Innovations in modern low-LET radiotherapy regimens for locally advanced non-small cell lung cancer: a meta-analysis and systematic review of high-dose-rate brachytherapy, stereotactic body radiotherapy, and hypofractionated proton therapy.

Abstract

Background: This study assesses recent treatments for locally advanced non-small cell lung cancer (LA-NSCLC) ineligible for surgery, comparing high-dose-rate (HDR) brachytherapy with conventional low linear energy transfer (LET) hypofractionated radiotherapy methods.

Methods: From 9435 papers, 8 meeting criteria were selected, covering 484 LA-NSCLC patients (2005-2019). Analysis focused on comparing outcomes, exploring biologically effective doses (BED), and examining toxicities.

Results: HDR brachytherapy had better effectiveness. Specific data revealed that the median overall survival (OS) with HDR brachytherapy was 38 months, with a significant 2-year OS rate of 68.0% (95% CI, 58.2-79.4%). In comparison, stereotactic body radiation (SBRT) and proton treatment had 2-year OS rates of 54% (95% CI, 36-71%), and 56% (95% CI, 42-70%), respectively. In terms of local control (LC), the 2-year LC rate for HDR brachytherapy stood at 87.1% (95% CI, 79-95%), whereas the 2-year LC rates for SBRT and proton therapy were 75% (95% CI, 63-86%) and 84% (95% CI, 68 -100%), respectively. The 2-year OS for BED₁₀ equal to or greater than 78 Gy was 62% (95% CI, 51-72%), compared to 38% (95% CI, 17-58%) for BED₁₀ less than 78 Gy. Acute toxicity was lower with HDR brachytherapy (95% CI, 0-10%) versus SBRT (95% CI, 8-16%), with no grade 3 + events reported for proton therapy. Furthermore, the rate of late toxicity events above grade 3 was 3% (95% CI, 0-6%) for SBRT and 14% (95% CI, 4-24%) for proton therapy, while no late toxicities above grade 3 were observed with brachytherapy.

Conclusions: Hypofractionated low LET irradiation is efficacious and safe for LA-NSCLC, while HDR brachytherapy provides significant OS and LC advantages with few toxicities. Achieving BED₁₀ ≥ 78 Gy significantly impacts OS. These findings guide clinical practice and stimulate further LA-NSCLC treatment advancements.