Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases

Abstract

Purpose: Stereotactic radiotherapy (SRT) is the standard treatment for brain metastases of non-small-cell lung cancer (NSCLC) and melanoma, mostly in combination with immunotherapy. The objective was to retrospectively evaluate the influence of the time-lapse between immunotherapy and stereotactic radiotherapy on toxicity. Patients and methods: From 2016 to 2019, 59 patients treated with SRT for 103 brain metastases of NSCLC (60%) and melanoma (40%) in combination with concomitant immunotherapy (≤ 30 days) were included. The prescribed dose was 20 Gy/1f or 33 Gy/3f at the isocentre and 14 Gy or 23.1 Gy (70%) respectively at the PTV envelope (PTV = GTV + 2 mm). The mean tumour diameter was 14 mm (4–52 mm). The immunotherapies used were anti-PD1 and anti-PDL1. The 103 metastases were classified into 3 groups according to the time-lapse between instatement of immunotherapy and instatement of SRT for the patient concerned: 7 (7%) in group A (≤ 7 days), 38 (37%) in group B (7 to 14 days) and 58 (56%) in group C (14 to 30 days). Results: The mean follow-up was 10.1 months. The median overall survival was 11.5 months for NSCLC and 12.5 months for melanoma. The percentage of local control (LC) at one year was 65.1% (93.6% for NSCLC and 26.5% for melanoma). The time-lapse between immunotherapy and SRT was not a significant predictor of LC (P = 0.86), while the histology was (P < 0.001). The proportion of grade ≥ 3 toxicities was 5.1%, and that of radionecrosis was 9.7% (among these patients, 80% were non-symptomatic): 0%, 13.1% and 8.6% for groups A, B and C respectively. The time-lapse between immunotherapy and SRT was not a significant predictor of toxicity. Only tumour volume was a significant predictive factor (P = 0.03). Conclusion: The time lapse between immunotherapy and SRT does not influence brain toxicity. The tumour volume remains the main factor.