JCO precision oncology · 2025
Longitudinal Evaluation of Circulating Tumor DNA as a Prognostic Biomarker to Detect Molecular Residual Disease in Germ Cell Tumors.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Hassoun Rebecca, Ben-David Reuben, Sfakianos John P, Laliotis George, Au Cherry, Cary Clint, Masterson Timothy A, Manage Kevin, Dutta Punashi, Tillu Neeraja, Cumarasamy Shivaram, King Jennifer, Rich Jordan, Rock Adam, Dorff Tanya, Patel Mukti, Sharma Shruti, ElNaggar Adam C, Liu Minetta C, Tan Alan, Einhorn Lawrence H, Adra Nabil, Chehrazi-Raffle Alexander
Аннотация
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.
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.