JCO precision oncology最新文献

{"title":"Sequencing of Fibroblast Growth Factor Receptor Inhibitors in Cholangiocarcinoma: A Review of Published Cases.","authors":"Daniel Dilg, Mike Blecker, Ana Vivancos, Teresa Macarulla, Arndt Vogel","doi":"10.1200/PO-25-01099","DOIUrl":"10.1200/PO-25-01099","url":null,"abstract":"<p><p>Cholangiocarcinomas (CCAs) are aggressive biliary tumors that can develop within the intrahepatic (iCCA) or perihilar and distal bile ducts. The prognosis of patients with iCCA is poor due to its relative resistance to chemotherapy. Comprehensive genomic profiling of CCA biopsies by next-generation sequencing has revealed a rich landscape of genomic alterations, including fibroblast growth factor receptor (FGFR) gene fusions and rearrangements that are constitutively active and oncogenic. Several FGFR inhibitors (FGFRis) targeting these <i>FGFR</i> genomic alterations have been developed as potential treatments for iCCA, each of which are highly potent but differ in structure, mechanism of inhibition (ie, adenosine triphosphate-competitive reversible <i>v</i> covalent/irreversible <i>v</i> allosteric), pharmacologic/pharmacodynamic profiles, and selectivity for the four FGFR isoforms. Because of these differences, and due to resistance mutations acquired during FGFRi treatment, determining the optimal sequencing of FGFRis for the treatment of CCA remains contentious and is the subject of ongoing debate. To address this question, this review conducted an analysis of the literature on the FGFRi currently approved or in development, focusing on their distinct mechanisms of action and FGFR selectivity. Publicly available data from case reports on FGFRi sequencing in second and later lines of treatment were compiled from a PubMed search of published congress abstracts and articles. The results support a hypothesis that strategic sequencing of reversible followed by irreversible FGFRi may potentially prolong the duration of treatment benefit from FGFR inhibition compared with nonsequenced treatments. A hypothetical treatment-sequencing algorithm for reversible and irreversible FGFRi is discussed.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2501099"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Prognostic Impact of IDH Mutations in Intrahepatic Cholangiocarcinoma.","authors":"Rachel N Harvey, Rebecca Gelfer, Esther Drill, Vinod Balachandran, Michael D'Angelica, Jeffrey Drebin, T Peter Kingham, Lily Saadat, Kevin Soares, Alice C Wei, Ghassan K Abou-Alfa, Andrea Cercek, James J Harding, Eileen M O'Reilly, Michail Doukas, Marjolein Y V Homs, Bas Groot Koerkamp, William R Jarnagin","doi":"10.1200/PO-25-01261","DOIUrl":"10.1200/PO-25-01261","url":null,"abstract":"<p><strong>Purpose: </strong>Isocitrate dehydrogenase 1 and 2 (<i>IDH1</i> and <i>IDH2</i>) mutations are common in intrahepatic cholangiocarcinoma (ICC), but their prognostic value is unclear. Using a large data set, we assessed their impact in resected and nonresected ICC.</p><p><strong>Methods: </strong>Adults from two medical centers (MSKCC and Erasmus) with ICC treated with curative-intent resection (resected) or managed nonoperatively (unresectable) who underwent next-generation sequencing were analyzed retrospectively. Kaplan-Meier and Cox regressions assessed the impact of IDH status on outcomes.</p><p><strong>Results: </strong>Of the 795 patients analyzed, 25% had <i>IDH1/2</i> mutations (<i>IDH</i>mut) and 43% underwent resection. Median overall survival (OS) of the cohort was 32 months in <i>IDH</i>mut and 28 months for <i>IDH</i>wt (<i>P</i> = .2). High-risk genetic alterations (<i>TP53</i>mut, <i>KRAS</i>mut, and <i>CDKN2A</i>del) were more frequent in <i>IDH</i> wild-type (<i>IDH</i>wt; odds ratio, 2.26; q < 0.001). OS was 19 months in patients with high-risk alterations versus 40 months in patients without (<i>P</i> < .001). In resected patients, recurrence-free survival (RFS) in <i>IDH</i>mut was 20 months versus 14 months for <i>IDH</i>wt (<i>P</i> = .018), and OS was 69 months versus 50 months, respectively (<i>P</i> = .2). However, after controlling for high-risk alterations, the potential benefit of <i>IDH</i>mut was no longer apparent (RFS: hazard ratio [HR], 0.78; <i>P</i> = .095; OS: HR, 0.88; <i>P</i> = .4). In unresectable <i>IDH</i>mut patients, progression-free survival was 9.4 months versus 9.1 months for <i>IDH</i>wt (<i>P</i> = .7), and OS was 22 months versus 18 months, respectively (<i>P</i> = .13). There remained no differences after controlling for high-risk alterations. <i>IDH</i> status was not a significant survival predictor in multivariable models.</p><p><strong>Conclusion: </strong>In this cohort of patients with ICC, <i>IDH</i>mut was not an independent predictor of survival, after controlling for high-risk alterations and clinical variables. <i>IDH</i> mutational status alone should, therefore, not be used to guide prognosis.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2501261"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge and Attitudes on Germline Pharmacogenomic Testing Among Clinical Oncologists.","authors":"Mattie Monroe, Hetanshi Naik, James M Ford, Michelle Whirl-Carrillo, Teri E Klein, Daniel L Hertz, Stuart A Scott","doi":"10.1200/PO-26-00353","DOIUrl":"https://doi.org/10.1200/PO-26-00353","url":null,"abstract":"<p><strong>Purpose: </strong>Despite increasing evidence supporting the validity and utility of pharmacogenomic (PGx)-guided prescribing, clinical PGx testing in oncology remains limited. However, expanding professional guidelines and recommendations have accelerated PGx implementation efforts in the United States. Given the availability of actionable PGx guidelines for several medications commonly prescribed to patients with cancer, this study evaluated US oncologists' knowledge, attitudes, and perceived barriers regarding PGx-guided medication management.</p><p><strong>Methods: </strong>A survey focused on oncology-relevant medications with actionable PGx guidelines, including fluoropyrimidines, thiopurines, irinotecan, and opiates/antidepressants, was distributed to clinical oncologists in the United States from December 2023 to August 2024 through ASCO Research Survey Pool, the Association of Northern California Oncologists, and regional ASCO-affiliated groups.</p><p><strong>Results: </strong>A total of 146 providers completed the survey, most through ASCO (n = 125). Opiates and antidepressants were the most frequently prescribed medications in the previous 6 months (92%), followed by fluoropyrimidines (75%). Nearly all respondents (93%) had heard of PGx, although most were only moderately familiar (57%), and PGx awareness for chemotherapies (92%) was much greater than opiates/antidepressants (47%). Reported barriers to PGx testing for chemotherapy management included uncertain utility, concerns for treatment delay, and unclear National Comprehensive Cancer Network recommendations, and barriers for opiate/antidepressant management included uncertain utility, lack of awareness, and uncertainty regarding test ordering and result interpretation.</p><p><strong>Conclusion: </strong>These findings provide valuable insights into the perspectives of oncologists on implementing PGx testing; however, awareness and utilization were higher than previously reported. Importantly, the identified implementation barriers for oncology are both actionable and timely, particularly given the evolving updates to drug labels and professional guidelines supporting PGx testing for medications relevant to patients with cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600353"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence for Oncology Patients With Rare <i>NTRK</i> Gene Fusions: Final Results From the German Multicenter Patient Cohort Study REALTRK.","authors":"Karin Potthoff, Sebastian Lange, Thomas Seufferlein, Kathrin Heinrich, Rainer Claus, Annalen Bleckmann, Matthias Zaiss, Corinne Vannier, Sina Grebhardt, Sophie Koszinowski, Larissa E Hillebrand, Kai Ringwald, Benjamin Kasenda","doi":"10.1200/PO-26-00283","DOIUrl":"10.1200/PO-26-00283","url":null,"abstract":"<p><strong>Purpose: </strong>TRK inhibitors (TRKis) have transformed the therapeutic landscape for patients with neurotrophic tyrosine receptor kinase (<i>NTRK</i>) gene fusion-positive tumors. However, approval of TRKis is based on evidence derived mainly from small, pooled, single-arm clinical trial cohorts. The REALTRK registry aims to describe real-world molecular diagnostic practices, treatment patterns, and clinical outcomes for adult patients with <i>NTRK</i> fusion-positive cancers.</p><p><strong>Patients and methods: </strong>The REALTRK registry was a multicenter cohort study that included adults with advanced solid tumors harboring <i>NTRK1</i>/<i>2</i>/<i>3</i> fusions, from Germany and Switzerland. Both retrospective and prospective data were collected from diverse clinical settings. <i>NTRK</i> fusions had to be diagnosed via validated assays.</p><p><strong>Results: </strong>Of 88 patients screened, 47 adults with advanced <i>NTRK</i> fusion-positive solid tumors were included in the full analysis set. Across all treatment lines after <i>NTRK</i> fusion diagnosis, 29 patients received TRKi therapy, eight received non-TRKi therapy, and 10 received no therapy. Lung cancer, colorectal cancer, and soft tissue sarcoma were the most common tumor types. Next-generation sequencing was the primary diagnostic method, with a median turnaround time of 2 weeks. After <i>NTRK</i> fusion diagnosis, TRKi therapy was immediately initiated in 26 patients, of whom 13 received TRKi as first-line treatment in the advanced/metastatic setting. About half of the patients responded to TRKi treatment as the first treatment line after <i>NTRK</i> fusion diagnosis (46.2%), with an overall response rate of 46.2% and a disease control rate of 73.1%. The median progression-free survival was 15.7 months, and the overall survival was 27.6 months in TRKi-treated patients.</p><p><strong>Conclusion: </strong>The REALTRK registry provides important real-world insights into the patient path of adult patients with locally advanced or metastatic solid tumors harboring <i>NTRK1</i>/<i>2</i>/<i>3</i> gene fusions.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600283"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Methylation and Copy Number Analysis for Noninvasive Bladder Cancer Detection in Urine.","authors":"Irene J Beijert, Birgit M M Wever, Norbert Moldovan, Yara van den Burgt, Annick Nouwens, Ymke van der Pol, Anouk E Hentschel, Judith Bosschieter, Birgit Lissenberg-Witte, Paul C Kauer, R Jeroen A van Moorselaar, Florent Mouliere, Jakko A Nieuwenhuijzen, Renske D M Steenbergen","doi":"10.1200/PO-25-00882","DOIUrl":"10.1200/PO-25-00882","url":null,"abstract":"<p><strong>Purpose: </strong>The molecular analysis of urine cell-free DNA offers a noninvasive tool to advanced bladder cancer (BC) management. Assessment of somatic copy number aberration (SCNA) and DNA methylation analysis have emerged as promising approaches for BC detection. Here, we developed an integrated analysis to assess both SCNA and targeted methylation changes from the same template molecules, which we named the integrated sequencing-based copy number and methylation analysis in urine (iSECURE) method.</p><p><strong>Materials and methods: </strong>Urine samples of 30 patients with primary BC, 28 patients with recurrent BC, and 31 hematuria controls were collected at home. Copy number profiling and tumor fraction (TF) estimation were performed by shallow whole-genome enzymatic methyl sequencing. Methylation sequencing libraries were also used for the measurement of a previously validated three-gene methylation marker panel (<i>GALR1/HAND2/NRN1</i>) by the quantitative methylation-specific polymerase chain reaction. Diagnostic accuracy was evaluated by logistic regression analysis using Youden's index for sensitivity and specificity and validated using leave-one-out cross-validation (LOOCV).</p><p><strong>Results: </strong>TF and methylation levels were significantly higher in patients with BC compared with controls (<i>P</i> < .0001). The individual assays yielded an AUC of 0.91 at 79% sensitivity and 97% specificity for the methylation marker panel and 0.81 at 74% sensitivity and 87% specificity for copy number profiling. The iSECURE workflow yielded a higher diagnostic accuracy with an AUC of 0.94 at 88% sensitivity (90% for primary tumors and 86% for recurrent tumors) and 94% specificity. LOOCV demonstrated an AUC of 0.91 at 84% sensitivity and 90% specificity.</p><p><strong>Conclusion: </strong>We developed a single workflow for copy number profiling and targeted methylation analysis, requiring less input DNA and hands-on time. The high accuracy of iSECURE in home-collected urine samples for detecting both primary and recurrent BC underscores its clinical potential.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2500882"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary Renal Cell Carcinoma Bearing the Genomic Signature of Prior Temozolomide Therapy.","authors":"Ting Zhao, Alanna J Church, Stephanie E Siegmund, Igor Odintsov","doi":"10.1200/PO-26-00506","DOIUrl":"https://doi.org/10.1200/PO-26-00506","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600506"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fam-Trastuzumab Deruxtecan in Recurrent Low-Grade Serous Ovarian Carcinoma With <i>CLU/NRG1</i> Fusion and Low Human Epidermal Growth Factor Receptor 2 Expression: A Case Report.","authors":"Aimee Keegan, Er Yue, Fang Fan, Emily Engelkemier, Thanh Dellinger, Edward Wenge Wang","doi":"10.1200/PO-26-00288","DOIUrl":"https://doi.org/10.1200/PO-26-00288","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600288"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative Mutant Allele Frequency Role in ctDNA-Guided Anti-Epidermal Growth Factor Receptor Rechallenge in Metastatic Colorectal Cancer.","authors":"Jesús Yaringaño, Patricia García Pastor, Francesc Salva, Nadia Saoudi González, Javier Ros, Iosune Baraibar, Marta Rodríguez Castells, Clara Salva de Torres, Pau Mascaró Baselga, Ariadna García, Caterina Vaghi, Ana Vivancos, Josep Tabernero, Elena Elez","doi":"10.1200/PO-26-00199","DOIUrl":"10.1200/PO-26-00199","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600199"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>DPYD</i>-Guided Dosing of Metronomic Capecitabine Plus Vinorelbine in Metastatic Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: A Real-World Retrospective Study.","authors":"Francesco Schettini, Alexandro Membrino, Giuseppe Di Grazia, Aldo Caltavituro, Carla Strina, Manuela Milani, Antonina Impeduglia, Leda Paganini, Anna Bosi, Sara Tedoldi, Marta Gatti, Valeria Cervoni, Marzia Alberio, Mario Giuliano, Sergio Venturini, Daniele Generali","doi":"10.1200/PO-26-00273","DOIUrl":"10.1200/PO-26-00273","url":null,"abstract":"<p><strong>Purpose: </strong>Metronomic chemotherapy with oral capecitabine + vinorelbine (Cape + VNL) provides synergistic cytostatic activity and antiangiogenic and immunomodulatory effects, potentially offering prolonged disease control with limited toxicity in HER2-negative metastatic breast cancer (MBC). However, efficacy in the real-world (RW) setting, especially in late lines, and the impact of dihydropyrimidine dehydrogenase (<i>DPYD</i>) polymorphisms on dose reduction and safety remain limited.</p><p><strong>Methods: </strong>In this retrospective study, 200 patients with human epidermal growth factor receptor 2 (HER2)-negative MBC were treated at the ASST Cremona Hospital (2015-2023) with metronomic Cape (1000 mg twice daily, in normal metabolizers; 500 mg twice daily, in <i>DPYD</i> variant carriers) + VNL (20 mg/day, once daily, 5-days-on/2-days-off). All patients underwent pretreatment <i>DPYD</i> genotyping and dose adjustment. Treatment was administered in the second-to-fourth setting. The primary end point was time-to-next treatment or death (TNTD); secondary end points included overall survival (OS), disease control rate (DCR) ≥24 weeks, overall response rate (ORR), safety, and genotype-toxicity correlations.</p><p><strong>Results: </strong>The median age was 61 years, and <i>DPYD</i> variants were present in 14.5% of patients; 34%, 41%, and 25% received therapy as second-, third-, and fourth-line treatment. The median TNTD was 22.0 weeks, and the OS was 64.0 weeks. The DCR was 38.5%, and the ORR was 22.0%. Efficacy was comparable between <i>DPYD</i> variant carriers and normal metabolizers (all <i>P</i> values > .05). In later lines, Eastern Cooperative Oncology Group performance status 2 and >2 metastatic sites were independent negative prognostic factors (all values <i>P</i> < .05). Overall, 7.5% grade 3 toxicities occurred, especially in variant carriers without dose reduction and grade 4-5 events.</p><p><strong>Conclusion: </strong>These RW data suggest that metronomic Cape + VNL may represent a clinically active and manageable option in heavily pretreated HER2-negative MBC. Our findings support prospective evaluation of <i>DPYD</i>-guided dose individualization as a strategy to optimize the benefit-risk balance of fluoropyrimidine-based metronomic regimens.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600273"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Age With Tumor Genomic Characteristics in Relapsed/Refractory Cancers Interrogated With the NCI-MATCH Trial Targeted Gene Panel Assay.","authors":"Hari Sankaran, Yuri Kotliarov, Yingdong Zhao, Lyndsay N Harris, James V Tricoli, Stanley R Hamilton, Sarah M Temkin, Chris Karlovich, Ting-Chia Chang, Victoria Wang, Robert J Gray, Zihan Wei, Sarah J Shin, Nita L Seibel, Biswajit Das, Brent Coffey, David Patton, Ming-Chung Li, Jessica Li, Ana F Best, P Mickey Williams, A John Iafrate, Jeffrey Sklar, Keith T Flaherty, Alice P Chen, Peter J O'Dwyer, Lisa M McShane","doi":"10.1200/PO-25-01183","DOIUrl":"10.1200/PO-25-01183","url":null,"abstract":"<p><strong>Purpose: </strong>Motivated by the rising incidence of cancers at younger ages, this study compares tumor genomic alterations between adolescents and young adults (AYAs; 18-39 years) and non-AYAs (40 years and older) and explores the relationship with continuous age in patients with relapsed/refractory ovarian, breast, and colorectal cancers accrued to the NCI-MATCH trial.</p><p><strong>Methods: </strong>Tumor genomic profiles generated by a next-generation sequencing 143-gene panel (NCI-MATCH assay, v2) were analyzed for association with age (AYA/total: 21/455 ovarian, 27/576 breast, 43/759 colorectal cancers). For each gene, AYA and non-AYA DNA alteration proportions were compared (Fisher exact test) and alteration association with continuous age (logistic regression) was evaluated (false discovery rate‑adjusted <i>P</i> value <.1 statistically significant). For colorectal cancer, sex-stratified analysis was also performed.</p><p><strong>Results: </strong>No significant AYA versus non-AYA differences were observed in the prevalence of gene mutations (single nucleotide variant [SNV]/indel). A significant association of gene amplification with AYAs (odds ratio [OR], 95% CI) was <i>CCND1</i> (0.2, 0.1-0.4), favoring AYAs in breast cancer. Examining age as a continuous variable, significant associations of gene mutations (SNV/indel) with older age, expressed as 5-year OR (OR [95% CI]), were observed: <i>TP53</i> (1.3 [1.1 to 1.4]), ovarian cancer; <i>CDH1</i> (1.4 [1.2 to 1.6]) and <i>PIK3CA</i> (1.1 [1.1 to 1.2]), breast cancer; and <i>BRAF</i> (1.4 [1.2 to 1.7]), female colorectal cancer. Associations with younger age included <i>SMAD4</i> (0.8 [0.7 to 0.9]), male colorectal cancer. Significant associations of gene amplification with age (continuous) were as follows: <i>CCNE1</i> (1.3 [1.1 to 1.6]), older ovarian cancer, and <i>CCND1</i> (0.8 [0.8 to 0.9]), younger breast cancer.</p><p><strong>Conclusion: </strong>Comparing AYAs with non-AYAs among patients having relapsed/refractory disease, no significant differences in SNV/indel prevalence were observed, but <i>CCND1</i> amplifications were more prevalent in AYA breast cancer. For several genes, DNA alterations were associated with continuous age and may depend on sex in colorectal cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2501183"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}