JCO precision oncology最新文献

{"title":"Erratum: 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-25-00058","DOIUrl":"https://doi.org/10.1200/PO-25-00058","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500058"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482112","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 Study of Copanlisib in Patients With PTEN Loss: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols Z1G and Z1H.","authors":"Mohamed A Gouda, Zihan Wei, Jordi Rodon, Michael A Davies, Filip Janku, Robert J Gray, Victoria Wang, Lisa M McShane, Larry V Rubinstein, David R Patton, P Mickey Williams, Stanley R Hamilton, Raymond Liu, Daniela A Bota, Paul L Swiecicki, Gary L Buchschacher, James V Tricoli, Barbara A Conley, Carlos L Arteaga, Lyndsay N Harris, Peter J O'Dwyer, Alice P Chen, Keith T Flaherty","doi":"10.1200/PO-24-00451","DOIUrl":"10.1200/PO-24-00451","url":null,"abstract":"<p><strong>Purpose: </strong>Copanlisib, a pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with activity predominantly against the PI3K-delta and PI3K-alpha isoforms, has shown promising results in preclinical cancer models with PTEN loss. Herein, we report the activity and safety data from the Z1G and Z1H subprotocols, which included patients with PTEN loss, of the National Cancer Institute Molecular Analysis for Therapy Choice trial.</p><p><strong>Methods: </strong>Patients with complete loss of cytoplasmic and nuclear PTEN as determined by immunohistochemistry regardless of <i>PTEN</i> mutation or deletion status were included in subprotocol Z1G, and patients with a deleterious mutation in the <i>PTEN</i> gene and retained expression of PTEN were included in subprotocol Z1H. Copanlisib was given intravenously over 1 hour at a dose of 60 mg on days 1, 8, and 15 in a 21-day-on and 7-day-off schedule in 28-day cycles. Patients continued treatment until disease progression or unacceptable toxicity.</p><p><strong>Results: </strong>Overall, 49 patients (20 patients in Z1G and 29 in Z1H) were included in the primary efficacy analyses. The objective response rates in both cohorts were 0% (Z1G; 90% CI, 0 to 13.9) and 3.4% (Z1H; 90% CI, 0.2 to 15.3), respectively. The median progression-free and overall survival durations were 1.8 months (90% CI, 1.4 to 3.9 months) and 13.7 months (90% CI, 6.8 to 18.3 months) for the Z1G cohort and 1.8 months (90% CI, 1.8 to 2.1 months) and 9.0 months (90% CI, 5.4 to 13.3 months) for the Z1H cohort, respectively.</p><p><strong>Conclusion: </strong>Our results do not support the antitumor activity of single-agent copanlisib in tumors with PTEN loss regardless of mutation or deletion status or <i>PTEN</i> deleterious mutations with PTEN expression.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400451"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364851","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":"Precision-Guided Durable Response From Venetoclax With Decitabine in a Patient With a Metastatic Refractory <i>IDH2</i>-Mutant Cholangiocarcinoma.","authors":"Eylül Özgü, Ünal Metin Tokat, Ashkan Adibi, Şevval Nur Bilgiç, Esranur Aydın, Onur Tutar, Mutlu Demiray","doi":"10.1200/PO-24-00652","DOIUrl":"https://doi.org/10.1200/PO-24-00652","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400652"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364853","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":"Challenging Conventional Diagnostic Methods by Comprehensive Molecular Diagnostics: A Nationwide Prospective Comparison in Children With ALL.","authors":"Judith M Boer, Marco J Koudijs, Lennart A Kester, Edwin Sonneveld, Jayne Y Hehir-Kwa, Simone Snijder, Esme Waanders, Arjan Buijs, Valérie de Haas, Inge M van der Sluis, Rob Pieters, Monique L den Boer, Bastiaan B J Tops","doi":"10.1200/PO-24-00788","DOIUrl":"10.1200/PO-24-00788","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment stratification in ALL includes diverse (cyto)genetic aberrations, requiring diverse tests to yield conclusive data. We optimized the diagnostic workflow to detect all relevant aberrations with a limited number of tests in a clinically relevant time frame.</p><p><strong>Methods: </strong>In 467 consecutive patients with ALL (0-20 years), we compared RNA sequencing (RNAseq), fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), karyotyping, single-nucleotide polymorphism (SNP) array, and multiplex ligation-dependent probe amplification (MLPA) for technical success, concordance of results, and turnaround time.</p><p><strong>Results: </strong>To detect stratifying fusions (<i>ETV6</i>::<i>RUNX1</i>, <i>BCR</i>::<i>ABL1</i>, ABL-class, <i>KMT2A</i>r, <i>TCF3</i>::<i>HLF</i>, <i>IGH</i>::<i>MYC</i>), RNAseq and FISH were conclusive for 97% and 96% of patients, respectively, with 99% concordance. RNAseq performed well in samples with a low leukemic cell percentage or low RNA quality. RT-PCR for six specific fusions was conclusive for >99% but false-negative for six patients with alternatively fused exons. RNAseq also detected gene fusions not yet used for stratification in 14% of B-cell precursor-ALL and 33% of T-ALL. For aneuploidies and intrachromosomal amplification of chromosome 21, SNP array gave a conclusive result in 99%, thereby outperforming karyotyping, which was conclusive for 64%. To identify deletions in eight stratifying genes/regions, SNP array was conclusive in 99% and MLPA in 95% of patients, with 98% concordance. The median turnaround times were 10 days for RNAseq, 9 days for FISH, 10 days for SNP array, and <7 days for MLPA and RT-PCR in this real-world prospective study.</p><p><strong>Conclusion: </strong>Combining RNAseq and SNP array outperformed current diagnostic tools to detect all stratifying genetic aberrations in ALL. The turnaround time is <15 days matching major treatment decision time points. Moreover, combining RNAseq and SNP array has the advantage of detecting new lesions for studies on prognosis and pathobiology.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400788"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527956","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":"Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers.","authors":"Mark Zobeck, Javed Khan, Rajkumar Venkatramani, M Fatih Okcu, Michael E Scheurer, Philip J Lupo","doi":"10.1200/PO-24-00556","DOIUrl":"10.1200/PO-24-00556","url":null,"abstract":"<p><strong>Purpose: </strong>Molecular markers increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.</p><p><strong>Methods: </strong>Clinical variables and somatic mutation data for 20 genes from 641 patients with RMS in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The Baseline Clinical (BC) model included treatment location, age, fusion status, and risk group. The Gene Enhanced 2 (GE2) model added <i>TP53</i> and <i>MYOD1</i> mutations to the BC predictors. The Gene Enhanced 6 (GE6) model further included <i>NF1</i>, <i>MET</i>, <i>CDKN2A</i>, and <i>MYCN</i> mutations, selected through least absolute shrinkage and selection operator regression. Model performance was assessed using likelihood ratio tests and optimism-adjusted, bootstrapped validation and calibration metrics.</p><p><strong>Results: </strong>The GE6 model demonstrated superior predictive performance compared with the BC model (<i>P</i> < .001) and GE2 model (<i>P</i> < .001). The GE6 model achieved the highest discrimination with a time-dependent area under the receiver operating characteristic curve of 0.766. Mutations in <i>TP53</i>, <i>MYOD1</i>, <i>CDKN2A</i>, <i>MET</i>, and <i>MYCN</i> were associated with higher hazards, while NF1 mutation correlated with lower hazard. Individual prognosis predictions varied between models in ways that may suggest different treatments for the same patient. For example, the 5-year EFS for a 10-year-old patient with high-risk, fusion-negative, <i>NF1</i>-positive disease was 50.0% (95% CI, 39 to 64) from BC but 76% (64 to 90) from GE6.</p><p><strong>Conclusion: </strong>Incorporating molecular markers into RMS prognosis models improves prognosis predictions. Individualized prognosis predictions may suggest alternative treatment regimens compared with traditional risk-classification schemas. Improved clinical variables and external validation are required before implementing these models into clinical practice.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400556"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364849","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":"Quantification of Microsatellite Instability Testing and Detection of Lynch Syndrome: Step Forward in Improving Mismatch Repair Testing in Clinical Practice.","authors":"Marija Staninova-Stojovska, Nadica Matevska-Geshkovska, Elizabeta Krstevska-Bozhinovikj, Rubens Jovanovic, Katerina Kubelka Sabit, Biljana Angelovska, Nenad Mitreski, Aleksandar Dimovski","doi":"10.1200/PO-24-00901","DOIUrl":"https://doi.org/10.1200/PO-24-00901","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400901"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527771","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 and Clinical Association of CD276 (B7-H3) Expression in Pleural Mesothelioma: Results From the European Thoracic Platform Mesoscape Project.","authors":"Martina Haberecker, Jan H Rüschoff, Charitini Andriakopoulou, Steven G Gray, Kristiaan Nackaerts, Marc De Perrot, Luka Brcic, Ernest Nadal, Sotirios Tsimpoukis, Luca Ampollini, Joachim G Aerts, Michaela B Kirschner, Kim Monkhorst, Birgit Weynand, Fatemeh Bavaghar-Zaeimi, Miroslav Samarzija, Roger Llatjos, Stephen P Finn, Enrico Silini, Jan Von Der Thüsen, Patrick Vagenknecht, Zoi Tsourti, Keith M Kerr, Roswitha Kammler, Solange Peters, Paul Baas, Isabelle Opitz, Rolf A Stahel, Alessandra Curioni-Fontecedro","doi":"10.1200/PO-24-00675","DOIUrl":"https://doi.org/10.1200/PO-24-00675","url":null,"abstract":"<p><strong>Purpose: </strong>CD276 (B7-H3) is an immunoregulatory protein that plays an important role in the inhibition of T-cell function. CD276 is overexpressed on a variety of human solid cancer cells with limited expression in normal tissues, making it an appealing target for innovative cancer immunotherapy approaches. Pleural mesothelioma (PM) is a highly aggressive disease with a need for new treatment options. Our objective was to investigate the expression of CD276 in the multicenter PM cohort of the European Thoracic Oncology Platform Mesoscape project and correlate the results with annotated clinical data.</p><p><strong>Materials and methods: </strong>Using tissue microarrays (TMAs), the expression of CD276, assessed using a semiquantitative aggregate <i>H</i>-score method on the membrane (and secondarily in the cytoplasm), was correlated with clinicopathologic characteristics and survival outcome.</p><p><strong>Results: </strong>CD276 immunohistochemistry results were available for 353 patients, with mostly epithelioid histology (71%). Membranous CD276 expression was present in 86%. High membranous CD276 expression (<i>H</i>-score ≥the median <i>H</i>-score of 120) was significantly more common in females (<i>P</i> = .0029; 71% <i>v</i> 47%) and in epithelioid histology (<i>P</i> < .001; 59% <i>v</i> 29%), whereas no significant association in clinical outcome (overall survival [OS]/progression-free survival) was found. Cross-validation of the TMA method using whole sections revealed a moderate agreement for membranous assessment (Cohen's kappa = 0.47) and a lower agreement for cytoplasm assessment (Cohen's kappa = 0.37). In an exploratory analysis, high cytoplasmic CD276 expression was associated with worse prognosis (OS, log-rank <i>P</i> = .043), but was not significant when adjusting for other clinical variables.</p><p><strong>Conclusion: </strong>Although no prognostic value of CD276 expression was found, its high membranous expression (86%) in the PM samples of the study supports further research of its potential as a therapeutic target for this disease.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400675"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408040","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":"Implementation of Cancer Genomics in the United States: Views of Payers and Other Stakeholders on Challenges and the Role of Payers in Solutions.","authors":"Julia R Trosman, Christine B Weldon, Allison W Kurian, Emily Mrig, Kathryn A Phillips","doi":"10.1200/PO-24-00822","DOIUrl":"10.1200/PO-24-00822","url":null,"abstract":"<p><strong>Purpose: </strong>Genomic testing is crucial in cancer risk identification, diagnosis, and treatment. However, health care implementation is challenging, even for tests covered by insurance. US payers are important health care participants and may contribute to addressing implementation challenges. We explored whether and how payers consider their role in genomic test implementation, and the perspectives of nonpayer stakeholders on payers' participation.</p><p><strong>Methods: </strong>We conducted a group interview with private payers (N = 12) to elucidate views on their role in genomic test implementation, implementation challenges, and potential solutions. Subsequently, we conducted individual interviews (N = 10) with nonpayer stakeholders-five cancer advocacy groups and five medical societies working in cancer, examining their reactions to payer input and capturing additional ideas. Qualitative research methods were used to frame the study and analyze results.</p><p><strong>Results: </strong>Payers considered cancer genomics implementation important and expressed willingness and ability to be involved. They articulated specific challenges relevant to them, including underutilization of covered tests in clinical practice, inequitable test use, and inconsistencies across guidelines, and suggested specific solutions to collaborate on with other stakeholders. Stakeholders viewed payers' participation in implementation as appropriate and feasible, expressed willingness to work with payers where relevant, and concurred with the key challenges noted by payers. Stakeholders' agreement with payers' solutions varied, but they offered additional ideas for addressing challenges.</p><p><strong>Conclusion: </strong>Both payers and other stakeholders considered payers' role in addressing genomics implementation challenges appropriate and feasible, and offered specific avenues for payer participation. Our findings inform efforts by payers and other stakeholders to address broad health care implementation. They may also help precision oncology professionals, cancer centers, and health systems to frame their own implementation efforts and influence a broader policy and implementation agenda.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400822"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527957","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-Time Monitoring in Renal Cell Carcinoma With Circulating Tumor DNA: A Step Forward, But How Far?","authors":"Zeynep B Zengin, Ritesh R Kotecha","doi":"10.1200/PO-25-00053","DOIUrl":"https://doi.org/10.1200/PO-25-00053","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500053"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527773","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 Susceptibility Gene Testing in Patients With Pancreatic Ductal Adenocarcinoma: Implementation in a Cancer Center Oncology Clinic.","authors":"Hassan Sinan, Dea Cunningham, Emy Abou Sleiman, Dana Petry, Thomas McPhaul, Kala Visvanathan, Deborah K Armstrong, Jin He, Richard Burkhart, Michael J Pishvaian, Lei Zheng, Neeha Zaidi, Nilofer S Azad, Daniel Laheru, Michael Goggins","doi":"10.1200/PO-24-00494","DOIUrl":"10.1200/PO-24-00494","url":null,"abstract":"<p><strong>Purpose: </strong>Current guidelines recommend offering genetic susceptibility testing to individuals with pancreatic cancer regardless of family history, but previous studies have reported only moderate test uptake, highlighting the need for efficient and accessible clinical pathways for delivering pretest genetic education and testing. We evaluated gene testing uptake offered at the point-of-oncology care by a nongenetics provider in an outpatient setting.</p><p><strong>Methods: </strong>A retrospective chart review was performed of patients with pancreatic cancer treated at the Johns Hopkins Hospital between January 2021 and December 2023. During their initial clinic visit, patients were educated about germline testing by an oncology nurse and provided with educational and instructional handouts and video links, including how to arrange testing (with saliva) with a commercial testing provider. Patients with pathogenic variants and variants of uncertain significance were referred for genetic counseling.</p><p><strong>Results: </strong>Of the 992 patients seen in the oncology clinic (52.1% male, 75.4% White, 15.4% African American, 6% Asian; median age at diagnosis, 66.9 ± 10.6 years), 90% were offered testing, 77.6% of whom completed it. Factors significantly associated with not going forward with testing included being single, older age, African American, and having advanced-stage disease. Among the tested individuals, 78 (11.3%) had a pathogenic variant identified, including 55 (7.9%) with a pancreatic cancer susceptibility gene variant; of these, 72 (92.3%) were referred for genetic counseling and 50 (69.4%) completed their counseling visit. Testing led to a change in chemotherapy regimen in 28 patients.</p><p><strong>Conclusion: </strong>The implementation of point-of-care encounters for cancer susceptibility gene testing by an oncology nurse in the outpatient setting yielded a high uptake of testing. Additional approaches are needed to increase testing rates and cancer genetics visits.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400494"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11824855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407985","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}