ctDNA Tumor Fraction Clearance Predicts Longer rwPFS/OS in NSCLC & SCLC

A tissue-agnostic ctDNA tumor-fraction (TF) assay measured 6–15 weeks after therapy start (prospective clinico-genomic registry; NCT04180176) associated undetectable TF with longer real-world outcomes: NSCLC mPFS 23.5 vs 9.5 mo (HR 0.34, 95% CI 0.22–0.53) and SCLC 15.9 vs 8.3 mo (HR 0.19, 0.08–0.42); ≥90% and ≥50% TF drops also predicted benefit. Discrimination was strongest for immunotherapy/targeted therapy (≥50% TF decrease in 91% of responders vs 24% of nonresponders) compared with chemotherapy/chemo-IO (86% vs 60%), and multivariable models improved when radiographic response (RECIST/iRECIST) was included—supporting ctDNA as complementary rather than a replacement.