Rebecca Hassoun, Reuben Ben-David, John P Sfakianos, George Laliotis, Cherry Au, Clint Cary, Timothy A Masterson, Kevin Manage, Punashi Dutta, Neeraja Tillu, Shivaram Cumarasamy, Jennifer King, Jordan Rich, Adam Rock, Tanya Dorff, Mukti Patel, Shruti Sharma, Adam C ElNaggar, Minetta C Liu, Alan Tan, Lawrence H Einhorn, Nabil Adra, Alexander Chehrazi-Raffle
{"title":"循环肿瘤DNA作为检测生殖细胞肿瘤分子残留疾病的预后生物标志物的纵向评价。","authors":"Rebecca Hassoun, Reuben Ben-David, John P Sfakianos, George Laliotis, Cherry Au, Clint Cary, Timothy A Masterson, Kevin Manage, Punashi Dutta, Neeraja Tillu, Shivaram Cumarasamy, Jennifer King, Jordan Rich, Adam Rock, Tanya Dorff, Mukti Patel, Shruti Sharma, Adam C ElNaggar, Minetta C Liu, Alan Tan, Lawrence H Einhorn, Nabil Adra, Alexander Chehrazi-Raffle","doi":"10.1200/PO-25-00176","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Serum tumor markers (STMs), including alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), are currently used in management of patients with germ cell tumors (GCTs). STMs in a substantial proportion of patients are normal or falsely elevated. We evaluated circulating tumor DNA (ctDNA) as a prognostic biomarker in patients with GCTs.</p><p><strong>Patients and methods: </strong>Longitudinal ctDNA testing was performed on a multi-institutional cohort of patients with GCTs using a clinically validated, personalized, tumor-informed 16-plex multiplex PCR-NGS ctDNA assay (Signatera, Natera Inc). ctDNA was evaluated preorchiectomy and during the molecular residual disease (MRD; 1-12 weeks postorchiectomy) and surveillance windows (>12 weeks postorchiectomy, after retroperitoneal lymph node dissection [RPLND], or postchemotherapy). The correlation between ctDNA status and event-free survival (EFS) was assessed.</p><p><strong>Results: </strong>ctDNA testing was performed for 74 patients (324 plasma samples) with clinical stages I to III GCTs. The median age was 34 years (IQR, 27-39), and the median follow-up was 17 months (IQR, 12-25). Disease management postorchiectomy included surveillance in 23% (17/74), RPLND in 7% (5/74), chemotherapy in 41% (30/74), and chemotherapy + RPLND in 29% (22/74) of patients. Preorchiectomy ctDNA was detectable in 14 of 15 patients. During the MRD (N = 42) and surveillance (N = 51) windows, patients who were ctDNA-positive versus ctDNA-negative showed a significantly inferior EFS during MRD (hazard ratio [HR], 5.11 [95% CI, 1.31 to 19.95]; <i>P</i> = .019) and surveillance windows (HR, 12.45 [95% CI, 4.32 to 35.85]; <i>P</i> < .0001). By contrast, elevated versus normal STM was not associated significantly with worse EFS (MRD: HR, 2.97 [95% CI, 0.68 to 13.05]; <i>P</i> = .149. surveillance: HR, 1.74 [95% CI, 0.75 to 4.02]; <i>P</i> = .194).</p><p><strong>Conclusion: </strong>Tumor-informed ctDNA analysis shows promise for MRD detection in patients with GCTs. With further study, ctDNA monitoring may be useful in clinical decision making. Larger prospective trials are planned to establish clinical utility.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2500176"},"PeriodicalIF":5.6000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Longitudinal Evaluation of Circulating Tumor DNA as a Prognostic Biomarker to Detect Molecular Residual Disease in Germ Cell Tumors.\",\"authors\":\"Rebecca Hassoun, Reuben Ben-David, John P Sfakianos, George Laliotis, Cherry Au, Clint Cary, Timothy A Masterson, Kevin Manage, Punashi Dutta, Neeraja Tillu, Shivaram Cumarasamy, Jennifer King, Jordan Rich, Adam Rock, Tanya Dorff, Mukti Patel, Shruti Sharma, Adam C ElNaggar, Minetta C Liu, Alan Tan, Lawrence H Einhorn, Nabil Adra, Alexander Chehrazi-Raffle\",\"doi\":\"10.1200/PO-25-00176\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Serum tumor markers (STMs), including alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), are currently used in management of patients with germ cell tumors (GCTs). STMs in a substantial proportion of patients are normal or falsely elevated. We evaluated circulating tumor DNA (ctDNA) as a prognostic biomarker in patients with GCTs.</p><p><strong>Patients and methods: </strong>Longitudinal ctDNA testing was performed on a multi-institutional cohort of patients with GCTs using a clinically validated, personalized, tumor-informed 16-plex multiplex PCR-NGS ctDNA assay (Signatera, Natera Inc). ctDNA was evaluated preorchiectomy and during the molecular residual disease (MRD; 1-12 weeks postorchiectomy) and surveillance windows (>12 weeks postorchiectomy, after retroperitoneal lymph node dissection [RPLND], or postchemotherapy). The correlation between ctDNA status and event-free survival (EFS) was assessed.</p><p><strong>Results: </strong>ctDNA testing was performed for 74 patients (324 plasma samples) with clinical stages I to III GCTs. The median age was 34 years (IQR, 27-39), and the median follow-up was 17 months (IQR, 12-25). Disease management postorchiectomy included surveillance in 23% (17/74), RPLND in 7% (5/74), chemotherapy in 41% (30/74), and chemotherapy + RPLND in 29% (22/74) of patients. Preorchiectomy ctDNA was detectable in 14 of 15 patients. During the MRD (N = 42) and surveillance (N = 51) windows, patients who were ctDNA-positive versus ctDNA-negative showed a significantly inferior EFS during MRD (hazard ratio [HR], 5.11 [95% CI, 1.31 to 19.95]; <i>P</i> = .019) and surveillance windows (HR, 12.45 [95% CI, 4.32 to 35.85]; <i>P</i> < .0001). By contrast, elevated versus normal STM was not associated significantly with worse EFS (MRD: HR, 2.97 [95% CI, 0.68 to 13.05]; <i>P</i> = .149. surveillance: HR, 1.74 [95% CI, 0.75 to 4.02]; <i>P</i> = .194).</p><p><strong>Conclusion: </strong>Tumor-informed ctDNA analysis shows promise for MRD detection in patients with GCTs. With further study, ctDNA monitoring may be useful in clinical decision making. Larger prospective trials are planned to establish clinical utility.</p>\",\"PeriodicalId\":14797,\"journal\":{\"name\":\"JCO precision oncology\",\"volume\":\"9 \",\"pages\":\"e2500176\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO precision oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/PO-25-00176\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO precision oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/PO-25-00176","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Longitudinal Evaluation of Circulating Tumor DNA as a Prognostic Biomarker to Detect Molecular Residual Disease in Germ Cell Tumors.
Purpose: Serum tumor markers (STMs), including alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), are currently used in management of patients with germ cell tumors (GCTs). STMs in a substantial proportion of patients are normal or falsely elevated. We evaluated circulating tumor DNA (ctDNA) as a prognostic biomarker in patients with GCTs.
Patients and methods: Longitudinal ctDNA testing was performed on a multi-institutional cohort of patients with GCTs using a clinically validated, personalized, tumor-informed 16-plex multiplex PCR-NGS ctDNA assay (Signatera, Natera Inc). ctDNA was evaluated preorchiectomy and during the molecular residual disease (MRD; 1-12 weeks postorchiectomy) and surveillance windows (>12 weeks postorchiectomy, after retroperitoneal lymph node dissection [RPLND], or postchemotherapy). The correlation between ctDNA status and event-free survival (EFS) was assessed.
Results: ctDNA testing was performed for 74 patients (324 plasma samples) with clinical stages I to III GCTs. The median age was 34 years (IQR, 27-39), and the median follow-up was 17 months (IQR, 12-25). Disease management postorchiectomy included surveillance in 23% (17/74), RPLND in 7% (5/74), chemotherapy in 41% (30/74), and chemotherapy + RPLND in 29% (22/74) of patients. Preorchiectomy ctDNA was detectable in 14 of 15 patients. During the MRD (N = 42) and surveillance (N = 51) windows, patients who were ctDNA-positive versus ctDNA-negative showed a significantly inferior EFS during MRD (hazard ratio [HR], 5.11 [95% CI, 1.31 to 19.95]; P = .019) and surveillance windows (HR, 12.45 [95% CI, 4.32 to 35.85]; P < .0001). By contrast, elevated versus normal STM was not associated significantly with worse EFS (MRD: HR, 2.97 [95% CI, 0.68 to 13.05]; P = .149. surveillance: HR, 1.74 [95% CI, 0.75 to 4.02]; P = .194).
Conclusion: Tumor-informed ctDNA analysis shows promise for MRD detection in patients with GCTs. With further study, ctDNA monitoring may be useful in clinical decision making. Larger prospective trials are planned to establish clinical utility.
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