Stereotactic reirradiation for in-field lung cancer recurrence after stereotactic ablative radiotherapy: A systematic review and meta-analysis.

Objective: There is paucity of data for thoracic in-field reirradiation with two courses of stereotactic ablative radiotherapy (SABR). This meta-analysis evaluates the safety and efficacy of repeat SABR as salvage therapy for in-field failures after definitive SABR.

Methods: A systematic search of PubMed, Cochrane Library, MEDLINE, and EMBASE databases was conducted in accordance with PRISMA guidelines. Studies were included if they involved adult patients treated with salvage SABR for in-field recurrences of lung cancer following prior SABR. To address varying definitions of local failure, studies were included if recurrence occurred within the original planning target volume (PTV). Studies with out-of-field failures (>1 cm from PTV) or those using non-SABR techniques were excluded. Pooled 1- and 2-year local control (LC) rates, overall survival (OS), and toxicities were calculated using a random-effects model. Population-weighted linear regression was employed to assess the relationship between dosimetric and clinico-pathologic variables and patient outcomes.

Results: Twelve studies involving 197 patients were included in the quantitative analysis. All patients received two courses of SABR, with a median total dose of 50 Gy in 5 fractions. Pooled 1- and 2-year LC rates were 78.2 % (95 % CI: 66-87 %) and 68.0 % (95 % CI: 55-79 %), respectively. Patients receiving a cumulative biologically effective dose (BED) ≥ 200 Gy had significantly higher LC rates (84.9 %, 95 % CI: 70-93 %) vs (64.9 %, 95 % CI: 54-75 %, p = 0.02). Median OS did not significantly differ between low and high BED groups, though there was a trend toward improved survival with higher BED (21.4 vs 32.6 months). The pooled median OS across all studies was 26.3 months (95 % CI: 25.4-27.1). Improved LC rates were associated with smaller tumours (<2 cm), higher BED from the initial treatment and longer interval (>12 months) between initial and repeat SABR (p < 0.01). Toxicities were minimal, with a pooled incidence of ≥ grade 2 pneumonitis at 6.4 % and only 0.10 % reporting ≥ grade 3 toxicity.

Conclusions: Salvage in-field reirradiation with SABR achieves high local control and low toxicity, particularly in patients receiving higher cumulative BED (≥200 Gy) and with longer intervals (≥12 months) between treatments. These results suggest that repeat SABR is a viable salvage option for selected patients. Further prospective studies are needed to optimise dosing and patient selection for safe and effective reirradiation.