JCO precision oncology最新文献

{"title":"Correlates of Cetuximab Efficacy in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Previously Treated With Immunotherapy.","authors":"Jong Chul Park, Jong Seok Ahn, Ross Merkin, Manisha Patel, Lori Wirth, Thomas J Roberts","doi":"10.1200/PO-24-00741","DOIUrl":"https://doi.org/10.1200/PO-24-00741","url":null,"abstract":"<p><strong>Purpose: </strong>Immune checkpoint inhibitors (ICIs) are now first-line therapy for most patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), and cetuximab is most often used as subsequent therapy. However, data describing cetuximab efficacy in the post-ICI setting are limited.</p><p><strong>Methods: </strong>We performed a single-institution retrospective analysis of patients with R/M HNSCC treated with cetuximab, either as monotherapy or in combination with chemotherapy, after receiving an ICI. We extracted objective response rate (ORR), duration of treatment (DOT), and overall survival (OS) and compared them on the basis of patient characteristics. Multivariable models assessed associations between patient and tumor characteristics and outcomes.</p><p><strong>Results: </strong>We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC. Overall, the ORR was 21.4%, the median DOT was 1.9 months, and the median OS was 6.3 months. Patients receiving cetuximab with chemotherapy had a higher ORR (27.7% <i>v</i> 8.7%) and longer median DOT but similar OS compared with monotherapy. Virus-independent HNSCC had higher ORR (28.6% <i>v</i> 10.7%), longer DOT (3.3 <i>v</i> 1.2 months; hazard ratio [HR], 0.47 [95% CI, 0.25 to 0.90]), and longer OS (8.1 <i>v</i> 4.6 months; HR, 0.40 [95% CI, 0.19 to 0.83]). In multivariable models, virus-independent disease and negative smoking history were associated with improved OS. Concurrent chemotherapy, age, and sex were not associated with differences in OS. When assessing genomic data, <i>TP53</i> mutations were associated with improved DOT (HR, 0.33 [95% CI, 0.15 to 0.70]) and OS (HR, 0.38 [95% CI, 0.17 to 0.86]).</p><p><strong>Conclusion: </strong>Cetuximab-based therapy shows limited efficacy in R/M HNSCC post-ICI, although outcomes were better in virus-independent HNSCC and nonsmokers. The findings may improve prognostication and patient selection for cetuximab after ICI in R/M HNSCC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400741"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052678","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":"Association of Germline Pathogenic Variants in <i>MUTYH</i> and Other DNA Damage Response Genes With Lung Cancer Risk Among Non-Hispanic Whites and African Americans.","authors":"Matthew R Trendowski, Christine M Lusk, Angela S Wenzlaff, Christine Neslund-Dudas, Kristen S Purrington, Jennifer L Beebe-Dimmer, Ann G Schwartz","doi":"10.1200/PO-24-00558","DOIUrl":"10.1200/PO-24-00558","url":null,"abstract":"<p><strong>Purpose: </strong>Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs).</p><p><strong>Materials and methods: </strong>Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database. These P/LP variants were genotyped in a sample of 3,040 lung cancer cases and controls from the Inflammation, Health, Ancestry, and Lung Epidemiology study (NHW: n = 1,915; AA: n = 1,125) and were tested for their association with lung cancer using multivariate logistic regression adjusting for age, sex, pack-years, and race.</p><p><strong>Results: </strong>We identified 49 unique rare P/LP variants in 21 genes among 156 carriers. Approximately 5.9% of lung cancer cases and 4.2% of controls carried at least one P/LP variant. P/LP variants in DDR genes were more common in lung cancer cases, particularly those diagnosed with adenocarcinoma (odds ratio [OR], 1.46 [95% CI, 1.00 to 2.14]). <i>MUTYH</i> variants were associated with lung cancer overall (OR, 1.82 [95% CI, 1.10 to 3.12]), with the strongest associations among never smokers (OR, 3.37 [95% CI, 1.08 to 10.26]), and in individuals who do not meet current USPSTF screening criteria (OR, 2.85 [95% CI, 1.20 to 7.53]).</p><p><strong>Conclusion: </strong>Germline variants in DDR genes appear to be associated with lung cancer, particularly when examined by gene subtype and morphologic subtype. <i>MUTYH</i>, a gene historically associated with colorectal and other GI malignancies, emerged as a candidate gene that should be examined in individuals who do not have a significant smoking history.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400558"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033112","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":"Human Epidermal Growth Factor Receptor 2 Alterations and Prognostic Implications in All Subtypes of Breast Cancers.","authors":"Arielle L Heeke, Andrew Elliott, Kaitlyn O'Keefe, Chad Livasy, James T Symanowski, Meghan R Steiner, Irene M Kang, Dave S B Hoon, Philip Walker, George W Sledge, Milan Radovich, Paula R Pohlmann, Sandra M Swain, Antoinette R Tan","doi":"10.1200/PO.23.00719","DOIUrl":"https://doi.org/10.1200/PO.23.00719","url":null,"abstract":"<p><strong>Purpose: </strong>Alterations in human epidermal growth factor receptor 2 (HER2; <i>ERBB2</i> gene) may be clinically relevant when considering HER2-targeted therapies. We have characterized the breadth of <i>ERBB2</i> alterations (mutation, fusion, and copy number amplification) in breast cancer and explored the relationship between <i>ERBB2</i> alterations and prognosis.</p><p><strong>Methods: </strong>DNA next-generation sequencing (592-gene panel and whole-exome sequencing) and RNA whole-transcriptome sequencing data from 12,153 breast samples were retrospectively reviewed for <i>ERBB2</i> alterations. Clinicopathologic features were described, including breast cancer subtype, age, and biopsy site. HER2 status was determined according to ASCO guideline recommendations, including HER2-low. Overall survival (OS) data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for defined patient cohorts. Statistical significance was determined using chi-square and Wilcoxon rank-sum tests.</p><p><strong>Results: </strong>Pathogenic <i>ERBB2</i> mutations (<i>ERBB2-</i>mut) were identified in 3.2% (N = 388) of tumors overall, most common in liver metastases (113/1,972, 5.7%). <i>ERBB2-</i>mut was more common among breast lobular than ductal (10% <i>v</i> 2.1%; <i>P</i> < .001) and HER2-positive (HER2+)/low tumors (≥3.8% <i>v</i> 1.5% TNBC; <i>P</i> < .05). The most common variant was <i>ERBB2</i>-L755S (1.0% prevalence), enriched in metastatic tumors (1.2% <i>v</i> 0.6% in primary; <i>P</i> < .001). <i>ERBB2</i> fusions were rare (0.3% prevalence). Coalterations associated with <i>ERBB2</i>-mutated tumors compared with <i>ERBB2</i> wildtype (WT) included <i>CDH1</i> (40.0% <i>v</i> 10.2%; <i>P</i> < .001) and <i>ERBB3</i> (10.6% <i>v</i> 0.8%; <i>P</i> < .001). Of the 10,115 tumor samples with outcome data, <i>ERBB2-</i>mut was associated with worse OS compared with WT.</p><p><strong>Conclusion: </strong><i>ERBB2-</i>mut and fusions were observed in all breast cancer subtypes-more commonly in HER2+/low, metastatic, and lobular histology tumors-and associated with poorer prognosis.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2300719"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070895","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":"Prevalence of FGFR2b Protein Overexpression in Advanced Gastric Cancers During Prescreening for the Phase III FORTITUDE-101 Trial.","authors":"Sun Young Rha, Yanqiao Zhang, Anneli Elme, Roberto Pazo Cid, Ahmet Alacacioglu, Dimitrios C Ziogas, Kohei Shitara, Anastasija Ranceva, Radim Nemecek, Armando Santoro, Carlos Alberto Calderon, Krittiya Korphaisarn, Tracy Davis, Anita Zahlten-Kuemeli, Christopher Conn, Mengyao Tan, Hayden Honeycutt, Zev A Wainberg","doi":"10.1200/PO-24-00710","DOIUrl":"10.1200/PO-24-00710","url":null,"abstract":"<p><strong>Purpose: </strong>Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC.</p><p><strong>Methods: </strong>As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.gov identifier: NCT05052801) were centrally tested for FGFR2b protein overexpression by immunohistochemistry (IHC) and had evaluable results. FGFR2b positivity was defined as both any % tumor cells (TC) and ≥10% TC exhibiting moderate-to-strong (2+/3+) membranous FGFR2b staining. Prevalence was analyzed across patient and sample characteristics.</p><p><strong>Results: </strong>FGFR2b protein overexpression at any % and ≥10%, 2+/3+ TC positivity was 37.8% (1,428/3,782 [95% CI, 36.2 to 39.3]) and 16.2% (612/3,782 [95% CI, 15 to 17.4]), respectively. Of any %, 2+/3+ TC-positive tumors, 42.9% (612/1,428 [95% CI, 40.3 to 45.4]) were FGFR2b ≥10%, 2+/3+ TC positive. FGFR2b prevalence was not notably different within multiple patient and sample characteristics examined (age, sex, collection method [biopsy <i>v</i> resection], collection site, location of primary tumor, and geographic region).</p><p><strong>Conclusion: </strong>As of the data cutoff date, we report the largest prevalence assessment of FGFR2b protein overexpression in GC with more than one third (37.8%) of patients with GC exhibiting FGFR2b protein overexpression (any % TC, 2+/3+) by a validated IHC assay. Approximately 16% of patients had FGFR2b protein overexpression in ≥10% of TC. FGFR2b prevalence was similar across geographic regions and within defined patient and sample variables regardless of the level of expression.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400710"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>NTRK</i> Fusion-Positive Thyroid Carcinoma: From Diagnosis to Targeted Therapy.","authors":"Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas","doi":"10.1200/PO.24.00321","DOIUrl":"10.1200/PO.24.00321","url":null,"abstract":"<p><strong>Purpose: </strong>Neurotrophic tropomyosin receptor kinase (<i>NTRK</i>) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.</p><p><strong>Methods: </strong>This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.</p><p><strong>Results: </strong>We included 65 patients (37 adult, 28 pediatric) with an <i>NTRK</i> fusion-positive thyroid carcinoma (24 <i>NTRK1</i>, 41 <i>NTRK3</i>), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven anaplastic thyroid carcinomas (ATC). In PTC, an extensive follicular growth pattern was seen in 22 (41%) patients. In adults, <i>NTRK3</i> fusions were 3 times more frequent (nine <i>NTRK1</i>, 28 <i>NTRK3</i>), whereas in pediatric patients their frequencies were similar (15 <i>NTRK1</i>, 13 <i>NTRK3</i>; <i>P</i> = .021). In patients with PDTC/ATC treated with larotrectinib, we detected four emergent solvent front mutations (three <i>NTRK3</i> G623R, one <i>NTRK1</i> G595R) causing resistance to drug and disease progression. Three of them (two ATC, one PDTC) received second-line selitrectinib on a clinical trial. Partial responses were seen in all three patients, but both patients with ATC progressed within a year.</p><p><strong>Conclusion: </strong><i>NTRK1</i>/<i>3</i> fusions are seen in PTC, PDTC, and ATC, and a follicular growth pattern was observed in a high proportion of cases. In patients treated with larotrectinib, <i>NTRK</i> solvent front mutations are the main resistance mechanism, frequently occurring in PDTC/ATC. Responses to single-agent TRK inhibitor are short-lived in patients with ATC; thus, these drugs should be used with caution in this population.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400321"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472507","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":"Clinical Effectiveness and Cost-Effectiveness of Multigene Panel Sequencing in Advanced Melanoma: A Population-Level Real-World Target Trial Emulation.","authors":"Emanuel Krebs, Deirdre Weymann, Cheryl Ho, Alison Weppler, Ian Bosdet, Aly Karsan, Timothy P Hanna, Samantha Pollard, Dean A Regier","doi":"10.1200/PO-24-00631","DOIUrl":"10.1200/PO-24-00631","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted therapy and immunotherapy promise improved survival in patients with advanced melanoma, yet the effectiveness and cost-effectiveness of multigene panel sequencing compared with single-gene <i>BRAF</i> testing to guide therapeutic decisions is unknown.</p><p><strong>Methods: </strong>Our population-based quasi-experimental retrospective target trial emulation used comprehensive patient-level data for 364 British Columbia, Canada, adults with an advanced melanoma diagnosis receiving multigene panel sequencing or single-gene <i>BRAF</i> testing between September 1, 2016, and December 31, 2018. We 1:1 matched multigene panel patients to controls using genetic algorithm-based matching. Outcomes included 3-year overall survival (OS) and health care costs (2021 Canadian dollars [CAD]) with incremental net monetary benefit for life-years gained (LYG). Outcomes were analyzed using inverse probability of censoring weighted linear regression for the intention-to-treat (ITT) effect. The per-protocol (PP) effect estimation also included stabilized inverse probability of treatment weights. We then used Weibull regression and Kaplan-Meier survival analysis.</p><p><strong>Results: </strong>We matched 147 multigene panel patients to controls, achieving balance for all covariates. After matching, ITT incremental costs were $19,447 CAD (95% CI, -$18,516 to $76,006) and incremental LYG were 0.22 (95% CI, -0.05 to 0.49). We found uncertainty in differences on OS using Kaplan-Meier (<i>P</i> = .11) and Weibull regression (hazard ratio [HR], 0.73 [95% CI, 0.51 to 1.03]) in the ITT. PP incremental costs were $36,367 CAD (95% CI, -$6,653 to $120,216]) and incremental LYG were 0.56 (95% CI, 0.39 to 1.24), with corresponding differences in OS using Kaplan-Meier (<i>P</i> = .02) and Weibull regression (HR, 0.56 [95% CI, 0.36 to 0.87]). The probability of multigene panels being cost-effective at $100,000/LYG CAD was 55% for ITT and 65% for PP.</p><p><strong>Conclusion: </strong>The cost-effectiveness of multigene panels was evenly poised at higher thresholds, even when accounting for treatment initiation. Health systems reimbursing multigene panels and expensive therapies may be confronted with a value tradeoff, in which there may be improved survival albeit with a modest change in cost-effectiveness.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400631"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472508","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":"Comparison of PREMM5 and PREMMplus Risk Assessment Models to Identify Lynch Syndrome.","authors":"Leah H Biller, Kate Mittendorf, Miki Horiguchi, Alyson Caruso, Anu Chittenden, Chinedu Ukaegbu, Hajime Uno, Sapna Syngal, Matthew B Yurgelun","doi":"10.1200/PO-24-00691","DOIUrl":"10.1200/PO-24-00691","url":null,"abstract":"<p><strong>Purpose: </strong>Clinical risk assessment models can identify patients with hereditary cancer susceptibility, but it is unknown how multigene cancer syndrome prediction models compare with syndrome-specific models in assessing risk for individual syndromes such as Lynch syndrome (LS). Our aim was to compare PREMMplus (a 19-gene cancer risk prediction model) with PREMM5 (a LS gene-specific model) for LS identification.</p><p><strong>Methods: </strong>We analyzed data from two cohorts of patients undergoing germline testing from a commercial laboratory (n = 12,020) and genetics clinic (n = 6,232) with personal and/or family histories of LS-associated cancer. Individual PREMMplus and PREMM5 scores were calculated for all patients. Using a score cutoff of <math><mrow><mo>≥</mo></mrow></math>2.5%, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for identifying LS with each model. Overall ability to discriminate LS carriers from noncarriers was measured using receiver operating characteristic (ROC)-AUC.</p><p><strong>Results: </strong>PREMMplus had higher sensitivity than PREMM5 in the laboratory- (63.7% [95% CI, 57.0 to 70.0] <i>v</i> 89.2% [95% CI, 84.4 to 93.0]) and clinic-based cohorts (60.8% [95% CI, 52.7 to 68.4] <i>v</i> 90.5% [95% CI, 84.8 to 94.6]). NPV was ≥98.8% for both models in both cohorts. PREMM5 had superior discriminatory capacity to PREMMplus in the laboratory- (ROC-AUC, 0.81 [95% CI, 0.77 to 0.84] <i>v</i> 0.71 [95% CI, 0.67 to 0.75]) and clinic-based cohorts (ROC-AUC, 0.79 [95% CI, 0.75 to 0.84] <i>v</i> 0.68 [95% CI, 0.64 to 0.73]).</p><p><strong>Conclusion: </strong>Both PREMM5 and PREMMplus demonstrated high NPVs (>98%) in LS discrimination across all patient cohorts, and both models may be used to identify individuals at risk of LS. The choice of which model to use can be based on the goals of risk assessment and patient population.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400691"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947928","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":"Detecting Early Recurrence With Circulating Tumor DNA in Stage I-III Biliary Tract Cancer After Curative Resection.","authors":"James Yu, Aiwu Ruth He, Mahmoud Ouf, Rutika Mehta, Daniel A Anaya, Jason Denbo, Catherine Bridges, Antony Tin, Vasily N Aushev, Charuta C Palsuledesai, Shruti Sharma, Adham Jurdi, Minetta C Liu, Richard D Kim","doi":"10.1200/PO-24-00443","DOIUrl":"10.1200/PO-24-00443","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess (1) the prognostic value of circulating tumor DNA (ctDNA) and (2) the ability of ctDNA to detect recurrence compared with standard surveillance in curatively resected early-stage biliary tract cancer (BTC).</p><p><strong>Methods: </strong>This retrospective, multicenter cohort study evaluated serial ctDNA testing for surveillance in patients with early-stage BTC after curative resection. We evaluated the relapse-free survival (RFS) by ctDNA positivity. The sensitivity of ctDNA in detecting a confirmed recurrence of BTC, defined as a biopsy-proven or true progression by radiographic tumor dynamics, was evaluated. The lead time was calculated from the first ctDNA detection to the confirmed recurrence.</p><p><strong>Results: </strong>A total of 56 patients with curatively resected stage I-III BTC were included in this study, with a median follow-up of 12.8 months from the date of surgery. ctDNA detection during the molecular residual disease window period (median RFS, 6.6 months <i>v</i> not reached; hazard ratio [HR], 26 [95% CI, 2.6 to 265]; <i>P</i> < .0001) and during the surveillance period (median RFS, 19.3 months <i>v</i> not reached; HR, 20 [95% CI, 2.6 to 153]; <i>P</i> < .0001) were associated with poorer RFS. Sixteen patients had confirmed recurrence. ctDNA identified recurrence in 93.8.% (15/16) of the recurred patients with an average lead time of 3.7 months. Carbohydrate antigen 19-9 levels did not show any significant correlation with RFS (HR, 1.17 [95% Cl, 0.24 to 5.71]; <i>P</i> = .844) in contrast to ctDNA.</p><p><strong>Conclusion: </strong>The findings from our real-world cohort study revealed the (1) promising value of ctDNA as a prognostic biomarker for relapse in curatively resected BTC and (2) potential early detectability of recurrence by ctDNA compared with standard surveillance.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400443"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948416","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":"Digital Pathology-Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase III Trial in Men With Nonmetastatic Castration-Resistant Prostate Cancer.","authors":"Felix Y Feng, Matthew R Smith, Fred Saad, Pooya Mobadersany, Shaozhou K Tian, Stephen S F Yip, Joel Greshock, Najat Khan, Margaret K Yu, Sharon McCarthy, Sabine D Brookman-May, Ariel B Bourla, Tamara Todorovic, Rikiya Yamashita, Huei-Chung Huang, Trevor J Royce, Timothy N Showalter, Jacqueline Griffin, Akinori Mitani, Andre Esteva, Eric J Small","doi":"10.1200/PO-24-00653","DOIUrl":"https://doi.org/10.1200/PO-24-00653","url":null,"abstract":"<p><strong>Purpose: </strong>The SPARTAN trial demonstrated that the addition of apalutamide to androgen deprivation therapy improves outcomes among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). We applied a previously reported digital histopathology-based multimodal artificial intelligence (MMAI) algorithm to estimate clinical outcomes in SPARTAN.</p><p><strong>Methods: </strong>Patients with available hematoxylin and eosin-stained slides from the primary tumor were included. Histopathology slides were digitized. MMAI scores ranging from 0 to 1 were generated from digital histopathology and baseline clinical parameters. Patients were categorized into MMAI non-high-risk and high-risk groups using previously validated cutoffs. Kaplan-Meier estimates were calculated for metastasis-free survival (MFS), second progression-free survival (PFS2), and overall survival (OS); comparisons were performed using Cox proportional hazards regression for treatment arms and MMAI risk. The interaction between treatment arm and risk group was evaluated using a Cox proportional hazards model.</p><p><strong>Results: </strong>The study included 420 evaluable patients after excluding those with missing clinical data or inadequate histopathology images. Of these, 63% (n = 266) were MMAI high risk and 37% (n = 154) were non-high risk. MMAI risk score was associated with shorter MFS (hazard ratio [HR], 1.72; <i>P</i> < .005), PFS2 (HR, 1.57; <i>P</i> < .005), and OS (HR, 1.41; <i>P</i> = .02). MMAI high-risk patients receiving apalutamide demonstrated significant improvement in MFS (HR, 0.19; <i>P</i> < .005), PFS2 (HR, 0.47; <i>P</i> < .005), and OS (HR, 0.6; <i>P</i> = .01). The interaction between MMAI risk score and treatment for MFS (<i>P</i> = .01) and PFS2 (<i>P</i> = .03) was significant, indicating greater benefit from apalutamide treatment in MMAI high-risk patients.</p><p><strong>Conclusion: </strong>MMAI is a prognostic marker in nmCRPC and may serve as a predictive biomarker with high-risk patients deriving the greatest benefit from treatment with apalutamide. These results represent the first extension of an MMAI classifier to patients with castration-resistant prostate cancer, warranting additional validation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400653"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070892","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":"Tailored Approaches in the Treatment of Patients With Colorectal Cancer Harboring Tropomyosin Receptor Kinase Fusion and Microsatellite Instability-High: A Case Report and Literature Review.","authors":"Samuel Kim, Malak Itani, Xiuli Liu, Lulu Sun, Kilannin Krysiak, Nicole Fox, Belal Firwana, Sameer Al Diffalha, Upender Manne, Andreas Seeber, Molly Karl, Michele Frank, Hannah Stubblefield, Katrina Pedersen, Kian-Huat Lim, Hassan Abushukair, Moh'd Khushman","doi":"10.1200/PO.24.00305","DOIUrl":"https://doi.org/10.1200/PO.24.00305","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400305"},"PeriodicalIF":5.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070905","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}