JCO precision oncology最新文献

{"title":"ALK Inhibition With Alectinib for Refractory Metastatic Renal Cell Carcinoma With ALK Rearrangement: A Rare Case Report and Literature Review.","authors":"Nikhita Kathuria-Prakash, Lidia P Lopez, Steven Raman, Huihui Ye, Jordan Anaokar, Anthony Sisk, Allan J Pantuck, Alexandra Drakaki","doi":"10.1200/PO.24.00154","DOIUrl":"https://doi.org/10.1200/PO.24.00154","url":null,"abstract":"<p><p>ALK-rearranged RCC refractory to several lines of treatment has a durable response when treated with alectinib.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419194","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":"Poly(ADP-Ribose) Polymerase Inhibitor Development: Promising Strategies to Move Beyond Approved Indications.","authors":"Carlos Torrado, Ruth Plummer, Timothy A Yap","doi":"10.1200/PO.24.00204","DOIUrl":"10.1200/PO.24.00204","url":null,"abstract":"<p><p>Biomarker-based patient selection and rational combinations show promise in expanding the use of PARP inhibitors.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310699","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":"Keratin-Positive Giant Cell Tumor of Bone and Soft Tissue With <i>HMGA2::NCOR2</i> Fusion in Children Under 10 With Response to Imatinib Therapy: A Case Series.","authors":"Phassawan Rungsiprakarn, Anne L Ryan, Daniel D Wong, Minjie Luo, Ken Kazahaya, Alexandre Arkader, Loretta M S Lau, Pamela Ajuyah, Erin Rudzinski, Portia A Kreiger, Derek J Roebuck, Lea F Surrey, Tiffany S Y Foo","doi":"10.1200/PO.23.00659","DOIUrl":"10.1200/PO.23.00659","url":null,"abstract":"<p><p>HMGA2::NCOR2 keratin-positive giant cell tumors in children with response to imatinib in an infant.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468088","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":"Inherited Germline Variants in Urinary Tract Cancer: A Multicenter Whole-Exome Sequencing Analysis and Correlation With Clinical Features and Tumor Genomics.","authors":"Wendy Kohlmann, David A Nix, Kristen Pauley, Samantha Greenberg, Aaron Atkinson, Kenneth M Boucher, Jill Kolesar, Eric A Singer, Stephen B Edge, Michelle L Churchman, Laura Graham, Bodour Salhia, Alejandro Sanchez, Yousef Zakharia, Kenneth G Nepple, Bryan P Schneider, Lindsey Byrne, Rohit K Jain, Jad Chahoud, Bing-Jian Feng, Sumati Gupta","doi":"10.1200/PO.23.00697","DOIUrl":"10.1200/PO.23.00697","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates a real-world multicenter cohort of patients with urinary tract cancer (UTC), with primary disease sites including the bladder, urethra, and upper tract, who enrolled for research molecular testing of their germline and tumor. The purpose of this study was to evaluate factors that could affect the likelihood of identifying a clinically actionable germline pathogenic variant (PV).</p><p><strong>Methods: </strong>Patients with UTC were identified from 10 cancer institutes of the Oncology Research Information Exchange Network consortium. The data set comprised abstracted clinical data with germline and tumor genomic data, and comparative analyses were conducted.</p><p><strong>Results: </strong>Clinically actionable germline PVs in cancer predisposition genes were identified in 16 (4.5%) of 354 patients. A higher proportion of patients with the urethra and the upper tract as the primary sites of disease had PVs with a prevalence of 11% (5/45), compared with only 3.6% (11/308) in those with the bladder as the primary site of disease (<i>P</i> = .04). There were no significant differences in markers of genomic instability (such as tumor mutational burden, microsatellite instability [MSI], and loss of heterozygosity, copy number, and chromosomal instability) between those with PVs and those without (<i>P</i> > .05). Of the PVs identified, 10 (62%) were in homologous recombination repair (HRR) genes, three (19%) in mismatch repair (MMR) genes, and three (19%) in genes associated with other pathways.</p><p><strong>Conclusion: </strong>Tissue-based assessment of genomic instability, such as MSI, does not reliably indicate germline PV. A comprehensive clinical germline testing approach that includes HRR genes in addition to MMR genes is likely to yield PVs in approximately one of 10 patients with nonbladder primary disease sites such as the upper tract and the urethra.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558796","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":"Metastatic Non-Small Cell Lung Cancer Mimicking Metaplastic Breast Cancer: A Case Report.","authors":"Tanmayi S Pai, Blake McKinley, Robert Seby, Jason T Lewis, Miglena K Komforti, Joseph Accurso, Sushilkumar Sonavane, Deborah A Baumgarten, Pooja P Advani, Yanyan Lou, Rohit Rao","doi":"10.1200/PO.24.00027","DOIUrl":"10.1200/PO.24.00027","url":null,"abstract":"<p><p>NGS used to diagnose and treat NSCLC patient with initial concern for metaplastic breast cancer.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436859","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":"Implementation of and Systems-Level Barriers to Guideline-Driven Germline Genetic Evaluation in the Care of Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia.","authors":"Lauren G Banaszak, Paloma L Cabral, Kelcy Smith-Simmer, Ayesha Hassan, Matthew Brunner, Michael Fallon, Kyle Shoger, Lauren Lovrien, Danielle Golner, Luke Zurbriggen, Ryan Mattison, Zhubin Gahvari, Aric Hall, Kalyan Nadiminti, Erica Reinig, Jane E Churpek","doi":"10.1200/PO.23.00518","DOIUrl":"10.1200/PO.23.00518","url":null,"abstract":"<p><strong>Purpose: </strong>Knowledge of an inherited predisposition to myelodysplastic syndrome (MDS) and AML has important clinical implications for treatment decisions, surveillance, and care of at-risk relatives. National Comprehensive Cancer Network (NCCN) guidelines recently incorporated recommendations for germline genetic evaluation of patients with MDS/AML on the basis of personal and family history features, but the practicality of implementing these recommendations has not been studied.</p><p><strong>Methods: </strong>A hereditary hematology quality improvement (QI) committee was formed to implement these guidelines in a prospective cohort of patients diagnosed with MDS/AML. Referral for germline genetic testing was recommended for patients meeting NCCN guideline criteria. Referral patterns and genetic evaluation outcomes were compared with a historical cohort of patients with MDS/AML. Barriers to evaluation were identified.</p><p><strong>Results: </strong>Of the 90 patients with MDS/AML evaluated by the QI committee, 59 (66%) met criteria for germline evaluation. Implementation of the QI committee led to more referrals for germline evaluation in accordance with NCCN guidelines (31% <i>v</i> 14%, <i>P</i> = .03). However, the majority of those meeting criteria were never referred due to high medical acuity or being deceased or in hospice at the time of QI committee recommendations. Despite this, two (17%) of the 12 patients undergoing genetic testing were diagnosed with a hereditary myeloid malignancy syndrome.</p><p><strong>Conclusion: </strong>Current NCCN guidelines resulted in two thirds of patients with MDS/AML meeting criteria for germline evaluation. A hereditary hematology-focused QI committee aided initial implementation and modestly improved NCCN guideline adherence. However, the high morbidity and mortality and prolonged inpatient stays associated with MDS/AML challenged traditional outpatient genetic counseling models. Further improvements in guideline adherence require innovating new models of genetic counseling and testing for this patient population.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288067","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":"Chemotherapy-Induced Peripheral Neuropathy and Falls in Cancer Survivors Relate to Digital Balance and Gait Impairments.","authors":"Vrutangkumar V Shah, Daniel Muzyka, Carolyn Guidarelli, Kristen Sowalsky, Fay B Horak, Kerri M Winters-Stone","doi":"10.1200/PO.23.00312","DOIUrl":"https://doi.org/10.1200/PO.23.00312","url":null,"abstract":"<p><strong>Purpose: </strong>Chemotherapy-induced peripheral neuropathy (CIPN) and falls can be persistent side effects of cancer treatment. Standing postural sway and gait tests with body-worn, inertial sensors provide objective digital balance and gait measures that represent several different domains controlling mobility. Specific domains of balance and gait that related to neuropathy and falls are unknown. The aim of this study was to determine which domains of balance and gait differed between cancer survivors who report (1) CIPN symptoms versus no symptoms, (2) a history of falls in the past 6 months versus no falls, and (3) prospective falls over 12 months versus no falls.</p><p><strong>Methods: </strong>Postural sway during 30 seconds of quiet standing and gait characteristics from a 7-m timed up and go test were recorded with six synchronized inertial sensors (Opals by APDM Wearable Technologies, a Clario Company) in 425 older, female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used to identify independent domains of mobility from 15 balance and gait measures.</p><p><strong>Results: </strong>PCA analysis revealed five independent domains (PC1 = sway amplitude, PC2 = gait pace, PC3 = sway frequency, PC4 = gait spatial-temporal, and PC5 = turning) that accounted for 81% of the variance of performance. Cancer survivors who reported CIPN symptoms had significantly higher sway frequency (PC3) than asymptomatic survivors. Past fallers had significantly larger sway area (PC1) and slower gait pace (PC2) than nonfallers. Prospective fallers showed a significantly smaller stride length (PC4) than nonfallers.</p><p><strong>Conclusion: </strong>Digital balance and gait measures using wearable sensors during brief standing and walking tests provide objective metrics of CIPN-related mobility impairment and fall risk that could be useful for oncology clinical trials.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419195","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":"Exceptional Response to Trastuzumab Deruxtecan in a Patient With Recurrent Ovarian Clear Cell Carcinoma With Human Epidermal Growth Factor Receptor 2 Expression.","authors":"Ben L Kong, Jayne M Stommel, Jamie M Keck, David Kilburn, Aaron Streblow, Julian Egger, Allison L Creason, Christopher G Suciu, Alexander R Guimaraes, Christopher L Corless, Gordon B Mills, Tanja B Pejovic","doi":"10.1200/PO.23.00686","DOIUrl":"10.1200/PO.23.00686","url":null,"abstract":"<p><p>Case report of a HER2-expressed ovarian clear cell carcinoma with exceptional response to trastuzumab deruxtecan.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436857","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":"MEK Inhibition in a Pilocytic Astrocytoma With a Rare <i>KRAS Q61R</i> Mutation in a Young Adult Patient: A Case Report.","authors":"Katrina Roberto, Julia Keith, Adrian Levine, Farhad Pirouzmand, Hany Soliman, Mary Jane Lim-Fat","doi":"10.1200/PO.24.00174","DOIUrl":"10.1200/PO.24.00174","url":null,"abstract":"<p><p>This case illustrates the utility and impact of molecular testing and molecular tumor board discussion in the management of AYA patients with brain tumors.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436858","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":"Clonal Hematopoiesis in Patients With Neuroendocrine Tumor Treated With Lutetium-177 and the Risk of Thrombocytopenia: A Prospective Study.","authors":"Yael Kusne, Terra Lasho, Christy Finke, Zaid Elsabbagh, Shaylene McCue, Timothy Hobday, Jason Starr, Tanios Bekaii-Saab, Thorvardur R Halfdanarson, Mrinal M Patnaik, Fang-Shu Ou, Mohamad Bassam Sonbol","doi":"10.1200/PO.24.00143","DOIUrl":"10.1200/PO.24.00143","url":null,"abstract":"<p><strong>Purpose: </strong>Thrombocytopenia is a relatively common dose-limiting toxicity during peptide receptor radionuclide therapy (PRRT) in patients with NET. Although uncommon, some patients develop persistent cytopenia and eventually therapy-related myeloid neoplasm (t-MN), which has a dismal prognosis. As the indications for PRRT are expanding, it is important to investigate factors that may predict cytopenias during/after PRRT. We prospectively evaluated the prevalence of clonal hematopoiesis (CH) and cytopenia in patients with NET undergoing PRRT.</p><p><strong>Materials and methods: </strong>Patients with metastatic NET with plan to receive four cycles of lutetium-177 were enrolled. CH was evaluated before PRRT using a panel of 220 genes with a targeted depth of ≥1,000×. Patients were followed during PRRT and every 3 months thereafter.</p><p><strong>Results: </strong>Of 37 patients enrolled, the median age was 68 years and 51.4% were male. Previous treatment exposures included alkylating agents in 30%, platinum agents in 8%, and external radiation in 13%. CH was detected in 35.1% using a variant allele frequency (VAF) cutoff of ≥2% and 45.9% with a VAF of ≥1%. The most common mutations were in age-related genes (<i>DNMT3A</i>, <i>TET2</i>). CH was not associated with anemia or neutropenia; however, it was associated with lower platelet count at baseline and more time spent in a thrombocytopenic state during/after PRRT. Five patients had bone marrow biopsies (BMBs) because of sustained hematologic dysfunction post-PRRT, and of those, diagnoses included clonal cytopenia of undetermined significance (CCUS) in three and idiopathic cytopenia of undetermined significance (ICUS) in two.</p><p><strong>Conclusion: </strong>CH is present in 35.1% of patients with NET and is associated with thrombocytopenia risk during PRRT. Future studies with long-term follow-up will delineate whether CH might be a predictor for higher risk of t-MN after PRRT.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558792","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}