JCO precision oncology最新文献

{"title":"Safety and Efficacy of Osimertinib in Patients With Non-Small-Cell Lung Cancer and Uncommon Tumoral Epidermal Growth Factor Receptor Mutations: A Systematic Review and Single-Arm Meta-Analysis.","authors":"Jonathan N Priantti, Yu Fujiwara, Francisco Cezar Aquino de Moraes, Isabella Michelon, Caio Castro, Natasha B Leighl, Ludimila Cavalcante, Alfredo Addeo, Jair Bar, Nobuyuki Horita, Alessio Cortellini, Amin H Nassar, Maysa Vilbert, Abdul Rafeh Naqash","doi":"10.1200/PO.24.00331","DOIUrl":"https://doi.org/10.1200/PO.24.00331","url":null,"abstract":"<p><strong>Purpose: </strong>The activity of osimertinib is not fully characterized in non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (<i>EGFR</i>) mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety and efficacy of osimertinib in patients with NSCLC harboring uncommon somatic <i>EGFR</i> mutations.</p><p><strong>Methods: </strong>PubMed, Embase, and the Cochrane Library were searched for eligible studies reporting the efficacy and safety of osimertinib in NSCLC with uncommon <i>EGFR</i> mutations defined as any mutations other than exon 19 deletion, L858R and T790M mutations, and exon 20 insertion, except when in compound. Then, we performed a meta-analysis to pool survival outcomes and antitumoral activity, including intracranial (ic) response and adverse events.</p><p><strong>Results: </strong>Fifteen studies comprising 594 patients were included. The most frequently observed uncommon solitary mutations were G719X in 25% (81/327) of patients and L861Q in 21% (69/327). The most common compound mutations were G719X with T790M in 12% (23/192) of patients and G719X with S768I in 11% (22/192). Pooled analysis showed an objective response rate (ORR) of 51.30% (95% CI, 45.80 to 56.81), a disease control rate (DCR) of 90.11% (95% CI, 86.27 to 92.96), a median progression-free survival of 9.71 months (95% CI, 7.96 to 11.86), and a median overall survival of 16.79 months (95% CI, 9.93 to 28.39). icORR was 45.96% (95% CI, 30.18 to 62.17), and icDCR was 95.76% (95% CI, 69.84 to 100). Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33).</p><p><strong>Conclusion: </strong>Osimertinib demonstrated robust response in NSCLC harboring uncommon <i>EGFR</i> mutations, without unanticipated safety concerns.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400331"},"PeriodicalIF":5.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693019","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":"Characterization and Clinical Outcome of Philadelphia Chromosome-Positive AML in Thrombocytopenia-Absent Radius Syndrome.","authors":"Alejandro Villar-Prados, Arman Odabas, Joshua R Menke, Kerry Kingham, Gabriel N Mannis","doi":"10.1200/PO-24-00411","DOIUrl":"10.1200/PO-24-00411","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400411"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406407","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":"Fully Automated Artificial Intelligence Solution for Human Epidermal Growth Factor Receptor 2 Immunohistochemistry Scoring in Breast Cancer: A Multireader Study.","authors":"Savitri Krishnamurthy, Stuart J Schnitt, Anne Vincent-Salomon, Rita Canas-Marques, Eugenia Colon, Kanchan Kantekure, Marina Maklakovski, Wilfrid Finck, Jeanne Thomassin, Yuval Globerson, Lilach Bien, Giuseppe Mallel, Maya Grinwald, Chaim Linhart, Judith Sandbank, Manuela Vecsler","doi":"10.1200/PO.24.00353","DOIUrl":"10.1200/PO.24.00353","url":null,"abstract":"<p><strong>Purpose: </strong>The proven efficacy of human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate therapy for treating HER2-low breast cancers necessitates more accurate and reproducible HER2 immunohistochemistry (IHC) scoring. We aimed to validate performance and utility of a fully automated artificial intelligence (AI) solution for interpreting HER2 IHC in breast carcinoma.</p><p><strong>Materials and methods: </strong>A two-arm multireader study of 120 HER2 IHC whole-slide images from four sites assessed HER2 scoring by four surgical pathologists without and with the aid of an AI HER2 solution. Both arms were compared with high-confidence ground truth (GT) established by agreement of at least four of five breast pathology subspecialists according to ASCO/College of American Pathologists (CAP) 2018/2023 guidelines.</p><p><strong>Results: </strong>The mean interobserver agreement among GT pathologists across all HER2 scores was 72.4% (N = 120). The AI solution demonstrated high accuracy for HER2 scoring, with 92.1% agreement on slides with high confidence GT (n = 92). The use of the AI tool led to improved performance by readers, interobserver agreement increased from 75.0% for digital manual read to 83.7% for AI-assisted review, and scoring accuracy improved from 85.3% to 88.0%. For the distinction of HER2 0 from 1+ cases (n = 58), pathologists supported by AI showed significantly higher interobserver agreement (69.8% without AI <i>v</i> 87.4% with AI) and accuracy (81.9% without AI <i>v</i> 88.8% with AI).</p><p><strong>Conclusion: </strong>This study demonstrated utility of a fully automated AI solution to aid in scoring HER2 IHC accurately according to ASCO/CAP 2018/2023 guidelines. Pathologists supported by AI showed improvements in HER2 IHC scoring consistency and accuracy, especially for distinguishing HER2 0 from 1+ cases. This AI solution could be used by pathologists as a decision support tool for enhancing reproducibility and consistency of HER2 scoring and particularly for identifying HER2-low breast cancers.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400353"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406408","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":"Amplification of <i>MYC</i> and Its Enhancer Correlates With Genetic Ancestry in Lung Squamous Cell Carcinoma.","authors":"Sejal Jain, Xuechun Bai, Samyukta Mallick, Branden Kinghorn, Benjamin May, Alexandria G Yao, Diane Allen-Gipson, Xiaoyang Zhang, Brian S Henick, Fatemeh Momen-Heravi, Jian Carrot-Zhang, Alison M Taylor","doi":"10.1200/PO.24.00223","DOIUrl":"10.1200/PO.24.00223","url":null,"abstract":"<p><strong>Purpose: </strong>In lung squamous cell carcinoma (LUSC), Black patients show significantly higher incidence and lower overall survival than White patients. Although socioeconomic factors likely contribute to this survival disparity, genomic factors have yet to be elucidated in LUSC.</p><p><strong>Methods: </strong>Using 416 LUSC tumor samples in the Cancer Genome Atlas (TCGA), we assessed genomic and transcriptomic profiles by ancestry. We replicated our analyses in pan-cancer data from TCGA, the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE), and Columbia University Medical Center.</p><p><strong>Results: </strong>We found increased <i>MYC</i> amplification, LUSC-specific <i>MYC</i> enhancer amplification, and chromosome arm 8q (chr8q) gain to be significantly associated with genetic AFR (African) ancestry in LUSC in TCGA. Furthermore, expression of <i>MYC</i> target genes was significantly enriched in AFR samples. Local ancestry analysis identified correlation of chr8q gain with AFR ancestry at the <i>MYC</i> locus in TCGA. We also found a significant correlation between chr8q and AFR ancestry in multiple cancer types and pan-cancer in TCGA. Similarly, in a pan-cancer subset of AACR GENIE data, we found a significant correlation between chr8q gain and race.</p><p><strong>Conclusion: </strong>Together, our data suggest that ancestry may influence amplification of not only <i>MYC</i> but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti-<i>MYC</i> therapeutic approaches.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400223"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500780","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":"CD8⁺ Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: A Review.","authors":"Kevin J Contrera, Matthew E Spector, Liron Pantanowitz, Ibrahim M Abukhiran, Lazar Vujanovic, Theresa L Whiteside, Yvonne M Mowery, Dan P Zandberg, Shaum S Sriharan, Seungwon Kim, Christopher Wilke, Heath D Skinner, Jose P Zevallos, Robert L Ferris","doi":"10.1200/PO.24.00183","DOIUrl":"https://doi.org/10.1200/PO.24.00183","url":null,"abstract":"<p><p>CD8⁺ tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8⁺ TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8⁺ TILs were analyzed. Consistent positive associations between elevated CD8⁺ TILs and overall survival have been observed across head and neck sites. CD8⁺ TILs have been found to predict response to treatment, most commonly immunotherapy, but also chemoradiation. Numerous trials have shown that increased CD8⁺ TIL frequencies in pretreatment biopsies could identify patients likely to respond to neoadjuvant therapies. CD8⁺ TIL infiltration has also been elevated in responders both during and after treatment. However, wider adoption of CD8⁺ TIL quantification as a biomarker has been limited by the need for clinical validation and universal measurement guidelines for head and neck SCC, as there are for other malignancies. Measurement variability includes which tumor compartment is sampled, how TILs are quantified, and which cutoffs are clinically relevant. For several head and neck SCC, measurement of CD8⁺ TILs in the central or intratumoral compartment, followed by the stromal compartment, has been most consistently associated with survival. Future studies are needed to evaluate subpopulations of CD8⁺ TILs and biomarker-based treatment selection.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400183"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681772","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":"Multiomic Characterization and Molecular Profiling of Nuclear Protein in Testis Carcinoma.","authors":"Gianna Kroening, Jia Luo, Mark G Evans, Tolulope Adeyelu, Sai-Hong Ignatius Ou, Zhaohui L Arter, Trisha M Wise-Draper, Ammar Sukari, Asfar S Azmi, David R Braxton, Andrew Elliott, David A Bryant, Matthew J Oberley, Chul Kim, Geoffrey I Shapiro, Christopher A French, Misako Nagasaka","doi":"10.1200/PO.24.00334","DOIUrl":"10.1200/PO.24.00334","url":null,"abstract":"<p><strong>Purpose: </strong>Nuclear protein in testis carcinoma (NC) is an underdiagnosed and aggressive squamous/poorly differentiated cancer characterized by rearrangement of the gene <i>NUTM1</i> on chromosome 15q14. Co-occurring alternations have not been fully characterized.</p><p><strong>Methods: </strong>We analyzed the genomic and immune landscape of 54 cases of NC that underwent DNA- and RNA-based NGS sequencing (Caris).</p><p><strong>Results: </strong>While NC is driven by <i>NUTM1</i> fusion oncoproteins, co-occurring DNA mutations in epigenetic or cell cycle pathways were observed in 26% of cases. There was no significant difference between the fusion partner of <i>NUTM1</i> and co-occurring gene mutations. RNA sequencing analysis showed increased <i>MYC</i> pathway activity in NC compared with head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC), which is consistent with the known pathophysiology of NC. Characterization of the NC tumor microenvironment using RNA sequencing revealed significantly lower immune cell infiltration compared with HNSCC and LUSC. NC was 10× higher in patients with HNSCC and LUSC younger than 50 years than in those older than 70 years.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first series of NC profiled broadly at the DNA and RNA level. We observed fewer intratumoral immune cells by RNA sequencing, which may be associated with anecdotal data of lack of immunotherapy benefit in NC. High <i>MYC</i> pathway activity in NC supports ongoing trials targeting <i>MYC</i> suppression. The incidence of NC among patients younger than 50 years with LUSC/HNSCC supports testing for NC in these patients. The prognosis of NCs remains dismal, and future studies should focus on improving the response to immunotherapy and targeting MYC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400334"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500782","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":"Using Artificial Intelligence to Support Informed Decision-Making on <i>BRAF</i> Mutation Testing.","authors":"Jennifer Webster, Jennifer Ghith, Orion Penner, Christopher H Lieu, Bob J A Schijvenaars","doi":"10.1200/PO.23.00685","DOIUrl":"10.1200/PO.23.00685","url":null,"abstract":"<p><strong>Purpose: </strong>Precision oncology relies on accurate and interpretable reporting of testing and mutation rates. Focusing on the <i>BRAFV600</i> mutations in advanced colorectal carcinoma, non-small-cell lung carcinoma, and cutaneous melanoma, we developed a platform displaying testing and mutation rates reported in the literature, which we annotated using an artificial intelligence (AI) and natural language processing (NLP) pipeline.</p><p><strong>Methods: </strong>Using AI, we identified publications that likely reported a testing or mutation rate, filtered publications for cancer type, and identified sentences that likely reported rates. Rates and covariates were subsequently manually curated by three experts. The AI performance was evaluated using precision and recall metrics. We used an interactive platform to explore and present the annotated testing and mutation rates by certain study characteristics.</p><p><strong>Results: </strong>The interactive dashboard, accessible at the BRAF dimensions website, enables users to filter mutation and testing rates with relevant options (eg, country of study, study type, mutation type) and to visualize annotated rates. The AI pipeline demonstrated excellent filtering performance (>90% precision and recall for all target cancer types) and moderate performance for sentence classification (53%-99% precision; ≥75% recall). The manual annotation of testing and mutation rates revealed inter-rater disagreement (testing rate, 19%; mutation rate, 70%), indicating unclear or nonstandard reporting of rates in some publications.</p><p><strong>Conclusion: </strong>Our AI-driven NLP pipeline demonstrated the potential for annotating biomarker testing and mutation rates. The difficulties we encountered highlight the need for more advanced AI-powered literature searching and data extraction, and more consistent reporting of testing rates. These improvements would reduce the risk of misinterpretation or misunderstanding of testing and mutation rates by AI-based technologies and the health care community, with beneficial impacts on clinical decision-making, research, and trial design.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2300685"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545622","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":"5-Hydroxymethylated Biomarkers in Cell-Free DNA Predict Occult Colorectal Cancer up to 36 Months Before Diagnosis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.","authors":"Diana C West-Szymanski, Zhou Zhang, Xiao-Long Cui, Krissana Kowitwanich, Lu Gao, Zifeng Deng, Urszula Dougherty, Craig Williams, Shannon Merkle, Chuan He, Wei Zhang, Marc Bissonnette","doi":"10.1200/PO.24.00277","DOIUrl":"https://doi.org/10.1200/PO.24.00277","url":null,"abstract":"<p><strong>Purpose: </strong>Using the prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial samples, we identified cell-free DNA (cfDNA) candidate biomarkers bearing the epigenetic mark 5-hydroxymethylcytosine (5hmC) that detected occult colorectal cancer (CRC) up to 36 months before clinical diagnosis.</p><p><strong>Materials and methods: </strong>We performed the 5hmC-seal assay and sequencing on ≤8 ng cfDNA extracted from PLCO study participant plasma samples, including n = 201 cases (diagnosed with CRC within 36 months of blood collection) and n = 401 controls (no cancer diagnosis on follow-up). We conducted association studies and machine learning modeling to analyze the genome-wide 5hmC profiles within training and validation groups that were randomly selected at a 2:1 ratio.</p><p><strong>Results: </strong>We successfully obtained 5hmC profiles from these decades-old samples. A weighted Cox model of 32 5hmC-modified gene bodies showed a predictive detection value for CRC as early as 36 months before overt tumor diagnosis (training set AUC, 77.1% [95% CI, 72.2 to 81.9] and validation set AUC, 72.8% [95% CI, 65.8 to 79.7]). Notably, the 5hmC-based predictive model showed comparable performance regardless of sex and race/ethnicity, and significantly outperformed risk factors such as age and obesity (assessed as BMI). Finally, when splitting cases at median weighted prediction scores, Kaplan-Meier analyses showed significant risk stratification for CRC occurrence in both the training set (hazard ratio, [HR], 3.3 [95% CI, 2.6 to 5.8]) and validation set (HR, 3.1 [95% CI, 1.8 to 5.8]).</p><p><strong>Conclusion: </strong>Candidate 5hmC biomarkers and a scoring algorithm have the potential to predict CRC occurrence despite the absence of clinical symptoms and effective predictors. Developing a minimally invasive clinical assay that detects 5hmC-modified biomarkers holds promise for improving early CRC detection and ultimately patient outcomes.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400277"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406406","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":"Palbociclib in Patients With Head and Neck Cancer and Other Tumors With <i>CDKN2A</i> Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.","authors":"Francis P Worden, Evan Pisick, Michael Rothe, Pam K Mangat, Elizabeth Garrett-Mayer, Maged F Khalil, Daniel R Carrizosa, Jessica R Bauman, Rom S Leidner, Herbert L Duvivier, Siqing Fu, Min S Park, Kathleen J Yost, Carmen J Calfa, Alissa S Marr, Ani S Balmanoukian, Deepti Behl, Timothy L Cannon, Lisle Nabell, Steven Francis Powell, Ramya Thota, Dominique C Hinshaw, Abigail Gregory, Gina N Grantham, Susan Halabi, Richard L Schilsky","doi":"10.1200/PO-24-00477","DOIUrl":"https://doi.org/10.1200/PO-24-00477","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Two cohorts of patients with cyclin-dependent kinase inhibitor 2A (<i>CDKN2A</i>)-mutated tumors treated with palbociclib are reported: one with head and neck cancer (HNC) with both squamous and nonsquamous cell histologies, and one with histology-pooled (HP) cancers.</p><p><strong>Methods: </strong>Eligible patients had measurable disease, 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 the HNC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included OR, safety, progression-free survival, overall survival, duration of response, and duration of SD.</p><p><strong>Results: </strong>Seventy patients with HNC (N = 28) or HP cancers (N = 42) were treated with palbociclib. For the HNC cohort, DC and OR rates were 40% (one-sided 90% CI, 27 to 100) and 4% (95% CI, <1 to 18), respectively. The null hypothesis was rejected (<i>P</i> = .002). For the HP cohort, DC and OR rates were 13% (one-sided 90% CI, 6 to 100) and 5% (95% CI, <1 to 17), respectively. The null hypothesis was not rejected. Thirty-one of 70 patients experienced treatment-related grade 3 to 4 adverse events (AEs) or serious AEs, the most common including neutropenia, thrombocytopenia, and leukopenia.</p><p><strong>Conclusion: </strong>Palbociclib met prespecified criteria to declare a signal of activity in patients with HNC with <i>CDKN2A</i> alterations, but not in the HP cohort.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400477"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465972","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":"Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors.","authors":"Rouba Ali-Fehmi, Harris Benjamin Krause, Robert T Morris, John J Wallbillich, Logan Corey, Sudeshna Bandyopadhyay, Mira Kheil, Leana Elbashir, Fadi Zaiem, M Ruhul Quddus, Evi Abada, Thomas Herzog, Anthony N Karnezis, Emmanuel S Antonarakis, Pashtoon Murtaza Kasi, Shuanzeng Wei, Jeffrey Swensen, Andrew Elliott, Joanne Xiu, Jaclyn Hechtman, David Spetzler, Jim Abraham, Milan Radovich, George Sledge, Matthew J Oberley, David Bryant","doi":"10.1200/PO.23.00648","DOIUrl":"https://doi.org/10.1200/PO.23.00648","url":null,"abstract":"<p><strong>Purpose: </strong>The new CAP guideline published in August 2022 recommends using immunohistochemistry (IHC) to test for mismatch repair defects in gastroesophageal (GE), small bowel (SB), or endometrial carcinoma (EC) cancers over next-generation sequencing assessment of microsatellite instability (NGS-MSI) for immune checkpoint inhibitor (ICI) therapy eligibility and states there is a preference to use IHC over NGS-MSI in colorectal carcinoma (CRC).</p><p><strong>Methods: </strong>We assessed the concordance of NGS-MSI and IHC-MMR from a very large cohort across the spectrum of solid tumors.</p><p><strong>Results: </strong>Of the over 190,000 samples with both NGS-MSI and IHC-MMR about 1,160 were initially flagged as discordant. Of those samples initially flagged as discordant, 50.9% remained discordant after being reviewed by an additional pathologist. This resulted in a final discordance rate of 0.31% (590/191,767). Among CRC, GE, SB and EC, 55.4% of mismatch repair proficient/MSI high (MMRp/MSI-H) tumors had at least one somatic pathogenic mutation in an MMR gene or <i>POLE</i>. Mismatch repair deficient/microsatellite stable (MMRd/MSS) tumors had a significantly lower rate of high tumor mutational burden than MMRp/MSI-H tumors. Across all solid tumors, MMRd/MSI-H tumors had significantly longer overall survival (OS; hazard ratio [HR], 1.47, <i>P</i> < .001) and post-ICI survival (HR, 1.82, <i>P</i> < .001) as compared with MMRp/MSS tumors. The OS for the MMRd/MSS group was slightly worse compared to the MMRp/MSI-H tumors, but this difference was not statistically significant (HR, 0.73, <i>P</i> = .058), with a similar pattern when looking at post-ICI survival (HR, 0.43, <i>P</i> = .155).</p><p><strong>Conclusion: </strong>This study demonstrates that NGS-MSI is noninferior to IHC-MMR and can identify MSI-H tumors that IHC-MMR is unable to detect and conversely IHC-MMR can identify MMRd tumors that NGS-MSI misses.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2300648"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681727","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}