Long-term Outcomes after Salvage Stereotactic Radiosurgery (SRS) following In-Field Failure of Initial SRS for Brain Metastases

Abstract

PurposeThe optimal treatment strategy following local recurrence after stereotactic radiosurgery (SRS) remains unclear. While upfront SRS has been extensively studied, few reports focus on outcomes after retreatment. Here, we report the results following a second course of SRS for local recurrence of brain metastases previously treated with SRS.MethodsUsing institutional database, patients who received salvage SRS (SRS2) following in-field failure of initial SRS (SRS1) for brain metastases were identified. Radionecrosis and local failure were defined radiographically by MRI following SRS2. The primary endpoint was defined as the time from SRS2 to the date of all-cause death or last follow-up [overall survival (OS)]. The secondary endpoints included local failure-free survival (LFFS) and radionecrosis-free survival, defined as the time from SRS2 to the date of local failure or radionecrosis, or last follow-up, respectively.ResultsTwenty-eight patients with 32 brain metastases were evaluated between years 2004 and 2015. The median interval between SRS1 and SRS2 was 9.7 months. Median OS was 22.0 months. Median LFFS time after SRS2 was 13.6 months. The overall local control rate following SRS2 was 84.4%. The 1- and 2-year local control rates are 88.3% (95% CI, 76.7–100%) and 80.3% (95% CI, 63.5–100%), respectively. The overall rate of radionecrosis following SRS2 was 18.8%. On univariate analysis, higher prescribed isodose line (p = 0.033) and higher gross tumor volume (p = 0.015) at SRS1 were associated with radionecrosis. Although not statistically significant, there was a trend toward lower risk of radionecrosis with interval surgical resection, fractionated SRS, lower total EQD2 (<50 Gy), and lack of concurrent systemic therapy at SRS2.ConclusionIn select patients, repeat LINAC-based SRS following recurrence remains a reasonable option leading to long-term survival and local control. Radionecrosis approaches 20% for high risk individuals and parallels historic values.

Repeated in-field radiosurgery for locally recurrent brain metastases: Feasibility, results and survival in a heavily treated patient cohort

“…Although a dose-response-relationship is known for SRS of brain metastases [ 48 ], these data are not mature enough to suggest a specific minimum inhomogeneity for re-SRS, which however may be needed, if the local recurrent metastasis is in fact deemed radio-resistant by definition of failure of initial SRS. On the other hand, some authors [ 42 , 43 ] found a significant correlation of prescribed dose or prescription isodose with radio-necrosis, so that further dose escalation (compared to the initial SRS) should be practiced very carefully, although such a relationship could not be identified in the present data. Data about a direct correlation of mean or maximum biologically effective dose (BED) and outcome, especially in the reirradiation setting are rare, however some authors could show a general correlation of higher doses and better local control after primary, first-line, SRS for brain metastases [ 49 , 50 ].…”

“…Importantly, the local control rate was significantly higher for breast cancer histology and the Karnofsky performance status significantly affected the survival rate. In the only other published gantry-based linear accelerator series of re-SRS, Rana et al re-treated 28 patients, 59% of them with single-fraction regimen and achieved 1-year OS of 90.6% and 1-year-LCR of 88.3% [ 42 ]. The overall rate of radio-necrosis was 18.8% and occurred only in lesions treated with single-fraction SRS.…”

Retrospective analysis of salvage surgery for local progression of brain metastasis previously treated with stereotactic irradiation: diagnostic contribution, functional outcome, and prognostic factors

“…Retrospective studies on the one-year outcome of repeated radiosurgery for local progression reported that local control was 61 to 88%, and OS was 37 to 90.6% [25][26][27]. Toxicity was reported as overall necrosis rates 9.2 to 19% after the repeated SRS or SRT [25,26].…”

Second Re-irradiation of Brain Metastases: A Review of Studies Involving Stereotactic Radiosurgery

“…The fifth eligible study included 11 patients of interest (a total number of 28 patients with 32 metastases, mainly melanoma [39%]) [18]. The median gross tumor volume (GTV) size was 0.5 and 1.4 cc, respectively and the median dose was 24 and 26.5 Gy, respectively.…”

“…Most studies failed to provide useful data for the patients treated with three courses. Only one reported all the time intervals between the three series (10 and 11 months) [18]. The others reported only one interval (median: 10, 12, 13, and 19 months).…”