JCO precision oncology最新文献

{"title":"Performance and Clinical Benefit of Comprehensive Genomic Profiling of GI Tumors in a Comprehensive Cancer Center.","authors":"Giulia Maddalena, Valentina Angerilli, Federico Nichetti, Gianmarco Ricagno, Jessica Gasparello, Elena Mattiuzzo, Maria Caterina De Grandis, Elena Carcea, Carlotta Ceccon, Anna Roma, Eleonora Perissinotto, Sara Sperotto, Giacomo Di Paolo, Marta Sbaraglia, Marco Maruzzo, Francesca Bergamo, Angelo Paolo Dei Tos, Matteo Fassan, Sara Lonardi","doi":"10.1200/PO-25-01168","DOIUrl":"10.1200/PO-25-01168","url":null,"abstract":"<p><strong>Purpose: </strong>Comprehensive genomic profiling (CGP) is increasingly adopted in the management of patients affected by GI cancers. However, the applicability, performance, and clinical utility of CGP in the real-world setting are still undefined.</p><p><strong>Methods: </strong>We retrospectively evaluated CGP performance and clinical benefit in consecutive patients with GI tumor at the Veneto Institute of Oncology-IRCCS, Padua. We assessed CGP success and its advantage over routine diagnostics in detecting actionable molecular targets. A custom list of gain alterations was defined, including targets not classified as ESMO Scale for Clinical Actionability of molecular Targets tier IA at the time of analysis.</p><p><strong>Results: </strong>Of the 1,450 samples, 140 (9.7%) were inadequate for CGP. Failure was mainly due to low quantity of extracted tumor DNA (<i>P</i> = .002). Of the 1,265 metastatic patients, GAs were detected in 355 (28.1%) cases, of whom 55 (15.5%) were treated with targeted therapy. Survival did not differ between patients with no GAs and those with GAs who were not treated accordingly (median overall survival 12.0 <i>v</i> 10.9 months), whereas it was significantly longer for those receiving treatment for actionable GAs (26.4 months). This advantage was confirmed in an exploratory, inverse probability of treatment-weighted analysis (adjusted hazard ratio, 0.72 [95% CI, 0.58 to 0.89]; <i>P</i> = .002). Among 283 (83.7%) untreated patients with complete follow-up, 41.6% did not receive targeted therapy due to lack of clinical trial or failure to meet inclusion criteria.</p><p><strong>Conclusion: </strong>Appropriate specimen selection and early molecular assessment at the time of advanced disease diagnosis are essential to detect clinically actionable molecular alterations and therapeutic opportunities in patients with GI cancers. Our results support CGP in comprehensive cancer centers.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 8","pages":"e2501168"},"PeriodicalIF":4.7,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724754","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":"Erratum: 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-26-00755","DOIUrl":"https://doi.org/10.1200/PO-26-00755","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2600755"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470823","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":"Afatinib for Advanced Cancers Carrying an EGFR, HER2, or HER3 Mutation: An Open-Label, Phase II, Belgian Precision Study.","authors":"Lore Decoster, Philippe Aftimos, Sylvie Rottey, Hans Prenen, Joelle Collignon, Jeroen Mebis, Jean Luc Canon, Vanessa Fastenaekels, Nadia Cappoen, Anna Kondrat, Sofie Joris, Jacques De Grève","doi":"10.1200/PO-25-01198","DOIUrl":"10.1200/PO-25-01198","url":null,"abstract":"<p><strong>Purpose: </strong>The Belgian Precision initiative aims to implement tumor-agnostic next-generation sequencing (NGS) in patients with advanced cancer and expand genotype-matching drug availability. The present investigator-driven trial aimed to study the efficacy of afatinib in patients with advanced solid tumors harboring an activating HER2, EGFR, or HER3 mutation.</p><p><strong>Patients and methods: </strong>This open-label phase II trial has three cohorts: <i>HER2-</i>, <i>EGFR-</i>, and <i>HER3-</i>mutated previously treated solid tumors. The primary end point was objective response rate (ORR). For each cohort, a Simon two-stage design was used. Observation of ≥2 responses in the first 10 patients prompted a further 19 to be included. Secondary end points were disease control rate (DCR), duration of response (DOR), progression-free survival, overall survival, and safety.</p><p><strong>Results: </strong>A total of 45 patients were included, with a median age of 62 years. For the <i>HER2</i> cohort (n = 30), ORR was 3.3% (one partial response) and DCR was 23.3%. In the <i>EGFR</i> cohort, a total of seven patients were included, resulting in an ORR in 2/7 (28.6%) patients, with a DOR of 6.6 and 15.4 months. In the <i>HER3</i> cohort, a total of eight patients were included, but none demonstrated an objective response. Safety data were consistent with the known safety profile of afatinib.</p><p><strong>Conclusion: </strong>The present phase II study, investigating afatinib in <i>HER2-, EGFR-,</i> or<i>HER3</i>-mutant pretreated solid tumors did not reach its primary end point in the <i>HER2</i> cohort. Neither the <i>EGFR</i> nor the <i>HER3</i> cohort reached full accrual, but clinically meaningful responses were observed in two <i>EGFR</i>-mutated patients. Further exploration of <i>HER</i> targeting in solid tumors is warranted.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501198"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396406","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":"Endometrial Cancer by ERBB2 Amplification (ERBB2amp) Status: Differences in Molecular Subtypes, Ancestry, and Real-World Outcomes.","authors":"Evelyn Cantillo, Vivek Podder, Natalie Danziger, Dale Lobo, Douglas I Lin, Ryon P Graf, Robert L Coleman, Bhavana Pothuri, Ramez N Eskander, Thomas J Herzog, Brian M Slomovitz","doi":"10.1200/PO-25-01157","DOIUrl":"10.1200/PO-25-01157","url":null,"abstract":"<p><strong>Purpose: </strong>Endometrial cancer (EC) has rising mortality rates and persistent racial disparities, particularly among non-Hispanic Black women who are more likely to present with aggressive histologic subtypes associated with worse survival. <i>ERBB2</i> amplification (<i>ERBB2</i>amp), a biomarker enriched in aggressive EC subtypes, is a therapeutic target. This study investigates <i>ERBB2</i>amp prevalence, molecular subtype, and histologic associations, as well as prognostic impact across diverse genetic ancestries using a large clinicogenomic database (CGDB).</p><p><strong>Methods: </strong>We analyzed 16,073 patients with EC who underwent tissue comprehensive genomic profiling via Foundation Medicine. Genetic ancestry was inferred using a single nucleotide polymorphism-based classifier. An outcomes cohort of 1,275 patients with advanced or recurrent EC from the Flatiron Health-Foundation Medicine CGDB was used to assess survival outcomes. Patients receiving human epidermal growth factor receptor 2 (HER2)-targeted therapy were excluded from the overall survival (OS) analysis. <i>ERBB2</i>amp prevalence, histologic and molecular correlations, and associations with OS were examined.</p><p><strong>Results: </strong><i>ERBB2</i>amp was identified in 8% of EC tumors, with the highest prevalence among patients of African ancestry (12% <i>v</i> 7% European ancestry; <i>P</i> < .001). There was a significant association between <i>ERBB2</i>amp and serous histology, <i>TP53</i> mutation presence, low tumor mutational burden, and microsatellite stability. In the outcomes cohort, <i>ERBB2</i>amp was not independently associated with OS (hazard ratio, 0.88 [95% CI, 0.65 to 1.17]; <i>P</i> = .37). In contrast, TP53mutation and poor performance status were independently associated with decreased OS. Notably, of patients with documented HER2 immunohistochemistry (IHC; n = 305), 22% of nonamplified tumors exhibited HER2 IHC 2+/3+ staining.</p><p><strong>Conclusion: </strong><i>ERBB2</i>amp is more common among patients with African genetic ancestry and frequently co-occurs with <i>TP53</i>mutations, providing molecular rationale for EC disparities. Self-reported race does not fully capture genetic ancestry; therefore, comprehensive tumor profiling and HER2 IHC testing should be performed to improve selection for targeted therapies and help address disparities in EC outcomes.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501157"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421259","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":"Cross-Platform Gene Signature to Predict Survival Outcomes for Nasopharyngeal Carcinoma.","authors":"Huaping Li, Qiuyu Jing, James Chung Hang Chow, Wah Cheuk, Kenneth Sik Kwan Chan, Suyu Hao, Kazi Anisha Islam, Wei Dai, Ka On Lam, Victor Ho Fun Lee, Wai Tong Ng, Roger Kai Cheong Ngan, Anne Wing Mui Lee, Jason Wing Hon Wong, Chi Leung Chiang","doi":"10.1200/PO-26-00029","DOIUrl":"https://doi.org/10.1200/PO-26-00029","url":null,"abstract":"<p><strong>Purpose: </strong>Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy often diagnosed at an advanced stage due to nonspecific early symptoms. Accurate prognostic stratification is essential for individualized therapy but remains challenging because of biological and clinical heterogeneity. This study aimed to develop and validate a gene expression-based prognostic signature for locally advanced NPC.</p><p><strong>Methods: </strong>This retrospective biomarker investigation combined transcriptomic profiling and survival analyses. A prognostic model was constructed using LASSO-Cox regression in the discovery cohort (N = 99) from the multicenter, randomized phase III trial NPC-0501, and validated in independent cohorts (N = 133) from Queen Elizabeth Hospital (QEH), Hong Kong, and Sun Yat-sen University Cancer Center (SYS), Guangzhou, using different profiling methods. Mechanisms underlying the signature were explored using single-cell RNA-seq (scRNA-seq) data. The primary outcome was 3-year progression-free survival (PFS), with 5-year overall survival (OS) as a secondary end point. Performance was evaluated using hazard ratios (HRs) and survival probabilities (SP).</p><p><strong>Results: </strong>A 5-gene signature (<i>SPP1</i>, <i>IL18BP</i>, <i>PALMD</i>, <i>WDR35</i>, and <i>SOCS6</i>) predicted 3-year PFS in the NPC-0501 cohort (HR, 0.046 [95% CI, 0.011 to 0.190]; <i>P</i> < .001), separating high-risk from low-risk patients (SP, 42.9% <i>v</i> 96.0%; <i>P</i> < .0001). It predicted survival in both validation cohorts, with associations with 5-year OS in QEH (SP, 72.7% <i>v</i> 100%; <i>P</i> < .001) and 3-year PFS in SYS (SP, 70.5% <i>v</i> 93.2%; <i>P</i> = .0059). It outperformed a published metastasis-related model. Single-cell analyses showed <i>SPP1</i> enrichment in M2 macrophages, linking high risk with an immunosuppressive tumor microenvironment.</p><p><strong>Conclusion: </strong>A robust five-gene signature was established and validated for prognostic stratification of locally advanced NPC. Reproducibility across transcriptomic platforms and biological relevance support clinical application to guide personalized treatment.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2600029"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368332","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":"Pre- and Post-Treatment Predictive Models of Peritoneal Recurrence After Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel-Chemotherapy and Surgery: An International Study.","authors":"Margaret M Lee, Darren J Wong, Katheryn Hall, Cuong P Duong, David I Watson, Claire L Donohoe, Tim Bright, Ahmad Aly, Kevin Chan, David L Chan, Neil Merrett, Sivakumar Gananadha, Yick Ho Lam, Harsh Kanhere, B Mark Smithers, Michael Bozin, Matthew Read, Krinal Mori, Mary-Ann Johnson, Enoch Wong, Sarah A Martin, Geraldine Ooi, Yahya Al-Habbal, Chon Hann Liew, Robert Bohmer, Jurstine Daruwalla, Mo Ballal, Rukshan Ranjan, Andrew D MacCormick, Sharon Pattison, Nicholas Evennett, Jason Robertson, James Tan, Alexandra Gordon, Simon Bann, Inian Samarasam, Ramesh Gurunathan, Jimmy So, Jonathan Yeung, Lorenzo Ferri, Ewen A Griffiths, Alexander W Phillips, Sheraz R Markar, David Chan, Thomas Murphy, John Reynolds, Magnus Nilsson, Guillaume Piessen, Bas Wijnhoven, Richard van Hillegersberg, Mark I van Berge Henegouwen, Pietro M Lombardi, Nicholas J Clemons, Zexi Allan, Anthony J Hamilton, David S Liu","doi":"10.1200/PO-25-01145","DOIUrl":"https://doi.org/10.1200/PO-25-01145","url":null,"abstract":"<p><strong>Purpose: </strong>Locally advanced gastroesophageal adenocarcinomas commonly relapse early with peritoneal disease, suggesting that a subset of patients harbor occult peritoneal micrometastases at diagnosis. These patients may benefit from peritoneal-directed therapy in the perioperative setting. To facilitate patient selection and evaluation of such therapies, we derived, validated, and compared prediction models for peritoneal recurrence after fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)-based multimodality treatment using pre- and post-treatment clinicopathologic predictors.</p><p><strong>Methods: </strong>A total of 2,240 patients from the international Survival and Patterns of Care in the Era-FLOT registry were analyzed. Using Fine-Gray competing-risk regression, patients who developed peritoneal recurrence were compared with those with nonperitoneal recurrence, those who died without recurrence, and those who remained disease-free at follow-up. Pre- and post-treatment variables, obtained at staging and post-FLOT/surgery, respectively, were used to construct pre- and post-treatment predictive models of peritoneal recurrence, with internal validation using bootstrap optimism correction.</p><p><strong>Results: </strong>Peritoneal recurrence was the most frequent (41% of all recurrences) and earliest site of disease relapse (median 9.8 <i>v</i> 11.4 months, <i>P</i> = .024) and was associated with poorer postrecurrence (median 4.4 <i>v</i> 9.8 months, <i>P</i> < .001) and overall (median 17.0 <i>v</i> 24.3 months, <i>P</i> < .001) survival compared with nonperitoneal recurrence. Six pretreatment and eight post-treatment variables independently predicted peritoneal recurrence and were incorporated into pre- and post-treatment models, respectively. At 12, 24, and 36 months postsurgery, both models demonstrated good discriminatory performance in predicting peritoneal relapse with comparable accuracy and risk calibration profiles. Decision curve analysis found that both models were superior to treat-none and treat-all approaches, highlighting their potential clinical utility.</p><p><strong>Conclusion: </strong>Peritoneal recurrence remains a common and important problem. We derived pre- and post-treatment prediction models for peritoneal recurrence, also available as web-based calculators. These tools can clinically prognosticate and may advance peritoneal-directed therapies for high-risk patients.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501145"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620254","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 Brain: Circulating Tumor Cells as a Tool for Diagnosis and Monitoring.","authors":"Francesca Lessi, Mariangela Morelli, Alessandro Di Gangi, Sara Franceschi, Francesca Di Lorenzo, Chiara Sandro, Paolo Aretini, Aldo Pastore, Gianmarco Ferri, Michele Menicagli, Francesco Pasqualetti, Carlo Gambacciani, Federico Villanacci, Vanna Zucchi, Samanta Cupini, Anna Luisa Di Stefano, Orazio Santo Santonocito, Chiara Maria Mazzanti","doi":"10.1200/PO-25-01199","DOIUrl":"10.1200/PO-25-01199","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive heterogeneity and inevitable recurrence. Although extracranial metastases are rare, circulating tumor cells (CTCs) are consistently detectable in patients with GBM, challenging the idea of GBM as a strictly localized disease and suggesting CTCs as a promising liquid biopsy tool.</p><p><strong>Methods: </strong>We analyzed genomic and phenotypic features of bulk CTCs (BCTCs) and single CTCs in 27 patients with GBM. Whole-exome sequencing of BCTCs and matched tumors confirmed tumor origin and assessed shared mutational and copy number alteration (CNA) profiles. Single CTCs isolated with DEPArray NxT underwent low-pass whole-genome sequencing. CTCs counts were compared across primary GBM, recurrent GBM, healthy donors, and non-GBM conditions. Single-cell RNA-seq from primary GBM cell lines was used to validate observations.</p><p><strong>Results: </strong>BCTCs showed genomic alterations overlapping with those of matched tumors. CTCs were significantly more abundant in primary GBM than in recurrent disease or healthy controls, enabling the definition of a diagnostic cutoff of 4 CTCs per 5 mL of blood. CTCs were absent in the small cohort of radionecrosis cases analyzed, suggesting a potential role for CTCs in distinguishing neoplastic from non-neoplastic lesions, although further validation in larger cohorts is required. Single-cell analysis revealed marked heterogeneity, including CTCs lacking detectable CNAs. Similar CNA-negative populations appeared in scRNA-seq data sets, suggesting possible origin from the tumor microenvironment rather than fully malignant clones.</p><p><strong>Conclusion: </strong>CTCs are tumor-derived and heterogeneous biomarkers with strong diagnostic potential in GBM. The identified cutoff improves distinction between GBM and non-neoplastic diseases, supporting CTCs as a useful liquid biopsy tool for detection and monitoring. Further studies should clarify the biologic roles of distinct CTCs subpopulations.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501199"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578756","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":"Identification of a Novel <i>GOLGB1-RET</i> Fusion in Papillary Thyroid Cancer With a Durable Response to Selpercatinib.","authors":"Shogen Boku, Takao Fujisawa, Shigenori Kadowaki, Hironaga Satake, Hisateru Yasui, Koushiro Ohtsubo, Yasushi Shimizu, Tomoyuki Otsuka, Bunya Kuze, Riu Yamashita, Taro Shibuki, Yoshiaki Nakamura, Hideaki Bando, Takayuki Yoshino, Milan Radovich, Susumu Okano","doi":"10.1200/PO-26-00237","DOIUrl":"10.1200/PO-26-00237","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2600237"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368414","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 Testing in Primary Advanced or Recurrent Endometrial Cancer: A Cost-Effectiveness Analysis.","authors":"Yilin Chen, Solomon J Lubinga, Scott Ramsey, Jean Hurteau, Jade Reynolds, Josh J Carlson","doi":"10.1200/PO-25-01110","DOIUrl":"10.1200/PO-25-01110","url":null,"abstract":"<p><strong>Purpose: </strong>We assessed the cost-effectiveness of Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) testing versus no molecular testing to guide initial treatment in stage III/IV primary advanced or recurrent endometrial cancer (pA/rEC) from payer and societal perspectives.</p><p><strong>Methods: </strong>A decision tree for molecular classification followed by a partitioned survival model estimated lifetime costs and outcomes for ProMisE versus no testing. Patients in the no testing arm received carboplatin + paclitaxel (CP), dostarlimab + CP, pembrolizumab + CP, or hormonal therapy (everolimus + letrozole). Patients in the ProMisE arm received the same treatments or bevacizumab + CP. Survival functions were derived from trial results. EQ-5D-5L utility values were from the RUBY trial (ClinicalTrials.gov identifier: NCT03981796). Costs were sourced from US databases and literature. The base case presented a US third-party payer perspective. A scenario analysis presented a modified societal perspective. Outcomes were total life-years (LYs), total quality-adjusted LYs (QALYs), total costs, and incremental cost-effectiveness ratio (ICER) of ProMisE versus no testing.</p><p><strong>Results: </strong>From a payer perspective, total LYs and total QALYs were 5.36 and 4.08 with ProMisE versus 3.83 and 2.89 with no testing, respectively. Total costs were $233,989 US dollars (USD) with ProMisE versus $155,305 USD with no testing. Incremental LYs and QALYs were 1.53 and 1.19 greater with ProMisE; incremental costs over a lifetime were $78,684 USD greater with ProMisE. Assuming a threshold of $150,000 USD per QALY gained, ProMisE was cost effective with an ICER of $66,321 USD per QALY gained. From a societal perspective, lifetime costs were lower (-$22,973 USD) and QALYs greater with ProMisE versus no testing.</p><p><strong>Conclusion: </strong>ProMisE testing is cost effective compared with no testing. Given the heterogeneity of molecular subtypes in stage III/IV pA/rEC, molecular testing enables personalized treatment that is both clinically meaningful and of high value from payer and societal perspectives.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2501110"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396359","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":"Development and Validation of a Computational Histology Artificial Intelligence-Powered Biomarker in Metastatic Hormone-Sensitive Prostate Cancer on Randomized Phase III Trials.","authors":"Christopher J Sweeney, Vrishab Krishna, Viswesh Krishna, Akshay Neema, Asit Tarsode, Vinod V Subhash, Lisa G Horvath, James G Kench, Martin R Stockler, Sonia Yip, Hayley Thomas, Umang Swami, Haochen Zhang, Snehal Sonawane, Waleed M Abuzeid, Vivek Nimgaonkar, Ekin Tiu, Drew Watson, Lesli Kiedrowski, Trevor J Royce, David D Yang, Phuoc T Tran, Charles J Ryan, Paul L Nguyen, Alicia K Morgans, Anirudh Joshi, Neeraj Agarwal, Ian D Davis","doi":"10.1200/PO-26-00321","DOIUrl":"10.1200/PO-26-00321","url":null,"abstract":"<p><strong>Purpose: </strong>Metastatic hormone-sensitive prostate cancer (mHSPC) is a heterogeneous disease state with multiple treatment options. Biomarkers are needed for risk stratification and to guide treatment intensification or deintensification. We used a computational histology artificial intelligence-based platform (CHAI) to develop and validate a digital image-only prognostic biomarker in mHSPC with participant-level data from two prospective, phase III randomized controlled trials.</p><p><strong>Methods: </strong>The CHAI platform extracted quantitative histomorphologic features from whole-slide images of hematoxylin and eosin-stained diagnostic specimens. Data from CHAARTED were used to construct a signature of features associated with overall survival (OS). A continuous risk score was dichotomized into favorable- and unfavorable-risk groups. The performance of the locked model was assessed in ENZAMET as an independent validation cohort using Kaplan-Meier methods and multivariable Cox proportional hazards models. Institutional review board approval was obtained for each participating data set. Given all patient information was deidentified, the study was considered institutional review board-exempt and consent waived.</p><p><strong>Results: </strong>Overall, 1,191 participants were included: 507 in development (CHAARTED) and 684 in validation (ENZAMET). In the validation cohort, CHAI unfavorable-risk participants had worse OS (hazard ratio [HR], 2.6 [95% CI, 2.0 to 3.4]; <i>P</i> < .001) and progression-free survival (PFS; HR, 2.2 [95% CI, 1.7 to 2.7]; <i>P</i> < .001). Five-year OS was 39% for unfavorable-risk versus 69% for favorable-risk participants. In adjusting for clinical variables, the biomarker remained prognostic for OS and PFS (<i>P</i> < .001). Among those who received doublet (androgen-deprivation therapy [ADT] plus androgen receptor pathway inhibitor [ARPI]) versus triplet systemic therapy (ADT plus docetaxel plus ARPI), there was a significant interaction between biomarker and treatment intensification for OS (<i>P</i> = .003) and PFS (<i>P</i> < .001), suggesting that patients at higher risk may benefit more from triplet therapy.</p><p><strong>Conclusion: </strong>We developed and validated an image-only AI-based biomarker associated with clinical outcomes and potential benefit from treatment escalation in mHSPC independent of conventional clinicopathologic risk factors.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 7","pages":"e2600321"},"PeriodicalIF":4.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412109","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}