Postoperative Stereotactic Radiosurgery Reduces Recurrence After Metastases Resection

Administering postoperative stereotactic radiosurgery (SRS) to the surgical cavity of patients who have had complete resection of 1 to 3 brain metastases significantly lowers local recurrence compared with observation alone, according to a study published in the Lancet Oncology.¹

Anita Mahajan, MD, from the Department of Radiation Oncology at the University of Texas MD Anderson Cancer Center in Houston, and colleagues conducted a randomized controlled phase 3 trial at a single tertiary cancer center in the United States (ClinicalTrials.gov identifier: NCT00950001) to evaluate whether postoperative SRS could be a substitute for whole-brain radiotherapy, which has been linked to cognitive adverse effects.^2-4

The final analysis comprised 128 patients (65 in the observation group and 63 in the SRS group) with a median age of 59 years (interquartile range, 20-80 years), a median dose of postoperative radiation of 16 Gy (range, 12-18 Gy) to the 50% isodose line, a median postoperative tumor maximal diameter of 3.0 cm (range, 0.6-5.3 cm) in the SRS group and 3.0 cm (range, 0.7-5.7 cm) in the observation group, and a median SRS-treated cavity volume of 8.9 cc (range, 0.9-28.6 cc).

In the observation group, 31 (48%) of 65 patients developed local recurrence of their treated lesion, whereas 15 (24%) of 63 patients in the SRS group developed local recurrence of their treated lesion. Of these patients, 9 in the observation group underwent whole-brain radiotherapy alone compared with 7 in the SRS group.

The time to local recurrence of treated lesions in the resection cavity was significantly higher after postoperative SRS than with observation alone, with 12-month freedom from local recurrence at 72% (95% CI, 60%-87%) in the SRS group and 43% (95% CI, 31%-59%) in the observation group (hazard ratio, 0.46; 95% CI, 0.24-0.88; P =.015).

“Treating the surgical cavity postoperatively with SRS is an appealing strategy to limit the neurocognitive insult while improving local tumor control,” Dr Mahajan and colleagues wrote. “Despite improvements in surgical techniques and adjuncts, our results show that surgery alone is insufficient to provide durable local control.”

The investigators made note of the following limitations, as they may have affected the study’s outcomes:

• Both groups had an overall median survival of more than 17 months, which is higher than other reports, and could be a result of the study being conducted at a tertiary cancer center and reflective of improvements in systemic treatments.
• The patient population at the tertiary cancer center might be eligible for clinical trials and specialized care that may not be widely accessible, and have the resources for increased clinical surveillance and imaging examinations.
• The duration of the study was more than 6 years, during which systemic treatments evolved, possibly influencing survival and local tumor control.
• The study is subject to certain biases, and both the patients and treatment physicians (excluding the neuroradiologist) were aware of patient allocation. The biases of a single-institution study may also be present.

References

1. 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. 2017;18(8):1040-1048.
2. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037-1044.
3. Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15(10):1429-1437.
4. Brown PD, Jaeckle K, Ballman DV, et al. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA. 2016;316(4):401-409.