Current status and recent advances in resection cavity irradiation of brain metastases

Abstract

Despite complete surgical resection brain metastases are at significant risk of local recurrence without additional radiation therapy. Traditionally, the addition of postoperative whole brain radiotherapy (WBRT) has been considered the standard of care on the basis of randomized studies demonstrating its efficacy in reducing the risk of recurrence in the surgical bed as well as the incidence of new distant metastases. More recently, postoperative stereotactic radiosurgery (SRS) to the surgical bed has emerged as an effective and safe treatment option for resected brain metastases. Published randomized trials have demonstrated that postoperative SRS to the resection cavity provides superior local control compared to surgery alone, and significantly decreases the risk of neurocognitive decline compared to WBRT, without detrimental effects on survival. While studies support the use of postoperative SRS to the resection cavity as the standard of care after surgery, there are several issues that need to be investigated further with the aim of improving local control and reducing the risk of leptomeningeal disease and radiation necrosis, including the optimal dose prescription/fractionation, the timing of postoperative SRS treatment, and surgical cavity target delineation. We provide a clinical overview on current status and recent advances in resection cavity irradiation of brain metastases, focusing on relevant strategies that can improve local control and minimize the risk of radiation-induced toxicity.

Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases

“…Cumulative incidence curves showed no significant differences in resection cavity control between the groups, confirming that SRS alone offers excellent local control also in radioresistant tumors. 15 In contrast, combination treatment was associated with significantly better distant intracranial control and OS, consistent with previous published series. 34–38 Differences in cumulative incidence of LMD and DBF between groups resulted in a significantly decreased risk of intracranial failure (32% at 1 year) and neurological death for patients receiving fSRS and immunotherapy, with 50% and 26% of patients expected to be alive at 2 and 5 years.…”

“…In contrast, in the North Central Cancer Treatment Group (NCCTG) N107C/CEC.3 prospective randomized trial of 194 patients with one resected BM who were assigned to either SRS or WBRT, Brown et al 10 found a rate of LMD of 7% at 1 year, and a similar low rate has been observed in other few series. 15 The variable range reported may, at least in part, be explained by differences in tumor histology, location of lesions, and type of surgical resection. Moreover, differences in imaging follow-up and under-reporting of nodular LMD, 22 which is generally seen as focal nodules adherent to the dura or pia near the site of cavity in contrast to the classic LMD, may account for variability in assessment.…”

“…The most feared adverse effects of combined surgery and SRS include the risk of developing leptomeningeal disease (LMD) and radiation-induced brain necrosis (RN). 15 According to the recent guidelines of the European Association of Neuro-Oncology (EANO) and the European Association for Medical Oncology (ESMO), 16 LMD is classified as linear, nodular, or both based on magnetic resonance image (MRI) patterns, and its development is presumably related to iatrogenic dissemination of tumor cells into the cerebrospinal fluid and meninges at the time of resection. Large retrospective series report a 1-year rate of LMD up to 31% after postoperative SRS of resected BM.…”

Whole-Brain Radiotherapy vs. Localized Radiotherapy after Resection of Brain Metastases in the Era of Targeted Therapy: A Retrospective Study

“…Furthermore, fractionated stereotactic radiation therapy (FSRT) has emerged as a treatment for large BM [ 15 ]. Moreover, local brain radiotherapy (LBRT) to the resection cavity showed similar LC compared with WBRT [ 16 , 17 , 18 ].…”

Modern Radiation Therapy for the Management of Brain Metastases From Non-Small Cell Lung Cancer: Current Approaches and Future Directions

“…The second issue is related to the uncertainties in the target delineation. The dynamic adaptation of the surgical cavity and of the surrounding tissues after surgical resection, cause significant changes in the shape of the target area, with an average cavity/volume reduction after surgery estimated in a range of 15-43% ( 47 ). This volume shrinkage and the timing needed to obtain a reasonable post-surgical clinical recovery, influence the timing for the administrations of adjuvant RT, generally performed within maximum 4-6 weeks after surgery.…”