JCO precision oncology最新文献

{"title":"Type II RAF Inhibitor Tovorafenib in Recurrent/Refractory Melanoma or Other Solid Tumors With <i>BRAF</i> Fusions or <i>CRAF/RAF1</i> Fusions or Amplification: Phase II FIRELIGHT-1 Substudy.","authors":"Maria Vieito, Elena Garralda Cabanas, Inderjit Mehmi, Caroline Gaudy-Marqueste, Bert H O'Neil, Theresa M Medina, Amy L Body, Ana Arance, Shivaani Kummar, Yana G Najjar, Philippe L Bedard, Andrew Rankin, Caroline Chu, Chris McKenna, Stephanie Hume, Lisa M Kopp, Jeeyun Lee","doi":"10.1200/PO-25-01187","DOIUrl":"10.1200/PO-25-01187","url":null,"abstract":"<p><strong>Purpose: </strong>Tovorafenib is an oral, selective, CNS-penetrant, type II inhibitor of BRAF and CRAF. <i>BRAF</i> fusions and <i>CRAF/RAF1</i> fusions and amplifications are rare oncogenic drivers in many solid tumors. The phase II DAY101-102a substudy of FIRELIGHT-1 (ClinicalTrials.gov identifier: NCT04985604) investigated the efficacy and safety of tovorafenib monotherapy in recurrent/refractory solid tumors with structural alterations in <i>BRAF</i> or <i>CRAF</i>.</p><p><strong>Patients and methods: </strong>Patients ≥12 years of age with a recurrent/refractory solid tumor with a <i>BRAF</i> fusion or <i>CRAF</i> fusion or amplification were enrolled into a melanoma cohort or tumor-agnostic cohort. The primary end point was overall response rate (ORR), as assessed by investigators. Tovorafenib was administered at 600 mg once weekly (adult dose), continuously, in 28-day cycles.</p><p><strong>Results: </strong>Twenty-three patients were enrolled; eight in the melanoma cohort and 15 in the tumor-agnostic cohort. The median age was 53 years (range, 21-71), and 57% of patients had ≥2 lines of prior therapy. Fourteen patients had tumors with <i>BRAF</i> fusion, six <i>CRAF</i> fusion, two <i>CRAF</i> amplification, and one <i>CRAF</i> fusions and amplification. The median duration of tovorafenib treatment was 5.3 months (range, 0.8-22.5). The ORR was 43% (10/23 patients), including 50% (4/8) in patients with melanoma and 40% (6/15) in patients with other tumors. The median time to response was 1.8 months. The median duration of response was 9.2 months. The most common treatment-related adverse events (any grade) were anemia (39%), pruritus (30%), increased creatine phosphokinase (26%), and rash (26%).</p><p><strong>Conclusion: </strong>Tovorafenib demonstrated single-agent clinical activity in solid tumors with <i>BRAF</i> fusions or <i>CRAF</i> fusions or amplification and had a manageable safety profile. Tovorafenib may offer a new targeted treatment option for adult patients with tumors harboring these rare genomic driver alterations.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 10","pages":"e2501187"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109540","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":"Medulloblastoma Spatial Transcriptomics Reveals Tumor Microenvironment Heterogeneity With High-Density Progenitor Cell Regions Correlating With High-Risk Disease.","authors":"Franklin Chien, Marina E Michaud, Mojtaba Bakhtiari, Chanel Schroff, Matija Snuderl, Jose E Velazquez Vega, Tobey J MacDonald, Manoj K Bhasin","doi":"10.1200/PO-25-01195","DOIUrl":"https://doi.org/10.1200/PO-25-01195","url":null,"abstract":"<p><strong>Purpose: </strong>No curative options are available for medulloblastoma (MB) in the relapse setting. The tumor microenvironment (TME) influences progression and therapy response, presenting a promising target for therapeutic advances. Prior single-cell analyses have characterized the cellular components of the TME but lack spatial context. We hypothesize that spatial architecture, beyond cell composition, influences tumor progression and treatment outcomes.</p><p><strong>Methods: </strong>We performed spatial transcriptomic sequencing on 18 pediatric MB samples obtained at diagnosis, including two matched diagnosis-relapse pairs. Samples at diagnosis were stratified into high- and standard-risk groups. Spatial data were analyzed for spatial proximity to other cell types, cell-cell communication networks, and expression of cell cycle dormancy signatures. Findings were validated using immunohistochemistry in the same cohort.</p><p><strong>Results: </strong>Our analyses revealed intertumoral and intratumoral heterogeneity within the TME, comprising tumor-associated astrocytes (TAAs), macrophages (TAMs), stromal components, and distinct subpopulations of MB cells at different stages of neuronal differentiation and cell cycle progression. We identified dense regions of quiescent progenitor-like MB cells enriched in patients with high-risk (HR) features and an increase in TAAs, TAMs, and dysregulated vascular endothelium following relapse.</p><p><strong>Conclusion: </strong>Our study presents novel insights into the spatial architecture and cellular landscape of the MB-TME, highlighting differential spatial patterns correlating with HR features. Future studies should evaluate their role in relapse and therapy resistance and may lead to uncovering novel therapeutic targets.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 10","pages":"e2501195"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181915","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":"Unlocking 30-Year-Old Archival Formalin-Fixed Paraffin-Embedded Breast Cancer Specimens (SWOG S8897): An Analytical Feasibility Study.","authors":"Donald J Johann, James Hicks, Kathy S Albain, William E Barlow, Andrew K Godwin, Daniel F Hayes, Laura F Hutchins, J Keith Killian, Erich A Peterson, Sergio Pina-Oviedo, Lajos Pusztai, James M Rae, Priyanka Sharma, Ik Jae Shin, Alastair M Thompson","doi":"10.1200/PO-26-00152","DOIUrl":"https://doi.org/10.1200/PO-26-00152","url":null,"abstract":"<p><strong>Purpose: </strong>Thin-cut formalin-fixed paraffin-embedded (FFPE) tumor sections on glass slides represent a large, underused biorepository for precision oncology, but their long-term room temperature storage raises concerns about nucleic acid integrity and analytical validity. We evaluated whether 20- to 30-year-old archival breast cancer FFPE slides could support contemporary DNA and RNA molecular profiling, including tumor subtyping using orthogonal DNA, and RNA-based approaches.</p><p><strong>Methods: </strong>Two archival cohorts were studied: (1) SWOG S8897 low-risk breast tumors stored as 6-µm unstained FFPE sections on slides for approximately 20-30 years (20 tumors; 19 matched cancer-free lymph nodes [LN]) and (2) similarly aged unrelated FFPE tumor blocks (n = 13) used for assay development. DNA and RNA were extracted with quality assurance/quality control. DNA profiling included low/ultra-low-pass whole genome sequencing for copy number analysis (CNA) and IntClust subtyping plus high-depth targeted sequencing using a 93-gene Unique Molecular Identifier (UMI)-based panel. RNA profiling included RNA-seq on block-derived specimens and a custom droplet digital polymerase chain reaction (ddPCR)-based reverse transcription-quantitative PCR (RT-qPCR) assay to enable subtype calling from highly fragmented RNA.</p><p><strong>Results: </strong>DNA and RNA were recovered from >90% of specimens, despite extensive fragmentation (RNA in a range of 30-100 nt). RNA Access/Exome and NanoString approaches were unsuccessful in the most degraded slide-derived RNAs, prompting development of the ddPCR-based RT-qPCR assay, which successfully quantified targets and enabled intrinsic-like subtype calling across archival tumors. DNA profiling achieved high success for CNA/subtyping and UMI-based mutation detection, and the dual RNA/DNA framework showed strong subtype concordance (ddPCR <i>v</i> IntClust approximately 87% among evaluable cases).</p><p><strong>Conclusion: </strong>Decades-old FFPE slide sections, stored at room temperature with no special conditions, can yield usable DNA along with highly degraded RNA for integrated multiomic molecular profiling and breast cancer subtyping. This capability expands access to legacy trial materials with long-term follow-up and supports efficient retrospective and virtual clinical trials.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 10","pages":"e2600152"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127583","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":"Sunitinib in Patients With Various Solid Tumors With <i>FGFR1</i>/<i>2</i> Alterations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.","authors":"Gordan Srkalovic, Michael Rothe, Elizabeth Garrett-Mayer, Kathryn F Mileham, Bamidele Adesunloye, Evan Pisick, Charles A Leath, Natalia Colocci, M Dwight Chen, Funda Meric-Bernstam, Alissa S Marr, Olatunji B Alese, Steven Powell, Jens Rueter, Amin Benyounes, Corbin Pontious, Mark A Lewis, Gary W Thomas, Yelena Kier, Carmen J Calfa, Margaret von Mehren, Jared D Acoba, Dominique C Hinshaw, Abigail Gregory, Gina N Grantham, Susan Halabi, Richard L Schilsky","doi":"10.1200/PO-26-00454","DOIUrl":"10.1200/PO-26-00454","url":null,"abstract":"<p><strong>Purpose: </strong>TAPUR 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 two cohorts of patients with various solid tumors with <i>FGFR1</i> or <i>FGFR2</i> alterations treated with sunitinib are reported.</p><p><strong>Methods: </strong>Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, 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+). Low accruing histology-specific cohorts with <i>FGFR1</i> or <i>FGFR2</i> alterations treated with sunitinib were collapsed into two histology-pooled cohorts for this analysis. The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test (alpha .10; 82% power) per cohort. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of SD, and safety.</p><p><strong>Results: </strong>Sixty-four patients with 20 different cancer types with <i>FGFR1</i> (N = 36) or <i>FGFR2</i> (N = 28) alterations were enrolled from April 2016 to June 2024 and collapsed into two histology-pooled cohorts (<i>FGFR1</i> and <i>FGFR2</i>) for analysis. Eight patients (all in the <i>FGFR1</i> cohort) were not evaluable for efficacy. DC rates for the <i>FGFR1</i> and <i>FGFR2</i> cohorts were 21% (one-sided 90% CI, 12 to 100) and 39% (one-sided 90% CI, 27 to 100), respectively. The null hypothesis was not rejected for the <i>FGFR1</i> cohort (<i>P</i> = .24) but was rejected for the <i>FGFR2</i> cohort (<i>P</i> = .0015). Twenty patients had at least one treatment-related grade 3-5 adverse event (AE) or serious AE.</p><p><strong>Conclusion: </strong>Sunitinib met the prespecified criteria to declare a signal of activity in patients with various solid tumors and <i>FGFR2</i> alterations but not <i>FGFR1</i> alterations.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 10","pages":"e2600454"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127611","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":"Genomic Landscape and Clinical Actionability of Skin Adnexal Carcinomas.","authors":"Valbert Oliveira Costa Filho, Mariana Macambira Noronha, Pedro Robson Costa Passos, Carlos Diego Holanda Lopes, Giuseppe G F Leite, Danielle Calheiros Campelo Maia, Carlos Wagner de Souza Wanderley, Samuel D Saibil, Erick F Saldanha","doi":"10.1200/PO-26-00300","DOIUrl":"https://doi.org/10.1200/PO-26-00300","url":null,"abstract":"<p><strong>Purpose: </strong>Skin adnexal carcinomas (SACs) are rare and heterogeneous tumors with no established systemic treatment options and poor long-term survival rates in the advanced disease setting. Here, we aimed to characterize the genomic landscape and clinically actionable alterations across SAC subtypes.</p><p><strong>Methods: </strong>We analyzed next-generation sequencing data from SACs in the American Association for Cancer Research Project GENIE. Mutations, copy number alterations, and structural variants were annotated using OncoKB. Actionable alterations were defined as Level 1-2 alterations or tumor mutational burden (TMB) ≥10 mut/Mb. TMB was compared across subtypes and with melanoma, cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC).</p><p><strong>Results: </strong>A total of 224 SACs were analyzed (49% extramammary Paget disease [EMPD], 33% apocrine/eccrine, 17% sebaceous, 1% follicular). In EMPD, the most frequent actionable alterations were in <i>PIK3CA</i> (25.7%) and <i>ERBB2</i> (22.9%). In sebaceous carcinoma, actionable alterations were mainly in <i>KRAS</i> (10.3%) and <i>PIK3CA</i> (10.3%). Apocrine/eccrine tumors also presented <i>ERBB2</i> and <i>PIK3CA</i> alterations, but at lower frequencies (5.5% and 8.2%, respectively). TMB-high occurred in 10.1% of EMPD, 28.2% of sebaceous, and 21.9% of apocrine/eccrine tumors, lower than in melanoma (52.1%), CSCC (64.4%), and BCC (63.3%). SAC drivers showed important heterogeneity across subtypes. Overall, 48.2% of SACs harbored at least one potentially actionable alteration.</p><p><strong>Conclusion: </strong>SACs frequently harbor clinically actionable alterations in a histotype-dependent manner. The identification of lineage-specific genomic differences underscores the clinical and translational relevance of integrating histology with genomic profiling for guiding therapeutic decision making.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 10","pages":"e2600300"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181852","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 Tumor-Informed Circulating Tumor DNA Dynamics and Survival Associations in Advanced Urothelial Cancer Treated With First-Line Enfortumab Vedotin and Pembrolizumab.","authors":"Vivek Nimgaonkar, Alyssa Arbuiso, Evangelia Vlachou, Burles Avner Johnson, Armine Smith, Max Kates, Sunil Patel, Nirmish Singla, Stephanie Russell, Kelli Rourke, Roy Elias, Andres Matoso, Ezra G Baraban, Noah M Hahn, Jean Hoffman-Censits","doi":"10.1200/PO-26-00691","DOIUrl":"https://doi.org/10.1200/PO-26-00691","url":null,"abstract":"<p><strong>Purpose: </strong>Enfortumab vedotin and pembrolizumab (EVP) is the standard first-line treatment for locally advanced and metastatic urothelial cancer (la/mUC) although response biomarkers remain an unmet need. Tumor-informed circulating tumor DNA (ctDNA) has proven to be useful as a marker of response in a variety of cancers. We sought to explore whether ctDNA dynamics is associated with survival outcomes.</p><p><strong>Methods: </strong>This retrospective study included patients with la/mUC receiving first-line EVP, who had plasma ctDNA collected using the Signatera assay within 3 months after treatment initiation. Associations between ctDNA clearance and overall survival (OS) and progression-free survival (PFS) were assessed using multivariable time-dependent Cox proportional hazard (CPH) models and landmark analyses at 1, 2, and 3 months after EVP initiation. Longitudinal ctDNA trends were examined in a subpopulation with baseline ctDNA values collected.</p><p><strong>Results: </strong>Fifty-eight patients were included. In multivariable time-dependent CPH models, ctDNA clearance was associated with both OS (hazard ratio [HR], 0.04 [95% CI, 0.01 to 0.24], <i>P</i> < .001) and PFS (HR, 0.09 [95% CI, 0.02 to 0.32], <i>P</i> < .001). In landmark analyses, ctDNA clearance was associated with longer OS and PFS at 2 months (log-rank test <i>P</i> = .003, <i>P</i> < .001, respectively). Among patients with baseline ctDNA (n = 42), 69% achieved ctDNA clearance after EVP initiation, whereas just 14% (n = 6) never had a decrease in ctDNA. The median time to clearance of ctDNA was 1.41 months (IQR, 0.85-1.94).</p><p><strong>Conclusion: </strong>While primarily hypothesis-generating, this study suggests that patients with la/mUC treated with first-line EVP frequently and rapidly clear ctDNA. Clearance of ctDNA in this population is associated with longer survival and merits further study.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 10","pages":"e2600691"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181984","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":"Plasma-Derived Genomic Instability Status and Rucaparib Outcomes in Metastatic Castration-Resistant Prostate Cancer: TRITON2.","authors":"Wassim Abida, Alan H Bryce, Simon Chowdhury, Akash Patnaik, Brooke Overstreet, Matthew Margolis, Pegah Safabakhsh, Karim Fizazi","doi":"10.1200/PO-26-00390","DOIUrl":"https://doi.org/10.1200/PO-26-00390","url":null,"abstract":"<p><strong>Purpose: </strong><i>BRCA1/2</i> mutation testing identifies patients with metastatic castration-resistant prostate cancer (mCRPC) eligible for poly(ADP-ribose) polymerase inhibitors; however, clinical outcomes remain heterogeneous within these genotypes. We evaluated whether plasma-derived genomic instability status (GIS) was associated with outcomes beyond <i>BRCA1/2</i> and <i>PALB2</i> mutation status in the phase II TRITON2 study.</p><p><strong>Methods: </strong>This retrospective biomarker analysis included TRITON2 patients with available baseline plasma profiled using Guardant360 Liquid. GIS is a probabilistic measure of homologous recombination deficiency (HRD) inferred from genome-wide copy number variants and somatic mutational signatures. Analyses were restricted to patients with baseline tumor fraction (TF) ≥ 25%. Radiographic progression-free survival (rPFS) was analyzed using Kaplan-Meier methods and Cox models adjusted for age and baseline TF. Secondary end points included objective response rate (ORR), serum prostate-specific antigen (PSA50) declines, and overall survival (OS).</p><p><strong>Results: </strong>Among 104 patients with TF ≥ 25%, 43 (41%) had GIS detected. Compared with GIS detected, absence of GIS was associated with shorter rPFS (hazard ratio [HR], 2.81 [95% CI, 1.61 to 4.93]; <i>P</i> <.001). Joint stratification demonstrated patients with both GIS detected and <i>BRCA/PALB2</i> mutation experienced the longest rPFS, whereas absence of GIS was associated with shorter rPFS regardless of <i>BRCA/PALB2</i> mutation status. In <i>BRCA2</i>-mutated patients, rPFS trended being longer in those with GIS detected (compared with those without GIS detected; HR, 2.02 [95% CI, 0.95 to 4.29]; <i>P</i> = .069), with numerically higher ORR (25.7% <i>v</i> 14.3%) and PSA50 response rate (65.7% <i>v</i> 42.9%). No statistically significant differences in OS were observed.</p><p><strong>Conclusion: </strong>Plasma-derived GIS was associated with improved rPFS and higher response rates in rucaparib-treated patients and further stratified outcomes within mutation-defined populations. These findings support genomic instability assessment as a complementary biomarker to mutation testing and warrant prospective validation.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 10","pages":"e2600390"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206893","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":"Anti-CD94 Monoclonal Antibody Dibotatug-Induced Response in a Refractory Primary CNS T-Cell Lymphoma.","authors":"Christian Grommes, Zhou Ting, Wan-Jen Hong, Lauren Schaff, Alissa Keegan, Ruoshi Shi, Marcel Smith, Alicia Assini, Ahmet Dogan, Steven Horwitz","doi":"10.1200/PO-26-00419","DOIUrl":"https://doi.org/10.1200/PO-26-00419","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600419"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919698","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":"Small Cell Lung Cancer Transformation in Actionable Genomic Alteration-Negative Non-Small Cell Lung Cancer With Response to Tarlatamab: A Case Report.","authors":"Cody E Cotner, Yin P Hung, Mari Mino-Kenudson, Justin F Gainor, Jessica J Lin","doi":"10.1200/PO-26-00538","DOIUrl":"https://doi.org/10.1200/PO-26-00538","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600538"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891211","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":"Clinical Relevance of Post-Treatment Circulating Tumor DNA Detection in Early Breast Cancer Using a Tissue-Free Epigenomic Assay: A 2-Year Landmark Analysis.","authors":"Thomas W P Friedl, Peter A Fasching, Andreas D Hartkopf, Hans Tesch, Ralf Lorenz, Georg Heinrich, Jens-Uwe Blohmer, Tanja Fehm, Volkmar Mueller, Andreas Schneeweiss, Matthias W Beckmann, Matthias Ruebner, Nadia Harbeck, Klaus Pantel, Derek Dustin, Mingyang Cai, Brigitte Rack, Wolfgang Janni","doi":"10.1200/PO-26-00095","DOIUrl":"10.1200/PO-26-00095","url":null,"abstract":"<p><strong>Purpose: </strong>Circulating tumor DNA (ctDNA) may serve as a biomarker to facilitate early identification of asymptomatic distant tumor spread in patients with breast cancer. The primary objective of this study was to assess clinical validity and prognostic value of post-treatment tissue-free ctDNA detection by evaluating its sensitivity for distant metastatic recurrence and its association with long-term outcomes.</p><p><strong>Patients and methods: </strong>Plasma samples were prospectively collected from patients with stage I-III early breast cancer who participated in the adjuvant SUCCESS-A phase III clinical trial (ClinicalTrials.gov identifier: NCT02181101). In this study, plasma samples collected approximately 2 years after completion of adjuvant chemotherapy from 313 SUCCESS A patients without evidence of prior disease recurrence were retrospectively analyzed using a tissue-free epigenomic ctDNA assay (Guardant Reveal). Survival analyses were performed using a landmark approach based on the time of sample collection.</p><p><strong>Results: </strong>Overall, ctDNA was detected in 18 of 313 samples (5.8%). Of all ctDNA detected samples, 94% (17/18) were from patients who subsequently developed a distant recurrence, with ctDNA detected at a median interval of 7.9 months before recurrence. ctDNA positivity was strongly associated with a significantly shorter distant recurrence-free interval (hazard ratio [HR], 33.3 [95% CI, 4.12 to 268]; <i>P</i> < .0001) and poorer overall survival (HR, 27.3 [95% CI, 1.15 to 647]; <i>P</i> < .0001). The sensitivity for distant recurrence in patients who had a sample collected within 1 year before recurrence was 73% (11/15). The specificity in nonrecurred patients was 99.6% (267/268).</p><p><strong>Conclusion: </strong>Tissue-free detection of ctDNA 2 years after adjuvant chemotherapy was highly prognostic in an early-stage breast cancer cohort, and can be used to stratify patients with early-stage breast cancer at high risk for recurrence during follow-up who may benefit from early interventions.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 9","pages":"e2600095"},"PeriodicalIF":4.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890989","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}