JCO precision oncology最新文献

{"title":"Response to Crizotinib After Entrectinib Resistance in <i>ROS1</i>-Rearranged, <i>MET</i>-Amplified Lung Adenocarcinoma.","authors":"Victor R Vaz, Malini M Gandhi, Biagio Ricciuti, Joao V Alessi, Arielle Elkrief, Marc Ladanyi, Chad Vanderbilt, Federica Pecci, Mihaela Aldea, Adriana Barrichello, Arushi Saini, Lynette Sholl, Jacob M Sands, Mark M Awad","doi":"10.1200/PO-24-00394","DOIUrl":"https://doi.org/10.1200/PO-24-00394","url":null,"abstract":"<p><p>Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400394"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390684","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":"Antibody-Drug Conjugates in Breast Cancer: Toward a Molecular Perspective Into Clinical Practice.","authors":"Roberto Paz-Manrique, Joseph A Pinto, Henry L Gomez Moreno","doi":"10.1200/PO.24.00173","DOIUrl":"https://doi.org/10.1200/PO.24.00173","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are at the forefront of cancer therapy, combining targeted precision with potent cytotoxicity. Conceived by Paul Ehrlich in the early 1900s, the concept of a magic bullet selectively eliminating cancer cells has evolved alongside bioengineering and cancer biology advancements. ADCs consist of a monoclonal antibody, linker, and cytotoxic payload, designed to target specific antigens on tumor cells while minimizing collateral damage. Mechanistically, ADCs are internalized via endocytosis, releasing the cytotoxic payload within the lysosome, potentially affecting neighboring tumor cells. ADC development has progressed through multiple generations, each addressing limitations of its predecessors. From gemtuzumab ozogamicin to trastuzumab emtansine (T-DM1), and now to third-generation agents such as trastuzumab deruxtecan (DS-8201) and disitamab vedotin (RC48), improvements have been made in target selectivity, potency, linker stability, and reduced off-target effects. Significant success has been seen in ADCs targeting human epidermal growth factor receptor 2 and trophoblast cell-surface antigen 2 antigens, especially in patients with breast cancer, including those resistant to previous therapies. The future of ADCs includes exploring new surface antigens, bispecific antibodies, immune-activating antibodies, radiopharmaceutical-loaded ADCs, and masked ADCs for tissue-specific activation. Ongoing research aims to optimize treatment efficacy while minimizing toxicity, expanding the potential of combination therapy. ADCs represent a promising frontier in precision cancer treatment, with continued research enhancing their potential in breast cancer and beyond. This review provides a comprehensive exploration of ADCs' evolution in breast cancer therapy, offering a molecular perspective to inform clinical practice and update colleagues on this dynamic field.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400173"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545620","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":"Development of a Composite Score Based on Carbohydrate Antigen 19-9 Dynamics to Predict Survival in Carbohydrate Antigen 19-9-Producing Patients With Pancreatic Ductal Adenocarcinoma After Neoadjuvant Treatment.","authors":"Ingmar F Rompen, Elisabetta Sereni, Joseph R Habib, Jonathan Garnier, Veronica Galimberti, Lucas R Perez Rivera, Deepa Vatti, Kelly J Lafaro, D Brock Hewitt, Greg D Sacks, William R Burns, Steven Cohen, Brian Kaplan, Richard A Burkhart, Olivier Turrini, Christopher L Wolfgang, Jin He, Ammar A Javed","doi":"10.1200/PO.24.00193","DOIUrl":"https://doi.org/10.1200/PO.24.00193","url":null,"abstract":"<p><strong>Purpose: </strong>Dynamics of carbohydrate antigen 19-9 (CA19-9) often inform treatment decisions during and after neoadjuvant chemotherapy (NAT) of patients with pancreatic ductal adenocarcinoma (PDAC). However, considerable dispute persists regarding the clinical relevance of specific CA19-9 thresholds and dynamics. Therefore, we aimed to define optimal thresholds for CA19-9 values and create a biochemically driven composite score to predict survival in CA19-9-producing patients with PDAC after NAT.</p><p><strong>Methods: </strong>Patients with PDAC who underwent NAT and surgical resection from 2012 to 2022 were retrospectively identified from three high-volume centers. CA19-9 nonproducers and patients with 90-day mortality, and macroscopically incomplete resections were excluded. A composite score was created on the basis of relative CA19-9 change and newly defined optimal thresholds of pre- and postneoadjuvant values for overall survival (OS) using patients from two centers and validated using data from the third center.</p><p><strong>Results: </strong>A total of 492 patients met inclusion criteria in the development cohort. Optimal CA19-9 cutoff values for predicting a difference in OS were 202 U/mL for preneoadjuvant and 78 U/mL for postneoadjuvant levels. Furthermore, increase in CA19-9 during neoadjuvant treatment was associated with worse OS (median-OS, 17.5 months <i>v</i> 26.0 months; <i>P</i> = .008). Not surpassing any or only one of these thresholds (composite score of 0-1) was associated with improved OS compared with patients with 2-3 points (median-OS, 29.9 months <i>v</i> 15.8 months; <i>P</i> < .001). Major serological response (90% decrease of CA19-9) had a positive and negative predictive value of 32% and 88%, respectively.</p><p><strong>Conclusion: </strong>The composite score consisting of CA19-9 levels at diagnosis, after neoadjuvant treatment, and its dynamics demonstrates prognostic discrimination between low and high scores. However, better predictive biomarkers are needed to facilitate treatment decisions during neoadjuvant treatment.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400193"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681838","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":"Dissecting the Significance of Acid Phosphatase 1 Gene Alterations in Prostate Cancer.","authors":"Nour Abdallah, Andrew Elliott, Norm Smith, Stephanie M Stanford, Neeraj Agarwal, Aditya Bagrodia, Rohan Garje, Nunzio Bottini, Rana R McKay","doi":"10.1200/PO-24-00444","DOIUrl":"https://doi.org/10.1200/PO-24-00444","url":null,"abstract":"<p><strong>Purpose: </strong>The acid phosphatase 1 (<i>ACP1</i>) gene encodes low-molecular-weight protein tyrosine phosphatase, which is overexpressed in prostate cancer (PC) and a potential therapeutic target. We analyzed <i>ACP1</i> expression in primary/metastatic PC and its association with molecular profiles and clinical outcomes.</p><p><strong>Methods: </strong>NextGen sequencing of DNA (592-gene/whole-exome sequencing)/RNA(whole-transcriptome sequencing) was performed for 5,028 specimens. <i>ACP1</i>-High/<i>ACP1</i>-Low expression was defined as quartile (Q4/1) of RNA transcripts per million (TPM). DNA mutational profiles were analyzed for <i>ACP1</i>-quartile-stratified samples. Gene set enrichment analysis was used for Hallmark collection of pathways. PD-L1+(≥2+, ≥5%; SP142) was tested by immunohistochemistry. Tumor microenvironment's (TME) immune cell fractions were estimated by RNA deconvolution/quanTIseq. Overall survival (OS) was assessed from initial diagnosis/treatment initiation to death/last follow-up.</p><p><strong>Results: </strong>We included 3,058 (60.8%) samples from the prostate, 634 (12.6%) from lymph node metastases (LNMs), and 1,307 (26.0%) from distant metastases (DMs). <i>ACP1</i> expression was higher in LNM/DM than prostate (49.8/47.9 <i>v</i> 44.1 TPM; <i>P</i> < .0001). <i>TP53</i> mutations were enriched in <i>ACP1</i>-Q4 (37.9%[Q4] <i>v</i> 27.0%[Q1]; <i>P</i> < .001) among prostate samples. Pathways associated with cell cycle regulation and oxidative phosphorylation were enriched in <i>ACP1</i>-Q4, whereas epithelial-mesenchymal transition and tumor necrosis factor-alpha signaling via nuclear factor kappa-light-chain-enhancer of activated B-cell pathways were enriched in <i>ACP1</i>-Q1. Neuroendocrine and androgen receptor signaling was increased in <i>ACP1</i>-Q4. M2 macrophages and natural killer cell fractions were increased, whereas T cells and M1 macrophages were decreased in <i>ACP1</i>-Q4. While OS differences between <i>ACP1</i>-Q1/Q4 were not statistically significant, there was a trend for worse OS among <i>ACP1</i>-Q4 prostate samples (Q4 <i>v</i> Q1: hazard ratio [HR], 1.19 [95% CI, 0.99 to 1.42]; <i>P</i> = .06) and DM (HR, 1.12 [95% CI, 0.93 to 1.36]; <i>P</i> = .22) but not LNM (HR, 0.98 [95% CI, 0.74 to 1.29]; <i>P</i> = .87).</p><p><strong>Conclusion: </strong>ACP1-High tumors exhibit a distinct molecular profile and cold TME, highlighting <i>ACP1</i>'s potential role in PC pathogenesis and novel therapeutic targeting.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400444"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347060","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":"Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database.","authors":"Hiroyuki Fujii, Hidekazu Hirano, Kouya Shiraishi, Hirokazu Shoji, Toshiharu Hirose, Natsuko Okita, Atsuo Takashima, Takafumi Koyama, Ken Kato","doi":"10.1200/PO.24.00284","DOIUrl":"10.1200/PO.24.00284","url":null,"abstract":"<p><strong>Purpose: </strong>Clinical utility of comprehensive genomic profiling (CGP) for precision medicine has become evident. Although there are several reports on the genomic landscape of GI stromal tumors (GISTs), large-scale data specific to GIST are limited, especially in Asia. Additionally, the applicability of molecular-targeted agents identified using CGP has not been extensively examined. We investigated the status of genomic alterations in Japanese patients with advanced GISTs using the National Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database to identify novel treatment strategies and drug development.</p><p><strong>Materials and methods: </strong>We retrospectively reviewed the clinical and CGP data of patients with advanced-stage GIST registered in the C-CAT database to assess the genomic landscape and potential actionable alterations.</p><p><strong>Results: </strong>Data from 144 patients were reviewed. Oncogenic alterations were detected frequently in <i>KIT</i> (78%), <i>CDKN2A</i> (37%), <i>CDKN2B</i> (29%), <i>RB1</i> (11%), <i>STK11</i> (10%), <i>TP53</i> (9%), <i>PDGFRA</i> (6%), and <i>SDHB</i> (6%). Loss of <i>CDKN2A</i>/<i>CDKN2B</i> was only observed in <i>KIT/PDGFRA</i>-mutated GISTs, while alterations in <i>SDHA/SDHB</i> were only detected in <i>KIT/PDGFRA</i> wild-type GISTs. Among 119 <i>KIT/PDGFRA</i>-mutated GISTs, 95 (80%) had oncogenic genomic alterations and 29 (24%) had actionable alterations, excluding <i>KIT</i> and <i>PDGFRA</i>. However, among 25 <i>KIT/PDGFRA</i> wild-type GISTs, 22 (88%) had oncogenic alterations and 11 (44%) had actionable alterations. Representative candidate drugs for genome-matched therapies in <i>KIT/PDGFRA</i>-mutated and wild-type GISTs were as follows: pembrolizumab for tumor mutation burden-high in one and two patients, respectively; poly-adenosine diphosphate ribose polymerase inhibitors for alterations related to homologous recombination deficiency in 12 and one patient, respectively; NTRK inhibitor for <i>ETV6-NTRK3</i> fusion in one with <i>KIT/PDGFRA</i> wild-type GIST; and human epidermal growth factor receptor 2-antibody-drug conjugate in one with <i>KIT/PDGFRA</i>-mutated GIST.</p><p><strong>Conclusion: </strong>This study highlights the genomic landscape of advanced GISTs and the important role of CGP in identifying rational molecular-targeted therapeutic options.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400284"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500781","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":"Prostate Cancer Risk Stratification in NRG Oncology Phase III Randomized Trials Using Multimodal Deep Learning With Digital Histopathology.","authors":"Jonathan David Tward, Huei-Chung Huang, Andre Esteva, Osama Mohamad, Douwe van der Wal, Jeffry P Simko, Sandy DeVries, Jingbin Zhang, Songwan Joun, Timothy N Showalter, Edward M Schaeffer, Todd M Morgan, Jedidiah M Monson, James A Wallace, Jean-Paul Bahary, Howard M Sandler, Daniel E Spratt, Joseph P Rodgers, Felix Y Feng, Phuoc T Tran","doi":"10.1200/PO.24.00145","DOIUrl":"10.1200/PO.24.00145","url":null,"abstract":"<p><strong>Purpose: </strong>Current clinical risk stratification methods for localized prostate cancer are suboptimal, leading to over- and undertreatment. Recently, machine learning approaches using digital histopathology have shown superior prognostic ability in phase III trials. This study aims to develop a clinically usable risk grouping system using multimodal artificial intelligence (MMAI) models that outperform current National Comprehensive Cancer Network (NCCN) risk groups.</p><p><strong>Materials and methods: </strong>The cohort comprised 9,787 patients with localized prostate cancer from eight NRG Oncology randomized phase III trials, treated with radiation therapy, androgen deprivation therapy, and/or chemotherapy. Locked MMAI models, which used digital histopathology images and clinical data, were applied to each patient. Expert consensus on cut points defined low-, intermediate-, and high-risk groups on the basis of 10-year distant metastasis rates of 3% and 10%, respectively. The MMAI's reclassification and prognostic performance were compared with the three-tier NCCN risk groups.</p><p><strong>Results: </strong>The median follow-up for censored patients was 7.9 years. According to NCCN risk categories, 30.4% of patients were low-risk, 25.5% intermediate-risk, and 44.1% high-risk. The MMAI risk classification identified 43.5% of patients as low-risk, 34.6% as intermediate-risk, and 21.8% as high-risk. MMAI reclassified 1,039 (42.0%) patients initially categorized by NCCN. Despite the MMAI low-risk group being larger than the NCCN low-risk group, the 10-year metastasis risks were comparable: 1.7% (95% CI, 0.2 to 3.2) for NCCN and 3.2% (95% CI, 1.7 to 4.7) for MMAI. The overall 10-year metastasis risk for NCCN high-risk patients was 16.6%, with MMAI further stratifying this group into low-, intermediate-, and high-risk, showing metastasis rates of 3.4%, 8.2%, and 26.3%, respectively.</p><p><strong>Conclusion: </strong>The MMAI risk grouping system expands the population of men identified as having low metastatic risk and accurately pinpoints a high-risk subset with elevated metastasis rates. This approach aims to prevent both overtreatment and undertreatment in localized prostate cancer, facilitating shared decision making.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400145"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500783","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":"Addressing the Intersection of Chemotherapy-Induced Peripheral Neuropathy and Fall Risk in Cancer Survivors: Insights and Future Directions.","authors":"Emad Shash","doi":"10.1200/PO-24-00421","DOIUrl":"https://doi.org/10.1200/PO-24-00421","url":null,"abstract":"","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400421"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465967","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":"Toxicity Adaptive Lists Design: A Practical Design for Phase I Drug Combination Trials in Oncology.","authors":"Massimiliano Russo, Francesco Mariani, James M Cleary, Geoffrey I Shapiro, Gregory M Coté, Lorenzo Trippa","doi":"10.1200/PO.24.00275","DOIUrl":"10.1200/PO.24.00275","url":null,"abstract":"<p><strong>Purpose: </strong>We introduce a novel algorithmic approach to design phase I trials for oncology drug combinations.</p><p><strong>Methods: </strong>Our proposed Toxicity Adaptive Lists Design (TALE) is straightforward to implement, requiring the prespecification of a small number of parameters that define rules governing dose escalation, de-escalation, or reassessment of previously explored dose levels. These rules effectively regulate dose exploration and control the number of toxicities. A key feature of TALE is the possibility of simultaneous assignment of multiple-dose combinations that are deemed safe by previously accrued data.</p><p><strong>Results: </strong>A numerical study shows that TALE shares comparable operative characteristics, in terms of identification of the maximum tolerated dose (MTD), to alternative approaches such as the Bayesian optimal interval design, the COPULA, the product of independent beta probabilities escalation, and the continual reassessment method for partial ordering designs while reducing the risk of overdosing patients.</p><p><strong>Conclusion: </strong>The proposed TALE design provides a favorable balance between maintaining patient safety and accurately identifying the MTD. To facilitate the use of TALE, we provide a user-friendly R Shiny application and an R package for computing relevant operating characteristics, such as the risk of assigning highly toxic dose combinations.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400275"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465986","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 a Polygenic Risk Score to Improve the Risk Prediction of Non-Small Cell Lung Cancer in Taiwan.","authors":"Po-Hsin Lee, I-Chieh Chen, Yi-Ming Chen, Tzu-Hung Hsiao, Jeng-Sen Tseng, Yen-Hsiang Huang, Kuo-Hsuan Hsu, Ho Lin, Tsung-Ying Yang, Yu-Hsuan Joni Shao","doi":"10.1200/PO.24.00236","DOIUrl":"https://doi.org/10.1200/PO.24.00236","url":null,"abstract":"<p><strong>Purpose: </strong>Low-dose computed tomography (LDCT) can help reducing lung cancer mortality. In Taiwan, the existing screening criteria revolve around smoking habits and family history of lung cancer. The role of genetic variation in non-small cell lung cancer (NSCLC) development is increasingly recognized. In this study, we aimed to investigate the potential benefits of polygenic risk scores (PRSs) in predicting NSCLC and enhancing the effectiveness of screening programs.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study that included participants without prior diagnosis of lung cancer and later received LDCT for lung cancer screening. Genetic data for these participants were obtained from the project of Taiwan Precision Medicine Initiative. We adopted the model of genome-wide association study-derived PRS calculation using 19 susceptibility loci associated with the risk of NSCLC as reported by Dai et al.</p><p><strong>Results: </strong>We studied a total of 2,287 participants (1,197 male, 1,090 female). More female participants developed NSCLC during the follow-up period (4.4% <i>v</i> 2.5%, <i>P</i> = .015). The only risk factor of NSCLC diagnosis among male participants was age. Among female participants, independent risk factors of NSCLC diagnosis were age (adjusted hazard ratio [aHR], 1.08 [95% CI, 1.04 to 1.11]), a family history of lung cancer (aHR, 3.21 [95% CI, 1.78 to 5.77]), and PRS fourth quartile (aHR, 2.97 [95% CI, 1.25 to 7.07]). We used the receiver operating characteristics to show an AUC value of 0.741 for the conventional model. With the further incorporation of PRS, the AUC rose to 0.778.</p><p><strong>Conclusion: </strong>The evaluation of PRS for NSCLC prediction holds promise for enhancing the effectiveness of lung cancer screening in Taiwan especially in women. By incorporating genetic information, screening criteria can be tailored to identify individuals at higher risks of NSCLC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400236"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347065","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":"Microsatellite Instability and Clinical Use in Sarcomas: Systematic Review and Illustrative Case Report.","authors":"Italo Fernandes, Douglas Dias E Silva, Vanderlei Segatelli, Renée Zon Filippi, Ana Carolina de Rezende, Paulo Campregher, Fernando Moura, Reynaldo Jesus-Garcia, Roberto Carmagnani Pestana","doi":"10.1200/PO.24.00047","DOIUrl":"10.1200/PO.24.00047","url":null,"abstract":"<p><p>Sarcomas, a diverse group of malignancies, exhibit substantial heterogeneity in both biological behavior and microenvironment, influencing their response to immunotherapy. Although pembrolizumab is approved for deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors regardless of histology, there is a paucity of data to support its effectiveness in dMMR/MSI-H sarcomas. This study presents a case of a metastatic undifferentiated pleomorphic sarcoma of the retroperitoneum with dMMR status demonstrating a sustained complete response to pembrolizumab. Our case revealed inconsistencies in identifying dMMR/MSI-H status through next-generation sequencing, immunohistochemistry, and polymerase chain reaction methods. Therefore, we conducted a systematic review to analyze various methods for assessing dMMR/MSI-H and to explore whether pembrolizumab's indications rely on this biomarker.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"8 ","pages":"e2400047"},"PeriodicalIF":5.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465971","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}