Estimating the long-term survival of unresectable stage III non-small cell lung cancer based on cure model analysis

Radiother Oncol. 2024 Aug:197:110341. doi: 10.1016/j.radonc.2024.110341. Epub 2024 May 23.

Abstract

Background: The predictors of long-term survival and appropriate surrogate endpoints in unresectable stage III non-small cell lung cancer (NSCLC) treated with radiotherapy remain unclear, especially in the immune therapy era.

Methods: This study retrospectively analyzed a prospective cohort of 822 patients treated at the Chinese National Cancer Center from 2013 to 2022. Cure fractions, surrogates for long-term survival, and associated factors were assessed using a mixture cure model, with validation against a matched Surveillance, Epidemiology, and End Results (SEER) dataset.

Results: 27.3% of patients with unresectable stage III NSCLC can achieve long-term survival after treated by radiotherapy. 4-year PFS and 5-year OS, when 80% of patients were considered cured, showed significant correlations with cure rates based on background mortality-adjusted PFS and relative survival, with R-squared values exceeding 0.85. Independent predictors of long-term survival included non-squamous cell carcinoma (non-SCC) pathological type, N category, gross tumor volume, and treatment combination with immune checkpoint inhibitors (ICIs).

Conclusions: Radiotherapy, especially when combined with ICIs, offers a potential cure for a proportion of patients with unresectable stage III NSCLC. Tumor burden and ICIs are key predictors of long-term survival. The study suggested 4-year PFS and 5-year OS as surrogate endpoints for cure and long-term survival assessment.

Keywords: Cure model; Immunotherapy; Long-term survival; Non-small cell lung cancer; Surrogate endpoint.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / radiotherapy
  • Lung Neoplasms* / therapy
  • Male
  • Middle Aged
  • Neoplasm Staging*
  • Retrospective Studies
  • Survival Rate

Substances

  • Immune Checkpoint Inhibitors