcode or fingerprint in the blood. Because of this, this is a much more sensitive way of looking for ctDNA, and obviously, this detects only that particular tumor that was sequenced originally. So, it is much more sensitive and specific to that tumor that was sequenced. You can argue for both approaches in different settings. We use them in different settings because they give us different information. The tumor agnostic approach gives us mutations, which can be used to determine what the next best therapy to use is, while the tumor informed assay is more sensitive, but it is not going to give us information on therapeutic targets. However, it is quantified, and we can follow it over time to see how it changes. We think that it is going to tell us how patients respond to treatment because we see our circulating tumor DNA levels rise and fall as the cancer burden increases or decreases. We decided to use the tumor informed approach in this particular study because we were really interested in how to determine if patients are having response to treatment versus if they are going to progress on their treatment, more so than looking for specific mutations. Dr. Rafeh Naqash: When you think about these tumor informed assays and you think about barcoding the mutations on the original tumor that you try to track or follow in subsequent blood samples, plasma samples, in your experience, if you have done it in non-lobular cancers, do you think shedding from the tumor has something to do with what you capture or how much you capture? Dr. Julia Foldi: Absolutely. I think there are multiple factors that go into whether someone has detectable ctDNA or not, and that has to do with the type of cancer, the location, right, where is the metastatic site? This is something that we do not fully understand yet: what are tumors that shed more versus not? There is also clearance of ctDNA, and so how fast that clearance occurs is also something that will affect what you can detect in the blood. ctDNA is very short-lived, only has a half-life of hours, and so you can imagine that if there is little shedding and a lot of excretion, then you are not going to be detecting a lot of it. In general, in the metastatic setting, we see that we can detect ctDNA in a lot of cases, especially when patients are progressing on treatment, because we imagine their tumor burden is higher at that point. Even with the non-tumor informed assays, we detect a lot of ctDNA. Part of this study was to actually assess: what is the proportion of patients where we can have this information? Because if we are only going to be able to detect ctDNA in less than 50 percent of patients, then it is not going to be a useful method to follow them with. Because this field is new and we have not been using a lot of tumor informed assays in the metastatic setting, we did not really know what to expect when we set out to look at this. We did not know what was going to be the baseline detection rate in this patient population, so that was one of the first things that we wanted to answer. Dr. Rafeh Naqash: Excellent. Now going to this manuscript in particular, what was the research question, what was the patient population, and what was the strategy that you used to investigate some of these questions? Dr. Julia Foldi: So, we partnered with Natera, and the reason was that their Signatera tumor-informed assay was the first personalized, tumor-informed, really an MRD assay, minimal residual disease detection assay. It has been around the longest and has been pretty widely used commercially already, even though some of our data is still lacking. but we know that people are using this in the real world. We wanted to gather some real-world data specifically in lobular patients. So, we asked Natera to look at their database of commercial Signatera testing and look for patients with stage 4 lobular breast cancer. The information all comes from the submitting physicians sending in pathologic reports and clinical notes, and so they have that information from the requisitions essentially that are sent in by the ordering physician. We found 66 patients who were on first-line or close to first-line endocrine-based therapies for their metastatic lobular breast cancer and had serial collections of Signatera tests. The way we defined baseline was that the first Signatera had to be sent within three months of starting treatment. So, it is not truly baseline, but again, this is a limitation of looking at real-world data is that you are not always going to get the best time point that you need. We had over 350 samples from those 66 patients, again longitudinal ctDNA samples, and our first question was what is the baseline detection rate using this tumor informed assay? Then, most importantly, what is the concordance between changes in ctDNA and clinical response to treatment? That is defined by essentially radiologic response to treatment. Dr. Rafeh Naqash: Interesting. So, what were some of your observations in terms of ctDNA dynamics, whether baseline levels made a difference, whether subsequent levels at different time points made a difference, or subsequent levels at, let us say, cycle three made a difference? Were there any specific trends that you saw? Dr. Julia Foldi: So, first, at baseline, 95 percent of patients had detectable ctDNA, which is, I think, a really important data point because it tells us that this can be a really useful test. If we can detect it in almost all patients before they start treatment, we are going to be able to follow this longitudinally. And again, these were not true baseline samples. So, I think if we look really at baseline before starting treatment, almost all patients will have detectable ctDNA in the metastatic setting. The second important thing we saw was that disease progression correlated very well with increase in ctDNA. So, in most patients who had disease progression by imaging, we saw increase in ctDNA. Conversely, in most patients who had clinical benefit from their treatment, so they had a response or stable disease, we saw decrease in ctDNA levels. It seems that what we call molecular response based on ctDNA is tracking very nicely along with the radiographic response. So, those were really the two main observations. Again, this is a small cohort, limited by its real-world nature and the time points that ctDNA assay was sent was obviously not mandated. This is a real-world data set, and so we could not really look at specific time points like you asked about, let us say, cycle three of therapy, right? We did not have all of the right time points for all of the patients. But what we were able to do was to graph out some specific patient scenarios to illustrate how changes in ctDNA correlate with imaging response. I can talk a little bit about that. Dr. Rafeh Naqash: That was going to be my question. Did you see patients who had serial monitoring using the tumor informed ctDNA assay where the assay became positive a few months before the imaging? Did you have any of those kinds of observations? Dr. Julia Foldi: Yes, so I think this is where the field is going: are we able to use this technology to maybe detect progression before it becomes clinically apparent? Of course, there are lots of questions about: does that really matter? But it seems like, based on some of the patient scenarios that we present in the paper, that this testing can do that. So, we had a specific scenario, and this is illustrated in a figure in the paper, really showing the treatment as well as the changes in ctDNA, tumor markers, and also radiographic response. So, this particular patient was on first-line endocrine therapy and CDK4/6 inhibitor with palbociclib. Initially, she had a low-level detectable ctDNA. It became undetectable during treatment, and the patient had a couple of serial ctDNA assays that were negative, so undetectable. And then we started, after about seven months on this combination therapy, the ctDNA levels started rising. She actually had three serial ctDNA assays with increasing level of ctDNA before she even had any imaging tests. And then around the time that the ctDNA peaked, this patient had radiographic evidence of progression. There was also an NGS-based assay sent to look for specific mutations at that point. The patient was found to have an ESR1 mutation, which is very common in this patient population. She was switched to a novel oral SERD, elacestrant, and the ctDNA fell again to undetectable within the first couple months of being on elacestrant. And then a very similar thing happened: while she was on this second-line therapy, she had three serial negative ctDNA assays, and then the fourth one was positive. This was two months before the patient had a scan that showed progression again. Dr. Rafeh Naqash: And Julia, like you mentioned, this is a small sample size, limited number of patients, in this case, one patient case scenario, but provides insights into other important aspects around escalation or de-escalation of therapy where perhaps ctDNA could be used as an integral biomarker rather than an exploratory biomarker. What are some of your thoughts around that and how is the breast cancer space? I know like in GI and bladder cancer, there has been a significant uptrend in MRD assessments for therapeutic decision making. What is happening in the breast cancer space? Dr. Julia Foldi: So, super interesting. I think this is where a lot of our different fields are going. In the breast cancer space, so far, I have seen a lot of escalation attempts. It is not even necessarily in this particular setting where we are looking at dynamics of ctDNA, but in the breast cancer world, of course, we have a lot of data on resistance mutations. I mentioned ESR1 mutation in a particular patient in our study. ESR1 mutations are very common in patients with ER-positive breast cancer who are on long-term endocrine therapy, and ESR1 mutations confer resistance to aromatase inhibitors. So, that is an area that there has been a lot of interest in trying to detect ESR1 mutations earlier and switching therapy early. So, this was the basis of the SERENA-6 trial, which was presented last year at ASCO and created a lot of excitement. This was a trial where patients had non-tumor-informed NGS-based Guardant assay sent every three to six months while they were on first-line endocrine therapy with a CDK4/6 inhibitor. If they had an ESR1 mutation detected, they were randomized to either continue the same endocrine therapy or switch to an oral SERD. The trial showed that the population of patients who switched to the oral SERD did better in terms of progression-free survival than those who stayed on their original endocrine therapy. There are a lot of questions about how to use this in routine practice. Of course, it is not trivial to be sending a ctDNA assay every three to six months. The rate of detection of these mutations was relatively low in that study; again, the incidence increases in later lines of therapy. So, there are a lot of questions about whether we should be doing this in all of our first-line patients. The other question is, even the patients who stayed on their original endocrine therapy were able to stay on that for another nine months. So, there is this question of: are we switching patients too early to a new line of therapy by having this escalation approach? So, there are a lot of questions about this. As far as I know, at least in our practice, we are not using this approach just yet to escalate therapy. Time will tell how this all pans out. But I think what is even more interesting is the de-escalation question, and I think that is where tumor informed assays like Signatera and the data that our study generated can be applied. Actually, our plan is to generate some prospective data in the lobular breast cancer population, and I have an ongoing study to do that, to really be able to tease out the early ctDNA dynamics as patients first start on endocrine therapy. So, this is patients who are newly diagnosed, they are just starting on their first-line endocrine therapy, and measure, with sensitive assays, measure ctDNA dynamics in the first few months of therapy. In those patients who have a really robust response, that is where I think we can really think about de-escalation. In the patients whose ctDNA goes to undetectable after just a few weeks of therapy with just an endocrine agent, they might not even need a CDK4/6 inhibitor in their first-line treatment. So, that is an area where we are very interested in our group, and I know that other groups are looking at this too, to try to de-escalate therapy in patients who clear their ctDNA early on. Dr. Rafeh Naqash: Thank you so much. Well, lots of questions, but at the same time, progress comes through questions asked, and your project is one of those which is asking an interesting question in a rarer cancer and perhaps will lead to subsequent improvement in how we monitor these individuals and how we escalate or de-escalate therapy. Hopefully, we will get to see more of what you are working on in subsequent submissions to JCO Precision Oncology and perhaps talk more about it in a couple of years and see how the space and field is moving. Thanks again for sharing your insights. I do want to take one to two quick minutes talking about you as an investigator, Julia. If you could speak to your career pathway, your journey, the pathway to mentorship, the pathway to being a mentor, and how things have shaped for you in your personal professional growth. Dr. Julia Foldi: Sure, yeah, that is great. Thank you. So, I had a little bit of an unconventional path to clinical medicine. I actually thought I was going to be a basic scientist when I first started out. I got a PhD in Immunology right out of college and was studying not even anything cancer-related. I was studying macrophage signaling in inflammatory diseases, but I was in New York City. This was right around the time that the first checkpoint inhibitors were approved. Actually, some of my friends from my PhD program worked in Jim Allison's lab, who was the basic scientist responsible for ipilimumab. So, I got to kind of first-hand experience the excitement around bringing something from the lab into the clinic that actually changed really the course of oncology. And so, I got very excited about oncology and clinical medicine. So, I decided to kind of switch gears from there and I went back to medical school after finishing my PhD and got my MD at NYU. I knew I wanted to do oncology, so I did a research track residency and fellowship combined at Yale. I started working early on with the breast cancer team there. At the time, Lajos Pusztai was the head of translational research there at Yale, and I started working with him early in my residency and then through my fellowship. I worked on several trials with him, including a neoadjuvant checkpoint inhibitor trial in triple-negative breast cancer patients. During my last year in fellowship, I received a Conquer Cancer Young Investigator Award to study estrogen receptor heterogeneity using spatial transcriptomics in this subset of breast cancers that have intermediate estrogen receptor expression. From there, I joined the faculty at the University of Pittsburgh in 2022. So, I have been there about almost four years at this point. My interests really shifted slowly from triple-negative breast cancers towards ER-positive breast cancers. When I arrived in Pittsburgh, I started working very closely with some basic and translational researchers here who are very interested in estrogen signaling and mechanisms of resistance to endocrine therapy, and there is a large group here interested in lobular breast cancers. During my training, I was not super aware even that lobular breast cancer was a unique subtype of breast cancers, and that is, I think, changing a little bit. There is a lot more awareness in the breast cancer clinical and research community about ILC being a unique subtype, but it is not even really part of our training in fellowship, which we are trying to change. But I have become a lot more aware of this because of the research team here and through that, I have become really interested also on the clinical side. And so, we do have a Lobular Breast Cancer Research Center of Excellence here at the University of Pittsburgh and UPMC, and I am the leader on the clinical side. We have a really great team of basic and translational researchers looking at different aspects of lobular breast cancers, and some of the work that I am doing is related to this particular manuscript we discussed and the next steps, as I mentioned, a prospective study of early ctDNA dynamics in lobular patients. I also did some more clinical research work in collaboration with the NSABP looking at long-term outcomes of patients with lobular versus ductal breast cancers in some of their older trials. And so, that is, in a nutshell, a little bit about how I got here and how I became interested in ILC. Dr. Rafeh Naqash: Well, thank you for sharing those personal insights and personal journey. I am sure it will inspire other trainees, fellows, and perhaps junior faculty in trying to find their niche. The path, as you mentioned, is not always straight; it often tends to be convoluted. And then finding an area that you are interested in, taking things forward, and being persistent is often what matters. Dr. Julia Foldi: Thank you so much for having me. It was great. Dr. Rafeh Naqash: It was great chatting with you. And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

What do you do when metastatic urothelial cancer responds dramatically to systemic therapy? In this episode of BackTable Urology, Dr. Abhinav Khanna (Mayo Clinic) speaks with host Dr. Daniel Roberson about the growing question of consolidative surgery after enfortumab vedotin plus pembrolizumab. They discuss how EV-pembro has reshaped treatment expectations, why unexpected complete or near-complete responses are prompting tumor board debates about cystectomy, and how careful multidisciplinary decision-making guides which patients may be considered for surgery. --- SYNPOSIS The conversation reviews early outcomes showing high rates of pathologic downstaging and the possibility that many patients may avoid additional systemic therapy after surgery, while emphasizing this approach is not yet standard of care. Dr. Khanna highlights coordination with medical oncology, radiology, and pathology, postoperative considerations, and the potential future role of biomarkers such as ctDNA. Ultimately, the episode underscores the need for clinical trials and thoughtful patient selection as clinicians navigate integrating surgery into an evolving systemic therapy landscape. --- TIMESTAMPS 00:00 - Introduction02:19 - The Evolution of Urothelial Carcinoma Treatment05:23 - Rationale for Consolidative Surgery12:32 - Patient Selection Criteria15:23 - Surgical Approach and Considerations23:58 - Pathologic Findings31:34 - The Role of Radiation39:38 - Biomarkers44:10 - Prospective Trials and Future Directions53:06 - Guidance for Urologists --- RESOURCES Consolidative Surgery for Advanced Urothelial Carcinoma Following Induction Enfortumab Vedotin and/or Immune Checkpoint Inhibitor Therapy: A Multicenter Analysishttps://pubmed.ncbi.nlm.nih.gov/40425390/ Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancerhttps://www.nejm.org/doi/full/10.1056/NEJMoa2312117 Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancerhttps://www.nejm.org/doi/abs/10.1056/NEJMoa2401497

Dr. Pedro Barata and Dr. Ugwuji Maduekwe discuss the evolving treatment landscape in gastroesophageal junction and gastric cancers, including the emergence of organ preservation as a selective therapeutic goal, as well as strategies to mitigate disparities in care. Dr. Maduekwe is the senior author of the article, "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Primetime?" in the 2026 ASCO Educational Book. TRANSCRIPT Dr. Pedro Barata: Hello, and welcome to By the Book, a podcast series from ASCO that features compelling perspectives from authors and editors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also the deputy editor of the ASCO Educational Book. Gastric and gastroesophageal cancers are the fifth most common cancer worldwide and the fourth leading cause of cancer-related mortality. Over the last decade, the treatment landscape has evolved tremendously, and today, organ preservation is emerging as an attainable but still selective therapeutic goal. Today, I'm delighted to be speaking with Dr. Ugwuji Maduekwe, an associate professor of surgery and the director of regional therapies in the Division of Surgical Oncology at the Medical College of Wisconsin. Dr. Maduekwe is also the last author of a fantastic paper in the 2026 ASCO Educational Book titled "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Prime Time?" We explore these questions in our conversations today.  Our full disclosures are available in the transcript of this episode as well. Welcome. Thank you for joining us today. Dr. Ugwuji Maduekwe: Thank you, Dr. Barata. I'm really, really glad to be here. Dr. Pedro Barata: There's been a lot of progress in the treatment of gastric and gastroesophageal cancers. But before we actually dive into some of the key take-home points from your paper, can you just walk us through how systemic therapy has emerged and actually allowed you to start thinking about a curative framework and really informing surgery decision-making? Dr. Ugwuji Maduekwe: Great, thank you. I'm really excited to be here and I love this topic because, I'm terrified to think of how long ago it was, but I remember in medical school, one of my formative experiences and why I got so interested in oncology was when the very first trials about imatinib were coming through, right? Looking at the effect, I remember so vividly having a lecture as a first-year or second-year medical student, and the professor saying, "This data about this particular kind of cancer is no longer accurate. They don't need bone marrow transplants anymore, they can just take a pill." And that just sounded insane. And we don't have that yet for GI malignancies. But part of what is the promise of precision oncology has always been to me that framework. That framework we have for people with CML who don't have a bone marrow transplant, they take a pill. For people with GIST. And so when we talk about gastric cancers and gastroesophageal cancers, I think the short answer is that systemic therapy has forced surgeons to rethink what "necessary" really means, right? We have the old age saying, "a chance to cut is a chance to cure." And when I started out, the conversation was simple. We diagnose the cancer, we take it out. Surgery's the default. But what's changed really over the last decade and really over the last five years is that systemic therapy has gotten good enough to do what is probably real curative work before we ever enter the operating room. So now when you see a patient whose tumor has essentially melted away on restaging, the question has to shift, right? It's no longer just, "Can I take this out?" It's "Has the biology already done the heavy lifting? Have we already given them systemic therapy, and can we prove it safely so that maybe we don't have to do what is a relatively morbid procedure?" And that shift is what has opened the door to organ preservation. Surgery doesn't disappear, but it becomes more discretionary. Necessary for the patients who need it, and within systems that can allow us to make sure that we're giving it to the right patients. Dr. Pedro Barata: Right, no, that makes total sense. And going back to the outcomes that you get with these systemic therapies, I mean, big efforts to find effective regimens or cocktails of therapies that allow us to go to what we call "complete response," right? Pathologic complete response, or clinical complete response, or even molecular complete response. We're having these conversations across different tumors, hematologic malignancies as well as solid tumors, right? I certainly have those conversations in the GU arena as well. So, when we think of pathologic CRs for GI malignancies, right? If I were to summarize the data, and please correct me if I'm wrong, because I'm not an expert in this area, the traditional perioperative chemo gives you pCRs, pathologic complete response, in the single digits. But then when you start getting smarter at identifying biologically distinct tumors such as microsatellite instability, for instance, now you start talking about pCRs over 50%. In other words, half of the patients' cancer goes away, it melts down by offering, in this case, immunotherapy as a backbone of that neoadjuvant. But first of all, this shift, right, from going from these traditional, "not smart" chemotherapy approaches to kind of biologically-driven approaches, and how important is pCR in the context of "Do I really need surgery afterwards?" Dr. Ugwuji Maduekwe: That's really the crux of the entire conversation, right? We can't proceed and we wouldn't be able to have the conversation about whether organ preservation is even plausible if we hadn't been seeing these rates of pathologic complete response. If there's no viable tumor left at resection, did surgery add something? Are we sure? The challenge before this was how frequently that happened. And then the next one is, as you've already raised, "Can we figure that out without operating?" In the traditional perioperative chemo era, pathologic complete response was relatively rare, like maybe one in twenty patients. When we go to more modern regimens like FLOT, it got closer to one in six. When you add immunotherapy in recent trials like MATTERHORN, it's nearly triple that rate. And it's worth noting here, I'm a health services-health disparities researcher, so we'll just pause here and note that those all sound great, but these landmark trials have significant representation gaps that limit and should inform how confidently we generalize these findings. But back to what you just said, right, the real inflection point is MSI-high disease where, with neoadjuvant dual-checkpoint blockade, trials like NEONIPIGAS and INFINITY show pCR rates that are approaching 50% to 60%. That's not incremental progress, that's a whole new different biological reality. What does that mean? If we're saying that 50% to 60% of the people we take to the OR at the time of surgery will end up having no viable tumor, man, did we need to do a really big surgery? But the problem right now is the gold standard, I think we would mostly agree, the gold standard is pathologic complete response, and we only know that after surgery. I currently tell my patients, right, because I don't want them to be like, "Wait, we did this whole thing." I'm like, "We're going to do this surgery, and my hope is that we're going to do the surgery and there will be no cancer left in your stomach after we take out your stomach." And they're like, "But we took out my stomach and you're saying it's a good thing that there's no cancer." And yes, right now that is true because it's a measure of the efficacy of their systemic therapy. It's a measure of the biology of the disease. But should we be acting on this non-operatively? To do that, we have to find a surrogate. And the surrogate that we have to figure out is complete clinical response. And that's where we have issues with the stomach. In esophageal cancer, the preSANO protocol, which we'll talk about a little bit, validated a structured clinical response evaluation. People got really high-quality endoscopies with bite-on biopsies. They got endoscopic ultrasounds. They got fine-needle aspirations and PET-CT, and adding all of those things together, the miss rate for substantial residual disease was about 10% to 15%. That's a number we can work with. In the stomach, it's a lot more difficult anatomically just given the shape of people's stomachs. There's fibrosis, there's ulceration. A fair number of stomach and GEJ cancers have diffuse histology which makes it difficult to localize and they also have submucosal spread. Those all conceal residual disease. I had a recent case where I scoped the patient during the case, and this person had had a 4 cm ulcer prior to surgery, and I scoped and there was nothing visible. And I was elated. And on the final pathology they had a 7 cm tumor still in place. It was just all submucosal. That's the problem. I'm not a gastroenterologist, but I would have said this was a great clinical response, but because it's gastric, there was a fair amount of submucosal disease that was still there. And our imaging loses accuracy after treatment. So the gap between what looks clean clinically and what's actually there pathologically remains very wide. So I think that's why we're trying to figure it out and make it cleaner. And outside of biomarker-selected settings like MSI-high disease, in general, I'm going to skip to the end and our upshot for the paper, which is that organ preservation, I would say for gastric cancer particularly, should remain investigational. I think we're at the point where the biology is increasingly favorable, but our means of measurement is not there yet. Dr. Pedro Barata: Gotcha. So, this is a perfect segue because you did mention the SANO, just to spell it out, "Surgery As Needed for Oesophageal" trial, so SANO, perfect, I love the abbreviation. It's really catchy. It's fantastic, it's actually a well-put-together perspective effort or program applying to patients. And can you tell us how was that put together and how does that work out for patients? Dr. Ugwuji Maduekwe: Yeah, I think for those of us in the GI space, we have SANO and then we also have the OPRA for rectum. SANO for the upper GI is what takes organ preservation from theory to something that's clinically credible. The trial asked a very simple question. If a patient with a GEJ adenocarcinoma or esophageal adenocarcinoma achieved what was felt to be a clinical complete response after chemoradiation, would they actually benefit from immediate surgery? And the question was, "Can you safely observe?" And the answer was 'yes'. You could safely observe, but only if you do it right. And what does that mean? At two years, survival with active surveillance was not inferior to those who received an immediate esophagectomy. And those patients had a better early quality of life. Makes sense, right? Your quality of life with an esophagectomy versus not is going to be different. That matters a lot when you consider what the long-term metabolic and functional consequences of an esophagectomy are. The weight loss, nutritional deficiencies that can persist for years. But SANO worked because it was very, very disciplined and not permissive. You mentioned rigor. They were very elegant in their approach and there was a fair amount of rigor. So there were two main principles. The first was that surveillance was front-loaded and intentional. So they had endoscopies with biopsies and imaging every three to four months in the first year and then they progressively spaced it out with explicit criteria for what constituted failure. And then salvage surgery was pre-planned. So, the return-to-surgery pathway was already rehearsed ahead of time. If disease reappeared, take the patient to the OR within weeks. Not sit, figure out what that means, think about it a little bit and debate next steps. They were very clear about what the plan was going to be. So they've given us this blueprint for, like, watching people safely. I think what's remarkable is that if you don't do that, if you don't have that infrastructure, then organ preservation isn't really careful. It's really hopeful. And that's what I really liked about the SANO trial, aside from, I agree, the name is pretty cool. Dr. Pedro Barata: Yeah, no, that's a fantastic point. And that description is spot on. I am thinking as we go through this, where can this be adopted, right? Because, not surprisingly, patients are telling you they're doing a lot better, right, when you don't get the esophagus out or the stomach out. I mean, that makes total sense. So the question is, you know, how do you see those issues related to the logistics, right? Getting the multi-disciplinary team, getting the different assessments of CR. I guess PETs, a lot of people are getting access to imaging these days. How close do you think this is, this kind of program, to be implemented? And maybe I would assume it might need to be validated in different settings, right, including the community. How close or how far do you think you see that being applied out there versus continuing to be a niche program, watch and wait program, in dedicated academic centers? Dr. Ugwuji Maduekwe: I love this question. So I said at the top of this, I'm a health equity/health disparities researcher, and this is where I worry the most. I love the science of this. I'm really excited about the science. I'm very optimistic. I don't think this is a question of "if," I think it's a question of "when." We are going to get to a point where these conversations will be very, very reasonable and will be options. One of the things I worry about is: who is it going to be an option for? Organ preservation is not just a treatment choice, and I think what you're pointing out very rightly is it's a systems-level intervention. Look at what we just said for SANO. Someone needs to be able to do advanced endoscopy, get the patients back. We have to have the time and space to come back every three to four months. We have to do molecular testing. There needs to be multi-disciplinary review. There needs to be intensive surveillance, and you need to have rapid access to salvage surgery. Where is that infrastructure? In this country, it's mostly in academic centers. I think about the panel we had at ASCO GI, which was fantastic. And as we were having the conversation, you know, we set it up as a debate. So folks were debating either pro-surveillance or pro-surgery. But both groups, both people, were presenting outcomes based on their centers. And it was folks who were fantastic. Dr. Molena, for example, from Memorial Sloan Kettering was talking about their outcomes in esophagectomies [during our session at GI26], but they do hundreds of these cases there per year. What's the reality in this country? 70% to 80% to 90%, depending on which data you look at, of the gastrectomies in the United States occur at low-volume hospitals. Most of the patients at those hospitals are disproportionately uninsured or on government insurance, have lower income and from racial and ethnic minority groups. So if we diffuse organ preservations without the system to support it, we're going to create a two-tiered system of care where whether you have the ability to preserve your organs, to preserve bodily integrity, depends on where you live and where you're treated. The other piece of this is the biomarker testing gap. One of the things that, as you pointed out at the beginning, that's really exciting is for MSI-high tumors. Those are the patients that are most likely to benefit from immunotherapy-based organ preservation. But here's the problem. If the patient isn't tested at time of initial diagnosis before they ever see me as a surgeon, the door to organ preservation is closed before it's ever open. And testing access remains very inconsistent across academic networks. And then there's the financial toxicity piece where, for gastrectomy, pancreatectomy, I do peritoneal malignancies, more than half of those patients experience significant financial toxicity related to their cancer treatment. We're now proposing adding at least two years, that's the preliminary information, right? It's probably going to be longer. At least a couple of years of surveillance visits, repeated endoscopies, immunotherapy costs. How are we going to support patients through that? We're going to have to think about setting up navigation support, geographic solutions, what financial counseling looks like. My patient for clinic yesterday was driving to see me, and they were talking about how they were sliding because it was snowing. And they were sliding for the entire three-hour drive down here. Are we going to tell people like that that they need to drive down to, right, I work at a high-volume center, they're going to need to come here every three months, come rain or snow, to get scoped as opposed to the one-time having a surgery and not needing to have the scopes as frequently? My concern, like I said, I'm an optimist, I think it is going to work. I think we're going to figure out how to make it work. I'm worried about whether when we deploy it, we widen the already existing disparities. Dr. Pedro Barata: Gotcha, and that's a fantastic summary. And as I'm thinking also of what we've been talking in other solid tumors, which one of the following do you think is going to evolve first? So we are starting to use more MRD-based assays, which are based on blood test, whether it's a tumor-informed ctDNA or non-informed. We are also trying to get around or trying to get more information response to systemic therapies out of RNA-seq through gene expression signatures, or development of novel therapeutics which also can help you there. Which one of these areas you think you're going to help this SANO-like approach move forward, or you actually think it's actually all of the above, which makes it even more complicated perhaps? Dr. Ugwuji Maduekwe: I think it's going to be all of the above for a couple of reasons. I would say if I had to pick just one right now, I think ctDNA is probably the most promising and potentially the missing piece that can help us close the gap between clinical and pathologic response. If you achieve clinical complete response and your ctDNA is negative, so you have clinical and molecular evidence of clearance, maybe that's a low-risk patient for surveillance. If you have clinical complete response but your ctDNA remains positive, I would say you have occult molecular disease and we probably need intensified therapy, closer monitoring, not observation. I think the INFINITY trial is already incorporating ctDNA into its algorithm, so we'll know. I don't think we're at the point where it alone can drive surgical decisions. I think it's going to be a good complement to clinical response evaluation, not a replacement. The issue of where I think it's probably going to be multi-dimensional is the evidence base: who are we testing? Like, what is the diversity, what is the ancestral diversity of these databases that we're using for all of these tests? How do we know that ctDNA levels and RNA-seq expression arrays are the same across different ancestral groups, across different disease types? So I think it's probably going to be an amalgam and we're going to have to figure out some sort of algorithm to help us define it based on the patient characteristics. Like, I think it's probably different, some of this stuff is going to be a little bit different depending on where in the stomach the cancer is. And it's going to be a little bit more difficult to figure out if you have a complete clinical response in the antrum and closer to the pylorus, for example. That might be a little bit more difficult. So maybe the threshold for defining what a clinical complete response needs to be is higher because the therapeutic approach there is not quite as onerous as for something at the GE-junction. Dr. Pedro Barata: Wonderful. And I'm sure AI, whether it's digitization of the pathology from the biopsies and putting all this together, probably might play a role as well in the future.  Dr. Maduekwe, it's been fantastic. Thank you so much for sharing your insights with us and also congrats again for the really well-done review published.  For our listeners, thank you for staying with us. Thank you for your time. We will post a link to this fantastic article we discussed today in the transcript of this episode. And of course, please join us again next month on the By the Book Podcast for more insights on key advances and innovations that are shaping modern oncology. Thank you, everyone. Dr. Ugwuji Maduekwe: Thank you. Thank you for having me. Watch the ASCO GI26 session: Organ Preservation for Gastroesophageal and Gastric Cancers: Ready for Primetime? Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:          Dr. Pedro Barata   @PBarataMD    Dr. Ugwuji Maduekwe @umaduekwemd Follow ASCO on social media:          @ASCO on X (formerly Twitter)          ASCO on Bluesky         ASCO on Facebook          ASCO on LinkedIn          Disclosures:       Dr. Pedro Barata:   Stock and Other Ownership Interests: Luminate Medical   Honoraria: UroToday   Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon   Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas   Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck    Dr. Ugwuji Maduekwe: Leadership: Medica Health Research Funding: Cigna    

Dr. Sonam Puri discusses the full update to the living guideline on stage IV NSCLC with driver alterations. She shares a new overarching recommendation on biomarking testing and explains the new recommendations and the supporting evidence for first-line and subsequent therapies for patients with stage IV NSCLC and driver alterations including EGFR, MET, ROS1, and HER2. Dr. Puri talks about the importance of this guideline and rapidly evolving areas of research that will impact future updates. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.0" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  https://ascopubs.org/doi/10.1200/JCO-25-02822    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Sonam Puri from Moffitt Cancer Center, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It's great to have you here today, Dr. Puri. Dr. Sonam Puri: Thanks, Brittany. Brittany Harvey: And then just before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Puri, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content that we're here today to talk about, Dr. Puri, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer with driver alterations is updated on an ongoing basis. So, what data prompted this latest update to the recommendations? Dr. Sonam Puri: So Brittany, non-small cell lung cancer is one of the fastest-moving areas in oncology right now, particularly when it comes to targeted therapy for driver alterations. New data are emerging continuously from clinical trials, regulatory approvals, real-world experience, which is exactly why these are living guidelines. The goal is to rapidly integrate important advances as they happen, rather than waiting for years for a traditional update. Since the last full update of the ASCO Stage IV Non-small Cell Lung Cancer Guideline with Driver Alterations published in 2024, there have been seven new regulatory approvals and changes in first-line therapy for some driver alterations. [This version] of the "Stage IV Non-small Cell Lung Cancer Guidelines with Driver Alterations" represents a full update, which means that the panel reviewed and refreshed every applicable section of the guideline to reflect the most current evidence across therapies including sequencing and clinical decision-making. This is to ensure that clinicians have up-to-date practical guidelines that keep pace with how quickly the field is evolving. Brittany Harvey: Absolutely. As you mentioned, this is a very fast-moving space and this full update helps condense all of those versions that the panel reviewed before into one document, along with additional approvals and new trials that you reviewed during this time period. So then, the first aspect of the guideline is there's a new overarching recommendation on biomarker testing. Could you speak a little bit to that updated recommendation? Dr. Sonam Puri: Yeah, definitely. So the panel has discussed and provided recommendations on comprehensive biomarker testing and its importance in all patients diagnosed with non-small cell lung cancer. Ideally, biomarker testing should include a broad-based next-generation sequencing panel, rather than single-gene tests, along with immunohistochemistry for important markers such as PD-L1, HER2, and MET. These results really drive treatment decisions, both in frontline settings for all patients diagnosed with non-small cell lung cancer and in subsequent line settings for patients with non-small cell lung cancer harboring certain targetable alterations. Specifically in the frontline setting, it helps determine whether a patient should receive upfront targeted therapy or immunotherapy-based approach. We now have strong data that shows that complete molecular profiling results before starting first-line therapy is associated with better overall survival and actually more cost-effective care. Using both tissue and blood-based testing can improve likelihood of getting actionable results in a timely way, and we've also provided guidance on platforms that include RNA sequencing, which are specifically helpful for identifying gene fusions that might be otherwise missed with other platforms. On the flip side, outside of a truly resource-limited setting, single-gene PCR testing really should not be routine anymore. This is what the panel recommends. It's less sensitive and inefficient and increases the risk of missing important actionable alterations. Brittany Harvey: Understood. I appreciate you reviewing that recommendation. It really helps identify critical individual factors to match the best treatment option to each individual patient. So then, following that recommendation, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer with a driver alteration? Dr. Sonam Puri: Since the last full update in 2024, there have been four additional interim updates which were published across 2024 and 2025. Compared to the last version, there have been several updates which have been included in this full update. One of the most important shifts has been in first-line treatment of patients with non-small cell lung cancer harboring the classical, or what we call as typical, EGFR mutation. The current version of the recommendation is based on the updated survival data from the phase III FLAURA2 and MARIPOSA studies, based on which the panel recommended to offer either osimertinib combined with platinum-pemetrexed chemotherapy or the combination of amivantamab plus lazertinib in the first-line treatment of classical EGFR mutations. And these recommendations, as I mentioned, are grounded in the results of the FLAURA2 and MARIPOSA trials, both of which demonstrated improvement in progression-free survival and overall survival compared to osimertinib alone in patients with common EGFR mutations. That being said, the panel actually spent significant time discussing the toxicities associated with these treatments as well. These combination approaches come with higher toxicity, longer infusion time, increased treatment frequency. So while combination therapy is now recommended as preferred, the panel has recommended that osimertinib monotherapy remains a reasonable option, particularly for patients with poor performance status and for those who are not interested in treatment intensification after knowing the risks and benefits. Brittany Harvey: Absolutely. It's important to consider both those benefits and risks of those adverse events that you mentioned to match appropriately individualized patient care. So then, beyond those recommendations for first-line therapy, what is new for second-line and subsequent therapies? Dr. Sonam Puri: So this is a section that saw several major updates, particularly again in the EGFR space. The first was an update on treatment after progression on osimertinib for patients with classical EGFR mutation. Here the panel recommends the combination of amivantamab plus chemotherapy, and this recommendation was based on the phase III MARIPOSA-2 trial, which compared amivantamab plus chemotherapy with chemotherapy alone with progression-free survival as the primary endpoint. The study met its primary endpoint, showing an improvement in median PFS with the combination of amivantamab plus chemotherapy compared to chemotherapy alone. And as expected, the combination was associated with higher toxicity. So, although the panel recommends this regimen, the panel emphasizes that patients should be counseled on the side effects which may be moderate to severe with the combination therapy approach. In addition, a new recommendation was added for patients who are not candidates for amivantamab plus chemotherapy. In those cases, platinum-based chemotherapy with or without continuation of osimertinib may be offered, and the option of continuing osimertinib with chemotherapy was recommended and supported by data from a recently presented phase III COMPEL study, which randomized 98 patients with EGFR exon 19 deletion or L858R-mutated advanced non-small cell lung cancer who had experienced no CNS progression on first-line osimertinib, and these patients were randomized to receive platinum-pemetrexed chemotherapy with osimertinib or placebo. Although this study was small, it demonstrated a PFS benefit with continuation of osimertinib with chemotherapy, and this approach may be appropriate for patients without CNS progression who prefer or require alternatives to more intensive treatment strategies. Next was an update on options for patients with EGFR-mutated lung cancer after progression on osimertinib and platinum-based chemotherapy. Here the panel recommended that for patients whose disease has progressed after both osimertinib and platinum-based chemotherapy, a new drug known as datopotamab deruxtecan can be offered as a treatment option. And this treatment recommendation was based on evaluation of pooled data from the TROPION-Lung01 and TROPION-Lung05 study, in which in the pooled analysis about 114 patients with EGFR-mutant non-small cell lung cancer were treated with Dato-DXd, 57% of whom had received three or more prior lines of treatment, and what was observed was an overall response rate of 45% with a median duration of response of 6.5 months. So definitely promising results. Next, we focused on updates to subsequent therapy options for patients with another type of EGFR mutation known as EGFR exon 20 insertion mutations. In this section, the panel added sunvozertinib as a subsequent line option after progression on platinum-based chemotherapy with or without amivantamab. Sunvozertinib is an oral, irreversible, and selective EGFR tyrosine kinase inhibitor with efficacy demonstrated in the phase II WU-KONG6 study conducted in Chinese patient population. In this study, amongst 104 patients with platinum-pretreated EGFR exon 20 mutated non-small cell lung cancer, the observed response rate was 61%. Staying in the EGFR space, the panel added a recommendation for patients with acquired MET amplification following progression on EGFR TKI therapy. In these situations, the panel recommended that treatment may be offered with osimertinib in combination with either tepotinib or savolitinib. As our listeners may know, MET amplification occurs in approximately 10% to 15% of patients with EGFR-mutated non-small cell lung cancer when they progress on third-generation EGFR TKIs, and detection of MET amplification is done with various methods, such as tissue-based methods like FISH, NGS, and IHC, as well as ctDNA-based NGS with variable cut-offs. Over the last few years, several studies have informed this recommendation. I'm going to be discussing some of them. In the phase II ORCHARD trial, 32 patients with MET-amplified non-small cell lung cancer after progression on first-line osimertinib were evaluated, where the combination of osimertinib plus savolitinib achieved an overall response rate of 47% with a duration of response of 14.5 months. More recently, the phase II SAVANNAH trial reported outcomes in 80 patients with MET-amplified tumors after progression on osimertinib, and in this patient population, the combination of savolitinib and osimertinib achieved an overall response rate of 56% with a median PFS of 7.4 months. And lastly, the phase II single-arm INSIGHT 2 trial assessed the efficacy of osimertinib plus tepotinib in patients with advanced EGFR-mutant non-small cell lung cancer who had disease progression following first-line osimertinib therapy. And in this study, in a cohort of 98 patients with MET-amplified tumors confirmed by central testing, the overall response rate with the combination was 50% with a duration of response of 8.5 months. So definitely informing this guideline recommendation. Next, we had an update on recommendation in patients with ROS1-rearranged non-small cell lung cancer. For patients with ROS1-rearranged non-small cell lung cancer, the panel recommended specifically for patients who progressed after first-line ROS1 TKIs, the addition of taletrectinib as a new option alongside repotrectinib. And this recommendation was based on analysis of the results of the TRUST-I and TRUST-II studies, which showed that amongst 113 tyrosine kinase inhibitor-pretreated patients, taletrectinib achieved a confirmed overall response rate of 55.8% with a median duration of response of 16.6 months and a median PFS of 9.7 months, a very promising agent. Finally, for patients with HER2 exon 20 mutated non-small cell lung cancer, the panel added two new oral HER2 tyrosine kinase inhibitors, zongertinib and sevabertinib, as options in addition to T-DXd and after exposure to T-DXd. These recommendations are based on early phase data from two trials: the phase I Beamion LUNG-01 study, which evaluated zongertinib, and the phase I/II SOHO-01 study that evaluated sevabertinib. In this study, zongertinib demonstrated an overall response rate of 71% in previously treated patients, with an overall response rate of 48% amongst patients who had received prior HER2-directed ADCs including T-DXd. Sevabertinib in its early phase study showed an overall response rate of 64% in previously treated but HER2 therapy-naive patients, and an overall response rate of 38% in patients previously exposed to HER2-directed therapy. The panel believes that both agents had manageable toxicity profile and represent meaningful new options for this patient population. Brittany Harvey: Certainly, it's an active space of research, and I appreciate you reviewing the evidence underpinning all of these recommendations for our listeners. So, it's great to have these new options for patients in the later-line settings. And given all of these updates in both the first and the later-line settings, what should clinicians know as they implement this latest living guideline update, and how do these changes impact patients with non-small cell lung cancer? Dr. Sonam Puri: Some great questions, Brittany. I think for clinicians when implementing this update, I think about two practical steps. First is reiterating the importance of comprehensive biomarker testing. That is the only way to identify key drivers and resistance mechanisms that we are now targeting. And second, picking a first-line strategy that balances efficacy and toxicity and patient preference for your specific patient. I think informed decision-making, shared decision-making is more important than any time right now. It has always been important, but definitely very important now. For patients, this guideline brings recommendations on more personalized treatment options for both first-line and post-progression settings, which potentially means better outcomes. But it is also very important for our patients to continue to have informed conversations about side effects, time commitment, and what matters most to them with their providers. The panel in this version of the guideline specifically acknowledges the real-world barriers that prevent patients from receiving guideline-concordant therapy, including challenges with access to comprehensive molecular testing and treatment availability, and the panel emphasizes on the importance of shared decision-making, and we provide practical discussion points to help clinicians navigate these conversations with the patient. In addition, the panel has also addressed common real-world clinical complexities, such as treating elderly or frail patients, managing multiple chronic conditions, considerations around pregnancy and fertility, and certain disease scenarios such as oligoprogression or oligometastatic disease. And where available, the guideline summarizes this existing data to support informed individual decision-making in these complex situations. Brittany Harvey: Shared decision-making is really paramount, especially with all of the options and weighing the risks and benefits and considering the individual circumstances of each patient that comes before a clinician. We've talked a lot about all of the new studies that the panel has reviewed, but what other studies or areas of research is the panel examining for future updates to this living guideline as it continues to be updated on an ongoing basis? Dr. Sonam Puri: Yes, definitely, so much to look forward to, right? Looking ahead, the panel is closely monitoring several rapidly evolving areas that are likely to shape future updates of the guideline. This includes emerging data from ongoing later-phase studies, particularly the studies that are evaluating these new targeted agents moving to earlier lines of therapy, alongside studies evaluating additional combination strategies or more refined approaches to treatment sequencing. We're also closely watching advances in biomarker testing, the evolving understanding of resistance mechanisms, development of new targets, and promising therapeutic agents. I think ultimately the living guideline exists to help clinicians and patients navigate this rapidly evolving field, and we would like to ensure that scientific advances are rapidly translated into better, more personalized patient care. Brittany Harvey: Definitely. We'll look forward to those updates from those ongoing trials and future areas of research that you mentioned to provide better options for patients with non-small cell lung cancer and a driver alteration. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Puri. Dr. Sonam Puri: Thanks so much. Thanks so much for the opportunity. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. There's also a companion episode with Dr. Reuss on the related living guideline on stage IV non-small cell lung cancer without driver alterations that listeners can find in their feeds as well. And if you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Is the era of cisplatin over, or are we simply becoming more precise about who benefits from it? As perioperative strategies in bladder cancer continue to evolve, emerging tools like circulating tumor DNA (ctDNA) are playing a bigger role in how clinicians assess recurrence risk and tailor treatment. In this episode of BackTable Tumor Board, host Alan Tan, medical oncologist at Vanderbilt-Ingram Cancer Center, is joined by bladder cancer experts Dr. Amanda Nizam and Dr. Brad McGregor to discuss recent advances in the diagnosis and treatment of urothelial carcinoma. --- SYNPOSIS The doctors examine the evolving management of muscle-invasive bladder cancer (MIBC), including the role of neoadjuvant and adjuvant therapies, the integration of immunotherapy, and the recent approval of enfortumab vedotin plus pembrolizumab. The discussion explores the rapidly changing perioperative landscape, the prognostic utility of ctDNA, and how biomarkers such as HER2 and FGFR are influencing treatment selection across disease states. They also address bladder preservation strategies, management of treatment-related toxicities, and the importance of multidisciplinary coordination. The episode concludes with a forward-looking discussion on emerging therapies and the potential to improve cure rates in bladder cancer. --- TIMESTAMPS 00:00 - Introduction01:44 - Overview of Bladder Cancer Treatment04:54 - Patient Staging and Treatment Goals10:12 - Bladder Preservation vs. Radical Cystectomy16:39 - Emerging Trials and Future Directions22:40 - ctDNA and Precision Medicine33:50 - Metastatic Disease and Biomarker Strategies42:16 - Managing Neuropathy in Metastatic Treatment48:44 - HER2 and FGFR in Bladder Cancer54:15 - Future Directions in Bladder Cancer Treatment --- RESOURCES EV-302/303 Trialhttps://newsroom.astellas.com/2023-12-15-PADCEV-R-enfortumab-vedotin-ejfv-with-KEYTRUDA-R-pembrolizumab-Approved-by-FDA-as-the-First-and-Only-ADC-Plus-PD-1-to-Treat-Advanced-Bladder-Cancer NIAGARA Regimenhttps://www.nejm.org/doi/full/10.1056/NEJMoa2408154 KEYNOTE-905 Studyhttps://www.annalsofoncology.org/article/S0923-7534(25)04894-X/fulltext

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.In this episode, Dr Matulonis sat down with guest Rebecca Porter, MD, PhD. Dr Porter is a physician at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School.Drs Matulonis and Porter discussed the evolving role of immunotherapy in gynecologic cancer management, focusing on recent clinical breakthroughs and future directions. They noted that although high-grade serous ovarian cancer has historically been refractory to immunotherapy, the phase 3 KEYNOTE-B96 trial (NCT05116189) demonstrated an efficacy benefit with the addition of pembrolizumab to weekly paclitaxel for patients with platinum-resistant disease. In particular, improvements in overall survival were noted in the PD-L1–positive patient population. Dr Porter attributed this success to the metronomic weekly dosing of paclitaxel, which may increase neoantigen levels and favorably alter the tumor microenvironment (TME).Moreover, the experts highlighted how immunotherapy has already become the standard of care for patients with mismatch repair–deficient advanced or recurrent endometrial cancer. However, they explained that for the mismatch repair–proficient population, this benefit is less clear and appears most significant in patients with measurable disease or specific molecular subtypes. They added that although circulating tumor DNA (ctDNA) assay results correlate with treatment outcomes, ctDNA is currently not an actionable biomarker for determining treatment duration or selection.Lastly, Drs Matulonis and Porter reported that the field of gynecologic oncology is shifting toward combination therapies and novel platforms beyond standard checkpoint inhibitors. Treatment advances include bispecific and trispecific antibodies that engage multiple cell types or signals; as well as adoptive cellular therapies, such as CAR T-cell and CAR natural killer–cell therapies. Ultimately, the experts concluded that the goal of managing challenging-to-treat diseases like ovarian cancer is to use combinatorial approaches—incorporating vaccines, anti-angiogenic therapies, and chemotherapy—to overcome the immunosuppressive nature of the TME.

Featuring an interview with Dr Scott Kopetz, including the following topics:  Circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy de-escalation in the treatment of Stage III colon cancer from the ctDNA-negative cohort of the DYNAMIC-III trial (0:00) Prognostic and predictive role of ctDNA in the management of Stage III colon cancer treated with celecoxib: Findings from the CALGB (Alliance)/SWOG 80702 trial (8:01) Phase III ALTAIR study comparing trifluridine/tipiracil to placebo for patients with molecular residual disease after curative resection of colorectal cancer (CRC); a methylation-based, tissue-free ctDNA test (12:51) ctDNA with locally advanced mismatch repair-deficient/microsatellite instability-high solid tumors; real-world evidence regarding ctDNA with resected CRC (17:31) CME information and select publications