SRS After Brain Metastases Resection Could Be ‘Standard of Care’

Research indicates that stereotactic radiosurgery may be an alternative to whole brain radiotherapy for patients after brain metastases surgery

medwireNews: Findings from two studies suggest that stereotactic radiosurgery (SRS) should be considered as a possible standard of care for patients who undergo surgery to remove brain metastases.

Paul Brown, from the Mayo Clinic in Rochester, Minnesota, USA, and co-workers report results from a phase III trial comparing postoperative SRS (single fraction of 12–15 Gy) with whole-brain radiotherapy (WBRT; 30 Gy in 10 daily fractions or 37.5 Gy in 15 fractions) for patients with a single resection cavity of less than 5.0 cm diameter.

After a median of 11.1 months, the 98 patients randomly assigned to receive SRS had longer survival free from cognitive deterioration than the 96 patients given WBRT, at a median of 3.7 versus 3.0 months and a hazard ratio (HR) of 0.47. Cognitive deterioration at 6 months was significantly less common with SRS than WBRT (52 vs 85%), the researchers add.

Although SRS was associated with a shorter time to intracranial tumour progression than WBRT (median 6.4 vs 27.5 months), overall survival did not significantly differ between the treatment arms (median 12.2 vs 11.6 months).

And SRS was associated with lower frequencies of the most common grade 3 or 4 treatment-related adverse events of hearing impairment (3 vs 9%) and cognitive disturbance (3 vs 5%).

“Taken in context with other phase 3 trials assessing SRS to the surgical bed, the implication for clinical care is that SRS in the postoperative setting is a viable treatment option to improve surgical bed control and should be considered a standard of care and a less toxic alternative than WBRT”, the researchers suggest.

“The implication for future research is that continued refinement of the SRS technique, such as fractionated or preoperative radiosurgery, is needed to further improve outcomes such as surgical bed control”, they state.

Anita Mahajan, from The University of Texas MD Anderson Cancer Center in Houston, USA, and co-investigators also studied the use of SRS after brain metastases resection, this time in patients who had one to three tumours removed, each with a maximum cavity diameter of 4 cm.

Twelve-month freedom from local recurrence was achieved by 72% of the 64 patients who were randomly assigned to receive a single SRS fraction of 12–16 Gy within 30 days of surgery but just 43% of the 68 patients who were assigned to receive observation alone, giving a significant HR of 0.46.

Median overall survival was at least 17 months in both treatment arms and the researchers note that this is higher than reported for studies comparing SRS and WBRT in patients with up to three cavities. “The higher survival could be because our study was done at a tertiary cancer centre and could also reflect improvements in systemic treatments”, they hypothesize.

The authors of a comment accompanying the articles in The Lancet Oncology describe the trials as being “of crucial importance” in providing evidence supporting a role for SRS in patients with surgical cavities.

Simon Lo, from the University of Washington School of Medicine in Seattle, USA, and co-writers say that the study by Anita Mahajan et al “confirms that radiation to surgical cavities is a standard of care and improves local control more than does observation, and that SRS is a safe and effective alternative to WBRT as a postoperative treatment.”

Observing that SRS did not give a sufficient radiation dose for control of microscopic disease in the study by Paul Brown et al, the commentators hypothesize that “postoperative hypofractionated SRS could be an attractive option to facilitate dose escalation while minimising the risk of radiation necrosis by widening the therapeutic window.”

But they note that a head-to-head trial comparing single-fraction versus hypofractionated SRS has yet to be performed and they emphasize the need for future research to also focus on understanding patterns of local and marginal failure, identification of a purported subgroup of patients who could avoid any radiation, and the optimal timing of adjuvant SRS.

References

Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol; Advance online publication 4 July 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30441-2

Mahajan A, Ahmed S, McAleer MF, et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial. Lancet Oncol; Advance online publication 4 July 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30414-X

Lo SS, Chang EL, Sahgal A. Radiosurgery for resected brain metastases–a new standard of care? Lancet Oncol; Advance online publication 4 July 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30448-5

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