Study design and patients
SCLC, active extra-cranial disease, brain failure, SRS
ADVERSE EVENT, SCLC, DISEASE, HEMATOLOGIC MALIGNANCY, SOLID TUMORS, SMALL CELL LUNG CANCER
The present is a single institute prospective randomized, double-arms phase 3 trial approved by our institutional review board, registered at the ClinicalTrials.gov site with the number NCT02355613. The trial was approved by the Institutional Review Board, and it was monitored by the institutional Data and Safety Monitoring Board. The study aimed to compare SRS treatments executed on a Gamma-Knife Perfexion unit (Elekta AB, Stockholm, Sweden), Arm-A, or an Edge treatment system (Varian Medical Systems, Palo Alto, USA), Arm-B. All patients provided written informed consent to the treatment and the use of their data for scientific purposes. Eligible patients were aged 18–85 years, Karnofsky performance status (KPS) ≥ 70, histo-pathologically confirmed primary solid tumors, 1–4 BMs up to 30 mm in maximum diameter, recursive partitioning analysis (RPA) class 1–2, estimated survival ≥ 3 months as from disease specific-grade prognostic assessment (DS-GPA) score. Patients with a primary diagnosis of small cell lung cancer (SCLC), hematologic malignancy, pregnancy or prior whole brain radiotherapy were excluded from the enrolment. The administration of bevacizumab (possibly included in some chemotherapy schemes) for at least two months after radiosurgery was another exclusion criterion since potentially altering the RN patterns. Patients could have an active extra-cranial disease, and a systemic agents treatment has been permitted while in the study. The primary endpoint was the occurrence of symptomatic RN in our patients expressed as cumulative incidence (CIRN). Symptomatic RN was defined as grade 2 (moderate symptoms; corticosteroids indicated), grade 3 (severe symptoms; intervention indicated), and grade 4 (severe symptoms; immediate intervention indicated) as for Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Radiologically, RN was defined as the radiographic evidence of lesion on postcontrast T1MRI not visible on T2MRI sequences (T1/T2 mismatch), absence of perfusion on perfusion MRI, and/or absence of uptake on 11CMETPET. Secondary endpoints were cumulative incidence of local progression (CILP), distant brain failure (DBF), disease-free survival (DFS), and overall survival (OS). CILP was evaluated (per-lesion) measuring lesion volume variation according to the Response Assessment in Neuro-Oncology (RANO) Working Group [The total beam-on time was recorded as complementary endpoints as efficiency indicators. The total treatment time was not effectively recorded for all patients and will not be reported.