JCO precision oncology最新文献

{"title":"Real-World Experience of Tarlatamab in Extensive-Stage Small Cell Lung Carcinoma Showed Promising Systemic and Intracranial Efficacy With Higher Neurologic Toxicity.","authors":"Mitchell Parma, Kaiwen Wang, Ceylan Altintas Taslicay, Komal Shah, Eric K Singhi, Melvin Rivera, Luisa Solis Soto, Wei-Lien Wang, Lingzhi Hong, Ziping Li, Mehmet Altan, Maria Franco Vega, Patricia de Groot, Alexa Halliday, Joshua Jacome, Jianjun Zhang, Xiuning Le, Jenny Pozadzides, Janet Tu, Celyne Bueno Hume, George Blumenschein, Ferdinandos Skoulidis, Tina Cascone, Frank Fossella, Marcelo Vailati Negrao, Natalie Vokes, Don Gibbons, Haniel Araujo, Anne Tsao, John Victor Heymach, Lauren Averett Byers, Carl Michael Gay, Bingnan Zhang","doi":"10.1200/PO-25-00836","DOIUrl":"https://doi.org/10.1200/PO-25-00836","url":null,"abstract":"<p><strong>Purpose: </strong>Tarlatamab, a CD3/delta-like ligand 3 bispecific T-cell engager, was approved in 2024 for relapsed extensive-stage small cell lung cancer (ES-SCLC) based on promising clinical trial results. As a T-cell effector therapy, it also has unique side effects, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In this article, we report a real-world series of patients treated with tarlatamab.</p><p><strong>Materials and methods: </strong>We retrospectively evaluated safety and efficacy in patients with relapsed ES-SCLC receiving tarlatamab from July 1, 2024, to February 15, 2025, at MD Anderson Cancer Center, including clinical response and toxicity and the radiographic response of brain metastases (BM) per Response Assessment in Neuro-Oncology (RANO)-BM.</p><p><strong>Results: </strong>27 patients were included in our analyses. The median age was 68 (range, 43-83) years, and 15 patients (56%) were women. Before tarlatamab, nine patients (33%) had no BM, and 11 (41%) had active, untreated BM. Of the 22 patients evaluable for response with a median follow-up time of 3 months, four patients (18.2%) had partial response (PR), 71 (31.8%) had stable disease (SD), and 11 (50%) had progressive disease (PD) based on RECIST criteria. Median progression-free survival was 5.9 months (95% CI, 2.6 to not reached). Of the 14 patients with prior BM and serial brain magnetic resonance imaging, based on RANO-BM criteria, two had complete response, one had PR, nine had SD, and only two had PD. Of the four patients without BM, none had new intracranial disease after starting tarlatamab. Of the 27 patients who received cycle 1 day 1 (C1D1) of tarlatamab, 10 (37%) patients developed CRS (1 grade ≥3) and 8 (30%) had ICANS (4 grade ≥3). Of the 25 patients who received C1D8 of tarlatamab, 10 (40%) developed CRS (1 grade ≥3) and 4 (16%) developed ICANS (none grade ≥3).</p><p><strong>Conclusion: </strong>Tarlatamab demonstrates both intracranial and extracranial efficacy in our real-world patient cohort. Our cohort's toxicity profile showed similar CRS but higher ICANS rates compared with those reported in clinical trials. More studies are needed to determine biomarkers of efficacy and toxicity.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2500836"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772108","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":"Prognostic Value of MammaPrint in Diverse Populations: Evaluating Racial Disparities in Breast Cancer Outcomes.","authors":"Reine Abou Zeidane, Samuel Lichtman-Mikol, Courtney Pisano, Benjamin Hauk, Yilun Sun, Priyanka S Rana, Citlally Lopez-Flores, Breanna N McBean, Kassidy M Jungles, Trisha Lal, Nihit Mehta, Philip Bomeisl, Amanda L Amin, Alberto J Montero, Siran Koroukian, Johnie Rose, Janice Lyons, Corey W Speers","doi":"10.1200/PO-25-00926","DOIUrl":"https://doi.org/10.1200/PO-25-00926","url":null,"abstract":"<p><strong>Purpose: </strong>MammaPrint (MP), a 70-gene expression profile assay, informs treatment decisions in early-stage breast cancer by classifying patients into high or low risk of recurrence categories. However, racial disparities in breast cancer outcomes necessitate an evaluation of MP's prognostic utility across diverse populations. This study explores differences in MP scores and associated outcomes among women of various racial backgrounds.</p><p><strong>Materials and methods: </strong>We retrospectively analyzed women with early-stage breast cancer who underwent MP testing (2013-2023) at University Hospitals Seidman Cancer Center. Patients were stratified by self-reported race and MP scores (high <i>v</i> low risk). Clinical outcomes, including recurrence-free survival (RFS) and overall survival (OS), were compared using Kaplan-Meier and Cox proportional hazards models.</p><p><strong>Results: </strong>Among 1,349 women, 15.7% were African American (AA), 83.4% White, 0.6% Asian, and 0.3% from other racial groups. Overall, 64.7% had low-risk and 35.3% had high-risk scores. AA women had a significantly higher proportion of high-risk MP scores compared with White women (49.1% <i>v</i> 32.7%). Although the 5-year RFS rates were comparable between AA and White women (76.5% <i>v</i> 77.2%), the 5-year OS rates were slightly lower for AA women compared with White women (77.8% <i>v</i> 78.2%). MP remained prognostic for RFS at 3, 5, and 10 years regardless of race. Multivariable analysis revealed no significant differences in OS (hazard ratio [HR], 0.94 [95% CI, 0.47 to 1.89]; <i>P</i> = .866) or RFS (HR, 0.83 [95% CI, 0.43 to 1.59]; <i>P</i> = .572) between AA and White women after adjusting for MP risk groups and other clinical factors. High-risk MP scores were associated with worse OS (HR, 3.06 [95% CI, 1.64 to 5.70]; <i>P</i> < .001) and RFS (HR, 2.68 [95% CI, 1.55 to 4.62]; <i>P</i> < .001) compared with low-risk scores. Other factors associated with worse RFS and OS were tumor size, nodal involvement, and age. Interaction models indicated no difference is OS or RFS in AA women and White women with either low-risk or high-risk MP, respectively.</p><p><strong>Conclusion: </strong>Despite AA women exhibiting a higher proportion of high-risk MP scores, survival outcomes were comparable with those of White women. These findings underscore MP's consistent prognostic performance across racial groups but further highlight the need to address additional clinical and social determinants influencing breast cancer outcomes beyond genomic risk alone.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2500926"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645334","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":"Inverse Relation Between Responses to Pembrolizumab Plus Chemotherapy and Subsequent Cetuximab Plus Paclitaxel in Head and Neck Cancer: Role of the Janus Kinase-Signal Transducer and Activator of Transcription Signaling Pathway.","authors":"Ken Saijo, Hiroo Imai, Tomoyuki Iwasaki, Ryo Ishii, Kenjiro Higashi, Akira Ohkoshi, Yuto Yamazaki, Tomoaki Shirakawa, Ryo Saito, Shonosuke Wakayama, Ryunosuke Numakura, Yuya Yoshida, Sakura Taniguchi, Yuki Kasahara, Kota Ouchi, Keigo Komine, Hidekazu Shirota, Masanobu Takahashi, Takashi Suzuki, Yukio Katori, Chikashi Ishioka, Hisato Kawakami","doi":"10.1200/PO-25-01050","DOIUrl":"https://doi.org/10.1200/PO-25-01050","url":null,"abstract":"<p><strong>Purpose: </strong>Cetuximab plus paclitaxel (CET + PTX) is frequently administered after immune checkpoint inhibitor (ICI) therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, the relation between responses to these two treatment lines has remained unclear. We aimed to clarify this relation and its potential mechanisms, focusing on the patients treated with pembrolizumab plus chemotherapy and subsequent CET + PTX.</p><p><strong>Patients and methods: </strong>We retrospectively reviewed patients with R/M-HNSCC who received pembrolizumab plus chemotherapy and subsequent CET + PTX at Tohoku University Hospital between April 2020 and November 2025. Clinical outcomes of CET + PTX were assessed according to response to prior pembrolizumab plus chemotherapy. Gene expression and immunohistochemical (IHC) analyses of pretreatment tumor samples, as well as HNSCC cell-based assays, were performed.</p><p><strong>Results: </strong>This study included 30 patients. The overall response rate (ORR) to subsequent CET + PTX was 57%. The ORR and progression-free survival (PFS) of CET + PTX were significantly greater in patients who showed progressive disease on pembrolizumab plus chemotherapy than in responders (<i>P</i> < .01). Gene expression analyses revealed enrichment of Janus kinase (JAK)-STAT signaling pathways in pembrolizumab plus chemotherapy nonresponders who responded to CET + PTX. Consistently, high tumor expression of phosphorylated STAT3 was observed exclusively in this subgroup by IHC. CET sensitivity across HNSCC cell lines correlated with STAT3 phosphorylation.</p><p><strong>Conclusion: </strong>Responses to pembrolizumab plus chemotherapy and subsequent CET + PTX were inversely associated in R/M-HNSCC. Activation of the JAK-STAT signaling pathway, particularly STAT3 phosphorylation, may identify tumors resistant to pembrolizumab plus chemotherapy but sensitive to CET + PTX, thereby guiding post-ICI treatment selection.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2501050"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772010","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":"Does Longitudinal Targeted Panel Sequencing Provide Clinically Relevant Information in Translocation-Associated Sarcomas?","authors":"Mohamed A Yakoub, Carla Saoud, Damon R Reed, Leonard Wexler, Emily Slotkin, William D Tap, Meera Hameed, Cristina R Antonescu","doi":"10.1200/PO-25-00909","DOIUrl":"https://doi.org/10.1200/PO-25-00909","url":null,"abstract":"<p><strong>Purpose: </strong>Translocation-associated sarcomas (TAS) represent a heterogeneous group of pathologic entities characterized by specific gene fusions and a low tumor mutational burden (TMB). Although RNA sequencing remains the hallmark molecular platform to establish the fusion type, targeted panel DNA next-generation sequencing (NGS) has been increasingly used in TAS to identify actionable alterations as well as potential mechanisms of resistance to therapy.</p><p><strong>Materials and methods: </strong>We herein investigate sequential targeted DNA sequencing (Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets) in a large cohort of 108 TAS, spanning six most common subtypes, with available longitudinal sequencing.</p><p><strong>Results: </strong>Overall, 53% of cases acquired alterations (n = 122) compared with the initial testing, of which 33 (27%) were oncogenic/likely oncogenic. Only two of the five patients with >3 tests/each acquired oncogenic mutations. Overall, 21% of cases did not acquire alterations in any assay. Subsequent NGS was initiated after systemic treatment (93%) and disease progression (83%). The number of oncogenic acquired alterations did not correlate with histotype (mean 0.4/case). In sequential NGS, the mean mutation count, TMB, and fraction of genome altered were significantly higher (<i>P</i> < .001, .04, and .03, respectively) compared with baseline. <i>TP53</i> alteration was the most common acquired mutation (10%), being detected mostly in the subsequent assay. By contrast, other common alterations, such as <i>STAG2</i> in Ewing sarcoma and gene amplifications in alveolar rhabdomyosarcoma, were detected at diagnosis. Although 27% of pathogenic alterations in the initial and 9% in the subsequent NGS were deemed as OncoKB levels 1-2 for other cancers, none were relevant for sarcomas.</p><p><strong>Conclusion: </strong>The role of multiple NGS testing in the context of TAS remains undetermined.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2500909"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771995","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":"Nivolumab Plus Ipilimumab in Patients With Solid Tumors With High Tumor Mutation Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.","authors":"Erin F Cobain, Michael Rothe, Elizabeth Garrett-Mayer, Timothy L Cannon, John K Chan, Kathryn F Mileham, Bamidele Adesunloye, Carmen J Calfa, Olatunji B Alese, Kathleen Yost Butler, Elie G Dib, Evan Pisick, Maria Bell, Kelsey A Klute, Inderjit Mehmi, Funda Meric-Bernstam, Pam K Mangat, Dominique C Hinshaw, Abigail Gregory, Gina N Grantham, Susan Halabi, Richard L Schilsky","doi":"10.1200/PO-25-01205","DOIUrl":"https://doi.org/10.1200/PO-25-01205","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of three cohorts of patients with colorectal cancer (CRC), breast cancer (BC), and other solid tumors (histology-pooled [HP]) with high tumor mutation burden (HTMB) treated with nivolumab plus ipilimumab (N + I) are reported.</p><p><strong>Methods: </strong>Eligible patients had tumors with HTMB (≥10 mutations per megabase), measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no 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. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was evaluated by a one-sided exact binomial test (α = .10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety.</p><p><strong>Results: </strong>Patients with CRC (N = 12), BC (N = 13), or other advanced cancers (N = 26) with HTMB were enrolled. The CRC cohort failed to reach the predetermined efficacy threshold to warrant expansion at the end of stage I. The BC cohort expanded to stage II but closed by company request before achieving the planned sample size. The DC rates (one-sided 90% CI) for BC and HP cohorts were 33% (15-100, <i>P</i> = .0976) and 32% (20-100), respectively. The null hypothesized 15% DC rate was rejected for the BC and HP cohorts but not the CRC cohort. Nineteen patients experienced treatment-related grade 3 adverse events (AE) or serious AEs.</p><p><strong>Conclusion: </strong>N + I demonstrated antitumor activity in patients with tumors with HTMB in the BC and HP cohorts but not the CRC cohort.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2501205"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814863","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":"Pertuzumab and Trastuzumab in Patients With <i>ERBB2/3</i>-Altered Urothelial or Ovary/Fallopian Tube Cancer: Results From the Targeted Agent and Profiling Utilization Registry Study.","authors":"John K Chan, Michael Rothe, Elizabeth Garrett-Mayer, Evan Pisick, Pooja Ghatalia, Andrew Gregory, Mollie deShazo, Kathryn F Mileham, Martina C Murphy, Olatunji B Alese, Elie G Dib, Peter C Kohler, Justin T Moyers, Pam K Mangat, Dominique C Hinshaw, Abigail Gregory, Gina N Grantham, Susan Halabi, Richard L Schilsky","doi":"10.1200/PO-25-01250","DOIUrl":"https://doi.org/10.1200/PO-25-01250","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 urothelial (UC) or ovarian/fallopian tube cancer (OC/FTC) with <i>ERBB2/3</i> alterations treated with pertuzumab plus trastuzumab (P + T) are reported.</p><p><strong>Methods: </strong>Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with <i>ERBB2/3</i> alterations, and no 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. Simon's two-stage design is based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety.</p><p><strong>Results: </strong>Patients with UC (n = 28) or OC/FTC (n = 25) with <i>ERBB2/3</i> alterations were enrolled from March 2017 to June 2023. In the UC cohort, the DC and OR rates were 37% (90% CI, 24 to 100) and 25% (95% CI, 11 to 45), respectively. The null hypothesis of 15% DC rate was rejected (<i>P</i> = .005). In the OC/FTC cancer cohort, the DC and OR rates were 23% (90% CI, 9 to 100) and 8% (95% CI, 1 to 26), respectively. The null hypothesis of 15% DC rate was not rejected (<i>P</i> = .35). Six patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to treatment.</p><p><strong>Conclusion: </strong>The combination of P + T met prespecified criteria to declare a signal of activity in patients with UC with <i>ERBB2/3</i> alterations, but not in patients with OC/FTC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2501250"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814963","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":"Living Guidelines for Tumor-Agnostic Therapies: A Pathway to Next-Generation Cancer Treatment.","authors":"Vivek Subbiah, Thomas K Oliver, Jim Palma, Razelle Kurzrock","doi":"10.1200/PO-25-00767","DOIUrl":"https://doi.org/10.1200/PO-25-00767","url":null,"abstract":"<p><p>Tumor-agnostic therapies represent a transformative shift in oncology, targeting molecular alterations irrespective of cancer histology. These therapies offer new hope for patients with rare and difficult-to-treat malignancies, yet their integration into clinical practice remains inconsistent because of the absence of guidelines. Traditional organ-based classifications hinder timely access to precision treatments, despite evidence supporting molecular-driven approaches. Living guidelines, continuously updated frameworks based on emerging data, are essential to bridge this gap. They enable just-in-time incorporation of new therapies, streamline biomarker-driven care, and address the unique needs of rare and ultrarare cancers. Regulatory approvals for tumor-agnostic agents, such as NTRK inhibitors and immunotherapies for microsatellite instability-high/mismatch repair-deficient tumors, underscore the urgency for unified guidance. Trials like TAPUR, TRACK, and NCI-MATCH demonstrate the feasibility and benefit of molecular profiling across diverse cancer types. Tools like ESMO's ETAC-S provide structured criteria for evaluating tumor-agnostic potential, yet real-world implementation lags. Living guidelines can harmonize testing practices, improve access, and educate clinicians on cross-tumor applicability. They also facilitate proactive biomarker testing, reduce treatment delays, and enhance patient safety through tailored toxicity management. As oncology evolves toward molecular precision, living tumor-agnostic guidelines are critical for ensuring equitable, evidence-informed care for all patients, particularly those with rare cancers. National organizations must prioritize their development to fully realize the promise of precision medicine.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2500767"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616044","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":"Longitudinal, Retrospective Use of a Circulating Tumor DNA Methylation Signature Successfully Captures Small Cell Evolution in a Patient With Metastatic EGFR-Mutant Non-Small Cell Lung Cancer.","authors":"Tejas Patil, Amy Guimarães-Young, Jill Tsai, Dara L Aisner, Leslie Bucheit, Anton Valouev","doi":"10.1200/PO-25-00795","DOIUrl":"10.1200/PO-25-00795","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2500795"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616104","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":"Circulating Tumor DNA Monitoring in Peptide Receptor Radionuclide Therapy-Treated Patients With Gastroenteropancreatic Neuroendocrine Tumors.","authors":"Christina Bogdani, Anita Karimi, Richard Li, Emily C Atkinson, Paul E Oberstein, Despina Siolas","doi":"10.1200/PO-25-00833","DOIUrl":"10.1200/PO-25-00833","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2500833"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616115","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":"Genome Sequencing of Undiagnosed European Patients Suspected of Hereditary Cancer: Diagnostic Yield and Identification of Candidate Causative Variants.","authors":"Nelson Martins, Mariona Terradas, José Garcia-Pelaez, Anna K Sommer, German Demidov, Leslie Matalonga, Mireia Ramos-Muntada, Iris B A W Te Paske, Isabel Spier, Arjen Mensenkamp, Janneke Schuurs-Hoeijmakers, Irene Gullo, Celina São José, Ana Maria Pedro, Raquel Gouveia Silva, Ana Berta Sousa, Pedro Amoroso Canão, Susana Fernandes, Luzia Garrido, Juliette Dupont, Sofia Maia, Gabriela Sousa, Arvids Irmejs, Valeria Barili, Ana Blatnik, Paula Rofes, Joan Brunet, Gabriel Capellá, Steven Laurie, Conxi Lázaro, Nicoline Hoogerbrugge, Richarda M de Voer, Stefan Aretz, Carla Oliveira, Laura Valle","doi":"10.1200/PO-25-00354","DOIUrl":"10.1200/PO-25-00354","url":null,"abstract":"<p><strong>Purpose: </strong>Hereditary cancers represent 5%-10% of all cancers, typically characterized by familial aggregation, early onset, and/or multiple primary tumors. Isolated cases with extreme early-onset or multiple unrelated cancers are rare and frequently underdiagnosed. This study aimed to improve genetic diagnostic yield in unresolved patients with strong clinical suspicion of hereditary cancer. Inclusion criteria were (1) ≥4 primary tumors in different organs (or ≥3 if two are rare), (2) adult-type cancers at ≤25 years, or (3) profuse gastrointestinal adenomatous polyposis before age 50 years or profuse polyposis of unknown type before age 30 years.</p><p><strong>Methods: </strong>Germline DNA from 98 patients selected through ERN-GENTURIS underwent short-read whole-genome sequencing (WGS). Ninety had received negative results from standard genetic testing, whereas eight had not been tested. Variant analysis was performed using the RD-Connect GPAP and Solve-RD frameworks.</p><p><strong>Results: </strong>Pathogenic or likely pathogenic variants in phenotype-related high-penetrance genes were found in 6% of patients, including <i>APC</i> and <i>TP53</i> mosaicisms and germline variants in <i>TP53</i>, <i>BAP1</i>, <i>BARD1</i>, and <i>MBD4</i> (homozygous). Three patients carried pathogenic variants in hereditary cancer genes unrelated to their phenotype, and a heterozygous <i>ERCC3</i> pathogenic variant was detected in a young patient with breast cancer. Suggestive variants of uncertain significance were identified, including a chromosome 3 inversion affecting <i>VHL</i> and <i>MLH1</i> in a patient with renal and gastric cancers. Potentially regulatory noncoding variants in phenotype-associated genes were observed in 15% of patients (22 variants).</p><p><strong>Conclusion: </strong>Comprehensive resequencing of patients suspected of hereditary cancer increased the diagnostic yield by 6%. Detected pathogenic variants involved phenotype-related genes not previously analyzed or missed because of mosaicism. WGS further enables identification of novel gene associations and structural, deep intronic, or regulatory variants.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"10 4","pages":"e2500354"},"PeriodicalIF":5.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698371","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}