Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis

Abstract

ObjectFollowing resection of a brain metastasis, stereotactic radiosurgery (SRS) to the cavity is an emerging alternative to postoperative whole-brain radiation therapy (WBRT). This approach attempts to achieve local control without the neurocognitive risks associated with WBRT. The authors aimed to report the outcomes of a large patient cohort treated with this strategy.MethodsA retrospective review identified 91 patients without a history of WBRT who received Gamma Knife (GK) SRS to 96 metastasis resection cavities between 2007 and 2013. Patterns of intracranial control were examined in the 86 cases with post-GK imaging. Survival, local failure, and distant failure were estimated by the Kaplan-Meier method. Prognostic factors were tested by univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses.ResultsCommon primary tumors were non–small cell lung (43%), melanoma (14%), and breast (13%). The cases were predominantly recursive partitioning analysis Class I (25%) or II (70%). Median preoperative metastasis diameter was 2.8 cm, and 82% of patients underwent gross-total resection. A median dose of 16 Gy was delivered to the 50% isodose line, encompassing a median treatment volume of 9.2 cm3. Synchronous intact metastases were treated in addition to the resection bed in 43% of cases. Patients survived a median of 22.3 months from the time of GK. Local failure developed in 16 cavities, for a crude rate of 18% and 1-year actuarial local control of 81%. Preoperative metastasis diameter ≥ 3 cm and residual or recurrent tumor at the time of GK were associated with local failure (p = 0.04 and 0.008, respectively). Distant intracranial failure occurred in 55 cases (64%) at a median of 7.3 months from GK. Salvage therapies included WBRT and additional SRS in 33% and 31% of patients, respectively. Leptomeningeal carcinomatosis developed in 12 cases (14%) and was associated with breast histology and infratentorial cavities (p = 0.024 and 0.012, respectively).ConclusionsThis study bolsters the existing evidence for SRS to the resection bed. Local control rates are high, but patients with larger preoperative metastases or residual/recurrent tumor at the time of SRS are more likely to fail at the cavity. While most patients develop distant intracranial failure, an SRS approach spared or delayed WBRT in the majority of cases. The risk of leptomeningeal carcinomatosis does not appear to be elevated with this strategy.

Operative and peri‐operative considerations in the management of brain metastasis

“…The addition of postoperative WBRT has been shown to reduce the risk of both local and distal tumor recurrence within the brain compared to surgery alone, with an absolute risk reduction of 36% (5 [10%] of 49 vs 21 [46%] of 46, P < .001) and 23% (7 [14%] of 49 vs 17 [37%] of 46, P < .01) for local and distal tumor recurrence, respectively, as reported in Patchell et al's landmark study in 1998 . However, the use of WRBT is limited by an associated increased risk of neurocognitive decline and decreased QOL . As patient survival improves, these long‐term toxicities are becoming less acceptable.…”

Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis

“…Other studies have reported on the high risk of LMD in patients receiving SRS to the resection cavity, and have cited incidence rates around 12–14% [32–34]. Breast cancer metastases have been shown to have a particularly high rate of LMD [32–34].…”

“…Breast cancer metastases have been shown to have a particularly high rate of LMD [32–34]. Additionally, many studies reported on the adverse side effects of WBRT, including physical symptoms such as alopecia, somnolence, hearing loss, skin changes, and neurocognitive decline, manifested as memory loss and learning impairment [2, 7, 18, 26].…”

Multicenter analysis of stereotactic radiotherapy of the resection cavity in patients with brain metastases

“…Only previously, several single-institution series have been published with, naturally, not insignificant differences in patients' characteristics as well as dose prescription recommendations [5,[8][9][10][11][12][13][14][15][16][17]. To provide a broader basis and to identify relevant prognostic factors, we pooled the data from two German institutions for Radiation Oncology and present the detailed data on outcome in the present manuscript.…”