Outcomes in Intact and Resected Brain Metastasis Patients Treated with Five-Fraction Stereotactic Radiosurgery

Abstract

<h3>Purpose/Objective(s)</h3> Stereotactic radiosurgery (SRS) is the preferred local treatment for many brain metastasis patients (pts), often combined with surgical resection for larger and/or symptomatic lesions. Advances in SRS technology now permit hypofractionated regimens to mitigate toxicity without compromising efficacy. Optimal target volumes and planning parameters for hypofractionated SRS (HF-SRS), however, remain a matter of debate. Herein, we report clinical outcomes and predictive factors following HF-SRS. <h3>Materials/Methods</h3> Pts undergoing HF-SRS for intact (iHF-SRS) or resected (rHF-SRS) brain metastases from 2008 to 2018 at our institution were retrospectively identified. They received linear accelerator-based image-guided HF-SRS in 5 fractions at 5, 5.5, or 6 Gy/fraction. Planning target volumes were created by expanding contrast-enhancing lesions and/or resection cavity by 1 mm and 2mm in iHF-SRS and rHF-SRS, respectively. Actuarial rates of local progression (LP), distant brain progression (DBP), leptomeningeal disease (LMD), and overall survival (OS) were calculated. Uni- (UVA) and multivariate (MVA) Cox models assessed the impact of clinical factors on OS. Fine and Gray's cumulative incidence model for competing events examined the effect of factors on LP and DBP. Logistic regression examined predictors of LMD. <h3>Results</h3> Among 445 pts, median age at HF-SRS was 63.5 years; 87% had KPS ≥70. Common primary tumor sites were lung (43%), breast (16%), GI (11%), and skin (11%). 77% of pts had evidence of systemic disease at time of HF-SRS, and 70% received immunotherapy or small molecule inhibitors (IT/SMI) following HF-SRS. 53% of pts underwent surgical resection, with ≥2 brain metastases present in 32% of rHF-SRS and 84% of iHF-SRS cases. 75% of pts received 5 Gy/fraction. Median OS was 5.1 (95% CI 4.3 - 6.0) months following iHF-SRS and 12.8 (95% CI 10.8 - 16.2) months following rHF-SRS. On MVA for iHF-SRS, OS was associated with receipt of IT/SMI (HR 0.48, 95% CI 0.33 – 0.69). For rHF-SRS, OS was associated with neurologic symptoms (HR 1.91, 95% CI 1.29 – 2.83), IT/SMI use (HR 0.43, 95% CI 0.28 – 0.65), and dural contact (HR 0.69, 95% CI 0.47 – 0.99). For LP, the cumulative incidence (CI) was 14.5% (95% CI 11.4 – 18.0%) at 18 months. On UVA, LP was not associated with any tumor or patient specific factors. For DBP, MVA showed CI to be significantly greater with rHF-SRS than iHF-SRS (p=0.01), with respective 24-month CI rates of 50.0% (95% CI 43.3 – 56.3%) and 35.7% (95% CI 29.2 – 42.2%). LMD (57 events: 33% nodular, 67% diffuse) was observed in 17.1% of rHF-SRS and 8.1% of iHF-SRS cases (OR 2.46, 95% CI 1.34 – 4.53), and was associated with primary site (lung versus breast OR 0.40, 95% CI 0.20 – 0.80; other versus breast OR 0.28, 95% CI 0.13 – 0.60). Biopsy-proven radionecrosis was observed in 17 (3.8%) pts. <h3>Conclusion</h3> 5-fraction HF-SRS demonstrated favorable rates of LC in post-operative and intact settings. Corresponding LMD rates are comparable to those of other studies.