Study of 177 patients with limited-stage small cell lung cancer demonstrates ctDNA’s potential to personalize consolidation immunotherapy decisions.

New research suggests that circulating tumor DNA (ctDNA) monitoring could help clinical laboratories provide more precise guidance for immunotherapy use in patients with limited-stage small cell lung cancer (LS-SCLC).

The study, presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer, analyzed ctDNA in 177 patients with LS-SCLC treated with chemoradiotherapy, including 77 who received consolidation immune checkpoint inhibitors. Researchers measured ctDNA at multiple time points to evaluate its ability to predict survival outcomes and immunotherapy benefits.

“This is the first study to show that early ctDNA detection after induction chemotherapy can help identify patients who are more likely to benefit from consolidation immunotherapy,” says Dr Nan Bi from the Chinese Academy of Medical Sciences, in a release. “It’s a step toward precision immunotherapy in limited-stage SCLC.”

Advanced Testing Methods Used

The research team employed next-generation sequencing with a 139-gene lung cancer panel to assess ctDNA at ultra-deep coverage of 30,000×. Advanced statistical models, including time-dependent Cox regression, were used to eliminate immortal time bias in the analysis.

Key Findings:

  • Consolidation immune checkpoint inhibitors (ICI) improved overall survival vs CCRT alone (HR: 0.41; p = 0.031).
  • Patients who were ctDNA-positive at post-induction had significantly better PFS and OS with ICI compared to CCRT alone.
  • ctDNA-negative patients did not show added benefit from ICI.
  • Maintaining ctDNA negativity during immunotherapy was associated with better prognosis.
  • ctDNA at post-induction (t1) was more predictive of treatment response than ctDNA post-radiotherapy (t2).

“These findings offer a compelling rationale for integrating ctDNA-based stratification in future LS-SCLC trials and may help guide real-time decisions on the use of consolidation ICIs,” Bi says.

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