Journal of Clinical Oncology最新文献

{"title":"Integrative Molecular Analysis Reveals Determinants of Clinical Outcomes in <i>TP53</i>-Mutated Diffuse Large B-Cell Lymphoma.","authors":"Manik Uppal, Bhavneet Bhinder, Andrew R Marderstein, Connie Lee Batlevi, Lorenzo Falchi, Paul Hamlin, Steven Horwitz, Anita Kumar, Ariela Noy, Andrew D Zelenetz, Jennifer K Lue, Pallawi Torka, Zachary D Epstein-Peterson, Maria Arcila, Ahmet Dogan, Brandon Imber, Joachim Yahalom, Santosha A Vardhana, Andrew Intlekofer, Sandeep Raj, Roni Shouval, Brendan Hodkinson, Matthew E Stokes, Adam S Kittai, Joshua D Brody, Olivier Elemento, Gilles Salles, Erel Joffe","doi":"10.1200/JCO-25-01928","DOIUrl":"https://doi.org/10.1200/JCO-25-01928","url":null,"abstract":"<p><strong>Purpose: </strong>Mutations in <i>TP53</i>, detected in over 20% of diffuse large B-cell lymphomas (DLBCLs), are associated with poor prognosis. However, clinical outcomes among patients with <i>TP53</i>-mutant disease vary, with some patients showing treatment responses similar to those with wild-type <i>TP53</i>. This study aims to understand the clinical and molecular determinants underlying poor outcomes in <i>TP53</i>-mutant DLBCL.</p><p><strong>Methods: </strong>Clinical and molecular data for 3,091 patients were derived from 10 cohorts of patients with newly diagnosed DLBCL treated with frontline rituximab-based immunochemotherapy regimens. Targeted or whole-exome/whole-genome sequencing was available for all patients. Bulk RNA-seq was analyzed for 591 patient samples. The primary outcome measures were progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong><i>TP53-</i>mutant DLBCL differed from wild-type disease in pattern and number of genetic lesions, malignant B-cell expression states, and tumor microenvironment composition. <i>TP53</i> mutations were 6-fold more prevalent than <i>MYC/BCL2/BCL6</i> double-/triple-hit status, but conferred similar adverse prognostic risk. Among patients with <i>TP53</i>-mutant disease, variant allele frequency (VAF) further stratified risk, with patients featuring VAF ≥ 75% (indicative of loss of heterozygosity) experiencing significantly inferior PFS/OS. Downregulation of interferon signaling and lower macrophage content were identified in <i>TP53</i>-mutant samples derived from patients with poor outcomes or VAF ≥ 75%. <i>TP53</i> mutations were adversely prognostic among patients with DLBCL assigned to specific LymphGen subtypes (EZB, MCD), malignant B-cell states (S1), and ecotypes (LE4, LE7, LE8), whereas outcomes were similar to wild-type disease within other molecular subtypes. In re-examination of the Phoenix trial data, addition of ibrutinib to R-CHOP improved PFS in patients with <i>TP53</i>-mutant DLBCL and abrogated the deleterious impact of high VAF, irrespective of patients' age.</p><p><strong>Conclusion: </strong>The poor prognosis of <i>TP53</i>-mutant DLBCL is dependent on intrinsic features, such as VAF, and modulated by co-occurring genomic lesions or lymphoma cell-intrinsic or microenvironmental expression patterns.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2501928"},"PeriodicalIF":41.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771511","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":"The Liver We Share.","authors":"Ryan P Wexler","doi":"10.1200/JCO-25-03106","DOIUrl":"https://doi.org/10.1200/JCO-25-03106","url":null,"abstract":"<p><p>A medical student's first encounter with a hepatectomy comes full circle when he becomes a living liver donor for his wife with metastatic pancreatic cancer, reshaping his understanding of medicine as they navigate the uncertainty of her diagnosis together.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2503106"},"PeriodicalIF":41.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771926","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":"In DeFi-ance of \"More Is Better\": Questioning Long-Term Nirogacestat Use in Desmoid Tumors.","authors":"Fahima Dossa,Chandrajit P Raut,Andrew J Wagner,Robin L Jones,Rebecca A Gladdy,Abha A Gupta,Kenneth Cardona,David E Gyorki,Tom W Chen,Herbert H Loong,Sylvie Bonvalot,Silvia Stacchiotti,Alessandro Gronchi","doi":"10.1200/jco-25-02927","DOIUrl":"https://doi.org/10.1200/jco-25-02927","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"27 1","pages":"JCO2502927"},"PeriodicalIF":45.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739026","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":"Reply to: In DeFi-ance of \"More Is Better\": Questioning Long-Term Nirogacestat Use in Desmoid Tumors.","authors":"Ravin Ratan,Bernd Kasper,Thierry Alcindor,Patrick Schöffski,Winette T van der Graaf,Noah Federman,Nam Q Bui,Gina D'Amato,Richard F Riedel,Steven Attia,Sant Chawla,Allison Lim,Brad Tumminello,Ana B Oton,Yucheng Chu,Shengfan Zhou,Mrinal Gounder","doi":"10.1200/jco-26-00107","DOIUrl":"https://doi.org/10.1200/jco-26-00107","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"11 1","pages":"JCO2600107"},"PeriodicalIF":45.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739028","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 Opinion on the Diagnosis and Treatment of Hematologic Malignancies During Pregnancy.","authors":"Daan Dierickx,Joosje H Heimovaara,Mar Bellido,Kristel Van Calsteren,Elyce Cardonick,Alvaro Cabrera Garcia,Adinda Baten,Andrew M Evens,Andres Ferber,Monica Fumagalli,Elzbieta Lampka,Lena Specht,Vincent Vandecaveye,Ivan R Vogelius,Markus Alber,Frédéric Amant","doi":"10.1200/jco-25-02351","DOIUrl":"https://doi.org/10.1200/jco-25-02351","url":null,"abstract":"The diagnosis and treatment of hematologic malignancies has undergone significant advancements over the past few decades, resulting in enhanced outcomes. For hematologic malignancies diagnosed during pregnancy, this poses new questions. As possibilities continue to expand and the rising global incidence results in an increasing number of diagnoses within the pregnant population, there is a pressing need to gain a deeper understanding of the potential options for pregnant women and the impact on the newborn. As knowledge of the effects of cancer treatment increases, more women are receiving adequate cancer diagnosis and treatment during pregnancy. This paper presents an expert opinion on the use of diagnostic modalities and treatment options, including chemotherapy, radiation therapy, and immunotherapy, for acute leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, myeloproliferative neoplasms, aplastic anemia, and multiple myeloma during pregnancy.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"1 1","pages":"JCO2502351"},"PeriodicalIF":45.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739025","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":"Postoperative Hepatic Arterial Infusion With Oxaliplatin After Surgery of Four or More Colorectal Liver Metastases: A Randomized Phase II Trial.","authors":"Maximiliano Gelli,Jacques Ewald,Marie-Laure Tanguy,Guillaume Passot,Francois Quenet,Yann Touchefeu,Hélène Senellart,Fabrice Muscari,Astrid Lievre,René Adam,Lambros Tselikas,Thomas Aparicio,Julien Taieb,Charles Mastier,Jean-Marc Regimbeau,Amani Asnacios Lecerf,David Tougeron,Valerie Boige,Thierry De Baere,David Malka,Diane Goéré","doi":"10.1200/jco-25-01737","DOIUrl":"https://doi.org/10.1200/jco-25-01737","url":null,"abstract":"PURPOSETo evaluate the efficacy and safety of adjuvant hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous (IV) fluorouracil/leucovorin (LV5FU2) after curative-intent surgery of ≥4 colorectal liver metastases (CRLM).METHODSPatients with an Eastern Cooperative Oncology Group performance status 0-1, who underwent resection or ablation of ≥4 CRLM after preoperative IV chemotherapy were enrolled. Patients were randomly assigned (1:1) to receive adjuvant oxaliplatin via HAI (HAI group, n = 50) or IV infusion (IV group, n = 49), both combined with IV LV5FU2 for at least 3 months. The primary end point was hepatic recurrence-free survival (h-RFS). Secondary end points included RFS, overall survival (OS), safety, and feasibility.RESULTSAfter a median follow-up of 59 months (IQR, 45-71), the median h-RFS was 25 (95% CI, 16 to 37) months in the HAI group versus 12 (95% CI, 8 to 19) months in the IV group (hazard ratio [HR], 0.63 [95% CI, 0.40 to 0.99]; P = .047). Median RFS was 14 months (95% CI, 10 to 20) in the HAI group versus 9 months (95% CI, 7 to 11) in the IV group (HR, 0.63 [95% CI, 0.41 to 0.97]; P = .03). Median OS was 74 months (95% CI, 51 to not defined) in the HAI group versus 57 months (95% CI, 37 to 69) in the IV group (HR, 0.61 [95% CI, 0.33 to 1.12]; P = .11). Five-year OS was 62% in the HAI arm compared with 47% in the IV arm. Grade 3 to 4 adverse events occurred in 58% of HAI patients and 32% of IV patients (P = .02). No treatment-related deaths were reported. Four or more cycles of adjuvant chemotherapy were delivered in 81% of patients in the HAI group and 78% in the IV group (P = .75).CONCLUSIONAdjuvant oxaliplatin HAI plus LV5FU2 improves h-RFS after curative-intent surgery of CRLM in high-risk patients, with an acceptable safety profile. These results support further evaluation in a phase III trial.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"25 1","pages":"JCO2501737"},"PeriodicalIF":45.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733319","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":"Histotripsy and the IDEAL Framework: A Clarion Call for the Responsible and Evidence-Based Application of New Technology.","authors":"Shoshana T Levi,Jeffrey Barkun,Peter McCulloch,Bruno C Odisio,Hop S Tran Cao","doi":"10.1200/jco-26-00174","DOIUrl":"https://doi.org/10.1200/jco-26-00174","url":null,"abstract":"The evaluation of novel health technologies is increasingly complicated by a landscape of pervasive social media influence and intense product marketing, factors that may distort evidence appraisal and contribute to suboptimal medical decision-making and patient outcomes. Within this context, interest in histotripsy, a novel technology approved for the treatment of liver tumors, has expanded rapidly. This accelerated adoption has outpaced the available evidence, challenging established principles of safety, efficacy, and appropriate patient selection and has generated substantial debate within the oncologic community. In this editorial, we provide an overview of the technology and available data, examine the external forces contributing to its accelerated application, and propose a well established, structured, evidence-based framework to guide its rigorous evaluation, responsible adoption, and optimal clinical implementation.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"136 1","pages":"JCO2600174"},"PeriodicalIF":45.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733317","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":"Notably Off Key: Questioning the Clinical Benefit of Perioperative Immunotherapy for Resectable Head and Neck Squamous Cell Carcinoma After KEYNOTE-689.","authors":"Musaddiq Awan,James Caudell,Stuart Wong,Baran Sumer,Kedar Kirtane,Joseph Zenga,David Sher","doi":"10.1200/jco-25-01990","DOIUrl":"https://doi.org/10.1200/jco-25-01990","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"54 1","pages":"JCO2501990"},"PeriodicalIF":45.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733975","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":"Duvelisib Induces Deep Responses in PTCL: Final Results of the Phase 2 PRIMO Trial of Duvelisib in Relapsed/Refractory Peripheral T-Cell Lymphoma.","authors":"Neha Mehta-Shah,Pier Luigi Zinzani,Eric D Jacobsen,Jasmine Zain,Monica Mead,Carla Casulo,Giuseppe Gritti,Lauren Pinter-Brown,Koji Izutsu,David Sidransky,Ohad S Bentur,Barbara Pro,Christopher P Fox,Jonathan E Brammer,Steven M Horwitz","doi":"10.1200/jco-25-03120","DOIUrl":"https://doi.org/10.1200/jco-25-03120","url":null,"abstract":"BACKGROUNDPeripheral T-cell lymphomas (PTCLs) are rare, heterogeneous, aggressive lymphomas. Five-year overall survival (OS) remains ∼30-40%, and most patients will develop relapsed or refractory (R/R) disease. Duvelisib is an oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and PI3K-γ isoforms. Here, we report on the final analysis of the phase 2 PRIMO trial (NCT03372057; Secura Bio, Inc.) evaluating duvelisib monotherapy in R/R PTCL.METHODSPRIMO was conducted in 2 phases (Dose Optimization and Dose Expansion [PRIMO-EP]) at 45 centers globally. Eligible patients were ≥18 years of age, had histologically confirmed diagnosis of PTCL, and had received ≥2 cycles of 1 standard regimen for PTCL. Based on Dose Optimization results, the selected regimen for PRIMO-EP was 75 mg BID for 2 cycles (to maximize disease control) followed by 25 mg BID (to reduce late toxicities), continued until progressive disease or unacceptable toxicity.RESULTSPRIMO-EP (N=123) outcomes included Independent Review Committee-assessed objective response rate (ORR): 48.0%, complete response rate (CRR): 33.3%, median progression-free survival (mPFS): 3.4 months, mOS: 12.4 months, median duration of response (mDOR): 7.9 months. In the AITL subgroup, outcomes were ORR: 62.2%, CRR: 51.4%, mPFS: 8.3 months, mOS: 18.1 months, mDOR: 11.3 months. Treatment-emergent adverse events (TEAEs) (any grade) occurred in 120 patients (97.6%), TEAEs grade ≥3 occurred in 91 patients (74.0%). TEAEs resulting in dose hold or dose reduction occurred in 44.7% and 9.8% of patients.CONCLUSIONSThe PRIMO study demonstrates significant activity and tolerability of duvelisib in patients with R/R PTCL, most notably in the AITL subgroup. This provides strong rationale for further development in PTCL, and more specifically in the subgroup of nodal T-follicular helper cell lymphoma.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"28 1","pages":"101200JCO2503120"},"PeriodicalIF":45.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733321","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":"Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study.","authors":"Paul E Oberstein,J Randolph Hecht,Kanwal Raghav,Filippo Pietrantonio,Dirk Arnold,Victor Moreno,Eric Van Cutsem,Rozita Abdul Malik,Yong Sang Hong,Myung Ah Lee,Harvey Yu-Li Su,Jeeyun Lee,Sreenivasa Chandana,Marcia Cruz-Correa,Ying Yuan,Azura Ahmad,Kuan-Ming Lai,Hung-Chih Hsu,Eric Xueyu Chen,Elena Elez,Chia-Chi Lin,Carlos Lopez,Hans Prenen,Susana Roselló-Keränen,Hector Velez,Yu-Min Yeh,Volker Heinemann,Cathy Eng,Seung-Hoon Beom,Sabine Tejpar,Sanjib Chowdhury,Xuesong Lyu,Medha Kamat,Joshua C Curtin,Bharvin Patel,John Xie,Rianka Bhattacharya,Robert W Schnepp,Emrullah Yilmaz,Ryota Iwasawa,Mahesh Daksh,Patricia Lorenzini,Meena Thayu,Mahadi Baig,Han Sang Kim,Sae-Won Han","doi":"10.1200/jco-25-02187","DOIUrl":"https://doi.org/10.1200/jco-25-02187","url":null,"abstract":"PURPOSEAmivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, is approved in non-small cell lung cancer (NSCLC). Effective treatments are limited for chemorefractory metastatic colorectal cancer (mCRC).METHODSOrigAMI-1 (ClinicalTrials.gov identifier: NCT05379595) is a phase Ib/II study evaluating amivantamab monotherapy in chemorefractory (2-3 prior lines) mCRC. Participants had centrally confirmed RAS/BRAF/EGFR ectodomain wild-type status, without ERBB2/HER2 amplification. Participants with left-sided mCRC without (cohort A) or with (cohort B) prior anti-EGFR antibody treatment, or right-sided mCRC (cohort C) regardless of prior anti-EGFR treatment, received intravenous amivantamab 1,050 mg (1,400 mg for ≥80 kg) once every 2 weeks. The primary end point was objective response rate (ORR) per RECIST v1.1.RESULTSBy October 31, 2024, 94 participants received amivantamab monotherapy (median follow-up, 11.9 months). The median age was 60 years, and 65% of participants were male, with a median of 2 prior lines (94%, prior bevacizumab). In left-sided cohorts, the ORR was 29% (5 of 17) in cohort A and 19% (10 of 54) in cohort B; the median duration of response (DoR) was 9.0 months and 6.1 months, and the median progression-free survival (PFS) was 5.7 months and 4.6 months, respectively. In the right-sided cohort, the ORR was 22% (10 of 23; 43% had prior anti-EGFR), the median DoR was 9.8 months, and the median PFS was 3.7 months. Most frequent treatment-related grade ≥3 adverse events (AEs) were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (4%). One participant discontinued amivantamab because of a treatment-related AE.CONCLUSIONAmivantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory mCRC, regardless of prior anti-EGFR therapy and the primary tumor location. The amivantamab safety profile in mCRC is consistent with experience in NSCLC. Amivantamab plus chemotherapy is currently being explored in two phase III studies in first-line and second-line mCRCs.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"9 1","pages":"JCO2502187"},"PeriodicalIF":45.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731609","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}