On demand Gamma-knife strategy can be safely combined with BRAF-inhibitors for the treatment of melanoma brain metastases
Menée sur 30 patients atteints d'une mélanome avec métastases cérébrales, cette étude met en évidence la faisabilité d'un traitement combinant une radiochirurgie stéréotaxique par Gamma Knife et un inhibiteur de BRAF
Background : Both Gamma-Knife radiosurgery (GKRS) and BRAF-inhibitors (BRAF-I) have been shown to be useful in melanoma patients with brain metastases (BM), thus suggesting that it could be interesting to combine their respective advantages. However cases of radiosensitization following conventional radiation therapy in BRAF-I treated patients have raised serious concerns about the real feasibility and risk/benefit ratio of this combination. Patients and methods : review by 2 independent observers of brain MRI follow-up pictures, and volume and edema quantifications, and survival assessment in all patients who had been treated by GKRS and BRAF-I at a single institution. Results : Among 53 GKRS performed in 30 patients who ever received BRAF-I and GKRS, 33 GKRS were performed in 24 patients while under BRAF-I treatment, from which only 4 with an interruption of BRAF-I. The 20 other GKRS were performed in 15 patients (including 9 of the 24) before initiation of BRAF-I treatment. No case of radiation-induced necrosis and no scalp radiation dermatitis occurred. A >20% increase in volume was observed in 35 out of the 263 BM treated by GKRS (13.3%), but only 3 clearcut edemas and 3 hemorrhages were detected within 2 months after GKRS, and 4 edemas and 7 hemorrhages later. Neither the MRI features nor the incidence of the volume changes, haemorrhage and edema were deemed unexpected for melanoma BM treated by GKRS. Median survival from 1st GKRS under BRAF-I and 1st dose of BRAF-I were 24.8, and 48.8 weeks, respectively. Conclusion : This series does not show immediate radiotoxicity nor radiation-recall, in melanoma patients with BRAF-I whose BMs are treated by GKRS. Interrupting BRAF-I for stereotactic radiosurgery of BM seems useless, although it is still advised for other radiation therapies. The potential benefit of combining stereotactic radiosurgery and BRAF-I can be safely tested.
Annals of Oncology 2014