Fraction Size, Total Dose and Respiratory Control Impact Local Control in Adrenal SBRT

Abstract

Stereotactic body radiotherapy (SBRT) is an effective treatment for oligometastatic disease in multiple sites, however, the optimal radiation dose for long term local control of adrenal metastases has not yet been determined. The aim of this study is to evaluate outcomes of adrenal SBRT and to evaluate factors that correlate with local control MATERIALS/METHODS: After IRB approval, a retrospective data review of patients treated with SBRT on adrenal metastases was conducted, at a medical center in Israel between 2015 and 2021. Biologic Equivalent Dose (BED) were calculated using an alpha beta ration of 10. Kaplan Meier and Cox regression were calculated to describe the hazard ratio for local control and survival using statistical software. Fifty-eight cases of adrenal SBRT were identified. The average age was 67 years (ranging 42-92). Forty-three percent of primary tumor was non-small cell lung cancer. The lesions were equally distributed between the right and left adrenal gland. Six patients had bilateral radiation treatment. Fifty-eight percent of the cases were in the setting of oligometastatic disease (less than 5 lesions) with the rest having progression in the adrenal. PET-CT scans were available for follow up in 55% of patients and CT in the rest. The average GTV volume was 42 cm2 respiratory control through 4D and breath hold was performed in 86% of cases. The median follow up time, for local control, was 10 months with a range of 1-54 mos. Univariate analysis local control, during the last follow up, was seen in 74% of cases. Total dosage was equal to or above 72 Gy and dosage per fraction was equal to or above 8 Gy. The use of respiratory motion was found significant for local control. Only a fraction size equal to or above 8 Gy and a total dosage equal to and above 72 Gy were found significant for local failure (HR = 0.26, p = 0.024 and HR = 0.28, p = 0.019). With multivariable analysis the dosage per fraction ≥8 Gy continued to be significant after adjusting for total dose, histology, side, and motion management. Two patients had clinical signs of adrenal insufficiency and both received bilateral adrenal radiation. Bowel toxicity was low: 1 patient had >G3 toxicity. In the largest single institution series reported to date, we found unilateral adrenal SBRT to be safe, however, bilateral treatment harbors a risk of adrenal insufficiency. Dose per fraction ≥8 Gy was the most powerful predictor of local control, and a total dose ≥72gy and motion management were also significant. In conclusion, we propose a treatment regimen with a fraction size of at least 8 Gy and a total dosage of at least 72 Gy for evaluation, in a prospective clinical trial.