A Phase II Trial of Intraoperative Radiotherapy after Surgical Resection of Brain Metastases: Feasibility and Efficacy NCT04847284

Abstract

Intraoperative radiation therapy (IORT) is an alternative to local radiation therapy for brain metastases, reducing total treatment time, and improving patient comfort, but the most effective dose is unknown. The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy. This trial is a single-institution, open-label, prospective, non-randomized study for intraoperative radiotherapy immediately after resection of brain metastases. Registered in January 2021, currently ongoing, planned to enroll 25 patients with IK ≥70, brain damage newly diagnosed by MRI, without dural contact and at least 1 cm to the optic nerve, chiasm and brainstem. In the baseline visit, the General Cognitive State will be carried out: Minimum Mental State Exams. Specific cognitive study: 1- Processing speed (SYmbol digit modalities test), 2- Executive function (TMT, back and forward digit span test, phonological and semantic verbal fluency test, Stroop color-word test), 3- Verbal memory (FCSRT). Quality of life will be monitored by completing the EORTC QL-C30 and BN20 questionnaires. Intraoperative radiation therapy will be performed with a 50 kV low energy X-ray portable linear accelerator using spherical applicators ranging from 1.5 to 4 cm kV to deliver 20 Gy to the surface. During IORT a maximum dose (DMax) of 8 Gy will be allowed to the optic nerve/chiasm and brainstem structures. MRI will be performed 72 hours after IORT. Neurocognitive Test and MRI after 6 weeks and every 3 months. The primary endpoint will be local progression free survival (PFS). Secondary endpoints will be overall survival, time to save cancer therapy, cognitive performance and quality of life, as well as IORT-related neurotoxicity complications will be evaluated according to the scale of the CTACAE version 4. The analysis of the median local progression free survival, overall survival will be analyzed using the Kaplan-Meier curve (long range test). All results will be considered statistically significant with a p value < 0.05. The statistical analysis will be carried out with statistical software. The trial is open and ongoing to recruitment; we have included 7 patients. The 85.7% were male, mean age was 61.4 years range (43-74). The 57.1% were lung cancer metastases. For now, no tumor recurrence or neurocognitive complications have been observed and then once you have the results ready, we will publish them. The limited current literature on the use of IORT in brain metastases appears to show efficacy and safety, but the most effective dose is unknown as well as whether it is as effective as other radiotherapy alternatives. Our study is ongoing and needs to be completed and evaluated with more follow-up in order to reach definitive conclusions.