JCO precision oncology最新文献

{"title":"Combination Therapy With Olaparib Plus Lenvatinib in a Patient With <i>BRCA2</i>-Mutated, Radioiodine-Refractory, Metastatic Papillary Thyroid Cancer: A Case Report.","authors":"Zachary Young, Jason Tasoulas, Marco Fajardo, Morgan Gwynn, Jacqueline Morris, Steven M Johnson, Siddharth Sheth","doi":"10.1200/PO-24-00802","DOIUrl":"10.1200/PO-24-00802","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400802"},"PeriodicalIF":5.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698602","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":"Elusive Promise of Predictive Biomarkers in Metastatic Urothelial Carcinoma.","authors":"Salvador Jaime-Casas, Shilpa Gupta","doi":"10.1200/PO-25-00305","DOIUrl":"https://doi.org/10.1200/PO-25-00305","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500305"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540258","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":"Intrapatient Variation in Response to Systemic Therapy in Advanced Hepatocellular Carcinoma.","authors":"Philip J Johnson, Ellen L Boswell","doi":"10.1200/PO-25-00015","DOIUrl":"https://doi.org/10.1200/PO-25-00015","url":null,"abstract":"<p><strong>Purpose: </strong>Progression-free survival (PFS) has been proposed as a surrogate end point in clinical trials for advanced hepatocellular carcinoma (aHCC). However, there have been concerns about the discrepancy between PFS and overall survival. Here, we aimed to characterize the behavior of individual lesions within the same patient/liver that play a key role in response assessment to a systemic treatment and how this changed temporally.</p><p><strong>Methods: </strong>We obtained serial lesion measurement data from six clinical trials undertaken in the modern era (by which we mean since the first controlled trial in aHCC). In each patient, the percentage change of their lesion size was calculated at each visit compared with the baseline/screening phase. To assess lesion behavior, the patients were classified according to the degree of divergence (DOD) categories that ranged from 0 (all lesions behaved similarly) to 2 (completely discordant behavior). Finally, the results were summarized per treatment arm as the proportion of patients in each divergence category per follow-up visit.</p><p><strong>Results: </strong>Of the 8,260 visits where DOD was assessed in patients, there was a considerable proportion of patients with divergent lesion behavior at the treatment arm level-approximately 58% were DOD 0, 38% were DOD 1, and 4% were DOD 2. Individually, there was evidence of lesions both increasing and decreasing in size within the same liver despite the treatment remaining the same.</p><p><strong>Conclusion: </strong>The evidence presented here suggests that caution should be exercised in the application of progression-based metrics such as PFS as an end point in HCC clinical trials. Ultimately, there was consistently a considerable proportion of patients who were classified as having lesions within their liver which had a divergent response to treatment.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500015"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649493","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":"Phase II Trial of TAS-102 in Colorectal Cancer Patients With Circulating Tumor DNA-Defined Minimal Residual Disease After Adjuvant Therapy: INTERCEPT-TT.","authors":"Andrew J Pellatt, Alisha Bent, Nicholas Hornstein, Christine Parseghian, Ryan Huey, Kanwal Raghav, Van Morris, Michael Overman, Pia Morelli, Jason Willis, Phat Le, John Paul Shen, Bryan Kee, Madhulika Eluri, Victoria Higbie, Kristin Alfaro-Munoz, Kathryn Aziz, Robert Kell, Ryan Sun, Scott Kopetz, Arvind Dasari","doi":"10.1200/PO-25-00142","DOIUrl":"10.1200/PO-25-00142","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether treatment with TAS-102 can induce circulating tumor DNA (ctDNA) clearance at 6 months and delay/prevent disease recurrence in colorectal cancer (CRC) patients with ctDNA-defined minimal residual disease (MRD) after completion of adjuvant therapy.</p><p><strong>Patients and methods: </strong>This was a single-arm, single-institution, phase II study. Fifteen patients with stage II to IV CRC and ctDNA-defined MRD after curative-intent therapy and adjuvant chemotherapy were enrolled prospectively. Participants received 6 months of therapy with TAS-102 35 mg/m² twice a day on days 1-5 and 8-12 of each 28-day cycle. Disease recurrence was monitored every 3 months with ctDNA and cross-sectional imaging. For comparison, 30 patients matched for key variables who received standard of care were retrospectively identified for a synthetic control (SC) cohort. The primary end point was 6-month ctDNA clearance. Secondary end points included 3-month ctDNA clearance, disease-free survival (DFS), and safety.</p><p><strong>Results: </strong>Among 15 patients enrolled, median age was 60.2 years (range, 37-73) and 80% were stage IV with an average of 2.1 lines of previous therapy (range, 1-3). At 3 and 6 months, respectively, seven (47%) and five (36%) patients had ctDNA clearance. In the SC, two patients (6.7%) had spontaneous ctDNA clearance at 3 months (<i>P</i> = .0034) sustained at 6 months (<i>P</i> = .025). Among patients receiving TAS-102, nine patients had radiographic recurrence with a median DFS of 9.4 months compared with 28 patients in the SC with radiographic recurrence and a median DFS of 5.75 months (<i>P</i> = .03).</p><p><strong>Conclusion: </strong>Additional treatment with TAS-102 after adjuvant chemotherapy in CRC patients with ctDNA-defined MRD can induce ctDNA clearance but this may be transient without long-term cures.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500142"},"PeriodicalIF":5.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649494","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":"Pansarcoma Analysis of Cyclin-Dependent Kinase and Cyclin Outlier Gene Expression Highlights CDK7 as a Potential Therapeutic Target in Chordoma.","authors":"Daniel S Lefler, Andrew Elliott, Wei Jiang, Ubaldo Martinez-Outschoorn, Jude Al-Sabah, Daniel M Freed, Caitlin M King, Robert G Maki, Richard F Riedel, Jaime F Modiano, Daniel Hübschmann, Hanno Glimm, Stefan Fröhling, Matthew Oberley, Sosipatros A Boikos, Atrayee Basu Mallick","doi":"10.1200/PO-25-00149","DOIUrl":"https://doi.org/10.1200/PO-25-00149","url":null,"abstract":"<p><strong>Purpose: </strong>Cyclin-dependent kinase (CDK)4/6 inhibitors are approved for the treatment of breast cancer, and they have more recently been used in patients with well-differentiated/dedifferentiated liposarcomas (WD-LPSs/DD-LPSs). However, targeting of these and other CDKs, including transcriptional CDKs, remains a promising avenue of investigation for various cancers. Therefore, we sought to characterize outlier overexpression of CDK and cyclin genes in sarcomas. On the basis of the initial results, further studies were undertaken to investigate the roles of CDK7 and CDK18 in chordomas.</p><p><strong>Materials and methods: </strong>An initial analysis of CDK/cyclin gene expression involved an American national biomarker database of deidentified patients (Caris Life Sciences, Phoenix, AZ; n = 3,757) using novel, strict definitions to identify outlier overexpressing samples across subtypes. Results were validated with a German national database (Molecularly Aided Stratification for Tumor Eradication Research [MASTER]; n = 943). Outlier overexpression for <i>CDK7/18</i> in chordoma was compared with immunohistochemical (IHC) expression using tissue microarrays, and a selective investigational CDK7 inhibitor was tested against four chordoma cell lines.</p><p><strong>Results: </strong>Initial analysis identified expected findings (eg, outlier overexpression of <i>CDK4</i> in 39%-66% of WD-LPSs/DD-LPSs), clinical correlates of fundamental scientific work (eg, <i>CCND1</i> in 29% of Ewing sarcomas), and novel associations (eg, <i>CDK7/CDK18</i> in 42%/37% of chordomas). Outlier overexpression for <i>CDK7</i> and <i>CDK18</i> in chordomas was corroborated in the MASTER database (40% and 26% of patients, respectively). IHC analysis confirmed strong and diffuse expression of both CDK7 and CDK18 in chordoma samples. Furthermore, CDK7 inhibition was highly effective in four chordoma cell lines.</p><p><strong>Conclusion: </strong>This study supports further investigation into targeting of CDKs and cyclins in select sarcoma subtypes, and it specifically suggests a therapeutic approach inhibiting CDK7 in chordoma.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500149"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553622","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":"Geneva Homologous Recombination Deficiency Test Is Predictive of Survival Benefit From Olaparib and Bevacizumab Maintenance in Ovarian Cancer.","authors":"Yann Christinat, Intidhar Labidi-Galy, Liza Ho, Sophie Clément, Catherine Genestie, Jalid Sehouli, Saverio Cinieri, Antonio Gonzalez-Martin, Vassiliki Kolovetsiou-Kreiner, Keiichi Fujiwara, Toon Von Gorp, Germana Tognon, Sakari Hietanen, Viola Heinzelmann-Schwarz, Isabelle Ray-Coquard, Eric Pujade-Lauraine, Thomas A McKee","doi":"10.1200/PO-24-00825","DOIUrl":"10.1200/PO-24-00825","url":null,"abstract":"<p><strong>Purpose: </strong>The ability of the Geneva homologous recombination deficiency (HRD) test to predict progression-free survival (PFS) in patients with high-grade ovarian cancer treated with poly (ADP-ribose) polymerase inhibitors has been demonstrated. Its performance with respect to overall survival (OS) has not been assessed yet.</p><p><strong>Methods: </strong>Using the final results of the PAOLA-1/ENGOT-ov25 phase III clinical trial with a median follow-up of 5 years, we evaluated the Geneva HRD test on 468 samples as part of the ENGOT HRD European Initiative. Results were evaluated in terms of final PFS and OS in the olaparib + bevacizumab and placebo + bevacizumab arms and compared with the Myriad MyChoice HRD test.</p><p><strong>Results: </strong>Final PFS was consistent with previously published data and confirmed the predictive value of the Geneva HRD test with a hazard ratio (HR) of 0.41 (95% CI, 0.30 to 0.57) for HRD-positive patients. The results for OS showed a HR of 0.56 (95% CI, 0.37 to 0.85) for HRD-positive patients and 1.6 (95% CI, 1.1 to 2.3) for HRD-negative patients. These results are consistent with those observed with the Myriad test, including the negative OS trend in the HRD-negative subgroup treated with olaparib + bevacizumab (HR, 1.2 [95% CI, 0.83 to 1.8]). A subgroup analysis of patients with intermediate HRD scores showed that the normalized large-scale state transition score used by the Geneva HRD test had both predictive and prognostic value.</p><p><strong>Conclusion: </strong>The Geneva HRD test predicts PFS and OS benefit from olaparib + bevacizumab. The potential detrimental effect of olaparib + bevacizumab on OS in the HRD-negative population is hypothesis-generating and needs to be confirmed prospectively.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400825"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553621","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":"Complete Response in Hairy Cell Leukemia to Anti-CD22 CAR T-Cell Therapy.","authors":"Robert J Kreitman, Brett Schroeder, Evgeny Arons, Constance Yuan, Hao-Wei Wang, Mark Raffeld, Liqiang Xi, Stefania Pittaluga, Hong Zhou, Mory Gould, Isaac Shpilman, Evrim Turkbey, Katherine R Calvo, Lacey James, Olena Sierra Ortiz, Steve Highfill, David Stroncek, Bonnie Yates, Ira Pastan, Nirali N Shah","doi":"10.1200/PO-25-00269","DOIUrl":"10.1200/PO-25-00269","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500269"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649492","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":"Real-World Germline BRCA Testing, Poly(ADP-ribose) Polymerase Inhibitor Utilization, and Survival Outcomes in Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer.","authors":"Siddhartha Yadav, Fergus J Couch, Sam Hillman, Linlin Luo, Weiyan Li, Qixin Li, Jennifer Fallas Hayes, Jagadeswara R Earla, Xiaoqing Xu","doi":"10.1200/PO-24-00814","DOIUrl":"10.1200/PO-24-00814","url":null,"abstract":"<p><strong>Purpose: </strong>Testing for germline <i>BRCA1</i> and/or <i>BRCA2</i> mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline <i>BRCA1</i> and/or <i>BRCA2</i> (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited.</p><p><strong>Methods: </strong>Deidentified patient data from adults diagnosed with HER2- mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database. gBRCA testing patterns and prevalence were examined by tumor subtype (hormone receptor-positive [HR+]/triple-negative) and disease stage at diagnosis. Demographic and clinical characteristics were described by receipt of gBRCA testing and PARPi. PARPi treatment patterns were assessed, and real-word overall survival (OS) was estimated in patients with gBRCAm diagnosed with mBC after January 1, 2018.</p><p><strong>Results: </strong>Of the 15,006 total patients, 4,654 (31.0%) received a gBRCA test. gBRCA testing rates mostly increased from 2014 to 2022 and were lower in patients with HR+ than triple-negative tumors. Of the patients who underwent gBRCA testing, 337 (7.2%) had gBRCAm. From 2018 to 2022, PARPi was initiated in 94 (45.6%) of 206 patients with gBRCAm. With a median follow-up of 22.8 months across patients with available first-line treatment start dates, real-world OS was numerically longer among 94 patients with gBRCAm who received PARPi (32.3 months [95% CI, 22.7 to 47.4]) than among 99 patients who did not (21.9 months [95% CI, 18.4 to not reached]).</p><p><strong>Conclusion: </strong>Although gBRCA testing increased over time, testing and PARPi utilization rates remained suboptimal in potentially eligible patients with HER2- mBC. Exploratory analysis showed numerically longer OS in patients who received PARPi. Wider and timelier gBRCA testing is warranted to inform potentially optimal treatment decisions.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400814"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649496","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":"Relationship Among DNA Damage Response Gene Alterations, Molecular Subtypes, and Survival Outcomes in Patients With Metastatic Bladder Cancer Treated on CALGB 90601.","authors":"Gopa Iyer, Woonyoung Choi, Bin Luo, Filipe Carvalho, Timothy Hanlon, Henning Reis, Brendan J Guercio, Megan Fong, Jack Mountain, Mingxiao Feng, Ashley M Regazzi, Linda McCart, Yujia Wen, Hikmat Al-Ahmadie, Kent W Mouw, Eliezer M Van Allen, Joaquim Bellmunt, Robert Dreicer, Thomas W Flaig, Susan Halabi, David J McConkey, Jonathan E Rosenberg","doi":"10.1200/PO-24-00938","DOIUrl":"10.1200/PO-24-00938","url":null,"abstract":"<p><strong>Purpose: </strong>In urothelial carcinoma, prior studies have indicated that the basal/squamous molecular subtype and the presence of select DNA damage response (DDR) gene alterations are associated with improved benefit from cisplatin-based chemotherapy. We sought to evaluate these biomarkers in specimens from the phase III Cancer and Leukemia Group B (CALGB) 90601 trial.</p><p><strong>Methods: </strong>We performed whole-transcriptome sequencing (n = 188) and exon capture DNA sequencing (n = 208) on pretreatment tumors from the CALGB 90601 randomized trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with treatment-naïve metastatic bladder cancer. Whole-exome sequencing (WES) was performed on tumors from 22 patients who exhibited rapid progression or durable response. Tumors were assigned to molecular subtypes using three different classifiers. Proportional hazards model was used to correlate molecular subtype with overall survival (OS) and progression-free survival (PFS), adjusting for stratification factors and treatment arm (for PFS).</p><p><strong>Results: </strong>Patients with basal tumors had the shortest PFS and OS in the entire cohort. PFS was numerically longer in patients with basal tumors receiving bevacizumab. DDR gene alterations were not associated with improved outcomes. <i>FRY</i>, a candidate predictive biomarker of chemosensitivity identified by WES, did not confer sensitivity to cisplatin or gemcitabine in functional studies.</p><p><strong>Conclusion: </strong>Molecular subtype and DDR alterations did not correlate with improved outcomes in CALGB 90601. Possible explanations for these results include the small cohort size, lack of strong therapeutic effects of the treatments, genomic heterogeneity between profiled specimens and the metastatic lesions under treatment pressure, and differences in biology associated with different disease states (muscle-invasive <i>v</i> metastatic disease).</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400938"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540260","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":"Cancer Testis Antigen Expression Correlates With Immune Activation and Survival in Small Bowel Neuroendocrine Tumors.","authors":"Reed I Ayabe, Y David Seo, Brenda Melendez, Brittany C Fields, Laurence P Diggs, Rossana Lazcano, Bharat B Singh, Khalida Wani, Davis Ingram, Sarah Johnson, Manoj Chelvanambi, Courtney Hudgens, Sharia D Hernandez, Nadim J Ajami, Jennifer A Wargo, Alexander J Lazar, Mark Knafl, Scott Woodman, Daniel M Halperin, Jeannelyn S Estrella, Jessica E Maxwell","doi":"10.1200/PO-25-00107","DOIUrl":"10.1200/PO-25-00107","url":null,"abstract":"<p><strong>Purpose: </strong>Small bowel neuroendocrine tumors (SBNET) frequently present with metastatic disease, and the efficacy of available systemic therapies, especially immune checkpoint blockade, is limited. Toward developing novel immunomodulatory strategies, we interrogated the tumor immune microenvironment of SBNETs using bulk transcriptional and digital spatial profiling (DSP).</p><p><strong>Methods: </strong>Patients with SBNET who underwent resection from 2003 to 2016 were retrospectively evaluated. Overall survival (OS) was assessed using the Kaplan-Meier method. The Cox proportional hazards model was used for multivariable analysis (MVA). Bulk transcriptional profiling was performed using the NanoString PanCancer-Immune Panel. Whole human transcriptome DSP was performed using PanCK to segment tumor and adjacent stroma.</p><p><strong>Results: </strong>Unsupervised clustering of gene expression in resected SBNET from 42 patients demonstrated dichotomization by cancer testis antigen (CTA) expression. CTA^high patients (12/42, 29%) demonstrated elevated interleukin expression and had significantly improved OS (hazard ratio, 0.211, 95% CI, 0.059 to 0.751). Increased CTA expression was also associated with objective response to atezolizumab/bevacizumab in patients with neuroendocrine tumors (<i>P</i> = .003). Spatial profiling revealed upregulation of genes involved in immune activation and epigenetic modification in CTA^high tumor regions (all <i>P</i> < .05). Immune deconvolution identified a trend toward increased CD8 T cells, NK cell activation, and dendritic cells in CTA^high tumor regions, whereas T-cell receptor (TCR) profiling revealed marked differences in TCR segment expression between CTA^high and CTA^low regions (<i>P</i> < .001).</p><p><strong>Conclusion: </strong>High CTA expression in resected SBNET is independently associated with improved survival. Epigenetic dysregulation and immune activation in CTA-enriched tumor regions highlight the potential for combination epigenetic modifiers and immunotherapy in future trials.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500107"},"PeriodicalIF":5.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608395","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}