JCO Global Oncology最新文献

{"title":"Erratum: Radiation Therapist Education and Training: An International Survey.","authors":"","doi":"10.1200/GO-24-00618","DOIUrl":"https://doi.org/10.1200/GO-24-00618","url":null,"abstract":"","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400618"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Cyclophosphamide for Patients With Metastatic Castration-Resistant Prostate Cancer in a Scenario of Limited Health Care Resources.","authors":"Diana Del Cisne Pineda, Gabriel Berlingieri Polho, Yumi Ricucci Shinkado, Gustavo Alves Contado, Nathalia de Souza Crusoe, Vivian Naomi Horita, Joao Carlos Resende, Jamile Almeida Silva, Guilherme Fialho de Freitas, David Queiroz Muniz, Caio V Suartz, Leopoldo Alves Ribeiro-Filho, Paulo M Hoff, José Mauricio Mota","doi":"10.1200/GO-24-00464","DOIUrl":"10.1200/GO-24-00464","url":null,"abstract":"<p><strong>Purpose: </strong>Prior noncontemporary studies showed that oral cyclophosphamide is an active treatment of metastatic castration-resistant prostate cancer (mCRPC). However, cyclophosphamide is currently underutilized in routine clinical practice given the lack of survival benefit and the emergence of more effective treatments.</p><p><strong>Methods: </strong>We retrospectively reviewed our institutional database to identify patients with mCRPC treated with cyclophosphamide. Prostate-specific antigen decrease ≥50% from baseline (PSA50) response was determined as the proportion of patients achieving a prostate-specific antigen (PSA) decline ≥50% from baseline. Radiographic responses and progression were evaluated by Prostate Cancer Working Group 3. Survival estimates used the Kaplan-Meier method, and correlations were made with Chi-square test for categorical variables.</p><p><strong>Results: </strong>From January 2011 to January 2023, 341 patients with mCRPC received oral cyclophosphamide at a tertiary cancer center in São Paulo, Brazil. The most common regimen (95%) was 100 mg once daily 21 days on, 7 days off. At prostate cancer diagnosis, the median age was 64.4 years (IQR, 59.4-70.8), 61.9% had metastatic de novo disease, and 55.5% had Gleason ≥8. The median number of previous treatment lines was three (IQR, 2-4). Any PSA decline was observed in 33.4%, and 13.2% had a PSA50 response. Median response duration was 2.1 months (IQR, 1.4-3.8). Ten patients (3%) were treated for ≥1 year. PSA50 response was associated with no prior docetaxel use and Eastern Cooperative Oncology Group performance status 0 or 1.</p><p><strong>Conclusion: </strong>Oral cyclophosphamide is a feasible treatment option for patients with mCRPC, particularly in a scenario of limited health care resources.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400464"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Testing in Brazil: Navigating Challenges and Harnessing Opportunities for Global Health Impact.","authors":"Guilherme Harada, Tiago Biachi de Castria, Fabio Y Moraes","doi":"10.1200/GO-24-00545","DOIUrl":"https://doi.org/10.1200/GO-24-00545","url":null,"abstract":"","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400545"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of <i>EGFR</i> Mutations in Patients With Resected Stage I to III Nonsquamous Non-Small Cell Lung Cancer: Results of India Cohort.","authors":"Ullas Batra, Kumar Prabhash, Vanita Noronha, Ramakant Deshpande, Sachin Khurana, Gull Mohammad Bhat, Rajesh Mistry, Vivek Agarwala, Sajjan Rajpurohit, Bhavesh Poladia, Mansi Sharma, Saquib Zaffar Banday","doi":"10.1200/GO-24-00353","DOIUrl":"10.1200/GO-24-00353","url":null,"abstract":"<p><strong>Purpose: </strong>The spectrum of <i>EGFR</i> is inadequately researched in patients with early-stage non-small cell lung cancer (NSCLC) in India. EARLY-epidermal growth factor receptor (EGFR) India (ClinicalTrials.gov identifier: NCT04742192), as part of a noninterventional, real-world global study, evaluated the prevalence of <i>EGFR</i> mutations in early-stage NSCLC in India.</p><p><strong>Methods: </strong>Prospective data from adult patients with surgically resected stage IA to IIIB (American Joint Committee on Cancer eighth edition) NSCLC between March 2021 and October 2022 were analyzed. In addition to descriptive statistics, Fisher's exact test with Monte Carlo was used to determine the association between <i>EGFR</i> mutations and clinicodemographic parameters.</p><p><strong>Results: </strong>Of 74 patients (median age, 57.0 [range, 33.0-77.0] years) enrolled from eight centers in India, 73.0% (54 of 74) were males, 56.1% (37 of 66) were nonsmokers, and 95.9% (71 of 74) had adenocarcinoma. The <i>EGFR</i> mutation prevalence was 26.0% (19 of 73), of which <i>Exon-19</i> deletions were the predominant subtype (13, 68.4%) followed by <i>Exon 21-L858R</i> (4, 21.1%), <i>Exon 20-T790M</i> (1, 5.3%), and compound (1, 5.3%) mutations. Nearly half (48.6%, 36 of 74) of the patients underwent only surgical resection. The remaining 51.4% (38 of 74) of the patients were prescribed neoadjuvant (n = 12; 16.2%) and adjuvant (n = 31; 41.9%) systemic therapies, and one patient (1.4%) received radiotherapy along with systemic therapy. In 60 patients with stage IB to IIIB NSCLC, systemic therapies, mainly platinum-based chemotherapy, were prescribed in 36 (60.0%). Only 8.1% (6 of 74) of the patients were prescribed EGFR-tyrosine kinase inhibitor (TKI), of which two received neoadjuvant and four were planned for adjuvant EGFR-TKI. Two (2.7%) patients were prescribed adjuvant immunotherapy. The univariate analysis showed higher odds of <i>EGFR</i> mutation for females (odds ratio, 3.96; <i>P</i> = .017).</p><p><strong>Conclusion: </strong>EARLY-EGFR India results showed the prevalence of <i>EGFR</i> mutation to be 26%. The study emphasized the pressing need for up-front biomarker testing at diagnosis to ensure optimal and timely personalized treatment.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400353"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changing Landscape of Head and Neck Squamous Cell Carcinoma and Nasopharyngeal Carcinoma Treatment and Survival Trends in Thailand: A 13-Year Multicenter Retrospective Study of Patients.","authors":"Nuttapong Ngamphaiboon, Arunee Dechaphunkul, Chanida Vinayanuwattikun, Pongwut Danchaivijitr, Thanaporn Thamrongjirapat, Anussara Prayongrat, Tanadech Dechaphunkul, Rungarun Jiratrachu, Poompis Pattaranutaporn, Chuleeporn Jiarpinitnun, Jiraporn Setakornnukul","doi":"10.1200/GO-24-00285","DOIUrl":"10.1200/GO-24-00285","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence and survival rates of head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) vary globally, influenced by factors such as ethnicity, lifestyle, and health care systems.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on patients with HNSCC treated between 2008 and 2020 in four major Thai academic cancer centers, using a multidisciplinary multicenter database. The study focused on the evolution of patient characteristics, survival changes, and treatment landscape alterations over time.</p><p><strong>Results: </strong>Among 6,319 patients, the most common primary sites were nasopharynx (33%), oral cavity (23%), oropharynx (17%), larynx (15%), and hypopharynx (8%). An increase in human papillomavirus-related oropharyngeal carcinoma was noted, from 13% in 2008 to 42% in 2019-2020. The majority of patients presented with locally advanced (LA) stages (IVa/b: 50%, III: 26%). Chemoradiotherapy (54%) and surgery (24%) were the main treatments, with cisplatin (79%) being most commonly used in chemoradiation. Overall survival (OS) improved annually across all subsites, correlating with an increase in intensity-modulated radiotherapy (IMRT) use, from 25% in 2008 to 90% in 2019-2020. The median follow-up duration was 4.59 years, with a minimum of 2.75 years. Patients treated with IMRT had significantly longer OS compared with those treated with non-IMRT techniques, in both NPC and non-NPC HNSCC (<i>P</i> < .001).</p><p><strong>Conclusion: </strong>To our knowledge, this is the largest study in Thailand that demonstrates increasing survival outcomes in patients with HNSCC and NPC, despite commonly presenting with LA stages. The increasing use of IMRT may be contributing to improved survival outcomes in both patients with NPC and non-NPC HNSCC patients.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400285"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape of Multilocus Inherited Neoplasia Allele Syndrome in Mexican Population.","authors":"Dione Aguilar, María L Garza-Rodríguez, Diana C Pérez-Ibave, Carolina E Muñiz-Garza, Victor Treviño, Cynthia M Villarreal-Garza, Oscar Vidal-Gutiérrez, Carlos H Burciaga-Flores","doi":"10.1200/GO.24.00065","DOIUrl":"https://doi.org/10.1200/GO.24.00065","url":null,"abstract":"<p><strong>Purpose: </strong>Hereditary cancer syndromes (HCS) explain 5%-10% of all cancer cases. Patients with more than one germline pathogenic variant (GPV) result in a clinical syndrome known as multilocus inherited neoplasia allele syndrome (MINAS). In recent years, an increasing number of MINAS cases have been reported. This study aims to identify the prevalence of MINAS and determine the effect of two GPVs in HCS on patients from Northern Mexico.</p><p><strong>Methods: </strong>Patients (N = 2,282) were recruited from four public oncology centers and two private institutions with hereditary cancer detection programs in Nuevo León, México. A medical geneticist collected all the patient's clinical data and gave genetic counseling. Patients with MINAS were detected using multigene panels to detect GPVs; findings were classified according to American College of Medical Genetics and Genomics guidelines. The genetic data of patients with MINAS were evaluated by their frequency and combination.</p><p><strong>Results: </strong>We found 386 (16.9%) patients with one or more variants and 23 (5.9%) MINAS patients (all females). The most frequent diagnosis was breast cancer (BC) in 20 (86.95%) cases, whereas 16 (69.56%) had triple-negative BC. We found 13 patients with <i>BRCA1</i> GPVs (56.52%) as the most frequent, followed by <i>MUTYH</i> with five cases (21.73%). The combinations of <i>BRCA1/CHEK2</i>, <i>BRCA1/CDKN2A</i>, and <i>BRCA1/BRCA2</i> were the most frequent. We found no atypical presentation in the cohort.</p><p><strong>Conclusion: </strong>This is the first Mexican MINAS report and the largest Latin American cohort. We detected a higher prevalence of MINAS than other populations (5.9%). We found a tendency for additive phenotypical effect and, in some MINAS combinations, a modification in the age of diagnosis.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400065"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Next-Generation Sequencing of Cell-Free DNA to Detect <i>MYC</i>-Immunoglobulin Translocation and Epstein-Barr Virus DNA in Plasma of Burkitt Lymphoma Patients in East Africa.","authors":"Clara Chamba, Daisy Jennings, Rehema Shungu, Heavenlight Christopher, Emmanuel Josephat, Kieran Howard, Helene Dreau, Adam Burns, William Mawalla, Priscus Mapendo, Leah Mnango, Ismail Legason, Edrick Elias, Caroline Achola, Anthony Cutts, Emmanuel Balandya, Anna Schuh","doi":"10.1200/GO.24.00210","DOIUrl":"https://doi.org/10.1200/GO.24.00210","url":null,"abstract":"<p><strong>Purpose: </strong>Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) affects children in sub-Saharan Africa, but diagnosis via tissue biopsy is challenging. We explored a liquid biopsy approach using targeted next-generation sequencing to detect the <i>MYC</i>-immunoglobulin (<i>MYC</i>-Ig) translocation and EBV DNA, assessing its potential for minimally invasive BL diagnosis.</p><p><strong>Materials and methods: </strong>The panel included targets for the characteristic <i>MYC</i>-Ig translocation, mutations in intron 1 of <i>MYC</i>, mutations in exon 2 of <i>MYC</i>, and three EBV genes: EBV-encoded RNA (EBER)1, EBER2, and EBV nuclear antigen 2. It was first tested in a small derivation cohort of four precharacterized BL-derived cell lines with known translocation status and eight precharacterized plasma samples with known EBV DNA status by quantitative polymerase chain reaction (qPCR). These different data modalities were combined to assess the accuracy of this approach in the diagnosis of BL in 20 patient plasma samples in Tanzania and Uganda.</p><p><strong>Results: </strong>The next-generation sequencing panel detected three of four <i>MYC</i>-Ig translocations in the BL-derived cell lines. EBV viral load by targeted sequencing correlated strongly with qPCR results (Spearman's rho = 0.94) in precharacterized plasma samples. Using the patient plasma samples, mutations in <i>MYC</i> intron 1 were associated with the presence of a <i>MYC</i> translocation with 25 or more mutations being predictive of a translocation with AUC, sensitivity, and specificity of 1. Overall, liquid biopsy parameters associated with a diagnosis of BL (<i>P</i> < .05) included cell-free DNA concentration, circulating tumor DNA concentration, <i>MYC</i> intron 1 mutations, <i>MYC</i>-Ig translocation, and autosome entropy. Integrating these parameters into a diagnostic model demonstrated excellent performance with an AUC of 0.95, sensitivity of 0.9, and specificity of 1.</p><p><strong>Conclusion: </strong>This analysis demonstrates the potential of liquid biopsy to improve BL diagnosis in settings with limited pathology resources. Validation of our approach in a larger data set is needed.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400210"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Landscape of Global Pediatric Oncology Publications: A Cross-Sectional Analysis.","authors":"María Fernanda García Garza, Oscar Gutiérrez Treviño, Saman K Hashmi, Carlos Rodríguez-Galindo, Daniel C Moreira","doi":"10.1200/GO-24-00320","DOIUrl":"https://doi.org/10.1200/GO-24-00320","url":null,"abstract":"<p><strong>Purpose: </strong>The academic field of global pediatric oncology is expanding as cancer becomes increasingly recognized as a global health priority for children and adolescents. Here, we aimed to explore the representation of authors, the geographic distribution of research, and the research approaches being used in global pediatric oncology.</p><p><strong>Methods: </strong>Articles published in <i>JCO Global Oncology</i> (<i>JCO GO</i>) and <i>Pediatric Blood and Cancer</i> on the topic of global pediatric oncology were analyzed. For each article, data were collected on the study design, the research location, and the authorship demographics. Descriptive frequencies were reported for all items.</p><p><strong>Results: </strong>Overall, 296 studies met the inclusion criteria to be considered relevant for global pediatric oncology. Of these, 259 (87.5%) were research articles. Of the research articles, 228 (88.0%) were observational and 117 (51.3%) were retrospective cohort analyses. Thirty-eight studies (12.8%) had a global focus or were unrelated to a geographic context, 54 (18.2%) were regional, and 204 (68.9%) were specific to a single country. Females represented 163 (55.8%) of first authors, 138 (46.6%) of senior authors, and 159 (53.7%) of corresponding authors. Furthermore, 121 (41.4%) first authors, 163 (55.1%) last authors, and 142 (48.0%) senior authors were from high-income countries (HICs). The United States (n = 81) and India (n = 40) had the most corresponding authors. Thirty-six (17.6%) articles had research conducted in low- and middle-income countries (LMICs), and the first, senior, and corresponding authors were from HICs.</p><p><strong>Conclusion: </strong>Our analysis shows that researchers from LMICs are under-represented as authors of global pediatric oncology publications. Further studies are needed to evaluate the factors that contribute to inequalities in global pediatric oncology research.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400320"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival Outcomes for Adolescent and Young Adults With Cancer in Low- and Middle-Income Countries: A Systematic Review.","authors":"Krista Ariello, Abdel-Nabi Hadi, Avram Denburg, Sumit Gupta","doi":"10.1200/GO-24-00326","DOIUrl":"https://doi.org/10.1200/GO-24-00326","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with adolescent and young adult (AYA) cancer are recognized as a vulnerable subpopulation in high-income countries (HICs). Although survival gaps between HIC and low- and middle-income country (LMIC) children with cancer are well described, LMIC AYAs have been neglected. We conducted a systematic review to describe cancer outcomes among LMIC AYAs.</p><p><strong>Methods: </strong>We captured English language studies published from 2010 onward reporting LMIC AYA cancer survival outcomes. LMICs were defined according to World Bank 2019 classifications, whereas AYAs were defined as diagnosed between age 15 and 39 years. Cohorts were considered AYA if >75% of patients were AYA, the mean/median age and standard deviation were between 15 and 39 years, or the range was within 5 years of the AYA range (ie, 10-45 years). Cohort characteristics were abstracted, including country, cancer type, and cancer outcomes.</p><p><strong>Results: </strong>Of 6,207 studies identified by the search strategy, 658 underwent full-text review; 60 met inclusion criteria. No low-income countries were represented. Forty-four (73.3%) studies were conducted in upper-middle-income countries (UMICs) although these represented only 12 of 55 countries currently classified as UMICs. The most common cancers studied were acute lymphoblastic leukemia (n = 13 studies), breast cancer (n = 5), and osteosarcoma (n = 3). Five-year overall survival was highly variable, ranging from 39% to 63% for ALL, 60%-85% for breast cancer, and 47%-83% for osteosarcoma.</p><p><strong>Conclusion: </strong>Although three billion AYAs reside in LMICs, their cancer outcomes are neglected in the current literature. Existing data indicate variable survival, ranging from comparable with HIC outcomes to substantially inferior. These studies, however, represent only a limited number of LMICs and are biased toward UMICs. Systematic efforts to describe and improve LMIC AYA cancer outcomes are required.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400326"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency and Impact of Constitutional Mismatch Repair Deficiency in Patients With High-Grade Glioma, a Retrospective Analysis of 7 Years in Pakistan: an IRRDC Study.","authors":"Naureen Mushtaq, Khurram Minhas, Farrah Bashir, Soha Zahid, Bilal Mazhar Qureshi, Gohar Javed, Shahzadi Resham, Anirban Das, Cynthia Hawkins, Uri Tabori, Eric Bouffet","doi":"10.1200/GO-24-00247","DOIUrl":"https://doi.org/10.1200/GO-24-00247","url":null,"abstract":"<p><strong>Purpose: </strong>Constitutional mismatch repair deficiency (CMMRD) is a genetic cancer predisposition syndrome among children and young adults. This study aimed to evaluate the frequency of CMMRD among patients with pediatric high-grade glioma (pHGG) in a single tertiary care center in Pakistan, a country with high consanguinity rates.</p><p><strong>Patients and methods: </strong>We reviewed the data of patients age <18 years with pHGG, anaplastic astrocytoma, and diffuse midline glioma (DMG) with CMMRD testing between 2016 and 2023. CMMRD testing was done using the Aronson et al criteria. A few patients were sent to Sick Kids, Toronto, to review the mismatch repair protein stains via multigene panels.</p><p><strong>Results: </strong>Forty-seven patients were identified, with a median age of 11 years (IQR, 8-16). Headache (89.4%) was the most common symptom. Thirty-seven patients had hemispheric tumors; 12.8% and 8.5% had posterior fossa and midline tumors, respectively. Histopathology revealed 70.2% glioblastoma, 23.4% anaplastic astrocytoma, and 6.4% DMG. CMMRD was positive in 15 of 47 patients (31.9%). Eight patients had loss of <i>PMS2</i>. Three had loss of <i>PMS2</i> and <i>MLH1</i>; two had loss of <i>MSH6</i>, one had loss of <i>MSH6</i> and <i>MSH2</i>, and only one patient had loss of <i>MSH2</i>. Consanguinity and family history of malignancy correlated with CMMRD (<i>P</i> = .009, <i>P</i> = .031, respectively). Two-year overall survival of all patients was 23.4% (median follow-up, 0.59 years [95% CI, 0.000 to 1.171]). Two-year overall survival of mismatch repair deficiency-positive patients was 20% (median follow-up, 0.910 years [95 CI, 0.380 to 1.440]).</p><p><strong>Conclusion: </strong>We found a high frequency of CMMRD among patients with pHGG, particularly with positive consanguinity. Our study highlights the significance of genetic testing and surveillance. It is essential to develop low and middle income country-tailored protocols due to limited access and financial constraints associated with using immune checkpoint inhibitors.</p>","PeriodicalId":14806,"journal":{"name":"JCO Global Oncology","volume":"11 ","pages":"e2400247"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}