Guiding Immunotherapy in Limited-Stage Small Cell Lung Cancer with ctDNA
ctDNA to Guide Immunotherapy in Limited-Stage SCLC
After CRT, consolidation IO benefit clusters in ctDNA-positive patients; minimal added benefit in ctDNA-negative.
Why it matters
Following ADRIATIC, CRT→durvalumab is standard. Yet not all benefit equally. Early ctDNA status may triage who truly needs consolidation IO.
What is ctDNA?
Tumor-derived DNA fragments in blood (“liquid biopsy”). This study used a fixed 139-gene lung panel and ~30,000× ultra-deep NGS.
Key numbers
PFS by early ctDNA
11.4 vs 49.4 mo
ctDNA+ vs ctDNA− post-induction
(HR 2.46; P<.001)
IO benefit (ctDNA+)
HR 0.29 / 0.05
PFS / OS improvement (P=.013 / P<.001)
IO benefit (ctDNA−)
NS
PFS HR 1.30; OS HR 1.14 (no added benefit)
PFS (months) — ctDNA+ vs ctDNA−
● ctDNA(+) ● ctDNA(−)
IO effect by ctDNA status
PFS HR & OS HR
P=.013 / P<.001
Not statistically significant
Who benefits from IO?
- ctDNA(+): clear PFS/OS gain with consolidation IO.
- ctDNA(−): little/no benefit; consider de-escalation.
ctDNA + Radiologic Response
Low risk ctDNA− & ≥60% shrink → excellent prognosis.
Mid risk Mixed features → IO benefit uncertain.
High risk ctDNA+ & <60% shrink → largest IO benefit (PFS HR 0.24; OS HR 0.06).
Assay: Tumor-agnostic fixed panel (not tumor-informed MRD). Mutations are predefined by the panel; blood is queried directly.
Data: WCLC 2025 (Bi N, et al.); ADRIATIC NEJM 2023 • 144 LS-SCLC pts; CRT±IO (serplulimab)
