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Non-small cell lung cancer (NSCLC) locoregional recurrence and second primary are common after (chemo)radiotherapy could be treated with re-irradiation (same area) and repeat radiotherapy (different area), respectively. Our aims were to investigate the outcomes of NSCLC patients treated with re-irradiation and repeat radiotherapy and compare to a matched cohort.

NSCLC patients who received two curative-intent thoracic radiotherapy courses in the Christie NHS Foundation Trust (Manchester, UK) [FC(NC1] were retrospectively analysed (2013-2019). Radiotherapy plans were rigidly co-registered, if available, to quantify treatment field overlap and differentiate re-irradiation from repeat radiotherapy. Re-irradiation was designated if >0.5cm³ of the thoracic region received a radiotherapy dose higher than the maximum dose delivered in either of the two radiotherapy plans. A NSCLC patient group who received a single course of curative-intent thoracic radiotherapy was utilized to generate a matched cohort based on age, gender, radiotherapy type (stereotactic ablative radiotherapy (SABR) vs fractionated intensity modulated radiotherapy (IMRT)), TNM stage and ECOG performance score. Logistic regression was used to create a propensity score model. The primary endpoint was overall survival (OS).

79 NSCLC patients (median age: 75) underwent two curative-intent thoracic radiotherapy courses (retreatment cohort). The second radiotherapy treatment (RT2) was SABR in 27 and fractionated IMRT in 52 patients. The tumour stage at RT2 was: stage I (n=47), stage II (n=7), stage III (n=7), stage IV (n=3) and unknown (n=15). The median prescribed dose (peaked for SABR) for the RT1 and RT2 was 57Gy (range: 45-88) and 57Gy (range: 54-60), respectively. Table 1 shows characteristics for the retreatment and matched cohort (n=77). The median OS (measured from RT1) for the retreatment cohort was 51m (95% CI: 45-58); fig1A. The median OS was 51m (95%CI: 49-NA) for patients treated with re-irradiation (n=25) and 58m (95%CI: 51-NA) for patients treated with repeat radiotherapy (n=28). After adjusting for lead time bias (OS measured from RT2), patients who underwent retreatment within 1y of the first radiotherapy had worse OS (median: 20m, 95% CI: 12-36) compared to patients where the inter-radiotherapy gap was >1y (median: 25m, 95% CI: 15-55); p=0.013 (fig1B). The type of radiotherapy and performance score were not prognostic in the retreatment cohort. After adjusting for lead time bias, there was no difference in OS for the retreatment (median: 21m, 95% CI: 15-33) and the matched cohort (median: 22m, 95%CI: 17-NA); p=0.436 (fig1C).

The lack of survival difference between retreatment and matched cohorts provide indirect evidence of the benefit of a second curative-intent thoracic radiotherapy course in NSCLC patients with locoregional recurrence and second primary. Prospective trials are needed to standardise retreatment dose and investigate toxicity and quality of life.