Early circulating tumor DNA shedding kinetics for prediction of platinum sensitivity in patients with small cell lung cancer Journal Article
| Authors: | Murciano-Goroff, Y. R.; Hui, A. B. Y.; Araujo Filho, J. A.; Hamilton, E. G.; Chabon, J. J.; Moding, E. J.; Bonilla, R. F.; Lebow, E. S.; Gomez, D.; Rimner, A.; Ginsberg, M. S.; Offin, M.; Kundra, R.; Allaj, V.; Norton, L.; Reis-Filho, J. S.; Razavi, P.; Drilon, A.; Jones, D. R.; Isbell, J. M.; Lai, W. V.; Rudin, C. M.; Alizadeh, A. A.; Li, B. T.; Diehn, M. |
| Article Title: | Early circulating tumor DNA shedding kinetics for prediction of platinum sensitivity in patients with small cell lung cancer |
| Abstract: | 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 Serial plasma samples were collected from patients receiving platinum-based AND METHODS 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 5 .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 5 .0004 and 21.7 v 6.4 months, log rank P 5 .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. © 2024 by American Society of Clinical Oncology. |
| Keywords: | adult; cancer chemotherapy; clinical article; controlled study; treatment response; aged; middle aged; overall survival; comparative study; progression free survival; multiple cycle treatment; clinical assessment; gene frequency; prediction; kinetics; blood analysis; platinum derivative; drug sensitivity; plasma; small cell lung cancer; premedication; radiological parameters; medical parameters; high throughput sequencing; chemical parameters; very elderly; human; male; female; article; circulating tumor dna; variant allele frequency; chloroplast dna; cancer personalized profiling by deep sequencing |
| Journal Title: | JCO Precision Oncology |
| Volume: | 8 |
| ISSN: | 2473-4284 |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2024-09-01 |
| Start Page: | e2400216 |
| Language: | English |
| DOI: | 10.1200/po.24.00216 |
| PUBMED: | 39231375 |
| PROVIDER: | scopus |
| PMCID: | PMC11376985 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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