Abstract

Abstract Background Stereotactic radiosurgery (SRS) is preferred to whole brain radiotherapy (WBRT) for the treatment of patients with a limited number of brain metastases, both as primary treatment and after surgery. SRS can be delivered in a single fraction (SF) or in multiple fractions (MF) depending on tumor size and location. The aim of this single-center retrospective study was to evaluate intracranial control and overall survival (OS) in patients who received SF and MF SRS for brain metastases. Material and Methods All patients treated with primary SRS for brain metastases at Aarhus University Hospital between 2015 and 2020 were identified. Independent of undergoing surgery, SF SRS (20 Gy) was administered for targets (gross tumor volume) <2 cm in diameter and MF SRS (24-27 Gy in 3 fractions) for targets >2 cm. SRS was not combined with WBRT. Treatment response was evaluated by 3-monthly MRI-scan. To evaluate intracranial control, first events were scored as local-only failure (tumor progression at the SRS treatment site), distant failure (tumor progression not at the SRS site), and combined failure (local and distant failure). Actuarial incidence of local failure (local-only and combined) and OS were estimated using the Kaplan-Meier method. To analyze the association of SF and MF SRS with local failure and OS, multivariable Cox regression analyses were used. Results The consecutive cohort consisted of 196 patients treated for 275 brain metastases. The most frequent primary disease was non-small cell lung cancer (NSCLC n=96), followed by renal cell carcinoma (n=26) and breast cancer (n=22). SRS was delivered to 1 (n=133), 2 (n=49), 3 (n=12), and 4 (n=2) targets per patient. SF and MF SRS was used in 99 (51%) and 97 (49%) patients, respectively. In 40 patients, SRS was administered after surgery (SF n=7, MF n=33). At a median (range) follow-up of 10 (0-93) months, 111 (57%) patients had intracranial progression, and 159 (81%) patients died. Local-only/distant/combined failure rate was 23 and 42%/59 and 35%/18 and 23%, in SF and MF SRS respectively. The median time to local failure was respective 9.0 (95% CI 5.4-12.6) and 6.0 (95% CI 5.0-7.0) months in the SF and MF SRS group. SF SRS and surgery were independently associated with a longer time to local failure. Salvage WBRT, SRS, and re-operation were performed in respective 36, 13, and 26 patients. Histopathological radiation necrosis was observed in 5 patients. All patients with necrosis had a primary diagnosis of NSCLC, and 4/5 patients were treated with SF SRS. For the total group, the median OS was 10.0 (95% CI 8.0 - 12.0) months. PS<2, surgery, stable extracranial disease and SF SRS were associated with a longer survival. Conclusion MF SRS was associated with a higher rate of and shorter time to local failure, and was a poor prognostic factor for survival, which is in line with the selection of patients with more unfavorable brain metastases for this treatment.

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