Journal of Clinical Oncology最新文献

{"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}

{"title":"Prescription Does Not Ensure Patient Access: Progress and Remaining Challenges in Addressing Access Barriers to Specialty Oral Anticancer Medications.","authors":"Aryana Sepassi, A Mark Fendrick","doi":"10.1200/JCO-26-02192","DOIUrl":"https://doi.org/10.1200/JCO-26-02192","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2602192"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182052","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":"Dose-Escalated Focal Salvage High-Dose-Rate Brachytherapy and Genomic Classifier Risk Stratification in Radiorecurrent Prostate Cancer: The F-SHARP Phase I/II Clinical Trial.","authors":"Abhishek A Solanki, William Adams, James A Proudfoot, Kristin Baldea, Güliz A Barkan, Alec M Block, Neil B Desai, Ahmer Farooq, Michael R Folkert, Aurelie Garant, Alex Gorbonos, Gopal Gupta, Hyejoo Kang, Eileen Kelly, Steven Kregel, Stanley L Liauw, Christopher K Luminais, Michael Mysz, Marcus L Quek, Timothy N Showalter, James S Welsh, Michael Woods, Elai Davicioni, William Small, Matthew M Harkenrider","doi":"10.1200/JCO-25-02730","DOIUrl":"https://doi.org/10.1200/JCO-25-02730","url":null,"abstract":"<p><strong>Purpose: </strong>Prospective data on the management of intraprostatic radiorecurrence (IPR) after definitive radiotherapy (RT) and use of genomic classifiers (GC) in this setting are limited. We hypothesized that dose-escalated focal salvage high-dose-rate brachytherapy (DE-fsHDR) would be safe and effective, and that GC would risk stratify patients who may benefit from treatment intensification.</p><p><strong>Methods: </strong>F-SHARP is a multi-institutional phase I/II trial of DE-fsHDR for IPR after any form of RT for localized prostate cancer. Patients received up to 30 Gy in 1-2 fractions. The primary objective was to determine the acute RT-related grade ≥3 CTCAE v4.03 genitourinary and GI toxicity rates. Secondary end points included all-grade toxicity, quality of life (QoL; EPIC-26 and International Prostate Symptom Score), disease control, and survival. GC analysis used a clinical-grade transcriptome assay (Veracyte, San Diego, CA). Time-to-event outcomes included biochemical progression-free survival (bPFS), radiographic progression-free survival (rPFS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS).</p><p><strong>Results: </strong>Twenty-four participants received one fraction and 38 received two fractions (N = 62). The median follow-up was 39.4 months. No acute grade 3 toxicities occurred. Two patients (3.2%) had late grade 3 toxicity. QoL changes did not meet criteria for a minimal clinically important difference. Three-year survival rates were 62.7% (bPFS), 67.5% (rPFS), 73.0% (LRFS), and 85.9% (MFS); there were no differences between fractionation groups (all <i>P</i> > .05). Among 31 patients with GC results, higher scores were associated with worse bPFS, rPFS, LRFS, and MFS. All patients with GC score >0.85 (n = 4) experienced biochemical, local, and metastatic recurrence.</p><p><strong>Conclusion: </strong>DE-fsHDR is a safe and effective salvage treatment for IPR. GC score is a promising prognostic tool in patients undergoing salvage local therapy for IPR and warrants further study to guide treatment intensification.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2502730"},"PeriodicalIF":44.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181821","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":"Randomized Trial of Hypofractionated Postmastectomy Radiation Therapy in Women With Breast Reconstruction (RT CHARM, Alliance A221505).","authors":"Matthew M Poppe, Jennifer J Le-Rademacher, Bruce G Haffty, Eric K Hansen, Jayant P Agarwal, Jamie L Wagner, Iwa Kong, Jane M Armer, Doug W Arthur, Timothy J Whelan, Odum Kour, Minji K Lee, Kathryn J Ruddy, Ann H Partridge, Lisa A Carey, Maryam Lustberg, Michael B Bernstein, Selina L Chow, Shane R Stecklein, David K Gaffney, Atif J Khan","doi":"10.1200/JCO-26-00474","DOIUrl":"10.1200/JCO-26-00474","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with breast cancer requiring postmastectomy radiation therapy (PMRT) often desire breast reconstruction. Reconstructions can be adversely affected by PMRT, and fear of reconstruction complications has discouraged adoption of short-course radiation therapy used after lumpectomy. To fill the evidence gap, we conducted a noninferiority trial of hypofractionated versus conventional PMRT in patients undergoing breast reconstruction. The primary outcome was reconstruction complication rate, a composite of wound healing, readmission, capsular contracture, unplanned reoperation, and reconstruction failure.</p><p><strong>Methods: </strong>Women with unilateral invasive breast cancer with planned immediate or delayed reconstruction and PMRT were randomly assigned (1:1) to 50 Gy (25 fractions/5 weeks) or 42.56 Gy (16 fractions/3 weeks). This study was designed with a noninferiority margin of 10%, assuming a 2-year reconstruction complication rate of 25% with conventional PMRT. Randomization was stratified by immediate versus delayed and autologous versus implant-only reconstruction.</p><p><strong>Results: </strong>Between 2018 and 2021, 898 patients enrolled with a median follow-up of 3.9 years; 825 patients were evaluable for the primary end point. The 24-month reconstruction complication rates were 12.3% (52/422) with hypofractionated PMRT and 10.2% (41/403) with conventional PMRT, corresponding to an estimated difference of -2.1% (95% CI, -6.5 to 2.2). The complication rate was higher (regardless of arm) with implant-only versus autologous reconstruction (odds ratio = 1.65). There was no statistically significant difference in 36-month locoregional recurrence rates: 1.5% (95% CI, 0.7 to 3.2) with hypofractionated and 2.2% (95% CI, 1.1 to 4.3) with conventional PMRT. Acute and late toxicity rates were not statistically different.</p><p><strong>Conclusion: </strong>A 16-fraction course of hypofractionated PMRT is safe and noninferior to conventional PMRT in women undergoing breast reconstruction after mastectomy.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2600474"},"PeriodicalIF":44.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Blood Test Informed Risk Prediction Model for Lung Cancer-The Copenhagen Lung Cancer Risk Model (CPH-Lung).","authors":"Sune Møller Skov-Jeppesen, Camilla Jannie Kobylecki, Søren Egstrand, Torben Riis Rasmussen, Erik Jakobsen, Ole Hilberg, Zaigham Saghir, Klaus Fuglsang Kofoed, Stig Egil Bojesen","doi":"10.1200/JCO-25-02326","DOIUrl":"https://doi.org/10.1200/JCO-25-02326","url":null,"abstract":"<p><strong>Purpose: </strong>Lung cancer screening reduces lung cancer mortality, but identifying high-risk individuals remains difficult. We wanted to develop a blood test-based risk model (CPH-Lung) to improve risk stratification before image-based screening.</p><p><strong>Materials and methods: </strong>We included individuals from two prospective general population cohorts to model 6-year lung cancer risk; the Copenhagen General Population Study (CGPS) for training and the Copenhagen City Heart Study (CCHS) for validation. We analyzed clinical and biochemical variables from ever-smokers (689 cases and 1,924 controls) nested within CGPS to train a 6-year lung cancer risk model. CPH-Lung was validated in a cohort of ever-smokers age ≥50 years in the Copenhagen City Heart Study (CCHS, 3,195 individuals) and compared with the validated PLCOm2012 model.</p><p><strong>Results: </strong>There were 689 and 68 events of 6-year lung cancer in the CGPS and the CCHS. In the CCHS validation study, the CPH-Lung versus the PLCOm2012 yielded AUCs of 0.783 (95% CI, 0.731 to 0.835) versus 0.720 (95% CI, 0.669 to 0.770) for detection of all 6-year lung cancers (<i>P</i> = .0059). The discrimination was similar in the CGPS. At specificity of 77.7% (as would have been achieved using currently applied screening criteria, eg, NELSON or NLST), sensitivities were 57.6% versus 39.2% in women (<i>P</i> < .0001) and 61.4% versus 54.7% in men (<i>P</i> = .004) for CPH-Lung versus PLCOm2012. The mean age at diagnosis was 68.2 years (standard deviation [SD], 7.50) in the 120 individuals with lung cancer predicted exclusively by CPH-Lung compared with 76.5 years (SD, 8.04) in the 37 individuals predicted exclusively by PLCOm2012 (<i>P</i> < .0001).</p><p><strong>Conclusion: </strong>After inclusion of blood test information, the CPH-Lung model was more sensitive in the Danish population than PLCOm2012 for prediction of 6-year lung cancer risk particularly among women and younger individuals.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"JCO2502326"},"PeriodicalIF":44.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165710","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":"Omitting Bone Marrow Sampling in FDG-Avid Rhabdomyosarcoma With 2-[¹⁸F]FDG PET-Negative Marrow: Results From an International Retrospective Study.","authors":"Federico Mercolini, Marissa Just, Barry L Shulkin, Natalie B Collins, Jacquelyn Crane, Douglas Harrison, Maria C Affinita, Wendy Allen-Rhoades, Alessandra Alessi, Sebastian D Asaftei, Michael A Arnold, Sonja Chen, Stefano Chiaravalli, Forrest FitzGerald, Martin T Freitag, Jessica L Iftner, Hedieh Khalatbari, Bart de Keizer, Irene von Luettichau, Christine Mauz-Körholz, Claudia Rossig, Guido Rovera, Stefan Rutkowski, Justin B Sims, Stephan D Voss, Ayami Yoshimi, Suzi Birz, Gianni Bisogno, Martin Ebinger, Johannes H M Merks, Monika Sparber-Sauer, Bernhard Haller, Aaron R Weiss, Corinne M Linardic, Reineke A Schoot, Simone Hettmer","doi":"10.1200/JCO-25-03080","DOIUrl":"10.1200/JCO-25-03080","url":null,"abstract":"<p><strong>Purpose: </strong>Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2-¹⁸F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging.</p><p><strong>Methods: </strong>Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples.</p><p><strong>Results: </strong>PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages.</p><p><strong>Conclusion: </strong>Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2835-2847"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and Predictive Effect of Age in Molecularly Defined Lower-Grade Gliomas.","authors":"Connor J Kinslow, Giuseppe Minniti, Paul D Brown, Michael A Vogelbaum, Karla V Ballman, Ann Mercurio, Markus D Siegelin, Emre Kocakavuk, Kyle Tuohy, Alireza Mansouri, Mehdi Touat, François Ducray, Caroline Dehais, Angelo Dipasquale, Matteo Simonelli, David M DeStephano, Jack Grinband, James B Yu, Henry Walch, Mitchell I Parker, Igor Shuryak, Soumyajit Roy, Shawn L Hervey-Jumper, Matthew Gallitto, David P Horowitz, Guy M McKhann, Michael B Sisti, Jeffrey N Bruce, Peter Canoll, Quinn T Ostrom, Alfred I Neugut, Luke R G Pike, Fabio M Iwamoto, Simon K Cheng, Lisa A Kachnic, Minesh P Mehta, Tony J C Wang","doi":"10.1200/JCO-25-01846","DOIUrl":"10.1200/JCO-25-01846","url":null,"abstract":"<p><strong>Purpose: </strong>Age ≥40 years is regarded as a high-risk feature and an indication for adjuvant chemoradiotherapy for patients with lower-grade glioma in clinical practice guidelines. It is unclear whether age remains a relevant prognostic factor for contemporary definitions of lower-grade gliomas in the molecular era.</p><p><strong>Methods: </strong>The Prospective Gliomas Research (PROGRES) database contains individual patient-level data from 11 prospective clinical trials or observational registries of histologically defined lower-grade 2-3 oligodendroglioma or astrocytoma. We determined the association of age (18-39 years <i>v</i> ≥40 years) with progression-free survival (PFS) stratified by isocitrate dehydrogenase 1 or 2 (<i>IDH1/2</i>) status, using log-rank tests and Cox regression models. We validated our findings in a separate multi-institutional retrospective cohort (Retrospective Glioma Research [REGRES] database).</p><p><strong>Results: </strong>We identified 1,619 and 1,292 eligible patients in the PROGRES and REGRES cohorts, respectively. <i>IDH</i>-wildtype tumors were more common in patients 40 years and older (38% <i>v</i> 5%, odds ratio: 11.3 [95% CI, 6.5 to 19.7]). Age was associated with PFS in <i>IDH</i>-wildtype (5-year PFS for ≥40 <i>v</i> 18-39 years: 6% <i>v</i> 24%, hazard ratio [HR], 1.74 [95% CI, 1.21 to 2.50]) but not in <i>IDH</i>-mutant glioma (60% <i>v</i> 59%, HR, 0.89 [95% CI, 0.76 to 1.05], <i>P</i>_interaction < .001). In <i>IDH</i>-wildtype tumors, older age predicted aggressive molecular features, including <i>TERT</i> promoter mutation (65% <i>v</i> 28%), <i>EGFR</i> amplification (41% <i>v</i> 15%), and chromosome +7/-10 alteration (57% <i>v</i> 25%). In a pooled analysis of four clinical trials, age was not predictive of a benefit from chemoradiotherapy versus radiotherapy alone for <i>IDH</i>-mutant glioma.</p><p><strong>Conclusion: </strong>In the absence of additional clinical or molecular risk factors, age alone should not be considered an indication for administration or deferral of adjuvant treatment. Practice guidelines should be revised to reflect contemporary prognostic factors in the molecular era.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2811-2823"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722978","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":"Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Disease: Primary Aggregated Analysis of All Baskets from the Phase II Randomized EXTEND Trial.","authors":"Alexander D Sherry, Cara Haymaker, Shuqi Wang, Suyu Liu, Tharakeswara K Bathala, Marina N Medina-Rosales, Aaron Seo, Kieko Hara, Jay Reddy, Stephen G Chun, Lauren L Mayo, Gary Walker, Shubham Pant, Dan Zhao, Craig A Kovitz, David Ramirez, Chul S Ha, Benjamin D Smith, Daniel Gomez, Lorenzo Cohen, Albert C Koong, Alexandre Reuben, Nizar Tannir, Paul G Corn, Phuoc T Tran, Bilal A Siddiqui, Sumit K Subudhi, Pavlos Msaouel, Ethan B Ludmir, Chad Tang","doi":"10.1200/JCO-25-02856","DOIUrl":"10.1200/JCO-25-02856","url":null,"abstract":"<p><strong>Purpose: </strong>We tested the hypothesis that adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy improves progression-free survival (PFS) among patients with oligometastatic disease.</p><p><strong>Methods: </strong>EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomly assigned to MDT + SOC versus SOC in one of the six baskets (breast, pancreas, kidney, two prostate baskets, and an other basket) with basket-specific stratification and powering. PFS, the primary end point, was prespecified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets. Exploratory end points included circulating tumor DNA (ctDNA) and immune profiling.</p><p><strong>Results: </strong>From 2018 through 2023, 521 patients were screened, 350 were randomly assigned, and 334 were analyzed per protocol (MDT + SOC, n = 166; SOC, n = 168). Radiotherapy was used as MDT for 98% of metastases (370/379). Overall, after a median follow-up of 53 months, PFS was improved with MDT + SOC (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72], <i>P</i> < .001). Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60 [95% CI, 0.40 to 0.89]). Within each basket, PFS superiority was identified for the pancreas, prostate, and other baskets, whereas the breast and kidney baskets were inconclusive. At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3 months postenrollment correlated with improved survival. MDT + SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority.</p><p><strong>Conclusion: </strong>The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease. Histology-specific efficacy signals were identified for phase III testing. Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA and point to systemic immune responses as a possible mechanism of benefit from MDT.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2787-2799"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the Gap: Mounting Evidence for Metastasis-Directed Therapy in Oligometastatic Disease.","authors":"Anna W LaVigne, Jennifer Lee","doi":"10.1200/JCO-26-01339","DOIUrl":"10.1200/JCO-26-01339","url":null,"abstract":"","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2768-2772"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880668","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":"COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer.","authors":"Caio Max Sao Pedro Rocha Lima, Greg Yothers, Thomas J George, Howard S Hochster, Hanna K Sanoff, Deirdre J Cohen, Katherine A Guthrie, Samuel A Jacobs, Anwaar Saeed, Scott Kopetz, Linda H Colangelo, Tanner J Freeman, Scott W Cole, Maged Khalil, Swapna Devanna, Dan S Zuckerman, Theodore S Hong, N Lynn Henry, Patricia A Ganz, Charles D Blanke, Norman Wolmark, Michael J Overman","doi":"10.1200/JCO-25-03052","DOIUrl":"10.1200/JCO-25-03052","url":null,"abstract":"<p><strong>Purpose: </strong>Immunotherapy for frontline mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective; however, nearly half of the patients treated with single-agent PD-1 therapy will progress within 12 months. Preclinical studies in CRC and clinical data from other cancers suggest that vascular endothelial growth factor inhibition and chemotherapy can synergize with PD-L1 inhibition.</p><p><strong>Methods: </strong>The NRG-GI004/SWOG-S1610 (COMMIT) three-arm prospective phase III open-label trial randomly assigned first-line dMMR/MSI-H mCRC patients (1:1:1) to either: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m², and 46-hour infusional 5-FU 2,400 mg/m²)/bevacizumab (FFX/bev), or atezolizumab (atezo) monotherapy (840 mg IV once every 2 weeks), or the combination of FFX/bev/atezo. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Because of KEYNOTE 177 results, the FFX/bev arm was closed after 20 patients were enrolled. The study continued with atezo alone versus FFX/bev/atezo, with a revised sample size of 100 patients in the two remaining arms (120 patients across all three arms).</p><p><strong>Results: </strong>From November 2017 to March 2025, a total of 102 patients were enrolled in the three arms: FFX/bev: n = 20, atezo: n = 41, and FFX/bev/atezo: n = 41. At a median follow-up of 46 months for the two arms (median age: 63.3 years; 47.6% female; 23.2% <i>BRAF V600E</i> mutated), PFS of FFX/bev/atezo was superior to that of atezo (hazard ratio [HR], 0.439 [95% CI, 0.23 to 0.84]; <i>P</i> = .0103) and below the critical value of 0.0152. The objective response rate was 86.1% versus 46%, and the disease control rate at 12 months was 64.7% versus 32.4% in the FFX/bev/atezo arm compared with the atezo-only arm, respectively. Grade 3 or higher adverse events of any attribution occurred in 52 patients (atezo: 18; combination arm: 34).</p><p><strong>Conclusion: </strong>The combination of FFX/bev plus atezo led to significantly longer PFS compared with atezo monotherapy in the first-line treatment of dMMR/MSI-H mCRC.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"2824-2834"},"PeriodicalIF":44.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}