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  11. Early Circulating Tumor Dna Shedding Kinetics For Prediction Of Platinum Sensitivity In Patients With Small Cell Lung Cancer

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

Yonina R Murciano-Goroff1, Angela B-Y Hui2, Jose A Araujo Filho3

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY.

JCO Precision Oncology
|September 4, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Early changes in circulating tumor DNA (ctDNA) can predict treatment response in small cell lung cancer (SCLC). A significant decrease in ctDNA by cycle 2 day 1 indicates platinum sensitivity and improved survival outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Small cell lung cancer (SCLC) exhibits rapid progression and resistance to platinum-based chemotherapy.
  • Identifying early markers of platinum sensitivity is crucial for effective SCLC management.

Purpose of the Study:

  • To investigate the utility of circulating tumor DNA (ctDNA) dynamics in predicting treatment response and survival in SCLC patients undergoing platinum-based chemotherapy.
  • To correlate early ctDNA kinetics with radiologic response and clinical outcomes.

Main Methods:

  • Serial plasma samples were collected from SCLC patients during platinum-based chemotherapy.
  • Tumor-informed ctDNA analysis was performed using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq).
  • Mean variant allele frequency (VAF) of pretreatment mutations was tracked and correlated with treatment response and survival.

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Main Results:

  • ctDNA kinetics were analyzed in 122 samples from 21 patients.
  • No significant difference in pretreatment VAF was observed between responders and non-responders.
  • A >2-fold decrease in mean VAF by cycle 2 day 1 was observed in all responding patients.
  • This decrease in ctDNA was significantly associated with longer progression-free survival (PFS) and overall survival (OS).

Conclusions:

  • A >2-fold decrease in ctDNA concentration by cycle 2 day 1 is a sensitive indicator of platinum-based therapy response in SCLC.
  • Early ctDNA dynamics serve as a valuable predictive biomarker for improved PFS and OS in SCLC patients.