Journal of Clinical Oncology最新文献

{"title":"Beyond Phlebotomy: Iron Homeostasis in the Next Phase of Polycythemia Vera Management.","authors":"Elena Torre, Claire Harrison","doi":"10.1200/JCO-26-01994","DOIUrl":"https://doi.org/10.1200/JCO-26-01994","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601994"},"PeriodicalIF":44.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-In-Human Study of ²¹¹At-CD45 Radioimmunotherapy With Nonmyeloablative Conditioning Hematopoietic Cell Transplantation for Adults With Hematologic Malignancies.","authors":"Phuong T Vo, Roland B Walter, Ted A Gooley, Donald K Hamlin, Robyn Haaf, Roger Wong, Manuela Matesan, Erlinda B Santos, Eric Dorman, David H Lewis, Sanaz Behnia, Robert C Emery, Yawen Li, Johnnie J Orozco, Hubert Vesselle, D Scott Wilbur, Rainer Storb, Brenda M Sandmaier","doi":"10.1200/JCO-26-00877","DOIUrl":"https://doi.org/10.1200/JCO-26-00877","url":null,"abstract":"<p><strong>Purpose: </strong>Relapse is the dominant cause of failure after allogeneic hematopoietic cell transplantation (HCT) for aggressive hematologic malignancies. CD45-directed radioimmunotherapy (RIT) has been investigated to intensify conditioning and augment antitumor efficacy. After gaining clinical experience with β-emitting radionuclides, attention is now shifting toward α-emitters, such as astatine-211 (²¹¹At), for their more potent and precise radiation delivery with minimized toxicity to surrounding tissues.</p><p><strong>Patients and methods: </strong>To our knowledge, in this first-in-human, two-stage dose-finding study, we administered a single infusion of ²¹¹At-labeled anti-CD45 monoclonal antibody before nonmyeloablative conditioning with fludarabine/2-3 Gy total body irradiation and allografting from HLA-matched or single-allele-mismatched donors in 45 adults (38-74 years of age) at a high relapse risk from myeloid malignancies or acute leukemia.</p><p><strong>Results: </strong>Seventeen patients were treated in stage I with 85-591 μCi/kg of ²¹¹At. The patient receiving 591 μCi/kg developed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), thereby establishing 500 μCi/kg as the protocol-defined maximum tolerated dose and prompting initiation of stage II at that dose in 28 patients. Infusion reactions were mild. ²¹¹At-CD45 RIT did not delay hematopoietic recovery, impair donor chimerism, or increase graft-versus-host disease (GVHD) rates. In stage II, six patients (all receiving sirolimus as part of GVHD prophylaxis for unrelated donor HCT) experienced VOD/SOS. Among the 13 patients with circulating blasts at baseline, blasts cleared in 12 before initiation of fludarabine/total body irradiation, demonstrating immediate cytotoxic activity. Estimated 1-year relapse-free and overall survival were 42% (95% CI, 28%-56%) and 49% (34%-62%), respectively.</p><p><strong>Conclusion: </strong>²¹¹At-CD45 RIT can be incorporated into nonmyeloablative conditioning, with liver toxicity defining activity limits. Evidence of antitumor efficacy supports phase II evaluation.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600877"},"PeriodicalIF":44.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert Histopathologic Evaluation and Molecular Analyses for Ambiguous Cutaneous Melanocytic Tumors.","authors":"Chiel F Ebbelaar, Anthonie W A Lensing, Gerben E Breimer, Marijke R van Dijk, Martin H Prins, Remco van Doorn, Anne M R Schrader, Wendy W J de Leng, Lourens T Bloem, Karijn P M Suijkerbuijk, Anne M L Jansen, Willeke A M Blokx","doi":"10.1200/JCO-26-00432","DOIUrl":"https://doi.org/10.1200/JCO-26-00432","url":null,"abstract":"<p><strong>Purpose: </strong>A subset of cutaneous melanocytic tumors has ambiguous histopathologic features that preclude reliable classification as benign or malignant. We evaluated the diagnostic yield and long-term clinical validity of expert histopathologic evaluation and, when inconclusive, additional molecular analyses in patients with ambiguous primary cutaneous melanocytic tumors.</p><p><strong>Methods: </strong>In this prospective cohort study, consecutive patients with primary cutaneous melanocytic tumors deemed ambiguous by referring pathologists were evaluated at a tertiary dermatopathology referral center in the Netherlands from September 2018 through December 2021. Tumors underwent expert histopathologic evaluation, with next-generation sequencing, single-nucleotide polymorphism array, and targeted RNA sequencing when inconclusive. Tumors were classified as nonmelanoma, melanoma, or borderline melanoma. Clinical validity was assessed by melanoma-related events during follow-up.</p><p><strong>Results: </strong>Among 258,562 patients with excised melanocytic tumors nationwide, 2,685 (1.0%) had ambiguous tumors. We included 994 patients and reached a diagnosis in 966 (97.2%): 417 (42.0%) after expert histopathologic evaluation alone and 549 (55.2%) after additional molecular analyses. Among 608 patients (61.2%) with a nonmelanoma diagnosis, no melanoma-related events occurred during median follow-up of 5.4 years (incidence, 0.0%; 95% CI, 0.0 to 0.6). Among 358 patients (36.0%) with a melanoma diagnosis, 33 of 186 (17.7%) had a positive sentinel node biopsy, and 20 developed melanoma-related events during median follow-up of 5.0 years (cumulative incidence, 5.7%; 95% CI, 3.3 to 8.1). No events occurred in 28 patients (2.8%) with a borderline melanoma diagnosis.</p><p><strong>Conclusion: </strong>Expert histopathologic evaluation combined with molecular analyses provided a definitive diagnosis in nearly all patients with ambiguous primary cutaneous melanocytic tumors. Long-term follow-up supported the clinical validity of this stepwise diagnostic approach.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600432"},"PeriodicalIF":44.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Insurance and Cost-Related Access Barriers to Specialty Oral Anticancer Medications for Blood Cancers in a Nationwide Sample of Medicare and Commercially Insured Patients.","authors":"Jalpa A Doshi, Pengxiang Li, Zhi Geng, Matthew J Klebanoff, Amy R Pettit, Katrina A Armstrong, Scott F Huntington, John K Lin","doi":"10.1200/JCO-26-02527","DOIUrl":"https://doi.org/10.1200/JCO-26-02527","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2602527"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation Oncology at a Crossroads: Interpreting the Evidence on Proton Versus Photon Radiotherapy for Oropharyngeal Cancer.","authors":"Sudarshan Ramanan, George Ashji, Khoi Nguyen, Danil Ratnikov, Eric J Sherman, Sean M McBride, Yingzhi Wu, Edward Christopher Dee, Nadeem Riaz, Nancy Y Lee","doi":"10.1200/JCO-26-01434","DOIUrl":"https://doi.org/10.1200/JCO-26-01434","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601434"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trial Prediction Markets.","authors":"Nicholas G Zaorsky","doi":"10.1200/JCO-26-01303","DOIUrl":"https://doi.org/10.1200/JCO-26-01303","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2601303"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Advanced Biliary Tract Cancer: ASCO Living Guideline, Version 2026.1.0.","authors":"Rachna T Shroff, Erin B Kennedy, Ashley Efrain Alarcon Rozas, Rajiv Agarwal, Melinda Bachini, Marina Baretti, Gagandeep Brar, Allen L Cohn, Madhu Eluri, Olumide B Gbolahan, John D Gordan, Lipika Goyal, James J Harding, Ishmael Jaiyesimi, Adel Kardosh, Robin Kate Kelley, Angela Lamarca, Arun Nagarajan, Vikas Ostwal, Michal Rose, Ardaman Shergill, Changqing Xie, Tim F Greten","doi":"10.1200/JCO-26-02462","DOIUrl":"https://doi.org/10.1200/JCO-26-02462","url":null,"abstract":"<p><strong>Purpose: </strong>This living guideline provides recommendations for liquid biopsy and treatment of patients with advanced biliary tract cancer<b>.</b></p><p><strong>Methods: </strong>The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for liquid biopsy and systemic therapy for patients with advanced biliary tract cancer.</p><p><strong>Results: </strong>Six studies provided estimates of concordance between liquid biopsy and tissue biopsy. Nine RCTs were included in the evidence base for first-line therapy. One phase III RCT and four phase II RCTs were included in the evidence for second-line chemotherapy. Eleven single studies or reviews supported biomarker-specific second-line therapy recommendations.</p><p><strong>Recommendations: </strong>Testing with broad-based tissue DNA and RNA NGS testing to determine the presence of targetable biomarkers is recommended at the time of diagnosis at any stage. Liquid biopsy with plasma is generally recommended only when tissue biopsy is unavailable. As first-line therapy for patients with pMMR/MSS advanced BTC, immune checkpoint inhibitors (ICIs) plus chemotherapy is recommended. Options for patients with advanced BTC who are not candidates for ICIs are included in the guideline. Pembrolizumab monotherapy is an option for patients with dMMR/MSI-H advanced BTC. For patients with disease progression on first-line treatment and who have no identified biomarkers, FOLFOX with active symptom control, or active symptom control alone are recommended; options for patients who are ineligible for oxaliplatin-based chemotherapy are included in the guideline. Second-line therapy options are recommended for patients with dMMR/MSI-H, <i>IDH1</i> mutations, <i>FGFR2</i> fusions or rearrangements, <i>BRAF</i> V600E mutations, HER2 overexpression, <i>RET, NTRK1/2/3,</i> or <i>NRG1</i> fusions.Additional information is available at https://ascopubs.org/guidelines/living-guidelines.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"101200JCO2602462"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selpercatinib in Pediatric and Adolescent Patients With <i>RET</i>-Altered Solid Tumors: Safety and Efficacy Results From the Phase I/II LIBRETTO-121 Study.","authors":"Theodore W Laetsch, Hyoung Jin Kang, Michela Casanova, Antoinette Anazodo, Steven G DuBois, Atsushi Manabe, Fariba Navid, Alberto Pappo, Adrienne M Gilligan, Olivera Grbovic-Huezo, Dan Liu, Subha Suriyapperuma, Nivedita Sharma, Patrick Peterson, Jennifer Wright, Cornelis M van Tilburg, Daniel Morgenstern","doi":"10.1200/JCO-25-03013","DOIUrl":"https://doi.org/10.1200/JCO-25-03013","url":null,"abstract":"<p><strong>Purpose: </strong>Selpercatinib, a highly selective oral RET inhibitor with CNS activity, has previously demonstrated durable responses and an acceptable safety profile in adults with <i>RET</i>-driven cancers. Consequently, the safety and efficacy of selpercatinib were investigated in pediatric/adolescent participants.</p><p><strong>Methods: </strong>LIBRETTO-121 (ClinicalTrials.gov identifier: NCT03899792) was a multicenter phase I/II trial of selpercatinib in participants age 0.5-21 years with advanced, <i>RET</i>-altered solid tumors. In phase I, the primary end point was safety, including dose-limiting toxicities. In phase II, the primary end point was objective response rate (ORR) as determined by independent review committee (IRC) per RECIST v1.1. Key secondary end points included ORR by investigator, duration of response (DOR), progression-free survival, overall survival, safety, and pharmacokinetics.</p><p><strong>Results: </strong>As of November 8, 2024, 36 participants age 2-20 years were treated with selpercatinib. Tumor types included <i>RET</i>-altered medullary thyroid cancer (MTC, n = 15), <i>RET</i> fusion-positive papillary thyroid cancer (PTC, n = 15), and other (n = 6). The most common treatment-emergent adverse events were diarrhea, nausea, elevated AST, pyrexia, abdominal pain, elevated ALT, headache, cough, and vomiting. No treatment discontinuations due to treatment-related adverse events or new adverse drug reactions were observed. ORR by IRC was 53% (19/36; 95% CI, 36 to 70). For participants with MTC and PTC, ORR by IRC was 60% (9/15; 95% CI, 32 to 84) and 53% (8/15; 95% CI, 27 to 79), respectively. The 24-month DOR rate was 100% (95% CI, 100 to 100).</p><p><strong>Conclusion: </strong>Selpercatinib showed durable efficacy in pediatric/adolescent participants with <i>RET</i>-altered thyroid cancer and was well tolerated, supporting targeting of <i>RET</i> alterations in pediatric/adolescent patients.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2503013"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Circulating Tumor DNA Profiling Defines Risk Classification in Patients With Ewing Sarcoma: A Report From the Children's Oncology Group and the LEOPARD Study.","authors":"David S Shulman, Kelly Klega, Nan Chen, Allen Buxton, Elliot Gohn, Sarah Sexton, Catherine Clinton, Mohammad Tanhaemami, Carrie Cibulskis, Edwin Choy, Thomas Cash, Kris Ann P Schultz, Leo Mascarenhas, Rochelle Bagatell, Christopher Kuo, Brian K Turpin, Bhuvana A Setty, Bradley D DeNardo, Douglas S Hawkins, Michael W Bishop, Avanthi Tayi Shah, Luke D Maese, Julia L Glade Bender, Damon Reed, Mark D Krailo, Natalie DelRocco, Wendy B London, Katherine A Janeway, Steven G DuBois, Brian D Crompton","doi":"10.1200/JCO-26-02524","DOIUrl":"https://doi.org/10.1200/JCO-26-02524","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2602524"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental Blueprint in Gliomas: Toward an Ontogenetic Multimodal Integrated Therapy.","authors":"Luis Padevit, Tobias Weiss, Flavio Vasella, Marian Christoph Neidert, Carlo Serra, Niklaus Krayenbühl, Gelareh Zadeh, Michael Weller, Luca Regli, Kevin Akeret","doi":"10.1200/JCO-25-02798","DOIUrl":"https://doi.org/10.1200/JCO-25-02798","url":null,"abstract":"<p><p>Neuroepithelial tumors, including diffuse gliomas and embryonal neoplasms, remain among the most lethal cancers despite major advances in molecular diagnostics and some novel targeted therapies for subsets of patients. A persistent barrier to progress is the lack of a unifying framework that integrates their cellular hierarchy, spatial heterogeneity, and distinctive patterns of progression. In this review, we synthesize converging evidence that neuroepithelial tumor biology represents a pathologic re-enactment of brain ontogeny. Integrating molecular, single-cell, histoarchitectonic, and anatomic observations, we propose that neoplastic transformation, aberrant lineage commitment, and dedifferentiation mirror and invert physiological ontogenetic trajectories. This ontogenetic logic provides a coherent explanation for key hallmarks of neuroepithelial tumors, including intratumoral mosaicism, directional anatomic spread, and the emergence of therapy-resistant tumor-propagating cell states. Ontogenetic multimodal integrated therapy is an anatomy-guided strategy that aligns neurosurgery, radiotherapy, and pharmacotherapy with tumor stage and ontogenetic architecture. By shifting emphasis from radiologically visible tumor bulk to compartment-based developmental logic, this framework offers testable hypotheses and a clinically oriented paradigm for diagnosis, treatment planning, and longitudinal monitoring in patients with neuroepithelial tumors.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2502798"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}