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

肺癌 化疗 医学 内科学 胃肠病学 肿瘤科 细胞周期 癌症
作者
Yonina R. Murciano‐Goroff,Angela BY Hui,José de Arimateia Batista Araújo-Filho,Emily G. Hamilton,Jacob J. Chabon,Everett J. Moding,Rene F. Bonilla,Emily S. Lebow,D.P. Gomez,Andreas Rimner,Michelle S. Ginsberg,Michael Offin,Ritika Kundra,Viola Allaj,Larry Norton,Jorge S. Reis-Filho,Pedram Razavi,Alexander Drilon,David R. Jones,James M. Isbell,W. Victoria Lai,Charles M. Rudin,Ash A. Alizadeh,Bob T. Li,Maximilian Diehn
出处
期刊:JCO precision oncology [Lippincott Williams & Wilkins]
卷期号: (8)
标识
DOI:10.1200/po.24.00216
摘要

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.
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