P03.12.A PHASE III RANDOMIZED TRIAL COMPARING PREOPERATIVE HYPOFRACTIONATED RADIOSURGERY (HSRS) TO POSTOPERATIVE HYPOFRACTIONATED RADIOSURGERY (HSRS) FOR PATIENTS WITH LARGE BRAIN METASTASES SUITABLE FOR SURGICAL RESECTION SUPPORT TRIAL

Abstract

Abstract BACKGROUND Standard of care for patients with large brain metastases (BMs) suitable for surgery is surgical resection followed by radiosurgery in single or multifractions (SRS/HSRS) on tumor bed. Although a satisfactory local control is obtained, an increasing rates of leptomeningeal disease (LMD) related to surgery, and symptomatic radionecrosis related to SRS/HSRS have been observed. In the last years the employ of preoperative SRS/HSRS has been investigated in retrospective studies. Advantages seem to be: better target delineation to intact lesion, reduction of normal brain irradiated considering useless of margins, potential prevention of any cells spilled during resection, greater oxygenation ratio of intact region, sterilization effect, and resection of majority of irradiated tissues. Preoperative HSRS versus postoperative ones will be investigated in multicentric randomized phase III trial. Primary endpoint is rate of leptmeningeal disease secondary endpoints, local control, symptomatic radiation necrosis, surgical morbidity, quality of life (QoL) and neurocognitive functions assessment between the two modalities; brain distant progression (BDP), and overall survival (OS) will be evaluated too. MATERIAL AND METHODS Inclusion criteria are: patients aged 18-80 years, diagnosed malignant primary tumor, KPS≥70, oligometastatic disease, limited brain metastases (up to 4), large BM suitable for surgery. Exclusion criteria are: prior WBRT, SCLC, or germinal cell tumour or Lymphoproliferative disease, prior neurosurgery, and incompatibility to perform MRI. Stratification factors will be: histology of primary tumor (Breast, NSCLC, Melanoma, Other) and BMs location (sovra-or infra-tentorial). In Arm A (experimental) patients undergo preoperative HSRS, 27 Gy in 3 fractions, followed by surgery. In Arm B (control): patients undergo surgical resection followed by postoperative HSRS at the same doses. Outcome evaluation will be assess using MRI, total body CT scan and/or CTPET, neuropsychological and Quality of life assessment before and after treatments. For distinguish RN occurrence and disease progression delayed-contrastMRI, and perfusion MRI will be employed. Considering that estimated 1 year LMD is 10% for postoperative HSRS, and ≤ 2% for preoperative enrolment of 146 patients is expected (73 per Arm). RESULTS Enrollment started at April 2023 and among first patients included the treatment has proven to be safe. CONCLUSION Preoperative HSRS in large BMs suitable for surgical resection need prospective evaluation aiming to improve outcome, and reduced treatments side effects.