JCO precision oncology最新文献

{"title":"Pemigatinib in the Treatment of Metastatic, Inflammatory Triple-Negative Breast Cancer With <i>FGFR2</i> Rearrangement: A Case Report and Review of the Literature.","authors":"Nihaal Reddy, Katarina Vasiljevic, Rebecca Shatsky","doi":"10.1200/PO-25-00628","DOIUrl":"10.1200/PO-25-00628","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2500628"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722239","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":"Multiomic Characterization of a Rare Case of Pediatric Acute Leukemia With a Novel <i>ANGPT1::HOXA10-AS</i> Fusion.","authors":"Haley Newman, Derek Wong, Jeffrey Schubert, Jinhua Wu, Juan Santana, Ariel Long, Zirui Zhou, Feng Xu, Jiani Chen, Moe Takeda, Lisa Eidenschink Brodersen, Kathrin M Bernt, Minjie Luo, Sarah K Tasian, Marilyn M Li, Yiming Zhong","doi":"10.1200/PO-26-00409","DOIUrl":"https://doi.org/10.1200/PO-26-00409","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600409"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874103","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":"Beyond the <i>P</i> Value: A Systematic Framework for Interpreting Oncology Clinical Trials.","authors":"Ruyue Li, Xue Dong, Xiujing Yao, Wenjie Chen, Hao An, Yintao Li","doi":"10.1200/PO-26-00271","DOIUrl":"10.1200/PO-26-00271","url":null,"abstract":"<p><p>In oncology, interpreting clinical trials solely through statistical significance (<i>P</i> < .05) often conflates true biological futility with methodological false negatives. This binary oversimplification risks prematurely abandoning active therapies while wasting resources on futile programs. We aimed to develop a structured framework to evaluate late-phase trials beyond simple <i>P</i> value assessments. Through a critical review of literature and landmark late-phase oncology trials, we analyzed common failure mechanisms and methodological pitfalls to construct a comprehensive, three-step methodology for the post hoc evaluation of negative studies. The review yielded a synthesized framework that approaches trial interpretation through three sequential steps. First, classification stratifies trials into five distinct categories: true negatives, false negatives, inconclusive trials, positive but irrelevant results, and nonsuperior but clinically valuable. Second, diagnosis uses root-cause analysis to identify underlying trial design flaws, execution biases, or statistical pitfalls. Third, recommendations outline targeted actionable strategies, including trial redesign, supplementary biomarker validation, precision medicine approaches, or scientific confirmation of therapeutic futility. This framework shifts trial interpretation from a simple win/loss assessment to a nuanced, value-based strategy. By systematically dissecting the root causes of trial failures, it empowers researchers to rescue therapies with latent clinical benefit or confidently confirm futility, thereby optimizing the evidence landscape for precision oncology.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600271"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13496032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760529","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":"Molecular Response Assessment From Circulating Tumor DNA in Patients With Ovarian Cancer Treated With the WEE1 Inhibitor Azenosertib.","authors":"Jinkil Jeong, Jianhui Ma, Mona Abed, Heekyung Chung, Doris Kim, Nandini Molden, Divya Rajendran, Changhwan Shim, Danielle D Jandial, Fiona Simpkins, Funda Meric-Bernstam, Leslie M Randall, Mark R Lackner, Olivier Harismendy","doi":"10.1200/PO-25-00844","DOIUrl":"10.1200/PO-25-00844","url":null,"abstract":"<p><strong>Purpose: </strong>Molecular response (MR) based on circulating tumor DNA (ctDNA) is emerging as a promising early biomarker of treatment efficacy in solid tumors; however, its clinical utility in high-grade serous ovarian cancer (HGSOC) remains to be established. This study evaluates the potential predictive value of ctDNA-based MR in with patients HGSOC treated with the WEE1 inhibitor azenosertib.</p><p><strong>Methods: </strong>Plasma cell-free DNA was collected at baseline and after the first and/or second cycle of treatment from 123 patients with recurrent HGSOC enrolled in clinical trials of azenosertib (N = 123). Using the set samples evaluable by high throughput DNA sequencing, MR was defined as a reduction of <i>TP53</i> variant allelic fraction >50% at the earliest evaluable on-treatment time point. MR was compared with radiographic response per Response Evaluation Criteria in Solid Tumors v1.1, time to progression (TTP), and CA-125 dynamics.</p><p><strong>Results: </strong>Molecular responders showed a higher objective response rate (<i>P</i> = .012, odds ratio = 0.26), greater tumor shrinkage (<i>P</i> = 5.1e-5, Kruskal-Wallis), and a significantly longer TTP than nonresponders (TTP median 5.49 months <i>v</i> 2.69 months, <i>P</i> = 3.8e-5, hazard ratios [HR] = 0.43). MR was able to identify patients with prolonged survival among those having stable disease at the first radiographic assessment (<i>P</i> = 3.8e-3, HR = 0.44), and their MR preceded the best overall response by several weeks. Accounting for matching collection time points, MR was evaluable in more patients than CA-125, 88% (102 of 116) versus 71% (85 of 116), respectively, leading to similar predictive value (HR = 0.41 <i>v</i> 0.45, TTP evaluation).</p><p><strong>Conclusion: </strong>Our findings support the validity and potential clinical utility of ctDNA-based MR as a minimally invasive, rapid, and reliable early surrogate end point in HGSOC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2500844"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828059","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":"Establishing a Multicenter Personalized Medicine Program in Childhood, Adolescent, and Young Adult Cancer in Spain: The SEHOP-PENCIL Project.","authors":"Andrea Vilaplana, Asbleidy Carolina Torres, Adela Escudero López, Elisa Izquierdo, Sergio Manresa-Vera, Josep Escrivá-Fernández, Piedad Alba-Pavón, Lide Alaña, Angela Gutierrez-Camino, Carlos Rodríguez-Antolín, Clara Venegas Mascaró, Sonia Paco Mercader, Noelia Salvador, Ana Chamorro-Vera, Teresa Imízcoz, Elena Panizo Morgado, Beatriz Vergara-Muñoz, Antonio Juan-Ribelles, Nuria Benavent, Alicia Castañeda Heredia, Carlota Rovira Zurriaga, Lorena Valero-Arrese, Raquel Díaz-Merchán, Irene Manzano-Benito, Saint T Cervera, Laura García-Calvo, Irene Jiménez, Nerea Domínguez-Pinilla, Cristina Nova-Lozano, Isabel Cuadrado-Torroglosa, Jesús Sánchez-Ruiz, Tamara Mondejar, Antonio Pérez-Martínez, Ana Fernández-Teijeiro, Palma Solano-Páez, Josep Roma, Jaime Font de Mora, Bárbara Meléndez, Alba Rubio-San-Simón, Cristina Saiz-Ladera, Itziar Astigarraga, Adela Cañete, Javier Alonso, Cinzia Lavarino, Ana Patiño-García, Lucas Moreno, Aroa Soriano","doi":"10.1200/PO-26-00074","DOIUrl":"https://doi.org/10.1200/PO-26-00074","url":null,"abstract":"<p><p>Pediatric cancer care in Spain lacked a national personalized medicine program. The SEHOP-PENCIL initiative, established by the SEHOP, was designed to address this gap. A national survey identified the genomic sequencing needs of hospitals treating pediatric patients with cancer. Results showed improved access to targeted next-generation sequencing panels but revealed persistent variability in implementation, limited availability of advanced sequencing (whole-exome sequencing, whole-genome sequencing, RNA sequencing, and DNA methylation profiling), and gaps in cancer predisposition clinics and molecular tumor boards (MTBs). SEHOP-PENCIL is organized as a network of 10 specialized genomic centers serving 45 hospitals through a centralized inclusion system. The program standardizes patient eligibility, genomic workflows, and result interpretation, supported by a national MTB. This framework enables informed clinical decision making, ensures access to molecular diagnosis and innovative therapies, and supports systematic data collection to advance pediatric cancer research and personalized care. SEHOP-PENCIL represents a pioneering national model for integrating precision oncology into pediatric cancer care in Spain. By fostering collaboration, standardizing genomic practices, and promoting equitable access, it aims to reduce disparities and improve outcomes, offering a scalable example for other decentralized health care systems.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600074"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874058","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":"Age-Specific Ovarian Cancer Risk Among Individuals With Pathogenic Variants in <i>PALB2</i>.","authors":"Koki Takabatake, Nicolas Kubista, Maria Sol Rosito, Yue Zhang, Stephen B Gruber, Gregory Idos, Giovanni Parmigiani, Danielle Braun","doi":"10.1200/PO-26-00167","DOIUrl":"https://doi.org/10.1200/PO-26-00167","url":null,"abstract":"<p><strong>Purpose: </strong>Pathogenic germline variants (PGVs) in <i>PALB2</i> are well-established risk factors for breast cancer, but their association with ovarian cancer (OC) remains less characterized. This study estimates age-specific OC risk among <i>PALB2</i> PGV carriers using a Bayesian segregation analysis approach.</p><p><strong>Methods: </strong>Family history, including OC diagnoses, was collected from probands with PGVs in <i>PALB2</i> from the Clinical Cancer Genomics Cancer Research Network (CCGCRN). CCGCRN is a consortium of 31 active community-based oncogenetic practices across 50 states in the United States and four countries in Latin America. A total of 140 probands with PGVs in <i>PALB2</i> were identified in CCGCRN, and family history was reported on 5,188 relatives (average family size is 38 individuals). Overall, 30 women had OC; of these, 5 cases were among probands and the remaining were among reported relatives. Age-specific penetrance of OC was estimated using the <i>penetrance</i> R package that employs a parametric Bayesian segregation analysis estimation approach, leveraging the family history.</p><p><strong>Results: </strong>The cumulative lifetime risk for OC for female carriers of <i>PALB2</i> PGVs at age 80 years was estimated to be 5.38% (95% CI [2.94 to 8.26]). This is significantly greater than the general population risk of 1.10% from the SEER data.</p><p><strong>Conclusion: </strong>We estimated a significantly increased risk of OC among individuals with <i>PALB2</i> PGVs compared with the SEER general population. However, our estimated credible interval was wide, likely because of the small sample number of probands and small number of OC cases. Further studies should continue to explore the association between PGVs in <i>PALB2</i> and OC risk.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2600167"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828879","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":"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":"https://doi.org/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":"","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":"","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":"https://doi.org/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":"","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":"","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}