High Dose Thoracic Re-Irradiation and Chemo-Immunotherapy for Centrally Recurrent NSCLC.

Abstract

Simple SummarySince the early 1980s, there has been a trend towards escalating radiation doses in pulmonary tumor recurrences with the aim of improving survival. In this context, we performed a literature search in order to summarize the evidence of curative thoracic re-irradiation for centrally recurrent lung cancer. Tumor relapse in this specific situation poses a major problem because of the proximity to mediastinal organs. Of the initial 227 studies, 11 fulfilled the inclusion criteria for this analysis. The median overall survival (mOS) was 18.1 months (range 9.3–25.1), the median progression-free survival (mPFS) was nine months (range 4.5–16), and the median locoregional control (mLRC) was 12.1 months (range 6.5–20). The total re-irradiation dose correlated with both mLRC (p-value = 0.012) and mOS (p-value = 0.007). As large-scale prospective trials in the field are missing, this literature review is primarily based on retrospective data. In today’s age of enhanced long-term survival rates after chemoradiotherapy followed by immune checkpoint inhibition, the current analysis provides valuable insights into radiation treatment options for patients with loco-regional lung cancer recurrence.Introduction: Thoracic re-irradiation for recurrent lung cancer dates back four decades, when the first small series on 29 patients receiving palliative doses was published. With 5-year overall survival rates of 57% in PDL-1 positive patients after primary chemo-radio-immunotherapy, the number of patients who experience loco-regional relapse will increase in the near future. In this context, centrally recurring lung tumors pose a major treatment challenge. Hence, the aim of the current review is to compile the available evidence on curatively intended thoracic re-irradiation for this special clinical situation. Methods: A systematic literature search according to the PRISMA guidelines was performed. A study was included when the following criteria were met: (1) 66% of the patients had NSCLC, (2) a total dose of 50 Gy in the second course and/or a biologically effective dose of at least 100 Gy in both treatment courses was administered, (3) re-irradiation was administered with modern radiation techniques, (4) 50% or more of the patients had a centrally located relapse, (5) the minimum cohort size was 30 patients. Results: Of the initial 227 studies, 11 were analyzed, 1 of which was prospective. Median overall survival (OS) was 18.1 months (range 9.3–25.1), median progression free survival (PFS) was nine months (range 4.5–16), and median loco-regional control (LRC) was 12.1 months (range 6.5–20). Treatment-related mortality rates ranged from 2% to 14%. The total dose at re-irradiation correlated with both LRC (p-value = 0.012) and OS (p-value = 0.007) with a close relation between these two clinical endpoints (p-value = 0.006). The occurrence of acute toxicity grade 1 to 4 depended on the PTV size at re-irradiation (p-value = 0.033). Conclusion: The evidence regarding curative re-irradiation for centrally recurrent NSCLC is primarily based on scarce retrospective data, which are characterized by a high degree of heterogeneity. The OS in this clinically challenging situation is expected to be around 1.5 years after re-treatment. Patients with a good performance score, younger age, small tumors, and a longer interval to recurrence potentially benefit most from re-irradiation. In this context, prospective trials are warranted to achieve substantial advances in the field.