Immunotherapy with hypofractionated radiotherapy in metastatic non-small cell lung cancer: An analysis of the National Cancer Database

Radiother Oncol. 2019 Sep;138:75-79. doi: 10.1016/j.radonc.2019.06.004. Epub 2019 Jun 25.


Purpose: Metastatic non-small cell lung cancer (NSCLC) is associated with an exceedingly poor prognosis. Recent advances in immunotherapy offer promise in enhancing overall survival (OS) in these patients. Preclinical evidence suggests that radiotherapy (RT), especially when offered in a high-dose per fraction hypofractionated RT (HRT) as in stereotactic ablative body radiotherapy (SABR), may augment the efficacy of immunotherapy. We aimed to assess the role of RT in patients with metastatic NSCLC receiving immunotherapy in a national hospital-based database.

Methods: Using the National Cancer Database (NCDB), we identified 6,383 patients treated with immunotherapy for metastatic NSCLC and 170,479 patients treated with RT but without immunotherapy. Patients receiving fractional doses of at least 5 Gy were designated as having received HRT, doses <5 Gy/fraction, were deemed standard fractionation (SFRT). The Kaplan-Meier analysis and proportional hazards modeling were performed, and propensity scores were generated via an inverse weighting method to evaluate the impact of RT on OS in this cohort.

Results: The median follow-up of the cohort is 12 months. Patients receiving HRT had numerically improved 1-year OS (59.0%) compared to those not receiving RT (55.7%), however this was not statistically significant (hazard ratio = 0.9, p = 0.22). Patients receiving non-HRT RT did substantially worse than those receiving no RT. Immunotherapy improved OS in patients receiving RT regardless of fraction size.

Conclusions: This hypothesis-generating retrospective analysis suggests that patients treated with immunotherapy with or without HRT in the upfront treatment of metastatic NSCLC experience similar survival. Further prospective evaluation of this combination should be undertaken in an attempt to maximize survival in this challenging disease.

Keywords: Abscopal effect; Cancer outcomes; Immunotherapy; Lung cancer; National Cancer Database analysis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Databases, Factual
  • Female
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Radiation Dose Hypofractionation*
  • Retrospective Studies