Dataset Information

Salvage resection plus cesium-131 brachytherapy durably controls post-SRS recurrent brain metastases.

ABSTRACT:

Background

Salvage of recurrent previously irradiated brain metastases (rBrM) is a significant challenge. Resection without adjuvant re-irradiation is associated with a high local failure rate, while reirradiation only partially reduces failure but is associated with greater radiation necrosis risk. Salvage resection plus Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced normal brain dose versus re-irradiation, however data are limited.

Methods

A prospective registry of consecutive patients with post-stereotactic radiosurgery (SRS) rBrM undergoing resection plus implantation of collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60 Gy at 5 mm from the cavity was analyzed.

Results

Twenty patients underwent 24 operations with Cs131 implantation in 25 tumor cavities. Median maximum preoperative diameter was 3.0 cm (range 1.1-6.3). Gross- or near-total resection was achieved in 80% of lesions. A median of 16 Cs131 seeds (range 6-30), with a median air-kerma strength of 3.5 U/seed were implanted. There was one postoperative wound dehiscence. With median follow-up of 1.6 years for survivors, two tumors recurred (one in-field, one marginal) resulting in 8.4% 1-year progression incidence (95%CI = 0.0-19.9). Radiographic seed settling was identified in 7/25 cavities (28%) 1.9-11.7 months post-implantation, with 1 case of distant migration (4%), without clinical sequelae. There were 8 cases of radiation necrosis, of which 4 were symptomatic.

Conclusions

With > 1.5 years of follow-up, intraoperative brachytherapy with commercially available Cs131 implants was associated with favorable local control and toxicity profiles. Weak correlation between preoperative tumor geometry and implanted tiles highlights a need to optimize planning criteria.

SUBMITTER: Imber BS

PROVIDER: S-EPMC9328626 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract BACKGROUND Salvage of recurrent of previously-irradiated brain metastases (rBrM) is a significant clinical challenge. High local failure rates are seen following salvage resection without adjuvant re-irradiation, while reirradiation is associated with high radionecrosis rates. Salvage surgery plus intraoperative Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced integral brain dose versus re-irradiation. METHODS A prospective registry of consecutively treated patients with rBrM after prior stereotactic radiosurgery (SRS) was analyzed. Following maximal-safe resection and intraoperative viable-disease confirmation, cavities were implanted with commercially-available, collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies). Prescribed dose was 60Gy at 5mm from the cavity. RESULTS Twenty patients underwent 24 operations with Cs131 implantation in 25 cavities. Previous SRS occurred a median of 358d preoperatively (range=56-1334). Median maximum preoperative diameter was 3.0cm (range=1.1-6.3) and enhancing volume was 9.5cm3 (range=0.6-69.7). Gross- or near-total resection was achieved in 60% of lesions. A median of 16 Cs131 seeds (range=6-30), with a median activity of 3.5U/seed were implanted. Maximal preoperative diameter and enhancing volume were weakly associated with the number of implanted seeds (correlation coefficients=0.50, 0.41, respectively). There was one postoperative wound dehiscence in a multiply resected and irradiated patient with hydrocephalus. With median follow-up of 12.5 months, 2 tumors recurred (one in-field, one marginal) resulting in a 1-year progression incidence of 9.8% (95%CI=0.0-23.2). Radiographic seed migration was identified in 7/25 cavities (28%) on surveillance scans ranging from 1.9-11.7 months post-implantation, without clinical sequelae. CONCLUSIONS With >1 year of follow-up, intraoperative brachytherapy with commercially-available Cs131 implants was associated with a high rate of local control and a favorable toxicity profile. Modest correlation between preoperative tumor geometry and implanted tiles in the context of high associated cost suggests a need to optimize planning criteria. A randomized trial of salvage resection with or without Cs131 is ongoing (NCT04690348) to assess the incremental benefit of brachytherapy.

Project description:Abstract Background The salvage treatment of recurrent brain metastases after failed irradiation is a clinical challenge. Adjuvant SRS is standard of care for resected brain metastases in the upfront post-resection setting given a significant local control advantage over surgery alone. However, the role of reirradiation following salvage resection of recurrent post-irradiation metastases is unclear owing to both reduced efficacy of subsequent courses of external beam radiation, and likely increased risk of radiation injury. Intracavitary cesium 131 (Cs131) brachytherapy offers a highly conformal adjunct radiation option that we hypothesize may allow for improved local control while also theoretically conveying a low risk of radiation necrosis. In this randomized controlled study, we aim to define the potential benefits and risks of resection plus permanently implanted, carrier-embedded intracavitary Cs131 brachytherapy versus conventional care (surgery alone). Methods This is a single-center randomized controlled study of patients undergoing resection of recurrent, previously-irradiated brain metastases. Exclusion criteria include prior in-field infection, prior radiation >100Gy (in 2Gy fraction equivalents), >5 additional active or untreated CNS lesions, or leptomeningeal carcinomatosis. Subjects are randomized 1:1 to undergo either surgery with placement of Cs131 brachytherapy or surgery alone. The primary endpoint is freedom from treated-site progression at 9 months. Secondary endpoints include wound complications at 3 months and time to local retreatment at the index site, and exploratory objectives include neurocognitive function prior to surgery and at 3 and 12 months postoperatively, with correlative analyses of the previously irradiated brain metastasis tissue. Accrual began on December 24, 2020 and 5 of a planned 76 patients have enrolled. This is the first randomized controlled trial of surgery plus permanently implanted intracavitary Cs131 brachytherapy versus surgery alone for recurrent brain metastases. ClinicalTrials.gov Identifier: NCT04690348