Podcasts about Sorafenib

On today's episode we'll discuss the findings from a phase 2 study of sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML, learn more about the inhibition of PLK4 in TP53-mutated AML, and discuss the role of CD44 in Plasmodium falciparum infection.

In this episode, we dive into the management of newly diagnosed and relapsed FLT3-positive AML with Dr. Alexander Perl.Here are the shownotes:1. Assessment of minimal residual disease in standard-risk AML https://www.nejm.org/doi/full/10.1056/nejmoa1507471 2. RATIFY study: Midostaurin plus chemotherapy for AML with a FLT3 mutationhttps://www.nejm.org/doi/full/10.1056/nejmoa1614359 3. QuANTUM-First trial: Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trialhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00464-6/fulltext 4. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groupshttps://ashpublications.org/blood/article/127/12/1551/35035/Benefit-of-high-dose-daunorubicin-in-AML-induction 5. Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.2017.72.8618?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 6. Phase 3 trial of gilteritinib plus azacitidine vs. azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapyhttps://ashpublications.org/blood/article/140/17/1845/486088/Phase-3-trial-of-gilteritinib-plus-azacitidine-vs 7. ADMIRAL: Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AMLhttps://www.nejm.org/doi/full/10.1056/nejmoa1902688 8. Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemiahttps://ascopubs.org/doi/10.1200/JCO.22.00602?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed 9. Levis MJ, Hamadani M, Logan B, et al: BMT-CTN 1506 (MORPHO): A randomized trial of the FLT3 inhibitor gilteritinib as post-transplant maintenance for FLT3-ITD AML. EHA 2023 Hybrid Congress. Abstract LB2711. Presented June 11, 2023. 10. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30455-1/fulltext?dgcid=raven_jbs_etoc_email

In the second portion of our two part-series on AML maintenance, Anthony and Bernie delve into the studies of post-transplant FLT3 inhibitor maintenance. We discuss the controversial MORPHO study of gilteritinib and whether these results will change practice! Sorafenib observational study: https://pubmed.ncbi.nlm.nih.gov/30809038/ SORMAIN (sorafenib): https://pubmed.ncbi.nlm.nih.gov/32673171/ Chinese Sorafenib Phase III: https://pubmed.ncbi.nlm.nih.gov/32791048/ RADIUS (midostaurin): https://pubmed.ncbi.nlm.nih.gov/33288862/ AMLSG 16-10 (midostaurin): https://pubmed.ncbi.nlm.nih.gov/30563875/ MORPHO (EHA abstract): https://library.ehaweb.org/eha/2023/eha2023-congress/391322/faculty.presenters.bmt-ctn.1506.28morpho29.a.randomized.trial.of.the.flt3.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dmorpho

On this episode of Oncology Unscripted, patient advocates Julie Johnson and Katie Coleman and radiation oncologist Dr. Matt Spraker continue The Insider's Guide to Radiation Therapy! This four episode series will cover radiation 101, stereotactic body radiation therapy (SBRT), and proton therapy!In this episode, we discuss SBRT, alternatively called stereotactic ablative body radiotherapy (SABR). We also discuss a related treatment, stereotactic radiosurgery (SRS).Here are some links to things we discussed during the show:Rare Cancer Research FoundationPattern.orgCount Me InJAMA Oncology SBRT/SABR patient pageCyberKnife information from the manufacturer (Accuray)GammaKnife information from the manufacturer (Eleckta)The patient-led Remove the Mask CampaignHere are some clinical and scientific publications mentioned during this show:Original Timmerman study of SBRT for early stage lung cancerDiscovery of the SBRT "No Fly Zone" in the chestInternational Radiosurgery Consortium of the Kidney (IROCK) meta-analysis of SBRT for primary kidney cancer (renal cell carcinoma).Here are some resources that may be of interest, but were not discussed in this episode:An excellent video on Stereotactic Radiosurgery (SRS) versus Whole Brain Radiotherapy (WBRT) for brain metastases from our friends at PRIMRRTOG 1112 Trial: Benefit of adding SBRT to Sorafenib in locally advanced liver cancer (hepatocellular carcinoma). (conference abstract only)TRENDY Trial: Suggests that SBRT is superior to trans-arterial chemoembolization (TACE) for early liver cancer (haptocellular carcinoma).MD Anderson Cancer Center Phase II Trial: Suggests that SBRT may be used to defer systemic therapy in patients with oligometastatic kidney cancer (renal cell carcinoma) Oncology Unscripted is a Photon Media production. Intro and Outro music by Emmy-award winning artist Lucas Cantor Santiago.Additional content from Katie Coleman can be found at her website, https://www.katiekickscancer.com/. This show and our opinions are meant for general informational purposes and are not medical advice. We encourage you to reach out to your doctors to discuss your individual case. 

A new research paper was published in Oncotarget's Volume 14 on April 10, 2023, entitled, “A phase I trial of riluzole and sorafenib in patients with advanced solid tumors: CTEP #8850.” Overexpression of metabotropic glutamate receptor 1 (GRM1) has been implicated in the pathogenesis of multiple cancers. Riluzole, an inhibitor of glutamate release, showed synergistic antitumor activity in combination with the multi-kinase inhibitor sorafenib in preclinical models. In a new phase I trial, researchers Kristen R. Spencer, Daniella E. Portal, Joseph Aisner, Mark N. Stein, Jyoti Malhotra, Weichung Shih, Nancy Chan, Ann W. Silk, Shridar Ganesan, Susan Goodin, Murugesan Gounder, Hongxia Lin, Jiadong Li, Robert Cerchio, Christina Marinaro, Suzie Chen, and Janice M. Mehnert from Rutgers University, Dana-Farber Cancer Institute, and the Perlmutter Cancer Center of NYU Langone Health identified the toxicity profile, dose-limiting toxicities, maximum tolerated dose (MTD), and pharmacokinetic and pharmacodynamic properties of riluzole combined with sorafenib in patients with advanced cancers. “Riluzole functions as an inhibitor of GRM1 signaling through antagonism of glutamate release, and sorafenib is a multi-kinase inhibitor targeting both the MAPK and PI3K/AKT pathways through the inhibition of RAF1, ARAF and, to a lesser extent BRAF, as well as a set of tyrosine kinases including VEGFR. Our phase I study determined the tolerable dose of this combination and investigated its biologic effects.” Patients with refractory solid tumors were enrolled utilizing a 3+3 dose-escalation design. Riluzole was given at 100 mg PO BID in combination with sorafenib, beginning at 200 mg PO daily and escalating in 200 mg increments per level in 28-day cycles. Restaging evaluations were performed every 2 cycles. In total, 35 patients were enrolled over 4 dose levels. The MTD was declared at dose level 3 (riluzole: 100 mg PO BID; sorafenib: 400 mg AM/200 mg PM). Pharmacokinetic analyses did not reveal definitive evidence of drug-drug interactions. Consistent decreases in phospho-forms of ERK and AKT in tumor tissue analyses with accompanying decrease in GRM1 expression and increase in pro-apoptotic BIM suggest target engagement by the combination. Best responses included a partial response in 1 (2.9%) patient with pancreatic acinar cell carcinoma with a KANK4-RAF1 fusion, and stable disease in 11 (36%) patients. “Combination therapy with riluzole and sorafenib was safe and tolerable in patients with advanced solid tumors. The partial response in a patient with a RAF1 fusion suggests that further exploration in a genomically selected cohort may be warranted.” DOI: https://doi.org/10.18632/oncotarget.28403 Correspondence to: Janice M. Mehnert - Janice.Mehnert@nyulangone.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28403 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - GRM1, riluzole, sorafenib, phase I, clinical trial About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ MEDIA@IMPACTJOURNALS.COM

In this podcast episode from Clinical Care Options (CCO), Heinz-Josef Klumpen, MD, PhD, and Chris Verslype, MD, PhD, discuss challenges in selecting and sequencing therapy for patients with advanced hepatocellular carcinoma. Topics include:Factors to consider before selecting frontline immunotherapyRole of TKIs in the frontlineImpact of Child-Pugh status on the efficacy of immunotherapy/VEGF inhibitor combination therapyReal-world evidence on frontline immunotherapy/VEGF combination therapyFactors to consider when selecting second-line therapy including the role of TKIs and planning for multiple lines of therapyPresenters:Heinz-Josef Klumpen, MD, PhDStaff Specialist, Medical OncologistDepartment of Medical OncologyAmsterdam UMCAmsterdam, The NetherlandsChris Verslype, MD, PhDProfessorClinical Digestive OncologyKULeuvenHead of ClinicHepatologyDigestive OncologyU.Z. LeuvenLeuven, Belgium

Q BioMed Inc CEO Denis Corin says a new study that shows the superior safety and efficacy of its Uttroside-B chemotherapeutic versus FDA-approved drug Sorafenib adds weight to the promise of an effective therapeutic for a patient population that desperately needs better and more treatment options. Corin told Proactive that the study provides additional data for Q BioMed to present to potential partners. "Our objective with this asset has always been to develop it and hopefully partner it with large pharma who are interested in this space," Corin added.

A infusão hepática de quimioterapia intra-arterial com fluorouracil infusional, leucovorin e oxaliplatina (HAIC-FO) vem demonstrando segurança e atividade antitumoral encorajadoras quando utilizados estudos prévio menores para pacientes com CHC localmente avançado.Neste episódio, Tiago Biachi e Allan Pereira discutem o estudo fase III, FOHAIC-1, que avaliou essa estratégia de infusão intra-arterial para pacientes com CHC avançado, previamente não tratados com terapia sistêmica vs. sorafenibe. Apesar de positivo, a principal crítica desse estudo é exatamente o braço controle com sorafenib, que não vem demonstrando ser o melhor tratamento para essa situação.Sejam bem vindos ao episódio 103 do Clinical Papers Podcast!Para saber mais sobre o paper, acesse:https://pubmed.ncbi.nlm.nih.gov/34905388/

In this second episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss how to identify, prevent and mitigate treatment-related adverse events, and review cases with careful considerations for patient-specific factors guiding treatment selection, followed by a question-and-answer session on the management of patients with HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this first episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss the latest data supporting their approach to selecting treatment regimens for patients with HCC, with topics including: the current challenges in the management of HCC, recommended initial workup strategies and the evolving treatment landscape in HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this podcast episode from Clinical Care Options (CCO), Josep M. Llovet, MD, PhD, and Markus Peck-Radosavljevic, MD, MBA, discuss second line treatment of patients with advanced hepatocellular carcinoma. Topics include:Available agents for the management of advanced hepatocellular carcinoma in the second lineThe current role of tyrosine kinase inhibitors in second-line treatment of advanced hepatocellular carcinomaOngoing clinical trials in the second-line settingPresenters:  Josep M. Llovet, MD, PhD, FAASLDProfessor of MedicineDirector, Mount Sinai Liver Cancer ProgramDivision of Liver DiseasesMount Sinai School of MedicineNew York, New YorkProfessor of ResearchLiver Unit, IDIBAPSHospital Clinic BarcelonaBarcelona, SpainUniv. Prof. Markus Peck-Radosavljevic, MD, MBAProfessor of MedicineMedical University of ViennaVienna, AustriaDepartment Chair, Innere Medizin und GastroenterologieKlinikum Klagenfurt am WörtherseeKlagenfurt am Wörthersee, AustriaLink to full program, including accompanying downloadable slidesets:https://bit.ly/2ZL9bxq

In this podcast episode from Clinical Care Options (CCO), Josep M. Llovet, MD, PhD, and Markus Peck-Radosavljevic, MD, MBA, discuss first-line treatment of patients with advanced hepatocellular carcinoma. Topics include:Atezolizumab plus bevacizumab as the current standard of careContraindications to atezolizumab plus bevacizumabThe current role of tyrosine kinase inhibitors in first-line treatment of advanced hepatocellular carcinomaOngoing clinical trials in the first-line settingPresenters:  Josep M. Llovet, MD, PhD, FAASLDProfessor of MedicineDirector, Mount Sinai Liver Cancer ProgramDivision of Liver DiseasesMount Sinai School of MedicineNew York, NYProfessor of ResearchLiver Unit, IDIBAPSHospital Clinic BarcelonaBarcelona, SpainUniv. Prof. Markus Peck-Radosavljevic, MD, MBAProfessor of Medicine, Medical University of ViennaVienna, AustriaDepartment Chair, Innere Medizin and GastroenterologieKlinikum Klagenfurt am WörtherseeKlagenfurt am Wörthersee, AustriaLink to full program, including accompanying downloadable slidesets:https://bit.ly/2ZL9bxq

In this episode, Scott R. Plotkin, MD, PhD, and Brian D. Weiss, MD, answer questions from a healthcare professional audience on topics related to NF1 and plexiform neurofibromas including:  Whole exome sequencing for diagnosisWhen to treat asymptomatic tumorsGenetic testing of family membersChoosing a MEK inhibitorSupportive care for acneiform rashOther RAS pathway inhibitorsPresenters:Scott R. Plotkin, MD, PhDExecutive DirectorPappas Center for Neuro-OncologyProfessor of NeurologyHarvard Medical SchoolBoston, MassachusettsBrian D. Weiss, MDClinical Professor of PediatricsCancer and Blood Diseases Institute Division of Oncology  Medical DirectorSolid Tumor ProgramCincinnati Children's Hospital Medical CenterCincinnati, OhioLink to full program, including downloadable slidesets, expert commentaries, and on-demand webcast:https://bit.ly/3AXckHQ

Oncotarget published this trending research paper on April 13, 2021, entitled, “Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib,” by researchers from the University of Texas MD Anderson Cancer Center, Massachusetts General Hospital, and Harvard Medical School. The majority of circulating insulin–like growth factor (IGF) is synthesized and secreted by the liver, and levels of IGF dramatically decrease in chronic liver disease and HCC. IGF can be a helpful tool to determine the prognosis of patients with advanced HCC while undergoing treatment with sorafenib. Researchers also use the Child-Turcotte-Pugh (CTP) qualitative scoring system to assess severity of liver cirrhosis, hepatic reserve, guide treatment decisions, and to stratify patients with HCC into three groups (A, B, and C). CTP class A has a better prognosis compared to classes B and C. “Assessing liver reserve in HCC is of a great value as a tool for stratification of patients in clinical trials as well as to predict HCC outcome and guide therapy decisions in routine practice.” In the researchers’ prospective study, 171 patients with HCC from the University of Texas MD Anderson Cancer Center were screened and included in this study. Of the patients, 116 were classified in CTP group A. Patient IGF/CTP scores were calculated and the researchers used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups. Based on CTP and the IGF/CTP scores, researchers reclassified group A patients into AA and AB risk groups, which differed significantly in terms of OS and PFS. The researchers followed up with all patients in the study until disease progression or death. Unfortunately, during the follow-up period, 100 patients passed away. “After IGF/CTP scoring, 87 of 116 CTP class A patients were reclassified as IGF/CTP-A (AA) and 29 patients were reclassified as IGF/CTP-B (AB).” Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27924 DOI - https://doi.org/10.18632/oncotarget.27924 Full text - https://www.oncotarget.com/article/27924/text/ Correspondence to - Ahmed O. Kaseb - akaseb@mdanderson.org Keywords - IGF-1, Child-Pugh, sorafenib, liver reserve, hepatocellular carcinoma About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Podcast Contents 0:00-01:54- Introduction by Dr. Adeline Boettcher 01:55-16:03- Dr. Adeline Boettcher interviews Dr. Umar Mahmood and Dr. Benjamin Larimer to discuss their work on the development and characterization of a PET tracer for granzyme B. 16:04-33:45- Dr. Nikita Consul interviews Dr. Eric T. Ahrens about his article entitled, Assessing Oximetry Response to Chimeric Antigen Receptor T-cell Therapy against Glioma with 19F MRI in a Murine Model. Chapelin et al, Radiology: Imaging Cancer 2021; 3(1):e200062 33:46-47:02- Dr. Wendy Tu interviews Dr. Dong-Hyun Kim about his article entitled, Development and Validation of Sorafenib-eluting Microspheres to Enhance Therapeutic Efficacy of Transcatheter Arterial Chemoembolization in a Rat Model of Hepatocellular Carcinoma. Park et al. Radiology: Imaging Cancer 2021; 3(1):e200006 47:03-47:37- Conclusion 

Reviewing the REFLECT (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30207-1/fulltext) study and its take-home points on selecting an agent for advanced HCC.

BARCELONA—Oral cabozantinib “significantly improved” overall survival (OS) and progression free survival (PFS) compared to placebo in patients with advanced hepatocellular carcinoma(HCC) whose disease had progressed despite sorafenib therapy in the phase 3 CELESTIAL trial reported to the 2018 ESMO World …Pilippe Marle AJO PRODUCTION MASTER

Successful treatment of advanced thyroid cancer often involves a combination of therapies. Dr. Sarika Rao discusses how we determine patient care plans.   TRANSCRIPT Intro: MedStar Washington Hospital Center presents Medical Intel where our healthcare team shares health and wellness insights and gives you the inside story on advances in medicine. Host: Thanks for joining us today. We’re talking to Dr. Sarika Rao, an oncologic endocrinologist at MedStar Washington Hospital Center. Today we’re talking about how to treat advanced thyroid cancer when standard treatments fail. Dr. Rao, can tell us about the main types of thyroid cancer? Dr. Rao: Yeah, sure. So thyroid cancer is, the eleventh most common cancer out there. Just briefly, it’s more prevalent in women, but tends to be a little bit more aggressive in men. There are two main types of cells within the thyroid gland - there are follicular cells and there are C cells, c as in cat. So, follicularly-derived thyroid cancer would include papillary, follicular thyroid cancer - which there’s a subsection: Hurthle - which goes with that as well as anaplastic, that’s the most advanced and most aggressive thyroid cancer but it is follicularly derived. And then the C cells that also exist and these are neuroendocrine cells - and thyroid cancer from that specific cell is called medullary thyroid cancer. So, your follicularly derived cancers are the most common, where papillary is the most prevalent. About 80 to 85 percent of all thyroid cancers are papillary. And then your follicular and Hurthle are about 10 to 15 percent and anaplastic is less than 2 percent, so that’s very rare.  And then your medullary is about 1 to 2 percent. Host: How is thyroid cancer diagnosed and treated? Dr. Rao: Generally, the treatment is, a patient finds a nodule, either on, other imaging studies, like a CAT scan or a PET scan for some other reason and a nodule is detected, or on physical exam, the physician or the patient finds, like a lump in the throat area. And then that is followed up with ultrasound and then potentially biopsy, depending on the features of the nodule. If it is thyroid cancer really the first step is surgery. Whether that’s taking out half the gland or taking out the entire gland, as well as lymph nodes, it depends on the type of thyroid cancer and the extent of the disease and the size of the nodule - it’s a very complex process but, you know, we always discuss this with, the endocrinologist and the surgeons to make a decision, in a multidisciplinary fashion. Many times, we take out the entire gland because, oftentimes, especially with the most common type of cancer which is papillary thyroid cancer, it can be multi-focal that you may not realize is on the other half of the gland. But usually a nodule is dominant when it’s greater than one centimeter that we can see on ultrasound. We can see smaller nodules than that, as well. Sometimes the ultrasound doesn’t pick up nodules on the other side. So, if a nodule is quite big on one side, then we are more likely to take out the entire gland because there’s a likely chance that a smaller cancerous site could be on the other side. But that’s a decision that’s made between the patient, surgeon and the endocrinologist. Host: Could you describe the patient care process after surgery? Dr. Rao: Right. So then, after surgery, we get the full pathology and determine the extent of the disease and how aggressive or not the cancer is. And then we follow that up with something called radioactive iodine ablative therapy. It’s a painless test. So, the way I like to explain it to my patients is, in general, thyroid loves iodine. But it involves a low iodine diet for a couple weeks prior to getting this treatment because you are trying to prime those remnant thyroid cells from, wanting that iodine even more, even though it’s a little bit different. So, making them hungry and taking up this radioactive iodine into the gland and then that will destroy any of the remnant tissue. So, they do this low iodine diet and then, most of the time, we do a diagnostic scan to see if there’s any evidence of uptake and by uptake I mean do any of those remnant cells take up that iodine and we can see it in a diagnostic scan, which is a low dose of this radioactive iodine that we give. Because, like we said before, your cells are very hungry for this iodine. We have a risk stratification for the patient. Like, depending on how advanced their disease is. And this form of treatment, by the way, is only for papillary follicular and maybe even Hurthle cell. There are two other forms of thyroid cancer which are a little bit more aggressive where we wouldn’t use this therapy, so I just want to be clear about that. So, depending on their risk stratification - how advanced their disease is and risk of recurrence, then we proceed forward with the ablative dose, which is usually a higher dose of this radioactive iodine. And then after that there are precautions where the patient needs to make sure that they’re keeping a little bit of distance from young children, or other animals, and that’s truly just so that no one else’s thyroid becomes affected. So, they’re radioactive, sort of, but it’s only for a few days and we give them a very instructive packet as to what to do. So, after that, and this, to me, is probably the most important aspect of thyroid treatment after your surgery, is TSH suppression. Host: What is TSH suppression? Dr. Rao: So, you don’t have a thyroid gland anymore, so you need that hormonal replacement with medications like Levothyroxine, which is a generic form, or Synthroid. And there are other different brands out there. In a patient who has a benign disease who had their thyroid out, we calculate a weight-based dosing for the replacement. Someone who had thyroid cancer, we actually give a little bit more of the Levothyroxine or the T4, which is the actual thyroid hormone that you no longer have, and this is so that, you give a little bit more of the dose in an effort to suppress a hormone that’s made in the pituitary which normally stimulates thyroid cells to function, called TSH. And TSH stands for thyroid stimulating hormone, so it does exactly that. So, by giving a higher dose of the actual thyroid hormone you’re effectively suppressing the TSH made in the pituitary so you’re preventing any form of stimulation of any remnant cells that may not have been ablated from the radioactive iodine or, in a patient who didn’t receive radioactive iodine, any remnant cells from getting bigger. So that is very important afterwards, and we have criteria for what we look at and what is safe for a patient. Remnant cells may or may not carry the thyroid cancer in it, but we just want to prevent recurrence of the disease. So, if you still have thyroid tissue the risk of recurrence could be higher in certain individuals and lower in others depending on, you know, the extent of the disease and that’s a risk stratification process. So, for remnant cells that are there, we try to ablate and kill them as much as we can because surgically there’s only so much you can take out. And cells, of course, you can’t see them they’re microscopic, so there’s likely to be some remnant cells after surgery and we just want to prevent recurrence of disease. That’s the goal. Host: What are the typical outcomes after treatment? Dr. Rao: So generally thyroid cancer is, in many situations, is well-behaved. Actually, in the SEER data, the percentage of death for thyroid cancer is only about 3 percent. It’s quite low. So usually, in my practice at least, I repeat an ultrasound at the six-month mark and then again at the one-year mark. And whether a patient received radioactive iodine therapy or not, at the one-year mark I will perform a test which is called a stimulated thyroglobulin test. The thyroglobulin is like our tumor marker for thyroid cancer, and its protein that’s made by the thyroid cells. So usually, you know, in someone who responded very well to therapy the thyroglobulin would be undetectable after surgery and/or radioactive iodine ablation. And that thyroglobulin is stimulated by TSH so that’s the whole purpose of keeping the TSH low because you don’t want it to be stimulated. Except when we do this test - we want to stimulate any remnant cells or any...whether it’s cancer or not, but especially if it’s in the thyroid bed. If it’s outside of the thyroid bed, then that is obviously more concerning for cancer. Host: What do you mean by thyroid bed? Dr. Rao: So, I call it thyroid bed because the thyroid is not there anymore, so at the base of the neck. Ok, so let’s say we are monitoring this patient and at the one-year mark have our ultrasound and maybe we see evidence of disease somewhere. We do this stimulated thyroglobulin level and we do another scan - again, this is with that low iodine diet that everyone quote unquote loves - and this is in an effort, to really identify disease in that manner. So, if you do the scan and you know that there is maybe evidence of disease in the ultrasound or maybe elsewhere that you’ve detected and that scan, when you perform the scan it does not take up that iodine anymore - or after several years of watching this you see growth of the disease after several treatments with radioactive iodine, then we call that radioactive refractory disease. And what that means is that your, those thyroid cells are no longer taking up the iodine, And also, in some of those cases, the tumor marker may or may not be as accurate anymore, again, due to the mutation that’s within that cell. So, at that point, you know, you decide on where the disease is - if it’s confined to the neck, maybe you want to consider reoperation. And that’s a discussion between you and the surgeon and the patient, whether they want that. Of course, all of this is dependent on age and other comorbidities and things like that, but, just in general, that’s one option, if it’s localized disease. Two, you could think about, there’s something called alcohol ablative therapy where maybe you just have one site of disease -  that has been proven by biopsy, by the way, you know, let’s say we know this is thyroid cancer but, you know, it’s failed standard therapies - then you can use the alcohol to just focally ablate that particular nodule. Host: So, you’re essentially killing the cancer cell? Dr. Rao: You are, yeah, or that nodule where the thyroid cancer lives. And this is all localized treatment. Three, you could consider radiation therapy which we less commonly use, but it is an option. Oftentimes, if the thyroid cancer metastasizes to bone, like the spine or the ribs or something like that, which we often see with the follicular thyroid cancer, radiation therapy to those sites may be indicated because those are harder to surgically resect, unless it’s large enough. If you have multiple sites of disease, and if it’s slow-growing, you could also just consider watching the patient, especially if they’re asymptomatic. And finally, we thankfully have newer drugs - they’re called Tyrosine Kinase Inhibitors and it’s a systemic therapy. It’s a form of oral chemotherapy basically. And, these are for patients who have maybe rapidly progressive disease, those who are symptomatic or those who are asymptomatic, but their disease is in locations that, you know, may be more threatening moving forward, especially if maybe there’s invasion of the cancer into the trachea. So, this is a systemic form of therapy and we have two drugs currently approved for differentiated thyroid cancer called Sorafenib, which came out a few years ago, and Lenvatinib, which was approved in 2015, I believe, and on the market. And, generally, most of the, you know, oncologists or endocrinologists would prefer Lenvatinib at this time, if needed. But there is a very high threshold to when we use those medications. So that’s kind of a last effort. We do very close surveillance with these patients and sometimes that’s the safer option actually is to just watch it. That can be very taxing on a patient to just know that they have thyroid cancer that’s still in them or a cancer that’s still in them. But I’ve actually been very surprised with the response that I have gotten from my patients because I’m just very reassuring that, you know, we are closely watching this and, if something does happen, you know, we will address this quickly and in, you know, in a proper way. But it’s very methodical, in my mind, at least initially, as to how to approach recurrent disease. Host: Thanks for joining us today, Dr. Rao. Conclusion: Thanks for listening to Medical Intel with MedStar Washington Hospital Center. Find more podcasts from our healthcare team by visiting medstarwashington.org/podcast or subscribing in iTunes or iHeartRadio.

Ezra Cohen, MD, is a board-certified oncologist and cancer researcher. He cares for patients with all types of head and neck cancers, including esophageal, thyroid and salivary gland cancers. Dr. Cohen is also an internationally recognized expert on novel cancer therapies and heads the Solid Tumor Therapeutics program at Moores Cancer Center. Much of his work has focused on squamous cell carcinomas and cancers of the thyroid, salivary gland, and HPV-related oropharyngeal cancers. As a physician-scientist, he is especially interested in developing novel therapies and understanding mechanisms of sensitivity or resistance; cancer screening; and using medication and other agents to delay or prevent cancer (chemoprevention). He was recently appointed chair of the National Cancer Institute Head and Neck Cancer Steering Committee, which oversees NCI-funded clinical research in this disease. Dr. Cohen is editor-in-chief of Oral Oncology, the most respected specialty journal in head and neck cancer. A frequent speaker at national and international meetings, he has authored more than 120 peer-reviewed papers and has been the principal investigator of multiple clinical trials of new drugs in all phases of development.  In this episode, topics include: Drug therapy for patients that fail standard therapy; including surgery and RAI Not all patients have same behavior for their cancer Some cancers are aggressive Not many thyroid cancer patients are affected by this; maybe a few thousand in the U.S., but not tens of thousands What is the treatment protocol for therapy? Lenvatinib or Sorafenib is the treatment for refectory thyroid cancer Lenvatinib tends to be more effective Sorafenib is tolerated by the patient better Other options to consider include, molecular profiling or some thyroid cancers carry mutation that is targetable, or BRAF BRAF inhibitors used with thyroid cancer patients Molecular profiling DNA sequencing Side effects include, what patient will feel and those that appear in blood tests Side effects include fatigue in 60% patients, hand or foot blisters, nausea and vomiting Side effects in blood tests include high blood pressure, increase in liver enzymes, and a reduction in blood counts VEGF receptor CT scans and ultra sounds or thyroglobulin as an indicator that thyroid cancer not responsive to traditional therapy We don’t want to make the patient feel worse; the question is when to treat the patient with drug therapy Drug treatment does no cure the disease Holidays from the drug and be rid of side effects When restarting drug, disease responds again Pediatric care Immunotherapy NOTES Ezra Cohen, MD American Thyroid Association  

Dr Naomi Balzer-Haas talks to ecancertv at ASCO GU 2015 about the initial results from the phase III ASSURE trial. It appears that adjuvant sorafenib or sunitinib do not benefit patients with unfavourable locally advanced renal carcinoma, but these findings raise more questions.

Dr Mark Beresford talks to ecancertv at ASCO GU 2015 reflecting on the initial results of the ASSURE trial where adjuvant treatment with sorafenib or sunitinib is used for localised renal carcinoma. Neither sorafenib nor sunitinib provide improved outcomes. Other trials such as SORCE which looks at sorafenib and ATLAS which looks at axitinib question the duration of treatment.

Dr Han talks to ecancertv at ASCO 2015 about a multicentre retrospective study to evaluate the efficacy of combination therapy over transarterial chemoembolisation (TACE) alone. The study compared the overall survival between patients with ≥ grade 2 sorafenib-related dermatologic adverse events in the combination therapy group and patients treated with TACE alone.

Dr Gyawali meets with ecancertv at ESMO 2016 to discuss the safety profile of sorafenib, with a 27% increase in the risk of grade 4 and 5 adverse events compared to standard care. He describes the context of the results from this meta-analysis, considering the balancing of risk and outcome for patients, and the impact of treatment-related hospitalisation on quality of life.

El sorafenib es el único tratamiento oral para el manejo del cáncer de hígado, pero se debe entender cual es el alcance de este tratamiento.

El cáncer de hígado es una de las enfermedades más agresiva en el sistema digestivo, algunos pacientes son sometidos a tratamientos con Sorafenib. ¿esto en que beneficia a los pacientes?

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Immunotherapy Forum Video #19: Dr. Lauren Harshman discusses treating kidney cancer with immunotherapy. In this video, she focuses on clinical trials studying PD-1 and PDL-1 agents.

Marcia Brose discusses results of a phase III trial of the kinase inhibitor sorafenib for treating radioactive iodine-refractory thyroid cancer.

Drs. Mary Pinder, Nate Pennell, and Jack West discuss whether the finding of improving progression-free survival with maintenance sorafenib for SCLC should change the standard of care for treatment of extensive stage disease.

Drs. Mary Pinder, Nate Pennell, and Jack West discuss whether the finding of improving progression-free survival with maintenance sorafenib for SCLC should change the standard of care for treatment of extensive stage disease.

Drs. Mary Pinder, Nate Pennell, and Jack West discuss whether the finding of improving progression-free survival with maintenance sorafenib for SCLC should change the standard of care for treatment of extensive stage disease.

Vemurafenib induces endoplasmic reticulum stress in melanoma cells.

Dr Georgina Long talks with ecancer at the 2012 ESMO meeting about a highly successful phase II trial that tested a BRAF and MEK inhibitor combination therapy against metastatic melanoma. The majority of patients quickly develop resistance to BRAF inhibitors so combination therapy was introduced to improve response and progression free survival. Results from the study showed 61 percent of patients, in the combination arm, to have reduction in risk, resistance and death, with prolonged response averaging 9.4 months. The most significant statistic from the study was an increase from 33 percent of patients reaching the 12-month survival mark two years ago to 79 percent of patients reaching that mark today. Side effects from the treatment, such as manageable toxicities, are explained through the biology of the treatment.

Background: Nelfinavir is an HIV protease inhibitor that has been used for a long period of time to treat HIVinfected individuals. It has recently emerged that nelfinavir could represent a prospective new anti-cancer drug, prompting us to test the effect of nelfinavir on leukemia cells. Methods: By combining in vitro and ex vivo studies, the effect of nelfinavir on leukemia cells and non-malignant, bone marrow-derived tissue cells was analyzed. Results: At a concentration of 9 mu g/ml, nelfinavir induced death of 90% of HL60, IM9, and Jurkat cells. At the same concentration and treatment conditions, less than 10% of aspirated human bone marrow cells showed nelfinavir-induced cell damage. Nelfinavir-induced death of leukemia cells was accompanied by activation of caspases 3, 7, and 8. Despite caspase activation, the upregulation of the anti-apoptotic bcl-2 family member protein mcl-1 that resulted from nelfinavir treatment stabilized the mitochondrial membrane potential, resulting in primarily mitochondria-independent cell death. Pharmacological downregulation of mcl-1 expression by treatment with sorafenib (2 mu g/ml) significantly enhanced nelfinavir-induced apoptosis even at lower nelfinavir concentrations (5 mu g/ml), but did not have additional detrimental effects on non-malignant bone marrow cells. Conclusions: The ability of nelfinavir to induce apoptosis in leukemia cells as a single agent in a mitochondria-independent manner might suggest it could be used as a second or third line of treatment for leukemia patients for whom standard mitochondria-directed treatment strategies have failed. Combination treatment with nelfinavir and sorafenib might further enhance the efficacy of nelfinavir even on chemo-resistant leukemia cells.

Background Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor is the main target of current antiangiogenic treatment strategies in AMD. However, other growth factors, such as platelet-derived growth factor (PDGF) and placenta growth factor (PlGF), have a substantial impact on development of AMD. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of growth factors in human retinal pigment epithelial (RPE) cells. Methods Primary human RPE cells were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reactions, immunohistochemistry and enzyme-linked immunosorbent assays. Results Light exposure decreased cell viability and increased expression and secretion of VEGF-A, PDGF-BB and PlGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 mu g/ml. Conclusion The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.

HCCUpdate.com – 67yo, unresectable Child-Pugh B HCC treated with sorafenib. Interviews conducted by Neil Love, MD. Produced by Research To Practice.

HCCUpdate.com – 62yo, emergency hepatic lobectomy for ruptured HCC; sorafenib for recurrent disease. Interviews conducted by Neil Love, MD. Produced by Research To Practice.