JCO precision oncology最新文献

{"title":"Cell-Free DNA Analysis With Clinicopathologic Factors for Early Detection and Refining Lymph Node Metastasis Risk in T1 Colorectal Cancer: Results From the COSMOS-CRC Study.","authors":"Tatsuro Murano, Hiroaki Ikematsu, Nobuhisa Matsuhashi, Yuichiro Tsukada, Manabu Shiozawa, Takeshi Kato, Eiji Oki, Toshifumi Yamaguchi, Yoshinori Kagawa, Akiyoshi Kanazawa, Takashi Ohta, Akira Ouchi, Hiroshi Uchigata, Chiemi Notake, Elmira Forouzmand, Yupeng He, Victoria M Raymond, Sven Duenwald, Hideaki Bando, Takayuki Yoshino, Yoshiaki Nakamura","doi":"10.1200/PO-25-00941","DOIUrl":"10.1200/PO-25-00941","url":null,"abstract":"<p><strong>Purpose: </strong>The Shield test is a blood-based assay that uses multimodal analysis of cell-free DNA (cfDNA) to enable noninvasive colorectal cancer (CRC) detection. The aim of this study was to assess the diagnostic performance of the cfDNA test for CRC and advanced precancerous lesions (APLs) and evaluate its potential clinical utility, particularly in early-stage disease.</p><p><strong>Methods: </strong>In this prospective, multicenter study, 451 patients with histologically confirmed CRC or APLs were enrolled across eight institutions. Blood samples collected before treatment were analyzed using the cfDNA test (Shield, Guardant Health, United States). We assessed the sensitivity of the test for different CRC stages and APLs. In addition, we examined the correlation between test positivity and clinicopathologic factors in stage I and T1 CRC.</p><p><strong>Results: </strong>The test showed 87.9% sensitivity for CRC overall, with stage-specific sensitivities of 71.2% for stage I and 97.4% for stages II-IV. Sensitivity for APLs was 37.0%. In stage I CRC, test positivity was significantly associated with tumor depth (T2: 88.6% <i>v</i> T1: 59.7%, <i>P</i> < .01). Among 70 patients with T1 CRC, the test detected all to have lymph node metastasis (LNM; 100% sensitivity). Compared with guideline-based pathologic criteria, the cfDNA test achieved higher specificity for LNM prediction (38.7% <i>v</i> 11.3%), thereby potentially reducing the frequency of unnecessary radical surgery from 78.6% to 54.3%.</p><p><strong>Conclusion: </strong>This cfDNA blood-based test shows a robust diagnostic performance in CRC detection. It may improve risk stratification and support more tailored clinical decision making, particularly in the management of T1 CRC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2500941"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368289","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":"Perspectives From an Expert-Guided Discussion on Maximizing the Research Potential of Small Biopsy Tissue.","authors":"Lokesh Agrawal, P Mickey Williams, Helen M Moore, Kelly B Engel, Sarah R Greytak, Alda L Tam, J Keith Killian, Daniel T Merrick, Ralph E Parchment, Stanley R Hamilton, Lyndsay N Harris, James H Doroshow","doi":"10.1200/PO-25-01152","DOIUrl":"10.1200/PO-25-01152","url":null,"abstract":"<p><strong>Purpose: </strong>Tissue biopsy specimens, both remnant diagnostic specimens and those collected for ancillary study, are an invaluable resource for clinical oncology research. However, using biopsy specimens for molecular research is associated with innate challenges, such as insufficient tissue and/or tumor content, and low nucleic acid yields as well as analyte degradation due to suboptimal preanalytical workflows.</p><p><strong>Methods: </strong>The National Cancer Institute's Biorepositories and Biospecimen Research Branch convened a meeting that included expert-guided discussions that centered on strategies to mitigate these challenges and their effects on molecular analysis.</p><p><strong>Results: </strong>Participants, who included medical oncologists, interventional radiologists, pathologists, and molecular biologists, offered best practice guidance on biopsy collection, preservation, storage, and extraction techniques. Their recommendations were largely based on the optimized workflows that were implemented at their respective institutions, which improved the likelihood of producing reproducible molecular data. Pre- and postcollection techniques, such as clear cross-team communication, prebiopsy scoring based on lesion- and patient-specific criteria, biopsy collection and handling practices, and tumor enrichment options, were also discussed.</p><p><strong>Conclusion: </strong>The proceedings revealed that increasing awareness of the challenges associated with research use of tissue biopsies is key to developing assay-specific strategies that ensure sufficient tumor specimens are available for molecular oncology research. The lessons shared here from large-scale and multicenter trials will, ideally, inform the design of new cancer research studies, thereby harnessing the full potential of valuable clinical biopsy specimens.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501152"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368429","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":"Revised Thyroid Differentiation Score for Risk Stratification in Papillary Thyroid Carcinoma.","authors":"Vicente R Marczyk, Chia Chin Wu, Sarah Hamidi, Sophie Li, Matthew A Loberg, Meghan Martin, Michelle D Williams, Sayed Mohsen Hosseini, Steven Waguespack, Mimi Hu, Steven I Sherman, Ying Henderson, Stephen Lai, Yaoyi Dai, Wenyi Wang, Anastasios Maniakas, Mark Zafereo, Quanhu Sheng, George J Xu, Eric C Huang, Vivian L Weiss, Maria Cabanillas, Jennifer R Wang","doi":"10.1200/PO-26-00207","DOIUrl":"https://doi.org/10.1200/PO-26-00207","url":null,"abstract":"<p><strong>Purpose: </strong>Loss of thyroid differentiation underlies the aggressive behavior of a subset of papillary thyroid carcinomas (PTCs). The Thyroid Differentiation Score (TDS), introduced by The Cancer Genome Atlas (TCGA), quantifies tumor differentiation but has limited reproducibility and clinical applicability. We developed and validated a revised score (xTDS) that enables reproducible assessment of tumor differentiation with prognostic relevance across cohorts.</p><p><strong>Methods: </strong>We analyzed RNA sequencing data from 570 patients with PTC across three independent cohorts: a discovery cohort from the MD Anderson Cancer Center (n = 111) and two external validation cohorts from Vanderbilt University (n = 69) and TCGA (n = 390). xTDS was evaluated for correlation with the original TDS, association with oncogenic drivers, and prognostic value for disease-specific survival (DSS) and progression-free survival (PFS).</p><p><strong>Results: </strong>xTDS showed near-perfect correlation with the original TDS (Spearman ρ = 0.98) and recapitulated known biological patterns, with <i>BRAF</i> V600E-driven tumors exhibiting the lowest differentiation scores and <i>RAS</i>-driven tumors the highest across all cohorts (<i>P</i> < .001). Low xTDS was associated with worse DSS in the MD Anderson (<i>P</i> < .001) and Vanderbilt (<i>P</i> = .005) cohorts and showed a similar numerical trend in TCGA, without statistical significance because of limited events. Low xTDS was consistently associated with worse PFS across all three cohorts (<i>P</i> = .048, <0.001, and 0.007, respectively).</p><p><strong>Conclusion: </strong>xTDS is a reproducible measure of thyroid differentiation that preserves the biological and prognostic relevance of the original TDS while overcoming technical constraints affecting reproducibility.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2600207"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578790","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":"Palbociclib in Patients With Ovarian Cancer With <i>CDKN2A</i> Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.","authors":"Dan S Veljovich, Michael Rothe, Elizabeth Garrett-Mayer, Hussein M Ali-Ahmad, R Wendel Naumann, Jean Siedel, John K Chan, Andrew Gregory, Evan Pisick, Bamidele Adesunloye, Rebecca C Arend, Maria Bell, Marina Frimer, Bernard Tawfik, Ramya Thota, Apostolia M Tsimberidou, Pam K Mangat, Dominique C Hinshaw, Abigail Gregory, Gina N Grantham, Susan Halabi, Richard L Schilsky","doi":"10.1200/PO-26-00456","DOIUrl":"10.1200/PO-26-00456","url":null,"abstract":"<p><strong>Purpose: </strong>The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations. Results of a cohort of patients with ovarian cancer (OC) with <i>CDKN2A</i> alterations treated with palbociclib are reported.</p><p><strong>Methods: </strong>Eligible patients had advanced OC, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with <i>CDKN2A</i> alterations, and no remaining standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+). Simon two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety.</p><p><strong>Results: </strong>Twenty-eight patients were enrolled from February 2017 to April 2023, and all had OC with a <i>CDKN2A</i> alteration (loss [n = 21], mutation [n = 5], and loss and mutation [n = 2]). One patient was not evaluable for efficacy because of an excluded genomic finding. Three patients had a partial response and seven had SD16+ for DC and OR rates of 38% (90% CI, 25 to 100) and 11% (95% CI, 2 to 29), respectively. The null hypothesis of 15% DC rate was rejected (<i>P</i> = .004). The median PFS was 8 weeks (95% CI, 8 to 18) and the median OS was 33 weeks (95% CI, 24 to 73). Nineteen patients (68%) had at least one treatment-related grade 3-4 adverse event (AE) or serious AE including anemia, dyspnea, fatigue, leukopenia, neutropenia, and thrombocytopenia.</p><p><strong>Conclusion: </strong>Palbociclib met the prespecified criteria to declare a signal of activity in patients with OC and <i>CDKN2A</i> alterations.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2600456"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455908","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":"Pragmatic, Multicenter, Double-Blind Evaluation of Circulating Cancer-Associated Macrophage-Like Cells for Detection of Cancer in Indeterminate Pulmonary Nodules.","authors":"Martin J Edelman, Anil Vachani, Dana Marie Haagen Zambino, Eric Ross, Rohit Kumar, Alan Haber, David Dibardino, Karen Ruth, Jordan Anaokar, Maruti Kumaran, Kirby P Gardner, Cha-Mei Tang, Daniel L Adams","doi":"10.1200/PO-25-01142","DOIUrl":"10.1200/PO-25-01142","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer-associated macrophage-like cells (CAMLs) are specialized myeloid polyploid cells that emanate from primary tumor masses and transit circulation in a variety of malignancies, which have the potential to track cancer progression and therapy response. Previous studies have demonstrated that larger CAMLs (≥30 μM and ≥50 μM) are particularly associated with disease progression. We hypothesized that CAMLs could provide additional cancer risk information for patients with indeterminate lung nodules.</p><p><strong>Materials and methods: </strong>This was a double-blind, multicenter study to evaluate CAMLs in the blood as diagnostic biomarkers for malignancy. We enrolled 203 patients with indeterminate nodules (0.8-3 cm) and no diagnosis of cancer. Blood samples were obtained at the time of the initial evaluation and before diagnostic procedures; physicians were blinded to the CAML results. We determined the prevalence of CAMLs ≥30 μM (CAML+) at the initial screening and calculated screening statistics including positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of CAML+ for any malignancy detected during follow-up.</p><p><strong>Results: </strong>Of the 203 enrolled patients, 200 had their samples sent for CAML analysis. For evaluable patients (n = 191), there were 41 with non-small cell lung cancer, four with small cell lung cancer, six with carcinoid, and five with other malignancies. For eight patients, a biopsy was either nondiagnostic or not feasible; they were treated for lung cancer with radiotherapy (and counted as cancer). CAMLs were detected in 45.0% of all patient samples (95% CI, 37.8% to 52.4%). For the detection of any malignancy, CAML PPV and NPV were 27.9% and 61.9%, respectively, and sensitivity and specificity were 37.5% and 51.2%, respectively. Defining CAML+ as larger CAML size (≥50 μM) did not significantly alter the results.</p><p><strong>Conclusion: </strong>CAMLs are neither sensitive nor specific to the presence of malignancy in indeterminate pulmonary nodules.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501142"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421311","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":"Erdafitinib in Patients With Advanced Solid Tumors With <i>FGFR</i> Alterations (RAGNAR): Results of Tumor-Specific Analyses and Secondary Cohorts.","authors":"Omar Carranza, Shubham Pant, Martin Schuler, Olaf Witt, Birgit Geoerger, Yohann Loriot, Sameer Farouk Sait, Dirk Arnold, Graziela Z Dal Molin, Iwona Lugowska, Helen Winter, Capucine Baldini, Marcelo Corassa, Shibu Thomas, Lauren Crow, Yichuan Xia, Spyros Triantos, Hussein Sweiti, David A Reardon","doi":"10.1200/PO-25-01094","DOIUrl":"10.1200/PO-25-01094","url":null,"abstract":"<p><strong>Purpose: </strong>Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, is approved for second-line treatment of locally advanced or metastatic urothelial carcinoma with susceptible <i>FGFR3</i> alterations. Primary histology-agnostic analysis from the phase II RAGNAR study (ClinicalTrials.gov identifier: NCT04083976) indicated a clinical benefit with erdafitinib in Broad Panel Cohort (BPC) patients. We present tumor-specific updated efficacy and safety results from the BPC and tumor-agnostic findings from the Exploratory and Pediatric Cohorts of RAGNAR.</p><p><strong>Methods: </strong>The Broad Panel, Exploratory, and Pediatric Cohorts enrolled patients with target (selected) <i>FGFR</i> alterations, nontarget <i>FGFR</i> alterations, and any <i>FGFR</i> alterations, respectively. Adults and pediatric patients (6 years and older) with advanced, unresectable, or metastatic disease who progressed after ≥1 prior line of systemic therapy and exhausted standard therapies were eligible. Erdafitinib 3-8 mg once daily (with possible uptitration) was administered orally until disease progression or intolerable toxicity.</p><p><strong>Results: </strong>Objective response rates (ORRs) in the BPC were 10.0% (3 of 30) for high-grade glioma, 26.1% (6 of 23) for non-small cell lung cancer, 28.6% for (2 of 7) low-grade glioma, 31.3% (5 of 16) for breast cancer, 33.3% (5 of 15) for head and neck squamous cell carcinoma, 55.6% (10 of 18) for pancreatic cancer, and 100% (5 of 5) for salivary gland cancer. The ORR was 3.8% (2 of 53) in the Exploratory Cohort. In the Pediatric Cohort (n = 11), there were one responder and seven patients with durable stable disease. Treatment-related adverse events (TRAEs) were consistent with the known safety profile of erdafitinib. Pediatric-specific TRAEs included epiphysiolysis and limb fracture.</p><p><strong>Conclusion: </strong>Encouraging activity was observed for erdafitinib across tumor types in patients with advanced malignancies and selected <i>FGFR</i> alterations who have exhausted treatment options. More limited activity was observed for erdafitnib in the Exploratory Cohort.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501094"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455888","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":"Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study.","authors":"Hannah E Hartley, Fang Chyi Fong, Alem S Gabriel, Louise K Stevenson, Emily Beckett, Lisa M Allinson, Angharad Goodman, Aaron Potts, Emily Whittle, Ruby Barford, Alice Lamparelli, Fiona Herd, Katia Mazzocco, Annalisa Pezzolo, Martina Morini, Martina Ardito, Alessandra Eva, Marzia Ognibene, Matthias Fischer, Sandra Ackermann, Carolina Rosswog, Barbara Hero, Graham R Smith, Adrienne A Unsworth, Michael McCorkindale, Sally L George, Jennifer Tall, Jan J Molenaar, Yvette Matser, Karin Langenberg, Godelieve Tytgat, Rosa Noguera, Ana P Berbegall, Jaime Font de Mora, Valérie Combaret, Gaelle Pierron, Annick Mühlethaler-Mottet, Jacqueline Schoumans, Joëlle Tchinda, Irina Banzola, Marta Jeison, Michal Hameiri-Grossman, Klaus H Beiske, Nathalie Auger, Nadine Van Roy, Nermine O Basta, Richard J Q McNally, Sabine Taschner-Mandl, Vassilios Papadakis, Andrea Di Cataldo, Kate Wheeler, Jose D Bermúdez, Maja Beck-Popovic, Vanessa Segura, Adela Canete, Gudrun Schleiermacher, Deborah A Tweddle","doi":"10.1200/PO-26-00045","DOIUrl":"10.1200/PO-26-00045","url":null,"abstract":"<p><strong>Purpose: </strong>Intermediate-risk neuroblastoma patients older than 18 months, with non-<i>MYCN</i> amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup.</p><p><strong>Methods: </strong>We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival.</p><p><strong>Results: </strong>Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (<i>CDK4/MDM2/TERT</i> coamplification (n = 1), <i>CDK4/MDM2</i> coamplification (n = 4), <i>CDK4</i> (n = 2), <i>TERT</i> (n = 1), and <i>MYC</i> (n = 1)), while 63/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%; <i>P</i> < .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3]; <i>P</i> < .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8] <i>v</i> 93.3% [95% CI, 81.5 to 100]; <i>P</i> < .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0% <i>v</i> 61.1% [95% CI, 50.3 to 74.3]; <i>P</i> < .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3] <i>v</i> 80.9% [95% CI, 71.8 to 91.3]; <i>P</i> < .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS.</p><p><strong>Conclusion: </strong>Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2600045"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368370","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":"Long-Term Outcomes and Surgical Conversion After Immunotherapy in Microsatellite Instability-H Biliary Tract Cancers.","authors":"Priyanshi Shah, Anina Peersen, Vaibhav Sahai, Amit Mahipal, Nikolas Naleid, Mitesh Borad, Tanios Bekaii-Saab, Mohamad Bassam Sonbol, Umair Majeed, Hani M Babiker, Conor D J O'Donnell, Midhun Malla, Garima Gupta, Caitlyn B Conboy, Lionel Kankeu Fonkoua, Leslie A Washburn, Thorvardur R Halfdanarson, Nicole Peterson, Robert R McWilliams, Ryan M Carr, Rondell P Graham, Patrick Starlinger, Rory Smoot, Susanne Warner, Sumera I Ilyas, Gregory J Gores, Lewis Roberts, Julie Heimbach, Fang-Shu Ou, Nguyen H Tran","doi":"10.1200/PO-25-01156","DOIUrl":"10.1200/PO-25-01156","url":null,"abstract":"<p><strong>Purpose: </strong>Deficient mismatch repair/microsatellite instability (dMMR, MSI-H) in biliary tract cancers (BTCs) is observed in 1%-5% of tumors. MSI-H across solid tumors has demonstrated durable response to immune checkpoint inhibitors (ICIs) regardless of the anatomic location. Here, we describe clinical outcomes and surgical conversion of MSI-H BTC treated with ICIs.</p><p><strong>Patients and methods: </strong>We conducted a multicenter, retrospective analysis of BTC patients with dMMR/MSI-H between 2017 and 2024 at Mayo Clinic, University of Michigan, and University Hospitals Seidman Cancer Center. Outcomes of interest were surgical resection rate, rate of pathologic response, 2-year overall survival (OS; time from initiation of treatment to death/last follow-up), and time to treatment discontinuation (TTD; time from initiation of treatment to cessation because of any cause). Analyses were descriptive.</p><p><strong>Results: </strong>Thirty patients with MSI-H BTC were identified: 19 with cholangiocarcinoma, three with gallbladder cancer, and 8 with BTC undefined. The median age at diagnosis was 61.5 years (range, 26-86). Twenty-six (86.7%) patients had advanced stage at diagnosis. Twenty-seven patients (90%) received first-line systemic therapy, and 13 (48.1%) continued onto second line. Six patients (23.1%) were restaged to resectable from advanced disease after ICI therapy and underwent resection; all remained recurrence-free at last follow-up. Of these six patients, 3 (50%) achieved a pathologic complete response. Among those receiving first-line therapy, the median TTD was 9.9 months (95% CI, 5.7 to 14.5 months) and the 2-year OS was 73% (95% CI, 56% to 94%).</p><p><strong>Conclusion: </strong>ICI therapy in patients with MSI-H BTC demonstrated durable response and downstaged some BTC to a resectable stage. dMMR/MSI-H should be performed up-front to guide treatment decisions.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501156"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421313","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 Radioproteomic Modeling for Early Recurrence Prediction and Metabolic Characterization in Hepatocellular Carcinoma.","authors":"Qiuyu Zhuang, Tongtong Xu, Xiaohua Xing, En Hu, Yang Zhou, Xiaoyuan Zheng, Lixia Bai, Yao Huang, Xiaolong Liu, Yutao Chen","doi":"10.1200/PO-25-00745","DOIUrl":"https://doi.org/10.1200/PO-25-00745","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with high recurrence rates after surgical resection posing a significant challenge. While deep learning (DL) approaches show promise in predicting HCC recurrence, their clinical translation is limited by poor interpretability and unclear mechanisms. Our study aimed to develop an interpretable DL framework that predicts recurrence while elucidating underlying biology through integration of radiologic imaging and multiomics profiling.</p><p><strong>Materials and methods: </strong>We developed a DL framework to predict early postoperative HCC recurrence using preoperative multiphase computed tomography imaging and generate an imaging-based early recurrence risk score (ERRS) for risk stratification. To decipher the biological basis of ERRS, we integrated DL features with proteomic data to identify key metabolic alterations, which were validated by metabolomics, immunohistochemistry, and enzymatic assays. Patient-derived organoids (PDOs) were used to assess the therapeutic potential of targeting these alterations.</p><p><strong>Results: </strong>The Multi-model_NC&ART&PV DL model showed improved performance compared with conventional single-phase models in predicting early postoperative recurrence, with high-ERRS patients exhibiting worse survival and more aggressive features. Mechanistically, radioproteomic analyses linked model predictions to dysregulated pyruvate metabolism, characterized by reduced pyruvate dehydrogenase complex expression/activity and elevated lactate dehydrogenase (LDH) activity. PDOs from patients with HCC were sensitive to LDH inhibitor stiripentol, with high-ERRS tumors showing greater therapeutic vulnerability than low-ERRS tumors.</p><p><strong>Conclusion: </strong>This study bridges artificial intelligence-driven imaging and mechanism-guided therapy by developing a biologically interpretable DL model for HCC recurrence prediction. Radioproteomic integration identified dysregulated pyruvate metabolism as a hallmark of high-risk HCC, enabling the repurposing of stiripentol as a potential therapy. This framework suggests a potential strategy linking noninvasive risk stratification with pathway-guided treatment although further validation and prospective studies are needed to establish its clinical utility.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2500745"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620190","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 Genomic Characteristics and Prognostic Association in Advanced Papillary Thyroid Carcinoma.","authors":"Soji Toda, Yukihiko Hiroshima, Hiroyuki Iwasaki, Mei Kadoya, Chihiro Suzuki, Haruhiko Yamazaki, Yoichiro Okubo, Aya Saito, Katsuhiko Masudo","doi":"10.1200/PO-25-00520","DOIUrl":"https://doi.org/10.1200/PO-25-00520","url":null,"abstract":"<p><strong>Purpose: </strong>Most thyroid cancers are initiated by alterations activating the mitogen-activated protein kinase (MAPK) pathway and progress via additional genomic events. Because papillary thyroid carcinoma (PTC) generally has a favorable prognosis and rarely advances, knowledge about later-acquired genomic alterations and their impact on prognosis is limited.</p><p><strong>Materials and methods: </strong>This study is a real-world database study using a nationwide database that contains clinical data and comprehensive genomic profiling (CGP) test results. We investigated gene alterations and their impact on prognosis in advanced PTC.</p><p><strong>Results: </strong>The study included 322 patients with advanced papillary carcinoma who underwent CGP tests for drug selection between June 2019 and April 2024. Metastases were present in 96% of cases, and 70% received systemic therapy. The most common genomic abnormalities were mutations in the <i>TERT</i> promoter and <i>BRAF</i>. <i>BRAF</i> alterations were mutually exclusive with <i>RBM10</i> and other MAPK pathway genes such as <i>RET, NRAS,</i> and <i>NTRK1</i>, but co-occurred with <i>TERT</i> and <i>AKT1</i>. The MAPK pathway had the highest frequency of alterations (96%), followed by the phosphoinositide 3-kinase (PI3K; 23%), cell cycle (13%), and p53 (11%) pathways. Survival analysis showed that alterations in <i>PTEN</i> and <i>CDKN2A</i> were independent poor prognostic factors. Patients harboring alterations in the PI3K or cell cycle pathway showed significantly shorter overall survival.</p><p><strong>Conclusion: </strong>Our study clarified the frequency, co-occurrence, and exclusivity of gene alterations in advanced PTC. Alterations in the PI3K or cell cycle pathways are linked to poor prognosis, and therapies targeting these pathways may warrant further investigation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2500520"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421317","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}