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In the context of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC), the objective of our study was to determine the impact on local control (LC) and overall survival (OS) of a continuous versus discontinuous schedule of radiotherapy.

A total of 490 consecutive NSCLC stage I patients treated in 4 French radiation oncology centers between January 2008 and July 2018, were retrospectively analyzed. The prescribed dose ranged from 30 to 75 Gy in 3 to 10 fractions with a median biologically effective dose of 125 Gy (α/β = 10 Gy). Based on the ratio between the treatment duration (TD) and the number of fractions (n), patients were divided into two groups: continuous (TD < 2n) versus discontinuous (TD ≥ 2n) schedule. Local control, overall survival and toxicity were compared using Cox regression analyses. In order to limit any differences between the two groups at baseline, a 1:1 propensity score matching (nearest neighbor matching algorithm, caliper distance of 0.2) was performed.

The median follow-up was 41 months. The median age was 74 years old. Two hundred and forty-five patients were treated according to the continuous regimen and 245 to the discontinuous regimen. The two groups were comparable in terms of the major potential confounding factors. The 3-year LC was 92% for the discontinuous treatment versus 84% for the continuous one (p = 0.0017) (Figure 1), with a Hazard Ratio (HR) of 0.48 (CI 95% 0.26-0.89). The 3-year OS was 64% for the discontinuous treatment versus 52% for the continuous one (p = 0.0024) (Figure 2), HR of 0.66 (CI 95% 0.5-0.86). 216 patient pairs were identified with propensity score matching. Discontinuous treatment schedule was still associated with better overall survival with a HR of 0.64 (95% CI 0.48 – 0.85), p = 0.0029 and better local control with a HR of 0.39 (95% CI 0.19 – 0.79), p = 0.0089. In multivariate analysis, only the irradiation schedule and the number of fractions were correlated with LC. The irradiation schedule, age, WHO performance status and T stage were significantly correlated with OS. Less than 2% of acute or post-treatment grade 3 pulmonary toxicity was reported for both groups.

Our study is the first to show a positive impact of a discontinuous versus continuous schedule on overall survival as well as on local control for early stage NSCLC treated by SBRT, with similar low profile of toxicity. A multicenter randomized prospective study will be started in order to validate our results.