Optimal timing of radiotherapy following brain metastases surgery

Abstract

Background There is growing evidence supporting the need for a short time delay before starting radiotherapy (RT) treatment post-surgery for most optimal responses. The timing of RT initiation and effects on outcomes have been evaluated in a variety of malignancies, but the relationship remains to be well established for brain metastasis. Methods Retrospective study of 176 patients (aged 18 to 89 years) with brain metastases at a single institution (03/2009 to 08/2018) who received RT following surgical resection. Time interval (≤ 22 days and > 22 days) from surgical resection to initiation of RT and any potential impact on patient outcomes were assessed. Results Patients who underwent RT > 22 days after surgical resection had a decreased risk for all-cause mortality of 47.2% (95% CI 8.60, 69.5%). Additionally, waiting > 40 days for RT after surgical resection more than doubled the risk of tumor progression; adjusted hazard ratio 2.02 (95% CI 1.12, 3.64). Conclusions Findings indicate that a short interval delay (> 22 days) following surgical resection is required before RT initiation for optimal treatment effects in brain metastasis. Our timing of RT post-surgical resection data add definition to current heterogeneity in RT timing, which is especially important for standardized clinical trial design and patient outcomes.

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases

“…It is also important to note that receipt of adjuvant radiation early can improve patient burden by reducing visits, scan requirements, and time to resumption of systemic cancer-directed therapy. 14,15,20 Importantly, OS was not different between RapidRT and StanRT cohorts or between cohorts stratified by time to radiation at any time point. This suggests that other retrospective studies that demonstrated poor survival in patients receiving ultra-early irradiation (<22-23 days) 14,15 may have been confounded by other potential correlates, such as rapidly progressive extracranial extent of disease.…”

“…Once the analyses were stratified by time to radiation within the larger combined cohort, this association became clearer. It is also important to note that receipt of adjuvant radiation early can improve patient burden by reducing visits, scan requirements, and time to resumption of systemic cancer-directed therapy . Importantly, OS was not different between RapidRT and StanRT cohorts or between cohorts stratified by time to radiation at any time point.…”

“…Substantial attention has been devoted to optimizing efficacy and reducing potential causes of institutional variability, with studies attempting to clarify the impacts of dosing, fractionation, and margins on outcome. Recent work has highlighted the importance of variable SRS timing after surgery on local control . These retrospective studies have highlighted improved outcomes with adjuvant SRS delivered before 3 to 6 weeks following surgery.…”

“…OS at 1 year did not significantly differ by time point stratification. LF rates were highest for patients receiving radiation more than 30 days from surgery (10.65%; 95% CI, 6.90%-15.32%) but comparable for patients receiving radiation within 14 days, between 15 There were very few wound complications overall and no wound complications within 14 days.…”

“…The timing of adjuvant SRS administration is an important factor that affects local control rates following surgery, with prolonged intervals between these paired treatments associated with increased risk of local failure. Several studies have demonstrated that SRS delivered within 1 month of surgery reduces the likelihood of local recurrence vs SRS delivered thereafter . However, concerns have been raised regarding early adjuvant SRS due to potential changes in postoperative cavity size, the potential for impaired wound healing, and challenges in coordinating preradiation imaging and SRS planning .…”