Volumetric Radiosurgery For One to Ten Brain Metastases: a Multi-Center, Single-Arm, Phase 2 Study
Mené sur 60 patients présentant 1 à 10 métastases cérébrales traitées entre 2010 et 2013 (durée médiane de suivi : 30,5 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse objective à 3 mois et du taux actuariel de contrôle à 1 an, et la tolérabilité d'une radiochirurgie volumique
Purpose : There is growing interest in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). Methods and Materials : We enrolled patients with ≥ 6-month estimated life expectancy and 1-10 brain metastases of diameter ≤ 3 cm at five cancer centers. VRS was delivered in five fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5Gy/5) to the metastases with no margin and 95% of 40 Gy (38Gy/5) to their 2-mm planning target volumes (PTVs), concurrent with 20 Gy to the whole brain PTV. The treatment was delivered with daily image guidance on conventional linear accelerators using volumetric modulated arc therapy. Magnetic resonance imaging was obtained every three months. The primary endpoint was three-month Objective Response in the brain by the Response Evaluation Criteria in Solid Tumors Version 1.1. The principal secondary endpoint was one-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events Version 4.0. This study is registered with ClinicalTrials.gov, number NCT########. Results : Between July 2010 and May 2013, 60 patients received VRS with 47.5 Gy/5 for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up was 30.5 months and the median survival was 10.1 months. For the 43 assessable patients at three months, Objective Response in the brain was 56%. By patient, treated metastases were controlled in 88% at one year and 84% at three years. Overall survival did not differ for patients with 4-10 versus 1-3 metastases (HR=1.18, p=0.6). Crude incidences of severe radionecrosis (grades 3-5) were 25% (3/12) per deep metastasis, 1.9% (4/219) per non-deep metastasis, and 10% (6/60) per patient. Conclusions : For non-deep brain metastases, 47.5Gy/5 was tolerable. VRS was effective for long-term control of treated brain metastases.
http://www.redjournal.org/article/S0360-3016%2815%2926582-0/abstract