Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial

Abstract

SUMMARYBackgroundAfter brain metastasis resection, whole-brain radiation therapy (WBRT) decreases local recurrence but may cause cognitive decline. We performed this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved local tumor tumor-free recurrence rates compared to surgical resection alone as an alternative to the need for immediate WBRT.MethodsThe main entry criteria for the study included patients >3 years of age, with a Karnofsky Performance Score ≥ 70, who were able to undergo an MRI scan and who had a complete resection of 1–3 brain metastases (the maximum diameter of the resection cavity had to be ≤4cm). Patients were assigned randomly to either SRS treatment of the resection cavity (within 30 days of surgery) or observation (OBS). Patients were stratified by histology, tumor size, and number of metastases. Patients were recruited at a single tertiary cancer center. The primary endpoint was time to local recurrence in the resection cavity assessed by blinded central review of brain MRI scans in the intention-to-treat population. The trial was registered at clinicaltrials.gov (Trial NCT00950001, status: closed to new participants).FindingsBetween 8/13/2009 and 2/16/2016, 132 patients were randomized to OBS (N=68) or SRS (N=64), with 128 patients available for analysis. We stratified by metastasis size (maximum diameter of ≥3 cm vs. <3 cm), histology (melanoma vs. other), and number of metastases (one vs. two or three). The 12-month local tumor recurrence-free rate was 43% (OBS) (95% CI 31%–59%) and 72% (SRS) (95% CI 60%–87%) (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.24–0.88, p=0.015).InterpretationThis prospective randomized trial of patients undergoing surgical resection for 1–3 brain metastases indicates that SRS administered to the resection cavity significantly lowers local recurrence compared to observation alone. Thus, the use of SRS after brain metastasis resection is an alternative to WBRT.

Tumor Cavity Recurrence after Stereotactic Radiosurgery of Surgically Resected Brain Metastases: Implication of Deviations from Contouring Guidelines

“…Others have questioned the benefit of routine coverage of the surgical tract [10]. The proposed guidelines recommend coverage of the surgical tract; however, this was not routinely incorporated in the MDACC and NCCTG studies [1, 2]. Neither the MDACC trial nor the NCCTG trial have reported their patterns of recurrence, but based on our data, there may be a benefit to inclusion of the surgical tract.…”

“…There has been a growing trend towards the use of postoperative surgical cavity SRS over WBRT to preserve neurocognition and improve local control, with a number of recent landmark trials evaluating the outcomes of surgical cavity SRS with variations in target definition as highlighted in Table 1 [1, 2]. Due to the heterogeneity seen in prospective trials, a set of guidelines proposed by Soliman et al [4] were created based on the surveyed opinion of 10 experts within the field.…”

“…2). The MDACC study used marginal doses ranging from 12 to 18 Gy (median dose 16 Gy) with a 1-year local control rate in the SRS group of 72% [2]. The NCCTG study saw a 1-year local control rate of 61% in the SRS group with marginal doses ranging from 12 to 20 Gy (median dose not reported) [1].…”

“…The importance of postoperative stereotactic radiosurgery (SRS) in improving local control of disease over surgery alone and reducing the neurocognitive effects seen with whole-brain radiation therapy (WBRT) has been recently highlighted in a number of landmark publications [1, 2]. The addition of a 2-mm margin to the resection cavity with the use of SRS has been previously shown to decrease local failure rates from 16 to 3% [3].…”

Effect of Postoperative Radiotherapy for Brain Metastases: An Analysis

“…Furthermore, the addition of WBRT to local treatment (surgery/radiosurgery) ameliorated intracranial disease control without a significant impact on OS [4, 21, 22]. Omission of RT after local treatment may cause local recurrences in >70% [21, 23]. A control collective (without postoperative RT) could not be provided as this treatment is standard of care in our institution as recommended by our neurooncology tumor board.…”