Impact of 2-staged stereotactic radiosurgery for treatment of brain metastases ≥ 2 cm

Abstract

OBJECTIVE Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2 cm in maximum diameter remains challenging and is associated with suboptimal local control (LC) rates of 37%-62% and an increased risk of treatment-related toxicity. To enhance LC while limiting adverse effects (AEs) of radiation in these patients, a dose-dense treatment regimen using 2-staged SRS (2-SSRS) was used. The objective of this study was to evaluate the efficacy and toxicity of this treatment strategy. METHODS Fifty-four patients (with 63 brain metastases ≥ 2 cm) treated with 2-SSRS were evaluated as part of an institutional review board-approved retrospective review. Volumetric measurements at first-stage stereotactic radiosurgery (first SSRS) and second-stage SRS (second SSRS) treatments and on follow-up imaging studies were determined. In addition to patient demographic data and tumor characteristics, the study evaluated 3 primary outcomes: 1) response at first follow-up MRI, 2) time to local progression (TTP), and 3) overall survival (OS) with 2-SSRS. Response was analyzed using methods for binary data, TTP was analyzed using competing-risks methods to account for patients who died without disease progression, and OS was analyzed using conventional time-to-event methods. When needed, analyses accounted for multiple lesions in the same patient. RESULTS Among 54 patients, 46 (85%) had 1 brain metastasis treated with 2-SSRS, 7 patients (13%) had 2 brain metastases concurrently treated with 2-SSRS, and 1 patient underwent 2-SSRS for 3 concurrent brain metastases ≥ 2 cm. The median age was 63 years (range 23-83 years), 23 patients (43%) had non-small cell lung cancer, and 14 patients (26%) had radioresistant tumors (renal or melanoma). The median doses at first and second SSRS were 15 Gy (range 12-18 Gy) and 15 Gy (range 12-15 Gy), respectively. The median duration between stages was 34 days, and median tumor volumes at the first and second SSRS were 10.5 cm (range 2.4-31.3 cm) and 7.0 cm (range 1.0-29.7 cm). Three-month follow-up imaging results were available for 43 lesions; the median volume was 4.0 cm (range 0.1-23.1 cm). The median change in volume compared with baseline was a decrease of 54.9% (range -98.2% to 66.1%; p < 0.001). Overall, 9 lesions (14.3%) demonstrated local progression, with a median of 5.2 months (range 1.3-7.4 months), and 7 (11.1%) demonstrated AEs (6.4% Grade 1 and 2 toxicity; 4.8% Grade 3). The estimated cumulative incidence of local progression at 6 months was 12% ± 4%, corresponding to an LC rate of 88%. Shorter TTP was associated with greater tumor volume at baseline (p = 0.01) and smaller absolute (p = 0.006) and relative (p = 0.05) decreases in tumor volume from baseline to second SSRS. Estimated OS rates at 6 and 12 months were 65% ± 7% and 49% ± 8%, respectively. CONCLUSIONS 2-SSRS is an effective treatment modality that resulted in significant reduction of brain metastases ≥ 2 cm, with excellent 3-month (95%) ...

Two-session Radiosurgery as Initial Treatment for Newly Diagnosed Large, Symptomatic Brain Metastases from Breast and Lung Histology

“…As our main goal was to avoid surgery in symptomatic patients, we felt that Infini would be more suitable for obtaining a quicker tumor response that hopefully traduced in faster neurological improvement. Further studies are needed to compare multifraction LINAC versus multifraction Gamma Knife and the results provided by two-or three-session Gamma Knife in the treatment of large brain metastases [18][19][20]22,23].…”

“…Radiosurgery apparently enhances the effects of low-dose steroids (e.g., 0.5 mg dexamethasone), resulting in rapid patient improvement. Our neoadjuvant radiosurgery protocol was replaced by the present study of two-session radiosurgery, inspired by staged radiosurgery schemes described by others, but with the hope to benefit not only those unsuitable for surgery, but rather those who could be operated by current recommendations standards [22][23]. It was exactly this group of patients for whom we sought to provide an apparent non-inferior, safe, effective, noninvasive alternative means of radiosurgery for rapid tumor response and control.…”

“…These histology subtypes are considered more radioresistant than the histology here presented and thus may limit the extrapolation of the results here described. Several recent studies have described different fractionation schemes that are intended to safely increase the biologically effective dose to large lesions, thereby improving long-term local control and survival when compared with historical reports of tumor control at one year of 45 and 49% in patients that received a lower dose in a single fraction such as 15 and 18 Gy, respectively [14,[16][17][18][19][20][22][23]. Recent results suggest that the classical scheme of surgery followed by SRS may be comparable to staged (two-session) radiosurgery with local tumor failure rate at one year of 8% [26].…”

Three-stage Gamma Knife treatment for metastatic brain tumors larger than 10 cm3: a 2-institute study including re-analyses of earlier results using competing risk analysis

“…The local recurrence rates in these studies ranged from 12.1% to 15.0% and complication incidences from 1.9% to 6.4%, results very similar to those obtained with 3-st-GK-Tx. 1,2,5 The next question is whether 3-st-GK-Tx or 2-st-GK-Tx is the better option in terms of patient outcomes. Very recently, Serizawa et al reported a multi-institutional retrospective study designed to compare the treatment results of these 2 protocols (i.e., 3-stage or 2-stage treatment).…”

Proceedings of the 2018 next-generation Gamma Knife research meeting

“…19,20 In contrast, radiosurgeons performing Gamma Knife therapy at the Cleveland Clinic use 2-stage radiosurgery (2 doses of 15 Gy, or 18 Gy then 12 Gy administered 1 month apart), and Asher et al and Angelov et al have described the successful use of lower-dose GKSRS as neoadjuvant radiosurgery prior to resection. 1,3 As an alternative to Asher et al's protocol, the Cleveland Clinic has an in-house protocol with dose escalation for neoadjuvant radiosurgery. This latter technique allows for easier GKSRS planning because the margins are better defined, and preliminary data suggest that it also decreases the rate of leptomeningeal spread of the cancer at the time of surgery.…”