Early Circulating Tumor DNA Shedding Kinetics for Prediction of Platinum Sensitivity in Patients With Small Cell Lung Cancer.

Autor:	Murciano-Goroff YR; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Hui AB; Stanford Cancer Institute, Stanford University, Stanford, CA., Araujo Filho JA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY., Hamilton EG; Stanford Cancer Institute, Stanford University, Stanford, CA., Chabon JJ; Stanford Cancer Institute, Stanford University, Stanford, CA., Moding EJ; Department of Radiation Oncology, Stanford University, Stanford, CA., Bonilla RF; Department of Radiation Oncology, Stanford University, Stanford, CA., Lebow ES; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Gomez D; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Rimner A; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Ginsberg MS; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY., Offin M; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Kundra R; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY., Allaj V; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY., Norton L; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Reis-Filho JS; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Razavi P; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Drilon A; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Jones DR; Department of Surgery, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Isbell JM; Department of Surgery, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Lai WV; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Alizadeh AA; Stanford Cancer Institute, Stanford University, Stanford, CA.; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA.; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA., Li BT; Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY., Diehn M; Stanford Cancer Institute, Stanford University, Stanford, CA.; Department of Radiation Oncology, Stanford University, Stanford, CA.; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2024 Sep; Vol. 8, pp. e2400216.
DOI:	10.1200/PO.24.00216
Abstrakt:	Purpose: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity. Materials and Methods: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response. Results: ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P = .17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P = .0004 and 21.7 v 6.4 months, log rank P = .04, respectively). Conclusion: A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu