Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis

Palmer, Joshua D.; Perlow, Haley K.; Matsui, Jennifer K.; Ho, Cindy; Prasad, Rahul N.; Liu, Kevin; Upadhyay, Rituraj; Klamer, Brett; Wang, Joshua; Damante, Mark; Ghose, Jayeeta; Blakaj, Dukagjin; Beyer, Sasha; Grecula, J.C.; Arnett, A.L.H.; Thomas, Evan M.; Chakravarti, Arnab; Lonser, Russell R.; Hardesty, Douglas A.; Prevedello, Daniel M.; Prabhu, Roshan S.; Elder, J. Bradley; Raval, Raju R.

doi:10.1007/s11060-022-04073-w

Cited by 18 publications

(16 citation statements)

References 17 publications

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“…While large-volume studies are needed to further characterize the risks and benefits of a neoadjuvant radiosurgery regimen, the current study confirms the favorable outcomes previously demonstrated in multiple single-institution studies, particularly the low rate of leptomeningeal disease. In conjunction with recent studies examining dose escalation and fractionated delivery of SRS for brain metastases, 31,54 this study helps to lay the groundwork for prospective trials utilizing more aggressive SRS dosing in combination with preoperative radiosurgery.…”

Section: Discussionmentioning

confidence: 91%

“…This strategy has been studied primarily in the setting of postoperative SRS, but Palmer et al recently demonstrated that fractionated preoperative SRS may offer improved rates of local disease recurrence, radiation necrosis, and leptomeningeal disease compared with postoperative SRS as well as single-fraction preoperative SRS. 54 Faruqi et al reported that the risks of adverse radiation effects were higher in patients who underwent fractionated SRS for intact lesions compared with resection cavities. 55 Of note, the median planning target volume was significantly smaller in the cohort of intact lesions.…”

Section: Discussionmentioning

confidence: 99%

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Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm

Coxon

Huang

et al. 2022

Neurosurgical Focus

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OBJECTIVE For patients with surgically accessible solitary metastases or oligometastatic disease, treatment often involves resection followed by postoperative stereotactic radiosurgery (SRS). This strategy has several potential drawbacks, including irregular target delineation for SRS and potential tumor "seeding" away from the resection cavity during surgery. A neoadjuvant (preoperative) approach to radiation therapy avoids these limitations and offers improved patient convenience. This study assessed the efficacy of neoadjuvant SRS as a new treatment paradigm for patients with brain metastases. METHODS A retrospective review was performed at a single institution to identify patients who had undergone neoadjuvant SRS (specifically, Gamma Knife radiosurgery) followed by resection of a brain metastasis. Kaplan-Meier survival and log-rank analyses were used to evaluate risks of progression and death. Assessments were made of local recurrence and leptomeningeal spread. Additionally, an analysis of the contemporary literature of postoperative and neoadjuvant SRS for metastatic disease was performed. RESULTS Twenty-four patients who had undergone neoadjuvant SRS followed by resection of a brain metastasis were identified in the single-institution cohort. The median age was 64 years (range 32–84 years), and the median follow-up time was 16.5 months (range 1 month to 5.7 years). The median radiation dose was 17 Gy prescribed to the 50% isodose. Rates of local disease control were 100% at 6 months, 87.6% at 12 months, and 73.5% at 24 months. In 4 patients who had local treatment failure, salvage therapy included repeat resection, laser interstitial thermal therapy, or repeat SRS. One hundred thirty patients (including the current cohort) were identified in the literature who had been treated with neoadjuvant SRS prior to resection. Overall rates of local control at 1 year after neoadjuvant SRS treatment ranged from 49% to 91%, and rates of leptomeningeal dissemination from 0% to 16%. In comparison, rates of local control 1 year after postoperative SRS ranged from 27% to 91%, with 7% to 28% developing leptomeningeal disease. CONCLUSIONS Neoadjuvant SRS for the treatment of brain metastases is a novel approach that mitigates the shortcomings of postoperative SRS. While additional prospective studies are needed, the current study of 130 patients including the summary of 106 previously published cases supports the safety and potential efficacy of preoperative SRS with potential for improved outcomes compared with postoperative SRS.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm

Coxon

Huang

et al. 2022

Neurosurgical Focus

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“…Fractionation may facilitate safer delivery of higher biological effective dose (BED) treatments which may improve the high LF rates seen in N107C, Mahajan et al, and the PROPS-BM cohort [5] , [7] , [8] . This has been shown in a previously published cohort that did not show any incidences of LF in patients who received pre-operative fractionated stereotactic radiation therapy (FSRT) [9] . Currently, Alliance A071801 is comparing post-operative SRS with post-operative FSRT, and NRG BN012 is comparing pre-operative SRS with post-operative SRS.…”

Section: Introductionmentioning

confidence: 79%

Comparing pre-operative versus post-operative single and multi-fraction stereotactic radiotherapy for patients with resectable brain metastases

Perlow

Matsui

et al. 2023

Clinical and Translational Radiation Oncology

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“…Fractionation may facilitate safer delivery of higher biological effective dose (BED) treatments which may improve the high LF rates seen in N107C, Mahajan et al, and the PROPS-BM cohort 5,7,8 . This has been shown in a previously published cohort that did not show any incidences of LF in patients who received pre-operative fractionated stereotactic radiation therapy (FSRT) 9 . Currently, Alliance A071801 is comparing postoperative SRS with post-operative FSRT, and NRG BN012 is comparing pre-operative SRS with postoperative SRS.…”

Section: Introductionmentioning

confidence: 79%

Comparing Pre-Operative Versus Post-Operative Single and Fractionated Stereotactic Radiotherapy for Patients with Resectable Brain Metastases

Perlow

Matsui

et al. 2022

Preprint

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BackgroundThe standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT. MethodsA multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined inclusive of events of 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results279 patients were eligible for analysis. The median follow-up time was 9 months. 87% of patients received fractionated treatment. 29% of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0%, 17%, 15%, and 7.5%, respectively. ConclusionsIn our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.

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Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis

Cited by 18 publications

References 17 publications

Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm

Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm

Comparing pre-operative versus post-operative single and multi-fraction stereotactic radiotherapy for patients with resectable brain metastases

Comparing Pre-Operative Versus Post-Operative Single and Fractionated Stereotactic Radiotherapy for Patients with Resectable Brain Metastases

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