Podcasts about idh

De Adviesraad Internationale Vraagstukken (AIV) heeft het kabinet een stevige opdracht meegegeven. Zorg voor een langetermijnstrategie voor voedselzekerheid. Nederland moet hier zelfs het voortouw nemen omdat het op dit terrein wereldwijd economisch en logistiek tot de toonaangevende landen behoort. Het briefadvies ‘Voedselzekerheid in een wankele wereld: een agenda voor Nederland’ schetst zo’n agenda. Niet alleen voor bewindslieden die zich met landbouw, handelsrelaties en ontwikkelingssamenwerking bezig houden, maar ook voor bedrijven, organisaties en kenniscentra die vanuit ons land wereldwijd vaak een prominente rol spelen. En het is ook een vraagstuk van economische veiligheid en weerbaarheid. Jaap Jansen en PG Kroeger praten hierover met de schrijver van het advies, Jorrit Oppewal (AIV), en Daan Wensing, ceo van Initiatief Duurzame Handel, waarin bedrijven en organisaties die bezig zijn met agrogrondstoffen en voedselketens hun krachten bundelen. *** Deze aflevering is mede mogelijk gemaakt met donaties van luisteraars die we hiervoor hartelijk danken. Word ook vriend van de show! Heb je belangstelling om in onze podcast te adverteren of ons te sponsoren? Zend ons een mailtje en wij zoeken contact. *** Jorrit Oppewal benadrukt dat voedsel en de grondstoffen daarvoor geopolitieke factoren zijn geworden. Daarom moet Nederland strategische samenwerkingsrelaties ontwikkelen. En dit houdt veel meer in dan 'klantrelaties' bij agrarische producten. Namelijk kennisdeling, netwerkopbouw, intensivering van contacten – ook diplomatiek - en nadrukkelijke wederkerigheid. Een langdurig perspectief van samenwerking met landen en regio’s in het Mondiale Zuiden (Afrika, Azië en Latijns-Amerika). De Verenigde Naties willen honger uitbannen, maar het aantal mensen met honger is de afgelopen jaren juist toegenomen. Daan Wensing schetst hoe de IDH-partners vanaf de Covid-pandemie in hun handelsketens tal van disrupties ondergingen. "Tot nu toe ging het nét niet mis.” Alle betrokkenen beseffen dat de afhankelijkheden groot, complex en riskant zijn. Ook bij agrogrondstoffen. De Iran-oorlog met de blokkade van de Straat van Hormuz bleek meteen de grondstoffenketen rond kunstmest lam te leggen. “Rampzalig voor Afrika en Azië en dus meteen ook voor ons." Ook voor grondstoffen als soja en palmolie, die voor allerlei producten nodig zijn, geldt die kwetsbaarheid. En het gaat om veel meer dan alleen de bekende producten uit de supermarkt. Omdat de VS en China hun eigen gang gaan en de multilaterale organisaties in het slop zitten, moet Nederland coalities sluiten met andere ‘middenmachten’. IDH bouwt aan het soort strategische partnerschappen waar de AIV over schrijft. "Zuid-Afrika is – via ons land - voor tropische groenten en fruit een groot leverancier aan Europa. Wij hebben daar een coalitie gevormd met bedrijven die met de kennis en netwerken bij ons grote stappen kunnen zetten. Daarmee zetten wij ook een soort 'soft power' in, waarmee intensieve relaties verder verdiept worden." De klassieke werkwijze van de ‘polder' krijgt in zulke samenwerkingspatronen een eigen, nieuwe variant. De term daarvoor is 'the Dutch Diamond'. "Belangrijk is dat we zo daarin samenwerken, dat het niet de indruk wekt, dat wij heel arrogant wel even komen vertellen hoe het moet", zegt Jorrit Oppewal. In het eigen actieplan van IDH, 'Agrohandel, zeker, veerkrachtig en duurzaam’ komt de alertheid ook naar voren. Daan Wensing: "We moeten beseffen dat we in een andere wereldorde leven waarin we met het Mondiale Zuiden gelijkwaardige partnerschappen vormen. Voor die partners is toegang tot de Europese Unie essentieel. Vaak voelen zij nog: "Wij staan achter in de rij.” Geopolitiek beschouwen zij de EU als net zo'n 'supermacht' als China of Amerika. Voor voedselzekerheid is Nederland voor hen vaak het gezicht van de EU. Ook dat gegeven maakt het voor de Nederlandse economie, bedrijven en kennisorganisaties cruciaal, het beleid Europees af te stemmen en hoog op de agenda te zetten. Grote langetermijn EU-programma's voor investeringen en connecties, zoals de Global Gateway – het Europese antwoord op het Chinese Belt & Road Initiative - krijgen in ons land opmerkelijk weinig aandacht. Voor de ketens en partnerschappen op dit terrein vormen ze een grote kans, mits we dat wereldwijd samen aanpakken. In de tweede helft van 2029 is Nederland EU-voorzitter. IDH pleit ervoor dat het nu vast begint met de voorbereiding van een speciale topconferentie over voedselzekerheid van de EU met die strategische partners. De Tweede Kamer ziet veel in het idee: deze week bleek brede steun voor een motie erover. Wensing: "We kunnen daar zoveel uitstekende vormen van samenwerking agenderen, met India, met Nigeria - en hopelijk ook met nieuwe partners erbij – zodat we als Europa met hen de strategische samenwerkingsverbanden fors versterken.” *** Verder lezen *** Verder luisteren 593 - Oud-Eurocommissaris Franz Fischler blikt terug en kijkt vooruit 585 - 'Nostalgie is geen strategie': Canada breekt met Amerika en kiest voor de EU 575 - Nederland staat niet langer op het menu, maar zit aan tafel 574 – Hormuz: eeuwenoud brandpunt van de wereld 537 – De kracht van de vijf Nederlandse zeehavens 458 - De gedroomde nieuwe wereldorde van Poetin en Xi 446 - Doe wat Draghi zegt of Europa wacht een langzame doodsstrijd 431 - Handelsland Nederland staat op het spel 427 - Europa wordt een grootmacht en daar moeten we het over hebben 409 - Nederland wereldwijd handelspartner, ook van communistisch Vietnam *** Tijdlijn 00:00:00 – Deel 1 00:28:24 – Deel 2 00:54:14 – Deel 3 01:14:43 – EindeSee omnystudio.com/listener for privacy information.

A convidada do JR ENTREVISTA desta quarta-feira (10) é a presidente da ABEEólica (Associação Brasileira de Energia Eólica) e vice-presidente da GWEC (Global Wind Energy Council), Elbia Gannoum. À jornalista Lívia Veiga, ela falou sobre a posição estratégica do Brasil na corrida global pela transição energética, destacando que o país possui uma das matrizes elétricas mais limpas do mundo. Segundo Gannoum, o Brasil vive hoje um “bônus verde” que precisa ser transformado em vantagem competitiva real para atrair investimentos e impulsionar a economia.Gannoum explica que, embora o Brasil utilize fontes renováveis há décadas, a valorização global desses recursos ganhou força após o Acordo de Paris, em 2015. Com a Europa passando a exigir produtos de baixo carbono a partir de 2026, o Brasil tem uma oportunidade estratégica única. “O Brasil é o país mais renovável do mundo. Estamos num processo de construção para transformar a vantagem comparativa em vantagem competitiva”, afirmou a especialista durante a entrevista.Um dos pontos centrais da discussão foi o paradoxo da sobra de energia durante o dia. Com o avanço da geração solar em telhados, o sistema produz em excesso entre as 10h e 16h, o que muitas vezes força o desligamento de grandes usinas por segurança. Para corrigir esse desperdício, ela defende o uso de baterias para armazenar o excesso e a adoção de tarifas mais baratas que incentivem o consumo nesse horário.O impacto socioeconômico do setor também foi pauta, com foco no Nordeste, que concentra 95% da produção eólica do país. Gannoum apresentou números que comprovam o alto retorno desses investimentos para a sociedade. “A cada R$ 1 que você investe em energia renovável, você devolve R$ 3 para a economia brasileira”. Esse fluxo financeiro foi fundamental para que o PIB (Produto Interno Bruto) da região crescesse 21% nos últimos 15 anos e o IDH (Índice de Desenvolvimento Humano) local saltasse 20% nas áreas que abrigam os parques eólicos.Apesar do otimismo, há um alerta sobre a perda de liderança para países como a China, que hoje domina o mercado global de transição energética. Elbia aponta que o Brasil está relativamente atrasado na regulamentação de leis cruciais, como as de eólicas offshore e hidrogênio verde, o que gera insegurança jurídica. Ela também criticou o descompasso entre o Executivo e o Legislativo, que por vezes aprova leis que contrariam o planejamento técnico e encarecem o sistema.Para o futuro, a aposta do setor reside na descarbonização da indústria e na atração de centros de dados de alta tecnologia. Gannoum reforça que a energia deve ser vista como uma alavanca de industrialização e crescimento do PIB. “O Brasil tem todas as condições para ocupar esse espaço... ele não precisa mais discutir o que tem que ser feito, ele precisa fazer”, concluiu, enfatizando a “urgência do presente” para que o país não perca a janela de oportunidade global.O programa também está disponível na Record News, no R7, nas redes sociais e no RecordPlus.

Podcast Host and Interviewee:  Host: John Fortunato Interviewee: Bob Jenkins  Podcast Description: Dr. John Fortunato interviews Dr. Bob Jenkins on his recent manuscript, titled "DNA copy number patterns reveal prognostic markers and elucidate mechanisms of evolution in IDH-mutant astrocytoma."

Send us Fan MailPaper Discussed in this Episode:The Performance of Artificial Intelligence in Classifying Molecular Markers in Adult-Type Gliomas Using Histopathological Images: Systematic Review. Almaabreh O, Al-Dafi R, Tabassum A, Othman A, Abd-alrazaq A. J Med Internet Res 2026; 28: e78377.Episode Summary: In this deep dive of the Digital Pathology Podcast, we explore the intersection of human limitations and computational power. Following the 2021 World Health Organization mandate requiring molecular data to diagnose adult-type gliomas, pathology has faced a massive bottleneck. Can artificial intelligence look at a standard pink-and-purple tissue slide and accurately predict hidden genetic mutations to serve as a diagnostic shortcut? We unpack a massive 2026 systematic review that evaluates the architectures, the "data diets," and the structural hurdles of using AI to "see the invisible".In This Episode, We Cover:• The 2021 WHO Diagnostic Shakeup: How the World Health Organization shifted glioma diagnosis from pure visual morphology (judging a book by its cover) to requiring precise genetic spelling (finding a typo on page 42), making the diagnostic process incredibly slow and expensive.• The Targets - IDH vs. 1p/19q: Why AI models are highly proficient at spotting the metaphorical "canyon" carved by early metabolic IDH mutations, but struggle to find the subtle visual clues of 1p/19q chromosomal codeletions.• The AI Toolkit - CNNs, MIL, and Transformers: ◦ CNNs (like DenseNet121): The heavy lifters of medical imaging, analyzing local cell structures and edges by constantly reusing foundational visual features. ◦ Multiple Instance Learning (MIL): The brilliant algorithmic solution to the excruciating human labor of pixel-by-pixel tumor annotation, allowing the AI to mathematically figure out what cancer looks like using only slide-level labels. ◦ Hybrid Models: By combining the microscopic focus of CNNs with the zoomed-out, global contextual awareness of Transformers, these models achieved the highest average accuracy at 92.80%.• The "Data Diet" and Domain Shift: The critical danger of training AI exclusively on single, homogeneous databases like the TCGA. We discuss why an algorithm that performs perfectly in a pristine "test kitchen" completely panics and drops in performance when faced with the varied stains, slice thicknesses, and scans of real-world community hospitals.• Multimodal Medicine: The revelation that AI models perform vastly better when fed diverse data streams, such as combining slide images with MRI scans and clinical notes. Implementing this necessitates a monumental structural integration between historically siloed hospital departments like radiology and pathology.Key Takeaway: AI is not replacing pathologists tomorrow; it is stepping into the co-pilot seat. While hybrid models show immense promise, their true standalone clinical adoption depends on breaking free from narrow training data, overcoming domain shift, and fundamentally restructuring our hospitals to feed these algorithms the multimodal context they need to thriveSupport the showGet the "Digital Pathology 101" FREE E-book and join us!

Veja também em youtube.com/@45_graus Pedro Conceição é diretor do Gabinete do Relatório de Desenvolvimento Humano na ONU, a publicação anual onde é publicado o Índice de Desenvolvimento Humano, juntamente com outros indicadores de desenvolvimento. O convidado é licenciado em Física pelo Instituto Superior Técnico e em Economia pelo Iseg e doutorado em Políticas Públicas pela Lyndon B. Johnson School of Public Affairs da Universidade do Texas em Austin, onde estudou com uma Bolsa Fulbright. _______________ Índice: De que falamos quando falamos de desenvolvimento humano? | Índice de Desenvolvimento Humano da ONU (IDH) Que países surpreendem no ranking de IDH face ao PIB? Governos levam o ranking muito a sério; às vezes demasiado. Que outros indicadores de desenvolvimento poderíamos acrescentar ao o índice? Desigualdade | Ambiente | Democracia e direitos humanos | Indicadores de saúde e educação mais precisos Paper Luís Bettencourt: Community Human Development Index Paper que usa IA e imagens de satélite para estimar IDH. Novo indicador do Banco Mundial, com métrica única de qualidade da educação Quais foram os países com melhor e pior evolução nas últimas décadas? Porque abrandou o crescimento do IDH no Mundo nos últimos anos? Os países começaram a divergir É possível aos governos “game” os indicadores de IDH, ou seja, passarem a gerir para o IDH sem gerar as melhorias de desenvolvimento subjacente?See omnystudio.com/listener for privacy information.

In this episode, editor in chief Joseph E. Safdieh, MD, FAAN, highlights articles about EMG expertise, GLP-1s and epilepsy risk reduction, and combination therapy for recurrent IDH-mutant astrocytoma.

In this episode, editor in chief Joseph E. Safdieh, MD, FAAN, highlights articles about EMG expertise, GLP-1s and epilepsy risk reduction, and combination therapy for recurrent IDH-mutant astrocytoma.

Do you know how to integrate IDH inhibitors into the glioma treatment algorithm? Join our expert panel as they discuss complex real-world cases and more! Credit available for this activity expires: 12/19/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1003175?ecd=bdc_podcast_libsyn_mscpedu

El Dr. José Antonio de la Peña, hematólogo adscrito al Centro Médico Nacional “20 de Noviembre”, ISSSTE, en la Ciudad de México, México, nos comenta lo más destacado del Congreso Anual de la Sociedad Americana de Hematología 2025.Síndrome mielodisplásico y leucemia mieloide agudaEstudio retrospectivo multicéntrico que evaluó el impacto de añadir venetoclax a agentes hipometilantes como tratamiento de primera línea en pacientes con síndrome mielodisplásico de riesgo intermedio-alto a muy alto, según el sistema internacional de puntuación pronóstica revisado. (1)Estudio retrospectivo que evaluó el valor pronóstico de la duración de la respuesta completa en pacientes con síndrome mielodisplásico de alto riesgo tratados con azacitidina. Se incluyeron pacientes que alcanzaron respuesta según criterios IWG 2006/2022, definiéndose respuesta completa duradera como aquella con una duración ≥ 6 meses. (2)El mantenimiento tras el trasplante de médula ósea en leucemia mieloide aguda debe considerarse de forma amplia, idealmente en todos los pacientes, incluso antes de contar con un análisis molecular completo. Existen terapias dirigidas disponibles para alteraciones específicas como FLT3 e IDH, que permiten estrategias de mantenimiento personalizadas. (3)PARADIGM fue un ensayo fase II, abierto, multicéntrico y aleatorizado, que comparó azacitidina + venetoclax frente a quimioterapia intensiva estándar (7+3) como tratamiento de primera línea en pacientes con leucemia mieloide aguda sin factores de alto riesgo. (4) Referencias:Murthy GSG, Ball S, Feld J, Abboud R, Haddadin M, Patel SA, Kishtagari A, Hawkins H, Guerra V, Dworkin E, et al. Hypomethylating agent with venetoclax versus hypomethylating agent alone in frontline management of myelodysplastic syndrome: impact of subgroups on clinical outcomes. Blood. 2025. Abstract presented at the American Society of Hematology Annual Meeting.Braisch TF, Sallman DA, Komrokji RS, et al. Durability of complete response is a stronger predictor of overall survival than complete response rate in patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2025. Abstract presented at the American Society of Hematology Annual Meeting.Levis MJ. Maintenance therapy after allogeneic stem cell transplantation for acute myeloid leukemia: who, when, why, and how long? Blood. 2023;141(9):1001–1010. https://doi.org/10.1182/blood.2022019287.Fathi AT, Uy GL, Montesinos P, et al. Azacitidine plus venetoclax versus intensive chemotherapy as frontline therapy for patients with newly diagnosed acute myeloid leukemia: results from the randomized phase II PARADIGM study. Blood. 2024;144(Suppl 1). Abstract presented at the American Society of Hematology Annual Meeting.

How might the advent of IDH inhibitors impact the practice of radiation oncologists and their role within the wider multidisciplinary team? Credit available for this activity expires: 11/20/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/highlights-san-francisco-evolving-role-radiation-oncologist-2025a1000uyk?ecd=bdc_podcast_libsyn_mscpedu

Para Belém, houve um antes e um depois da COP30, a Conferência do Clima das Nações Unidas, sediada este ano na capital paraense. A cidade recebeu R$ 5 bilhões em investimentos para obras de melhoria em diversos pontos críticos, como saneamento, urbanização e infraestrutura de transportes. Mas a permanência e a continuidade dos avanços preocupam os moradores. Lúcia Müzell, enviada especial da RFI a Belém Um rápido passeio pela região central já escancara as diferenças: os principais monumentos históricos foram restaurados, como o Teatro da Paz, a Catedral Metropolitana, a Basílica de Nossa Senhora de Nazaré e os mercados Ver-o-Peso, símbolo de Belém, e de São Brás, totalmente revitalizado. A auxiliar de limpeza Marlene de Jesus Amaral está maravilhada. “Belém estava meio esquecida, mas agora deu uma grande melhorada. Está linda, maravilhosa, cheia de turistas, gente nova”, diz. "Isso é muito importante para nós, paraenses." O próprio Parque da Cidade, local onde acontece a conferência, será um legado inquestionável do evento, assim como a revitalização das Docas, transformadas em centro cultural e gastronômico da cidade e frequentadas pela população local. A capital carecia desses espaços de lazer, afirma o fiscal de obras Edgar Veloso. "Tinha alguns, mas eram contados. Agora, com as entregas de algumas obras e a expansão de algumas ruas, surgiram mais alternativas e, de certo modo, mais cidadania. Isso melhora a qualidade de vida e deixa as pessoas mais felizes”, comenta. Para o prefeito Igor Normando, a principal obra não é física: é "o senso de pertencimento da população com a cidade”. “É a volta do orgulho do belenense de viver numa cidade que, depois de séculos, voltou a ter um protagonismo relevante mundial”, avaliou. Ele destaca ainda o potencial de alavancar o turismo, a bioeconomia e de a cidade se tornar o novo polo logístico após a requalificação do porto de Outeiro. Trânsito mais fluido “Eu, que rodo por tudo, nem reconheço a cidade. Passo em algumas áreas, principalmente em Umarizal, nas Docas, e foram obras que partiram do zero. Mudou da água para o vinho muito rápido”, observa o motorista Marcelo Augusto Freitas Lobato, que há 13 anos transporta passageiros pelas redondezas. "Eu nem acreditei quando eu vi aquilo ali. Parecia que eu estava em outro país, 'não é Brasil aqui, não estou na cidade de Belém'”, brinca. A vinda da COP30 teve um impacto direto no seu trabalho: a construção de dois viadutos em Ananindeua diminuiu os congestionamentos na entrada da cidade. Além disso, a abertura de ciclovias tornou o trânsito mais seguro, nota o motorista. "O carro não precisa mais estar disputando espaço com o ciclista, com o pedestre. Cada um tem o seu espaço”, aponta. "Até os nossos amigos motoqueiros têm o espaço deles, com uma via exclusiva na avenida Pedro Álvares Cabral." Os investimentos em transporte público, entretanto, deixaram a desejar. Marlene não notou qualquer redução no tempo que leva para ir de Ananindeua, onde mora, até o trabalho, no bairro de Nazaré — entre 1h e 1h30 por dia —, apesar da renovação de parte da frota de ônibus, com mais de 300 veículos menos poluentes e equipados com ar condicionado, e a criação de duas novas linhas.  Um dos piores IDHs entre as capitais brasileiras A vigilante Virginia Cardoso reconhece os benefícios para a capital, mas salienta que eles foram desiguais. "O grande legado que vai ficar é para a cidade de Belém. Nas periferias, a situação continua ruim e eu acredito que vai continuar, porque o governador vai mudar, a COP vai acabar, e é aí que nós vamos ver”, teme. Com um IDH de 0,74, Belém ocupa uma das piores posições no ranking de desenvolvimento humano entre as capitais brasileiras, em 22⁠º lugar. O déficit de saneamento é o maior símbolo da precariedade, com esgoto correndo a céu aberto nas sarjetas, inclusive nos bairros mais nobres. Apenas 20% dos habitantes têm acesso ao sistema de saneamento. Dois parques em volta dos canais da Nova Doca e de Tamandaré buscaram amenizar o problema. Entretanto, durante a realização das obras, o esgoto de um deles foi desviado para a comunidade carente de Vila da Barca, que se mobilizou contra o projeto. Os trabalhos ainda não estão concluídos e preveem o tratamento dos dejetos e um novo sistema de drenagem na comunidade, conhecida como a quarta maior favela do Brasil. “Belém vai aumentar a sua capacidade em até 50% até 2028”, promete o prefeito. “A COP30 nos mostrou que é possível ter ajuda da comunidade internacional para financiar esses projetos, seja através de créditos ou de fundos filantrópicos. A Vila da Barca vai poder ter acesso ao tratamento de água de esgoto, que não tinha antes." No total, 13 canais estão sendo modernizados pelas obras de macrodragagem, 11 deles na periferia. Vendedora ambulante em frente à Basílica de Nazaré, Edina Bahia Batista percebeu a diferença. "Com certeza fez bem. Estávamos precisando. Principalmente o saneamento, que foi ótimo”, avalia. "Quando chovia, enchia tudo. Agora, deu umas chuvas fortes e foi tudo bem." Melhorias até quando?  O fiscal Edgar Veloso atuou nos preparativos da COP30 e concorda que as periferias receberam menos atenção do que os bairros centrais de Belém. Em bairros como Guamá, a pavimentação das ruas se limitou a trechos essenciais, embora o eixo seja importante para os eventos paralelos à conferência. "Pessoas que precisam mais do que eu estão sentindo. A macrodrenagem, o asfalto, estão chegando”, constata. "Não solucionou, não está 100%. Mas pelo menos está sendo feita alguma coisa.” A vigilante Virginia Cardoso salienta que serviços essenciais à população, como a saúde, continuam tão precários quanto antes – o que a leva a duvidar da permanência das melhorias promovidas na cidade. "Agora durante a COP, está tudo magnífico. Muitas coisas melhoraram e vai ficar muito legado. O problema é a manutenção depois”, destaca. "Essa é a grande verdade: sem manutenção, nada sobrevive, e aí nós vamos voltar à estaca zero novamente. No momento, só estão vivendo esse brilho de COP30, mas eu acho que vai continuar da mesma forma que era antes.” Outro motorista de aplicativo, Reginaldo Gomes, concorda: "Volte aqui daqui a um ano para você ver. Vai estar tudo pichado de novo e em 10 anos, tudo como era antes", lamenta. "Em plena região nobre, tem uma ponte que caiu em cima do canal de esgoto há uns 20 anos e até hoje não foi consertada. É uma vergonha", constata. Um efeito colateral das obras é a aceleração da gentrificação dos bairros de classe média, os mais procurados para hospedagens durante a conferência. Na preparação para o evento, moradores foram obrigados a partir depois que os proprietários dos imóveis se recusaram a renovar os contratos de aluguel, de olho nos potenciais lucros da COP. Depois das melhorias nas infraestruturas, os valores agora tendem a subir.

This Social Impact Pioneers episode forms part of the Business Fights Poverty Climate Series 2025. Katie Hyson sits down with Matthew Spencer, Global Director of Landscapes at IDH – The Sustainable Trade Initiative, for a timely conversation recorded live from COP 2025 in Belém, Brazil. With climate risks intensifying and global supply chains under unprecedented pressure, Matthew explores why landscape-level collaboration is emerging as one of the most effective solutions for protecting the world's most vulnerable ecosystems — while strengthening livelihoods for millions of smallholder farmers. Matthew shares IDH's ambitious goal to protect and restore five million hectares of vulnerable landscapes by 2030, addressing deforestation, biodiversity loss, and climate impacts through integrated, jurisdictional approaches – working with communities, businesses and governments. Drawing on career of experience, he explains why landscape initiatives not only deliver environmental gains but also help companies share risk, reduce costs, build resilience, and secure long-term supply. Listeners will hear real-world success stories — from palm oil landscapes in Aceh, Indonesia, to sustainable beef production in Mato Grosso, Brazil — where public-private partnerships have cut deforestation and improved farmers' incomes. Matthew also highlights the rapidly growing landscape platform SourceUp, which now hosts over 65 initiatives (expected to reach 100 next year), helping businesses fast-track participation by identifying opportunities by commodity, country, or sustainability priority. Matthew's Social Impact Pioneer credentials include time with Greenpeace and Oxfam, he's helped secure the UK's phase-out of coal while at the think tank Green Alliance and he's a Turner Fellow at the Cambridge Conservation Initiative, researching what has worked in tropical forest protection over the last three decades. Listen in for Matthew's views on why climate action and poverty reduction must go hand-in-hand, and what truly drives lasting change in forest protection and sustainable land use. Packed with practical insights for business leaders, sustainability professionals, and anyone working at the intersection of climate and development, this episode offers rare optimism — and a clear roadmap for collective action. Tune in to learn how landscape collaboration can drive climate resilience, restore forests, and transform global value chains. Links: IDH - idh.org Matthew Spencer - idhsustainabletrade.com/people/matthew-spencer and linkedin.com/in/matthew-spencer-90b46a46 SourceUp - sourceup.org Tropical Forest Forever Facility - tfff.earth And if you liked this, take a look at the wider Business Fights Poverty Climate Series 2025 here: https://businessfightspoverty.org/climate-series/

Featuring an interview with Dr Eunice S Wang, including the following topics: Hypomethylating agent/venetoclax combinations for the treatment of acute myeloid leukemia (AML); integration in community practice (0:00) All-oral regimen of decitabine/cedazuridine with venetoclax for patients with newly diagnosed AML not eligible for intensive induction chemotherapy (9:39) Efficacy of targeted therapy options for AML; potential role of MRD (minimal residual disease) assays in monitoring treatment response (13:07) Treatment approach for patients with FLT3-mutant AML; mutation profiles and predicting response to quizartinib (20:14) Targeting the differentiation of AML tumor cells with IDH and menin inhibitors; associated differentiation syndrome (29:24) Efficacy and tolerability of the IDH inhibitors ivosidenib and olutasidenib (36:54) Key clinical data with approved and investigational menin inhibitors for AML; current and potential integration of menin inhibitors in the AML treatment algorithm (42:30) CME information and select publications

Featuring a slide presentation and related discussion from Dr Eunice S Wang, including the following topics: All-oral regimen of decitabine/cedazuridine with venetoclax for patients with newly diagnosed acute myeloid leukemia (AML) not eligible for intensive induction chemotherapy (0:00) Quizartinib-based treatment approaches for FLT3-ITD-mutated and FLT3-ITD wild-type AML (5:21) First- and second-generation IDH inhibitors for AML (17:40) Updated results from the AUGMENT-101 Phase II study of the menin inhibitor revumenib for relapsed/refractory KMT2A-rearranged AML (22:59) Phase Ib/II KOMET-001 study of ziftomenib for relapsed/refractory NMP1-mutant AML (26:42) Novel combination approaches with menin inhibitors for AML (29:11) CME information and select publications

O Brasil já viveu um 7 x 1 no futebol. Mas existe outro, muito pior, que acontece todos os dias: o massacre silencioso da nossa educação. Enquanto países pobres, como o Vietnã, superam nações ricas investindo em escolas e professores, nós seguimos presos ao atraso. Este episódio fala de disciplina, ansiedade, esperança e da urgência de transformar exceções em regra. Porque sem educação, a derrota é permanente. O comentário do ouvinte é patrocinado pela Vinho 24 Horas. Já pensou em ter um negócio que funciona 24h, sem precisar de funcionários? Uma adega autônoma instalada no seu condomínio, com vinhos de qualidade, controle pelo celular e margem de 80%. Com apenas R$ 29.900, você inicia sua franquia e ainda ganha 100 garrafas de vinho. Acesse Vinho24.com.br e comece seu novo negócio! A Terra Desenvolvimento revoluciona a gestão agropecuária com métodos exclusivos e tecnologia inovadora, oferecendo acesso em tempo real aos dados da sua fazenda para estratégias eficientes. A equipe atua diretamente na execução, garantindo resultados. Para investidores, orienta na escolha das melhores atividades no agro. Com 25 anos de experiência, transforma propriedades em empreendimentos lucrativos e sustentáveis. Conheça mais em terradesenvolvimento.com.br. Inteligência a serviço do agro! ...................................................................................................................................................................

Featuring an interview with Dr Jorge Cortes, including the following topics: Overview of common molecular profiles in newly diagnosed acute myeloid leukemia (AML) (0:00) Clinical presentation of AML with a FLT3 mutation; implications of clinical data from the Phase III RATIFY trial of the FLT3 inhibitor midostaurin (5:38) Potential incorporation of a FLT3 inhibitor with azacitidine/venetoclax for transplant-ineligible patients with FLT3-mutant AML (10:32) Clinical benefit with quizartinib for patients with FLT3-like genetic profile; selection of FLT3 inhibitor as a component of initial therapy for individuals with AML with a FLT3-ITD mutation (14:04) Overview of FDA-approved IDH inhibitors enasidenib, ivosidenib and olutasidenib; differentiation syndrome as a class effect of IDH inhibitors in AML (20:31) Case: A woman in her late 60s with newly diagnosed AML with FLT3-ITD and NPM1 mutations receives 7+3 chemotherapy in combination with quizartinib (31:07) Case: A patient in their late 70s with multiple comorbidities and newly diagnosed IDH1-mutant AML (37:53) CME information and select publications

Neste episódio do "Agro em Pauta", Lígia Pedrini recebe Nilson Caldas para uma conversa profunda sobre produtividade agrícola, estratégias de manejo e o papel do CESB no desenvolvimento da sojicultura brasileira. Nilson compartilha sua trajetória como filho de produtor rural, sua formação em agronomia e sua atuação no CESB, destacando o impacto do Desafio Nacional de Máxima Produtividade da Soja como ferramenta de inovação aberta. FICHA TÉCNICAApresentação: Lígia PedriniProdução: Agro ResenhaConvidado: Nilson CaldasEdição: Senhor A - https://editorsenhor-a.com.brSee omnystudio.com/listener for privacy information.

Surah al-Ḥujurāt Begins!السَّلَامُ عَلَيْكُمْ وَرَحْمَةُ اللَّهِ وَبَرَكَاتُهُWe've kicked off Term 3 of the BeQuranic journey, and this term we'll be diving into Surah al-Ḥujurāt — a short but deeply powerful surah, full of lessons on adab, respect, and community.This week, we're beginning slowly and deliberately with just the first two ayāt. Why? Because each line is loaded with both tajwīd gems and practical life reminders — so we want to sit with them, reflect, and read with clarity.Tajwīd Highlights This WeekWe started by revising two key etiquette phrases that open every recitation:* Al-Isti‘ādhah: أَعُوذُ بِاللَّهِ مِنَ الشَّيْطَانِ الرَّجِيمِ* Basmalah: بِسْمِ اللَّهِ الرَّحْمَٰنِ الرَّحِيمِFrom there, we explored several tajwīd rules in-depth:* Madd Jā'iz Munfaṣil: Appears in phrases like “يَا أَيُّهَا”, requiring a 4-beat stretch.* Lafdh al-Jalālah (اللَّه): Read heavy if preceded by a fatḥah or ḍammah, light if preceded by a kasrah.* Ghunna with Shaddah: Don't cut the ghunna short in phrases like “إِنَّ اللَّهَ” — stretch it with intent.* Idh-hār with ḥalqī letters: Recognising throat letters (ع، ح، غ، خ، ه، ء) helps avoid nasalisation where it doesn't belong.* Rules of Rā': When to read it heavy vs. light depending on the vowel before it.We also worked through tricky sections like:يَا أَيُّهَا الَّذِينَ آمَنُوا لَا تُقَدِّمُوا بَيْنَ يَدَيِ اللَّهِ وَرَسُولِهِوَلَا تَجْهَرُوا لَهُ بِالْقَوْلِ كَجَهْرِ بَعْضِكُمْ لِبَعْضٍYour Assignment This WeekWith only two ayāt, the focus is on smoothness and mastery.Slow is smooth. Smooth is fast.Break the verses down into parts, repeat them until you hit fluency, and pay attention to where you stumble. Work on those sections. Aim to iron out the kinks.Even if you stutter — don't be discouraged. The Prophet ﷺ said the one who struggles with Qur'an gets double the reward. But don't settle. Keep refining.See You ThursdayOn Tafsīr Thursday, we'll explore the meanings of these two opening ayāt: how they set the tone for respectful interaction with Allah and His Messenger ﷺ — and with one another.Until then — rehearse, reflect, and get ready.وَالسَّلَامُ عَلَيْكُمْ وَرَحْمَةُ اللَّهِ وَبَرَكَاتُهُ This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit bequranic.substack.com/subscribe

Discover breakthrough targeted therapies for IDH-mutant gliomas and transform patient care with evidence-based approaches.   Credit available for this activity expires: 7/2/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002677?ecd=bdc_podcast_libsyn_mscpedu

Featuring an interview with Dr Patrick Y Wen, including the following topics: Glioma classification (0:00) Efficacy and safety of vorasidenib in the management of IDH-mutant gliomas (4:50) Case: A woman in her early 30s with a Grade 2 astrocytoma and an IDH R132H mutation and residual disease postoperatively (11:55) Case: A man in his early 40s experiencing stable disease with vorasidenib after subtotal resection (21:46) Ongoing trial investigating vorasidenib in IDH-mutant gliomas (27:30) Current and emergent strategies for the management of glioblastoma (31:27) Optimizing patient care and quality of life (46:24) CME information and select publications

Dr Patrick Wen from the Dana-Farber Cancer Institute in Boston, Massachusetts, discusses the current and future management of IDH-mutant gliomas. CME information and select publications here.

Featuring a slide presentation and related discussion from Dr Patrick Y Wen, including the following topics: Classification and pathologic diagnosis of gliomas (0:00) Role of IDH inhibitors in the management of low-grade gliomas (6:37) Ongoing trials and remaining questions in the management of IDH-mutant gliomas (19:53) CME information and select publications

Dr Patrick Wen from the Dana-Farber Cancer Institute in Boston, Massachusetts, discusses the current and future management of IDH-mutant gliomas. CME information and select publications here.

Which patients with IDH-mutant glioma should receive an isocitrate dehydrogenase (IDH) inhibitor? A top neurosurgeon weighs in. Credit available for this activity expires: 6/9/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002598?ecd=bdc_podcast_libsyn_mscpedu

At ASCO 2025, Servier presented data in the IDH-mutated cancer space. Onsite at McCormick Place in Chicago, pharmaphorum web editor Nicole Raleigh spoke with Becky Martin, chief US medical at Servier about the key data from the company's Tibsovo and Voranigo programmes, as well as the implications for patients and the wider themes of the Congress this year. Listen to this and other interviews from ASCO 2025 here.

Researchers at Brown University have developed a combination treatment that significantly increases survival in mice with glioblastoma (GBM), a highly aggressive and treatment-resistant brain cancer. The approach uses a new class of drugs called imipridones along with radiation therapy and standard chemotherapy. This triple therapy, known as IRT, was recently detailed in a study published in Oncotarget. Understanding Glioblastoma and the Need for Better Therapies Glioblastoma is the most common and aggressive malignant brain tumor in adults. It grows quickly and is difficult to treat, often leading to poor outcomes. Most patients survive less than 15 months after diagnosis, even when treated with surgery, radiation, and the chemotherapy drug temozolomide (TMZ). This treatment may slow the disease, but it does not typically stop it. Full blog - https://www.oncotarget.org/2025/06/04/experimental-triple-therapy-improves-survival-in-glioblastoma-mouse-model/ Paper DOI - https://doi.org/10.18632/oncotarget.28707 Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Video short - https://www.youtube.com/watch?v=Q_mXy8mana0 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28707 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, glioblastoma multiforme, IDH, ONC201, ONC206, MGMT, temozolomide, radiotherapy To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - 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/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Brasil sobe cinco posições em ranking de IDH e supera patamar pré-pandemia pela primeira vez. E Conclave para escolher novo papa começa hoje no Vaticano.See omnystudio.com/listener for privacy information.

Confira nesta edição do JR 24 Horas: O Brasil subiu cinco posições no ranking do Índice de Desenvolvimento Humano, o IDH. Os dados divulgados pelo Programa de Desenvolvimento das Nações Unidas são referentes a 2023. O Brasil aparece na 84ª posição da lista de 193 países. No ano anterior, o Brasil estava na 89ª posição. O documento leva em consideração os indicadores de expectativa de vida, escolaridade e produto interno bruto per capita, ou seja, por pessoa. E ainda: Diesel fica R$ 0,16 mais barato nas refinarias.

Confira nesta edição do JR 24 Horas: O chefe de uma quadrilha especializada em roubar motos de luxo foi preso, nesta terça-feira (6), na zona leste de São Paulo. Durante a operação, a polícia localizou também um desmanche clandestino de motos. A quadrilha tinha como alvo preferencial motocicletas de luxo, que custam mais de R$ 100 mil. A polícia chegou aos criminosos com a ajuda de um rastreador em uma das motos roubadas. E ainda: Brasil avança cinco posições e chega ao 84° lugar no ranking internacional de IDH das Nações Unidas.

No podcast ‘Notícia No Seu Tempo’, confira em áudio as principais notícias da edição impressa do jornal ‘O Estado de S.Paulo’ desta terça-feira (06/05/2025): Nomeado na sexta-feira em substituição a Carlos Lupi, o novo ministro da Previdência Social, Wolney Queiroz, assinou proposta quando era deputado federal, em 2021, que adiou o prazo de fiscalização do desconto de mensalidades feito por associações e sindicatos na folha de pagamento de aposentados e pensionistas do INSS. A medida foi levada à Câmara por duas associações agora suspeitas de efetuar as cobranças indevidamente. Procurado, Wolney Queiroz não comentou. Uma medida provisória assinada pelo então presidente Jair Bolsonaro (PL), em 2019, estabelecia que todos os descontos na folha de pagamento precisariam ser revalidados ano a ano. Após o lobby de associações que se beneficiaram com esses descontos, o prazo foi adiado duas vezes e a necessidade de revalidação foi extinta em 2022. Wolney Queiroz estava presente na reunião em que Lupi foi alertado sobre as fraudes no INSS, em junho de 2023. E mais: Política: Com baixa aprovação entre as mulheres, Lula confirma troca de ministra da pasta Metrópole: Cardeais discutem divisões da Igreja Internacional: Netanyahu aprova plano para ampliar campanha militar e ‘capturar’ GazaSee omnystudio.com/listener for privacy information.

Texcoco  estrena la Universidad para el Bienestar "Benito Juárez García  Abierta convocatoria para operadoras de TrolebúsIrreversible la victoria de Albanese en Australia  Más información en nuestro podcast

Dr. Nimish Mohile and Dr. Jaishri Blakeley share the new rapid recommendation update to the therapy for diffuse astrocytic and oligodendroglial tumors in adults guideline. They review the evidence from the INDIGO trial that prompted this update, and how to incorporate the use of vorasidenib into clinical practice. They discuss the importance of molecular testing, particularly for IDH1 or IDH2 mutations and outstanding questions for treatment of patients with oligodendrogliomas and astrocytomas. Read the latest update, “Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline Rapid Recommendation Update.” Transcript This guideline, clinical tools, and resources are available at http://www.asco.org/neurooncology-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in Journal of Clinical Oncology.   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. Jaishri Blakeley from Johns Hopkins University School of Medicine and Dr. Nimish Mohile from the Department of Neurology and Wilmot Cancer Institute at the University of Rochester Medical Center, co-chairs on “Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: American Society of Clinical Oncology-Society for Neuro-Oncology Guideline Rapid Recommendation Update.”  Thank you for being here today, Dr. Blakeley and Dr. Mohile.  Dr. Jaishri Blakeley: Thank you.  Dr. Nimish Mohile: Thank you for having us.  Brittany Harvey: And then 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. Blakeley and Dr. Mohile who have 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 jump into the content here, Dr. Mohile, could you start us off by describing what prompted this rapid update to the ASCO-SNO therapy for diffuse astrocytic and oligodendroglial tumors in adults guideline, which was previously published in 2021?  Dr. Nimish Mohile: Yeah. So the key reason for this update is the publication of a study in 2023. And this was a study called the INDIGO study that looked at a new class of therapies, something called IDH inhibitors. And in this study with a drug called vorasidenib, changed how we think about the treatment of oligodendrogliomas and astrocytomas, so particularly the grade 2 oligodendrogliomas and grade 2 astrocytomas. Because of the results of that study, we decided that we needed to do an update to inform clinicians about some of these changes and how we might approach these tumors differently today.  Brittany Harvey: Great. I appreciate that background. So then, based off the new data from the INDIGO study, what are the updated and new recommendations from the expert panel?  Dr. Nimish Mohile: So the key findings from the INDIGO study involved people who had grade 2 astrocytomas and grade 2 oligodendrogliomas. And in the setting after surgery, they were treated with vorasidenib, and what they found is that this delayed the time to next intervention. And the key aspect of that is that it delayed when we could start radiation and chemotherapy in these patients.   So what we did in the guidelines is that for both low grade oligodendrogliomas and low grade astrocytomas, we added one additional guideline statement. Our previous guideline in 2021 offered the options for observation or treatment with radiation and chemotherapy. And now in this guideline, we have options for observation, treatment with vorasidenib in those in whom we feel it is safe to defer radiation and chemotherapy, and then treatment with radiation and chemotherapy. So we've added in an additional option here. And the key message of the guideline is really on how, as clinicians, we think about using the vorasidenib and what the ideal setting for using the vorasidenib is.  Brittany Harvey: Excellent. It's great to hear about this new option for patients. So then you were just talking about how we think about who to offer this IDH inhibitor to. So, Dr. Blakeley, what should clinicians know as they implement these new recommendations into practice?  Dr. Jaishri Blakeley: Yes. So, first and foremost, let's go back to 2021, and a key note from those guidelines was the importance of molecular testing. And at that point, the importance of molecular testing, which in large part was focused on IDH1 or IDH2 mutations, was prognostic. We could say there's a difference in an IDH1 mutant astrocytoma and an IDH1 wild type astrocytoma, but we didn't have a specific therapeutic recommendation attached to that, like Dr. Mohile just said. And the big shift here is now we have a specific therapeutic for that population with IDH1 or IDH2 mutant glioma.   So for clinicians, we hope that they've been getting molecular testing on newly diagnosed glioma already, but now there's an additional motivation to do so because it may change your treatment plan in the right circumstance. So since the publication of the phase III INDIGO study that Dr. Mohile mentioned, and the FDA approval of vorasidenib, if you meet the specified criteria in the clinical trial - which the guidelines point out is a little different than what's on the FDA label, so clinicians might want to dig into that a little bit - then there is a treatment option that is new and different than combined chemoradiation or radiation alone or observation.  Brittany Harvey: I appreciate those clarifications there.   So then also, Dr. Blakeley, how does this update impact patients with astrocytic or oligodendroglial tumors?  Dr. Jaishri Blakeley: So first, patients also should know if they have IDH mutant gliomas. And this update only applies to people with IDH1/2 mutant glioma. Perhaps, we're not sure, it might only apply to people who are in the newly or newly-ish diagnosed category because the INDIGO study required that people were within the first five years of their surgical diagnosis and had not had other treatment. So there are a lot of people who have astrocytoma or oligodendroglioma who may or may not know their IDH1/2 status and may have already had another therapy - this update doesn't apply to them. We hope that future research will teach us about that. This update is for people who are newly diagnosed and just starting the journey to figure out the best therapy. It does say that if you do have that IDH1/2 alteration in your tumor, there is a drug therapy that is different from the drug therapies we would offer gliomas that do not have the IDH1/2 mutation.  Brittany Harvey: Absolutely. I think both that emphasis on molecular testing is very important and also thinking about that study inclusion criteria and how it impacts who's eligible for this treatment.   So then finally, Dr. Mohile, what are the outstanding questions about vorasidenib or other interventions for gliomas in adults?  Dr. Nimish Mohile: I think the key question for clinicians is exactly who we're going to use this in. The challenges with inclusion criteria in clinical trials is they don't actually always match what we're seeing in the clinic. And I think it brings up the question of, in low grade oligodendrogliomas which we think of as very slow growing tumors, do we have the option outside of the strict inclusion criteria to use that drug in other settings? I think it brings up the question for some clinicians in some of the higher grade tumors, in the grade 3 tumors, we don't yet have data in that area and our guideline doesn't address that. But I think some will be asking what the clinical activity of vorasidenib is in that setting. There are some suggestions that the IDH inhibitors may impact seizure control, and I think that that's data that we're continuing to wait on.   So I think that there's several outstanding questions there that we will have answers for hopefully in the next several years. I think the big question that we don't have an answer for and that will take a long time to know is whether the addition of vorasidenib in this setting actually improves how long people live. And given how long people with low grade oligodendrogliomas and low grade astrocytomas live today, we probably won't have an answer to that question for more than a decade.  Brittany Harvey: Definitely. We'll look forward to these ongoing developments and eventually longer term data on overall survival on these agents.   So, I want to thank you both so much for your work to rapidly include this information from this new trial. And thank you for your time today, Dr. Blakeley and Dr. Mohile.  Dr. Jaishri Blakeley: Thank you so much.  Dr. Nimish Mohile: Thank you Brittany.  Brittany Harvey: And 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/neurooncology-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have 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. 

IDH Living Wage Road Map WebsiteIDH LIving Wage ToolsCheck out our website!: https://www.globalseafood.org/podcastFollow us on social media!Twitter | Facebook | LinkedIn | InstagramShare your sustainability tips with us podcast@globalseafood.org!If you want to be more involved in the work that we do, become a member of the Global Seafood Alliance: https://www.globalseafood.org/membership/ The views expressed by external guests on Aquademia are their own and do not reflect the opinions of Aquademia or the Global Seafood Alliance. Listeners are advised to independently verify information and consult experts for any specific advice or decisions.

Dr. John Sweetenham and Dr. James Foran discuss the evolving treatment landscape in acute myeloid leukemia, including new targeted therapies, advances in immunotherapy, and the current role for allogeneic transplantation. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. There has been steady progress in the therapies for acute myeloid leukemia (AML) in recent years, largely based on an increasing understanding of the molecular mechanisms which underlie the disease. On today's episode, we'll be discussing the evolving treatment landscape in AML. We'll explore risk group stratification, new targeted therapies, advances in immunotherapy for AML, and also a little about the current role for allogenic transplantation in this disease.  I'm delighted to welcome Dr. James Foran to this discussion. Dr. Foran is a professor of medicine and chair of the Myeloid Malignancies and Blood and Marrow Transplant Disease Group at the Mayo Clinic Comprehensive Cancer Center. He's based in Jacksonville, Florida.  Our full disclosures are available in the transcript of this episode.  James, it's great to have you join us on the podcast today, and thanks so much for being here. Dr. James Foran: I'm delighted and thank you for the invitation. Thank you very much. Dr. John Sweetenham: Sure, James, let's get right into it. So, our understanding of the molecular mechanisms underlying AML has resulted not only in new methods for risk stratification in this disease, which have added refinement to cytogenetics, but also has resulted in the development of many new targeted agents. Understanding that this is a complex area of investigation, and our time is somewhat limited, can you give us a high-level update on the current state of the art in terms of how risk factors are being used for treatment selection now? Dr. James Foran: Absolutely. I think in the past, you know, we had things broken down pretty simply into make a diagnosis based on morphology, do cytogenetics, break patients into the groups of those who were more likely to benefit from therapy – so-called favorable risk – those where the intensive therapies were less likely to work – so-called poor adverse risk, and then this large intermediate group that really had variable outcomes, some better, some worse. And for a long time, the progress was in just identifying new subtle cytogenetic risk groups. And then, late 1990s, we began to understand that FLT3 mutations or NRAS mutations may be more adverse than others that came along. In the first part of this millennium, in the, you know, 2000-2010 range, a lot of work was being done to understand better or worse risk factors with single genes. The ability to do multiplex PCR, and then more recently NGS platforms, have allowed us to really look at many genes and identify many mutations in patients. At the beginning that was used just to sort of refine – who did a little better, who did a little worse with intensive therapy – helped us decide who may benefit more from an allogeneic transplanter for whom that would not be necessary.  But the good news is that really, we're now starting to target those mutations. One of the first molecularly targeted treatments in leukemia was FLT3 mutations, where we knew they were adverse. Then along came targeted treatments. I was involved in some of those early studies looking at sunitinib, sorafenib, more recently midostaurin, now quizartinib, FDA approved, and gilteritinib in the relapse refractory setting.  So we're moving into a state where we're not just refining prognosis, we're identifying targets. You know, it's been slow progress, but definite incremental progress in terms of outcomes by looking for FLT3 mutations, then looking for IDH mutations, and more recently, mutations involving NPM1 or rearrangement of what we used to call the MLL gene, now the lysine methyltransferase 2A or KMT2A rearrangement, where we now have targets. And it's not just for refinement of prognosis, but now we're identifying therapeutic targets for patients and ways to even look for measurable residual disease which is impacting our care. Dr. John Sweetenham: That's great, James. And I'm going to expand on that theme just a little bit and perhaps ask you to elaborate a little bit more on how the introduction of these new therapies have specifically impacted frontline therapy. And a couple of ancillary questions maybe to go along with that: First of all, is ‘7+3' a standard therapy for anybody in 2025? And maybe secondly, you know, could you comment also maybe briefly on older patients with AML and how you think maybe the treatment landscape is changing for them compared with, say, 5 or 10 years ago? Dr. James Foran: I'll start with the therapy and then work my way back. So we've had ‘7+3' cytarabine daunorubicin or cytarabine anthracycline since 1976, and we're still using it as the backbone of our intensive therapy. There is still an important role for it, particularly in younger or fitter patients, and particularly for those with intermediate or favorable risk genetic groups or cytogenetic risk groups just because we achieve high rates of remission. Our 30-day induction mortality rates are lower now than they were 10 and 20 years ago. Our supportive care is better. And we still have a busy inpatient hospital service here at Mayo Florida and my colleagues in Rochester and Arizona as well giving intensive therapy. So that remains the backbone of curative therapy for younger adults. We are trying to be a little more discriminating about who we administer that to. We are trying to add targeted agents. We know from, now, two different randomized trials that the addition of a FLT3 inhibitor, either midostaurin or more recently quizartinib, has a survival advantage in patients with a FLT3 mutation, or for quizartinib, a FLT3/ITD mutation. And so yes, ‘7+3' remains important.  Off protocol for somebody who just comes in with acute leukemia in a 40-year-old or 30-year-old or even early 60s and fit, we would still be considering ‘7+3' therapy and then waiting for an expedited gene mutation panel and an expedited cytogenetics panel to come back to help us discriminate is that a patient for whom we should be giving a FLT3 inhibitor? I think there's a little more nuance about when we do a day 14 bone marrow, do they really matter as much anymore? I still do them. Some of my colleagues find them less important. But we're still giving intensive therapy. We're still giving high-dose ARA-C consolidation for younger patients who achieve complete remission.  In older adults, it's a different story. You know, it was only in the early part of the 2000s – 2004, 2007 range – where we really got buy-in from randomized studies that low-dose therapy was better than no therapy. There was a lot of nihilism before then about therapy for older adults, especially over age 75. We know that low-dose ARA-C is better than nothing. It looked like azacitidine was better than ARA-C or at least equivalent or slightly better. But with the advent of venetoclax it was a game changer. I ran a national randomized study of intensive therapy in AML. It was the last national randomized study of intensive therapy in older patients right before venetoclax got approved. And we were very excited about our results, and we thought we had some really interesting clinical results. And suddenly that's a little bit obsolete in patients over 70 and particularly over age 75 because of the high remission rates with azacytidine venetoclax or hypomethylating agents, so-called HMAs and venetoclax and the survival advantage. Now, it's not a home run for everybody. We quote 60% to 70% remission rates, but it's a little different based on your cytogenetics and your mutation profile. You have to continue on therapy so it's continuous treatment. It's not with curative intent, although there are some people with long-term remission in it. And the median survival went from 10 months to 15 months. So home run? No, but definitely improved remissions, meaningful for patients off transfusions and better survival. So right now it's hard to find an older adult who you wouldn't give azacitidine and venetoclax or something similar, decitabine, for instance, and venetoclax, unless somebody really was moribund or had very poor performance status or some reason not to. And so ‘7+3' is still relevant in younger adults. We're trying to get better results with ‘7+3' by adding targeted agents and azacitine and venetoclax in older adults.  I think the area of controversy, I guess there are two of them, is what to do in that overlap age between 60 and 75. Should people in that age still get intensive therapy, which we've used for years – the VIALE-A trial of aza-venetoclax was age 75 plus – or with cardiac comorbidities? And I think if you're 68 or 72, many of us are starting to bias towards aza-venetoclax as generally being better tolerated, generally being more outpatient, generally being slow and steady way to get a remission. And it doesn't stop you from going to transplant for somebody who might still be a candidate.  The other area of controversy is somebody under 60 who has adverse cytogenetics where we don't do very well with ‘7+3,' we still give it and we might do just as well with decitabine venetoclax. A lot of us feel that there's equipoise in the 60 to 75 group where we really can ask a question of a randomized study. Retrospective studies might suggest that intensive therapy is a little better, but there are now a couple of randomized studies happening saying, “Can we replace ‘7+3' in that intermediate age with aza-venetoclax?” And for younger adults similarly, we're looking to see how we apply that technology. Those are the areas where we're really trying to investigate what's optimal for patients and that's going to require randomized trials. Dr. John Sweetenham: Oh, that's great, thank you. And I'll just extend that question a little bit more, particularly with respect to the new targeted therapies. How much are they impacting the treatment of these patients in the relapse and refractory setting now? Dr. James Foran: Oh, they're definitely impacting it. When I trained and probably when you trained, AML was still a medical emergency. But that was the thing that you admitted to the hospital immediately, you started therapy immediately. The rule was always that's the one thing that brings the fellow and the consultant in at night to see that new patient on a Friday or Saturday. Now, we'll still admit a patient for monitoring, but we try not to start therapy for the first three or five or seven days if they're stable, until we get those genetics and those genomics back, because it helps us discriminate what therapy to pursue. And certainly, with FLT3 mutations, especially FLT3/ITD mutations, we're adding FLT3 inhibitors and we're seeing a survival advantage. Now, on the surface, that survival advantage is in the range of 7% or 10%. But if you then pursue an allogeneic transplant in first remission, you're taking disease where we used to see 30%, 40% long-term survival, maybe less, and you're pushing that to 60%, 70% in some studies. And so we're now taking a disease that– I don't want to get off topic and talk about Ph+ ALL. But that's a disease where we're actually a little excited. We have a target now, and it used to be something really adverse and now we can do a lot for it and a lot about it.  The other mutations, it's a little more subtle. Now, who knew until 2010 that a mutation in a sugar metabolism gene, in isocitrate dehydrogenase, or IDH was going to be so important, or even that it existed. We know that IDH1 and IDH2 mutations are still a minority of AML, certainly less than 10% to 15%, maybe overall. But we're able to target those with specific IDH1 and IDH2 inhibitors. We get single-agent responses. There are now two approved IDH1 inhibitors on the market. We don't yet have the randomized data that adding those to intensive therapy is better, but we're getting a very strong hint that it might be better in older adults who have an IDH mutation, maybe adding those is helpful and maybe adding those to low-intensity therapy is helpful. Those studies are ongoing, and we're also trying with low-intensity treatments to add these agents and get higher remission rates, deeper remissions, longer remissions. I think a lot of work has to be done to delineate the safety of that and the long-term efficacy. But we're getting hints it's better, so I think it is impacting.  The other area it's impacting is when you pick up adverse mutations and those have crept into our classification systems like an ASXL1 mutation or RUNX1 mutation for instance, or some of the secondary AML mutations like BCOR and others, where that's helping us discriminate intermediate-risk patients who we think aren't going to do as well and really helping us select a group who's more likely to get benefit from allogeneic transplant or for whom at least our cure rates without allo transplant are low. And so I think it's impacting a lot. Dr. John Sweetenham: Great. And I'm going to pick up now, if I may, on a couple of things that you've just mentioned and continue the theme of the relapsed and refractory setting. We've started to see some reports which have looked at the role of immune strategies for patients with AML, in particular CAR T or NK cells. Can you comment a little on this and let us know whether you think either these two strategies or other immune strategies are likely to have a significant role in AML in the future? Dr. James Foran: They are, but I think we're still a step behind finding the right target or the right way to do it. If you think of allogeneic transplantation as the definitive immune therapy, and we know for adverse AML we can improve survival rates and cure rates with an allotransplant, then we know inherently that immune therapy matters. And so how do we do what they've done in large cell lymphoma or in CD19 targeting for B cell malignancies? How do we bring that to acute myeloid leukemia? There have been a number of efforts. There have been at least 50 trials looking at different targets. CD33, CD123, CD7, others, CLL-1. So, there have been a number of different trials looking at how to bind a CAR T or a CAR T construct that can be active. And we have hints of efficacy. There was kind of a provocative paper in the New England Journal of Medicine a year ago in April of last year from a Chinese group that looked at a CD7-based CAR T and it was 10 patients, but they used CD7 positive acute leukemia, AML or ALL and had a CD7-targeted CAR T and they actually incorporated that with a haploidentical transplant and they had really high remission rates. People tolerated it quite well. It was provocative. It hasn't yet been reproduced on a larger scale, but the strong hints that the strategy is going to work.  Now, CD33 is a little tricky to have a CAR T when CD33 is expressed on normal hematopoietic cells. CD123 likewise. That's been something where there's, I think, still promise, but we've struggled to find the trials that make that work. Right now, there's a lot of interest in leveraging NK cells and looking, for a couple of reasons, but NK cells are attractive and NK cell markers might be attractive targets. NK cells might have similar degrees of immune efficacy. It's speculative, but they are likely to have less cytokine release syndrome and less neurotoxicity than you see with CAR T. And so it's kind of attractive to leverage that. We have had some ongoing trials looking at it with bispecifics and there certainly are trials looking at it with CAR NK-based strategies. One of the antigens that people looked at is the NK group 2D. NK group 2D or NKG2D is overexpressed in AML and its ligands overexpressed. And so that's a particular potential target. So, John, it's happening and we're looking for the hints of efficacy that could then drive a pivotal trial to get something approved.  One of the other areas is not restricting yourself just to a single antigen. For instance, there is a compound that's looking at a multi-tumor-associated antigen-specific T-cell therapy, looking at multiple antigens in AML that could be overexpressed. And there were some hints of activity and efficacy and actually a new trial looking at a so-called multi-tumor associated antigen-specific T cell therapy. So without getting into specific conflicts of interest or trials, I do think that's an exciting area and an evolving area, but still an investigational area. I'll stop there and say that we're excited about it. A lot of work's going there, but I'm not quite sure which direction the field's going to pivot to there. I think that's going to take us some time to sort out. Dr. John Sweetenham: Yeah, absolutely. But as you say, exciting area and I guess continue to watch this space for now.  So you've mentioned allogeneic stem cell transplants two or three times during this discussion. Recognizing that we don't have an imatinib for AML, which has kind of pushed transplant a long way further back in the treatment algorithm, can you comment a little on, you know, whether you think the role of stem cell transplantation is changing in AML or whether it remains pretty much as it was maybe 10 years ago? Dr. James Foran: By the way, I love that you use imatinib as an introduction because that was 6 TKIs ago, and it tells you the evolution in CML and you know, now we're looking at myristoyl pocket as a target, and so on. That's a great way to sort of show you the evolution of the field.  Allogeneic transplant, it remains a core treatment for AML, and I think we're getting much smarter and much better about learning how to use it. And I'm just going to introduce the topic of measurable residual disease to tell you about that. So I am a little bit of a believer. Part of my job is I support our allogeneic transplant program, although my focus is acute myeloid leukemia, and I've trained in transplant and done it for years and did a transplant fellowship and all that. I'm much more interested in finding people who don't need a transplant than people who do. So I'm sort of looking for where can we move away from it. But it still has a core role. I'll sidestep and tell you there was an MDS trial that looked at intermediate or high-risk MDS and the role of allogeneic transplant that shows that you about double your survival. It was a BMT CTN trial published several years ago that showed you about double your three-year survival if you can find a donor within three months and get to a transplant within six months. And so it just tells you the value of allotransplant and myeloid malignancy in general. In AML we continue to use it for adverse risk disease – TP53 is its own category, I can talk about that separately – but adverse risk AML otherwise, or for patients who don't achieve a really good remission. And I still teach our fellows that an allotransplant decreases your risk of relapse by about 50%. That's still true, but you have to have a group of patients who are at high enough risk of relapse to merit the non-relapse mortality and the chronic graft versus host disease that comes with it. Now, our outcomes with transplant are better because we're better at preventing graft versus host disease with the newer strategies such as post-transplant cyclophosphamide. There are now new FDA-approved drugs for acute and chronic graft versus host disease, ruxolitinib, belumosudil, axatilimab now. So we have better ways of treating it, but we still want to be discriminating about who should get it.  And it's not just a single-minded one-size-fits-all. We learned from the MORPHO study that was published in the JCO last year that if you have FLIT3-positive AML, FLIT3/IDT-positive AML, where we would have said from retrospective studies that your post-transplant survival is 60% give or take, as opposed to 15% or 20% without it, that we can discriminate who should or shouldn't get a transplant. Now that trial was a little bit nuanced because it did not meet its primary endpoint, but it had an embedded randomization based upon MRD status and they used a very sensitive test of measurable residual disease. They used a commercial assay by Invivoscribe that could look at the presence of a FLT3/ITD in the level of 10 to the minus 5th or 10 to the minus 6th. And if you were MRD-negative and you went through a transplant, you didn't seem to get an advantage versus not. That was of maintenance with gilteritinib, I'll just sort of put that on there. But it's telling us more about who should get a transplant and who shouldn't and who should get maintenance after transplant and who shouldn't.  A really compelling study a year ago from I don't know what to call the British group now, we used to call them the MRC and then the NCRI. I'm not quite sure what to call their studies at the moment. But Dr. Jad Othman did a retrospective study a year ago that looked at patients who had NPM1 mutation, the most common mutation AML, and looked to see if you were MRD positive or MRD negative, what the impact of a transplant was. And if you're MRD negative there was not an advantage of a transplant, whereas if you're MRD positive there was. And when they stratified that by having a FLT3 mutation that cracked. If you had a FLT3 mutation at diagnosis but your NPM1 was negative in remission, it was hard to show an advantage of a transplant. So I think we're getting much more discriminating about who should or should not get a transplant by MRD testing for NPM1 and that includes the patients who have a concomitant FLT3 mutation. And we're really trying to learn more and more. Do we really need to be doing transplants in those who are MRD-negative? If you have adverse risk genetics and you're MRD-negative, I'll really need good data to tell me not to do a transplant, but I suspect bit by bit, we'll get that data. And we're looking to see if that's really the case there, too. So measurable residual disease testing is helping us discriminate, but there is still a core role of allogeneic transplant. And to reassure you, compared to, I think your allotransplant days were some time ago if I'm right. Dr. John Sweetenham: Yes. Dr. James Foran: Yeah. Well, compared to when you were doing transplants, they're better now and better for patients now. And we get people through graft versus host disease better, and we prevent it better. Dr. John Sweetenham: That's a great answer, James. Thanks for that. It really does help to put it in context, and I think it also leads us on very nicely into what's going to be my final question for you today and perhaps the trickiest, in a way. I think that everything you've told us today really emphasizes the fact that the complexity of AML treatment has increased, primarily because of an improved understanding of the molecular landscape of the disease. And it's a complicated area now. So do you have any thoughts on what type of clinical environment patients with AML should be evaluated and treated in in 2025? Dr. James Foran: Yeah, I want to give you a kind of a cautious answer to that because, you know, I'm a leukemia doctor. I work at a leukemia center and it's what we focus on. And we really pride ourselves on our outcomes and our diagnostics and our clinical trials and so on. I am very aware that the very best oncologists in America work in private practice and work in community practice or in networks, not necessarily at an academic site. And I also know they have a much harder job than I have. They have to know lung cancer, which is molecularly as complicated now as leukemia, and they have to know about breast cancer and things that I don't even know how to spell anymore. So it's not a question of competence or knowledge. It's a question of infrastructure. I'll also put a little caveat saying that I have been taught by Rich Stone at Dana-Farber, where I did a fellowship a long time ago, and believe Rich is right, that I see different patients than the community oncologists see with AML, they're seeing different people. But with that caveat, I think the first thing is you really want to make sure you've got access to excellence, specialized hematopathology, that you can get expedited cytogenetics and NGS testing results back. There was a new drug, approved just a few months ago, actually, for relapsed AML with a KMT2A rearrangement, revumenib. We didn't talk about the menin inhibitors. I'll mention them in just a second. That's a huge area of expansion and growth for us. But they're not found on NGS platforms. And normal cytogenetics might miss a KMT2A-rearrangement. And we're actually going back to FISH panels, believe it or not, on AML, to try to identify who has a KMT2A-rearrangement. And so you really want to make sure you can access the diagnostic platforms for that.  I think the National Referral Labs do an excellent job. Not always a really fast job, but an excellent job. At my institution, I get NGS results back within three days or four days. We just have an expedited platform. Not everybody has that. So that's the key, is you have to be able to make the diagnosis, trust the pathologist, get expedited results. And then it's the question of trying to access the targeted medications because a lot of them are not carried in hospital on formulary or take time to go through an insurance approval process. So that's its own little headache, getting venetoclax, getting gilteritinib, getting an IDH1 inhibitor in first line, if that's what you're going for. And so I think that requires some infrastructure. We have case managers and nurses who really expedite that and help us with it, but that's a lot of work. The other piece of the puzzle is that we're still with AML in the first month and maybe even the second month. We make everybody worse before we make them better. And you have to have really good blood bank support. I can give an outpatient platelet transfusion or red cell transfusion seven days a week. We're just built for that. That's harder to do if you're in a community hospital and you have to be collaborating with a local blood bank. And that's not always dead easy for somebody in practice. So with those caveats, I do find that my colleagues in community practice do a really good job making the diagnosis, starting people on therapy, asking for help. I think the real thing is to be able to have a regional leukemia center that you can collaborate with, connect with, text, call to make sure that you're finding the right patients who need the next level of diagnostics, clinical trial, transplant consults, to really get the best results.  There was some data at ASH a couple of years ago that looked at – the American Society of Hematology and ASCOs had similar reports – that looked at how do we do in academic centers versus community practice for keeping people on therapy. And on average, people were more likely to get six cycles of therapy instead of three cycles of therapy with azacitidine venetoclax at an academic center. Now, maybe it's different patients and maybe they had different cytogenetics and so on, but I think you have to be patient, I think you have to collaborate. But you can treat those patients in the community as long as you've got the infrastructure in place. And we've learned with virtual medicine, with Zoom and other platforms that we can deliver virtual care more effectively with the pandemic and beyond. So I think we're trying to offer virtual consults or virtual support for patients so they can stay in their home, stay in their community, stay with their oncologists, but still get access to excellent diagnostics and supportive care and transplant consults, and so on. I hope that's a reasonable answer to that question. It's a bit of a nuanced answer, which is, I think there's an important role of a leukemia center, and I think there's a really fundamental role of keeping somebody in the community they live in, and how we collaborate is the key to that. And we've spent a lot of time and effort working with the oncologists in our community to try to accomplish that.  John, I want to say two other things. I didn't mention in the molecular platforms that NPM1 mutations, we can now target those on clinical trials with menin inhibitors. We know that NPM1 signals through the Hoxa9/Meis1 pathway. We know that similar pathways are important in KMT2A rearrangements. We know that there are some other rare leukemias like those with NUP98 rearrangement. We can target those with menin inhibitors. The first menin inhibitor, revuminib, was approved by the FDA for KMT2A. We have others going to the FDA later this year for NPM1. There are now pivotal trials and advanced expanded phase 1/2 studies that are showing 30% response rates. And we're looking to see can we add those into the first-line therapy. So, we're finding more targets.  I'll say one last thing about molecular medicine. I know I'm a little off topic here, but I always told patients that getting AML was kind of like being struck by lightning. It's not something you did. Now, obviously, there are risk factors for AML, smoking or obesity or certain farm environments, or radioactive exposures and so on. But bit by bit, we're starting to learn about who's predisposed to AML genetically. We've identified really just in the last five or eight years that DDX41 mutations can be germline half the time. And you always think germline mutations are going to cause AML in a younger patient, but the median age is 60 to 70 just like other AMLs. They actually might do pretty well once they get AML. We've reported that in several papers. And so we're trying to understand who that has a RUNX1 mutation needs germline testing, who with a DDX41 needs germline testing. And we're trying to actually come up with a cleaner pathway for germline testing in patients to really understand predisposition, to help with donor selection, to help with family counseling. So I think those are other areas where a leukemia center can contribute for somebody in who's community practice to understand genomic or genetic complexity in these patients. And we're starting to develop the databases that support that. Dr. John Sweetenham: Yeah, great. Thanks, James. I loved your answer about the clinical environment too. And I know from a patient-centric perspective that I know that patients would certainly appreciate the fact that we're in a situation now where the folks taking care of them will make every effort to keep them close to home if they possibly can.  I want to thank you, James, for an incredible review of a very complex subject and I think you did a great job. I think we all will have learned a lot. And thanks again for being willing to share your insights with us today on the ASCO Daily News Podcast. Dr. James Foran: John, it's my pleasure. And as you know, I'll do anything for a latte, so no problem at all. Dr. John Sweetenham: Okay. I owe you one, so thank you for that.  And thank you to our listeners for your time today. You'll find links to the studies we've discussed today in the transcript of this episode. And finally, if you value the insights that you hear on 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. Find out more about today's speakers:  Dr. John Sweetenham  Dr. James Foran Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook  ASCO on LinkedIn  Disclosures:    Dr. John Sweetenham:    No relationships to disclose Dr. James Foran: Stock and Other Ownership Interests: Aurinia Pharmaceuticals Consulting or Advisory Role: Peerview, CTI BioPharma Corp, Remix Therapeutics, Cardinal Health, Medscape, Syndax, Autolus Therapeutics Research Funding (Inst.): Chordia Therapeutics, Abbvie, Actinium Pharmaceuticals, Kura Oncology, Sellas Life Sciences, Novartis, Roivant, Celgene/Bristol-Myers Squibb, Astellas Pharma, SERVIER Travel, Accommodations, Expenses: Peerview

This week, Jonathan is joined by Eytan Stein, Chief of the Leukaemia Service and an Attending Physician at Memorial Sloan Kettering Cancer Center, New York, USA.  Timestamps:      (00:00)-Introduction  (01:05)-The current landscape of treatments  (02:26)-The promise and peril of differentiation therapy  (05:55)-Highlighting the most impactful clinical trials  (08:38)-Epigenetics and the future of targeted therapies  (10:40)-The BEAT AML master clinical trial  (12:57)-The latest research into IDH inhibitors  (16:10)-Therapies for splicing factor mutations  (19:29)-Reducing patient fear with education   (22:46)-Stein's three wishes for healthcare   

“I didn't set out to be an entrepreneur, but when I couldn't find a company doing what I believed in, I built my own.” In part two of our conversation with Kate Yen, Founder and CEO of Auron Therapeutics, we explore her journey from leading a novel cancer therapy program at Agios to founding her own biotech company. Kate shares insights into drug development, clinical trials, and the business of biotech, highlighting the importance of translational biology, strategic partnerships, and lean operations in building a successful biotech startup. Kate earned her Ph.D. in Biological Chemistry from UCLA, where she also completed her postdoc. Before Auron, she held roles at Merck and as a UCLA professor before joining Agios Pharmaceuticals, where she led the IDH translational research team behind two FDA-approved IDH mutant inhibitors and co-led the discovery of vorasidenib, a promising glioma therapy now in clinical development.

Part 1 of 2: Our guest today is Kate Yen, Founder and CEO of Auron Therapeutics. Auron Therapeutics leverages cutting-edge science and AI-powered analysis to develop next-generation cancer therapies by mapping key drivers of tumorigenesis. Kate earned her Ph.D. in Biological Chemistry from UCLA, where she also completed her postdoc. She held roles at Merck and as a UCLA professor before joining Agios Pharmaceuticals, where she led the IDH translational research team behind two FDA-approved IDH mutant inhibitors and co-led the discovery of vorasidenib, a promising glioma therapy now in clinical development. With deep expertise in preclinical and clinical research, a proven track record in advancing breakthrough therapies, and a passion for oncology, Kate's journey and insights are invaluable.

In a conversation with CancerNetwork®, Shewetal Mehta, PhD, spoke about her research team's focuses in moving novel brain cancer therapies down the pipeline as part of an early phase clinical trials program at the Ivy Brain Tumor Center. Mehta, the deputy director and pre-clinical core leader at the Ivy Brain Tumor Center of Barrow Neurological Institute in Phoenix, Arizona, underscored a scientifically rigorous, patient-driven philosophy that drives her team members to deliver timely answers to those with brain cancer via work in a clinical lab and a pre-clinical arm. This collaboration helps identify therapeutic agents that may demonstrate activity in the brain while determining patient populations who are suitable to enroll on clinical trials. As part of her institution's early phase trial program, Mehta specifically highlighted work associated with a phase 0/1 clinical trial (NCT06072586) evaluating BDTX-1535, a brain-penetrant fourth-generation EGFR inhibitor, for those with recurrent high-grade glioma harboring oncogenic EGFR alterations or fusions.1 Investigators are incorporating liquid biopsy, sampling cerebrospinal fluid from patients on treatment to monitor potential evolutions or changes in brain tumors. Regarding biomarker testing, Mehta described the roles that gene sequencing and immunohistochemistry can play in identifying targetable alterations in patients with brain cancer. She mentioned vorasidenib (Voranigo), which received approval from the FDA in August 2024, as an example of a targeted therapy that may be suitable for use in patients who are found to have actionable IDH mutations. “Over the last year, we've seen that we were capable of not just doing these early phase clinical trials [but of entering] this phase of moving drugs into phase 3 [studies]. That's exciting,” Mehta stated regarding her outlook on the current state of brain cancer treatment. “Right now, we are excited about these new classes of agents that are within the space, like the proteolysis targeting chimeras, protein degraders, and antibody-drug conjugates, which have shown amazing promise in the rest of the oncology space.” References 1.        Study of BDTX-1535 in recurrent high-grade glioma (HGG) participants with EGFR alterations or fusions. ClinicalTrials.gov. Updated January 15, 2025. Accessed January 15, 2025. https://tinyurl.com/m6kwr2b3 2.        FDA approves vorasidenib for grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. News release. FDA. August 6, 2024. Accessed January 20, 2025. https://tinyurl.com/25r9fkvy

In today's episode, supported by Servier Pharmaceuticals, we had the pleasure of speaking with Jennie W. Taylor, MD, MPH, about the FDA approval of vorasidenib (Voranigo) for patients with IDH-positive grade 2 astrocytoma or oligodendroglioma. Dr Taylor is an associate professor of clinical neurology at the University of California, San Francisco (UCSF), as well as the community engagement liaison in the Neurologic Oncology Program at the UCSF Helen Diller Family Comprehensive Cancer Center. On August 6, 2024, the FDA approved vorasidenib for the treatment of adult and pediatric patients at least 12 years of age with grade 2 astrocytoma or oligodendroglioma harboring susceptible IDH1 or IDH2 mutations who have previously undergone surgery including biopsy, sub-total resection, or gross total resection. This regulatory decision was backed by findings from the phase 3 INDIGO trial (NCY04164901), in which, at a median follow-up of 14.0 months (interquartile range [IQR], 10.1-17.9), vorasidenib (n = 168) produced a median progression-free survival of 27.7 months (95% CI, 17.0-not estimated) vs 11.1 months (95% CI, 11.0-13.7) in the placebo arm (n = 163) at a median follow-up of 14.3 months (IQR, 10.0-18.1; HR, 0.39; 95% CI, 0.27-0.56; P < .001). In our exclusive interview, Dr Taylor discussed the significance of this approval, key data from INDIGO, and where vorasidenib fits into the astrocytoma or oligodendroglioma treatment paradigms.

Dr. Maya Graham interviews Drs. Mary Jane Lim-Fat and Kee Kiat Yeo about their recent manuscript entitled "A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients", published online in Neuro-Oncology in July 2024. Link: https://doi.org/10.1093/neuonc/noae142

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, we had the pleasure of speaking with Tarita Thomas, MD, PhD, MBA, and Rimas Lukas, MD, about abstracts presented during a brain cancer­–focused clinical science symposium at the 2024 ASCO Annual Meeting. Dr Thomas is an associate professor of radiation oncology and Dr Lukas is an associate professor of neurology (neuro-oncology; hospital neurology) at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.  In our exclusive interview, Drs Thomas and Lukas discussed the results of 4 abstracts presented during the symposium. In particular, their discussion highlighted findings with ST101 in window-of-opportunity cohorts of patients with recurrent glioblastoma (GBM), the prognostic utility of cerebrospinal fluid circulating tumor DNA in recurrent high-grade glioma, the genomic drivers of GBM, and preclinical data with navtemadlin (KRT-232) in IDH wild-type GBM.  ___ That's all we have for today! Thank you for listening to this episode of OncLive On Air. Check back on Mondays and Thursdays 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, 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, Amazon Music, 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. 

Matthew Spencer, global director of landscapes at IDH, talks with Innovation Forum's Toby Webb about implementing landscape and jurisdictional approaches for sustainable land management. They share practical insights on stakeholder engagement, overcoming political challenges and scaling successful landscape models, using real-world examples from Kenya, Brazil and more.

This week: IDH's global director of landscapes talks with Innovation Forum's Toby Webb about the practicalities and challenges of implementing a landscape or jurisdictional approach to commodity sourcing. They discuss insights into how business and stakeholders can align their efforts for long-term sustainability and environmental protection, emphasising the importance of collaboration at both local and governmental levels.   Plus: cocoa giants including Mars Wrigley, Ferrero and Tony's Chocoloney back EUDR amid calls for delay; Nestlé's cocoa plan expands to Ghana to boost yield and farmer incomes; Adidas, PVH, Zalando join Fashion for Good's circular footwear initiative; and, global wind targets fall short of tripling goal, according to an environmental group Ember, in the news digest.   Host: Ian Welsh    IDH will be at the upcoming sustainable commodities and land use forum in Amsterdam (22nd-23rdOctober). If you'd like to continue the conversation, click here for more information on how to get involved.

Dr Bill Nelson talks with Dr Matthias Holdhoff about the treatment of brain cancer and a significant FDA approval of a new drug treatment for a type of brain cancer, called low-grade glioma. The drug, called vorasidenib, is a targeted cancer therapy that works by inhibiting the activity of a mutated gene called IDH, slowing the growth of the cancer. Read more here 

Radiology read to you! Andrew reads the Radiopaedia article on glioblastoma to Frank. Definitions have changed in this area over the last decade with IDH-wildtype molecular status now forming the basis of diagnosis. Change can often cause confusion, but hopefully this episode helps keep everyone up to date and on the same page… for now at least. Radiopaedia's glioblastoma IDH-wildtype article  ► https://radiopaedia.org/articles/glioblastoma-idh-wildtype Radiopaedia 2024 Virtual Conference ► https://radiopaedia.org/courses/radiopaedia-2024-virtual-conference Become a supporter ► https://radiopaedia.org/supporters Get an All-Access Pass ► https://radiopaedia.org/courses/all-access-course-pass Andrew's X ► https://twitter.com/drandrewdixon Frank's X ► https://twitter.com/frankgaillard Ideas and Feedback ► podcast@radiopaedia.org   The Reading Room is a radiology podcast intended primarily for radiologists, radiology registrars and residents. 

The May 2024 replay features four episodes on neuro-oncology for brain cancer awareness month. The episode begins with Dr. Philipp Karschnia discussing the assessment of whether MTHFR polymorphisms affect the risk for leukoencephalopathy. The episode continues with Dr. Ingo Mellinghoff discussing new treatment opinions for isocitrate dehydrogenase (IDH)–mutant grade 2 gliomas. The third interview leads into a conversation with Dr. Linda Liau on the study of vaccine-based therapy for GBM. The episode concludes with Dr. Teddy Totimeh talking about brain tumor programs in Asia and Africa. Podcast Links: MTHFR Polymorphisms and Leukoencephalopathy Risk in CNS Lymphoma Patients   New Treatment for IDH mt Gliomas  Study of Vaccine-Based Therapy for GBM Brain Tumor Programs in Asia and Africa  Article Links: https://doi.org/10.1212/WNL.0000000000207670  https://www.nejm.org/doi/full/10.1056/NEJMoa2304194 https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847 https://doi.org/10.1016/j.wneu.2023.04.067 Disclosures can be found at Neurology.org.

Last Thursday melanoma researcher Professor Georgina Long was announced as Australian of the Year, along with colleague and friend Professor Richard Scolyer. As co-medical directors of the Melanoma Institute Australia, the pair are credited with saving thousands of lives. Their pioneering immunotherapy treatments for advanced forms of the cancer have resulted in 5 year survival rates increasing from less than 5% to more than 50%. In June of last year Professor Scolyer was diagnosed with glioblastoma IDH wild-type, a cancer that is usually fatal within six to nine months. Rather than undergoing traditional treatment, Prof Scolyer decided to experiment on himself, with Professor Long designing world-first treatments based on their melanoma work.