title: On demand Gamma-Knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases.
abstract: BACKGROUND
  Both Gamma-Knife radiosurgery (GKRS) and BRAF inhibitors (BRAF-I) have been shown to be useful in melanoma patients with brain metastases (BMs), 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.
  
  
  METHODS
  Review by two independent observers of brain magnetic resonance imaging (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 carried out in 30 patients who ever received BRAF-I and GKRS, 33 GKRS were carried out in 24 patients while under BRAF-I treatment, from which only 4 with an interruption of BRAF-I. The 20 other GKRS were carried out 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 of the 263 BM treated by GKRS (13.3%), but only 3 clear-cut 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, hemorrhage and edema were deemed unexpected for melanoma BM treated by GKRS. Median survival from first GKRS under BRAF-I and first dose of BRAF-I were 24.8 and 48.8 weeks, respectively.
  
  
  CONCLUSIONS
  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 (SRS) of BM seems useless, although it is still advised for other radiation therapies. The potential benefit of combining SRS and BRAF-I can be safely tested.
authors: Department of Dermatology and Skin Cancers, UMR911 CRO2. Electronic address: caroline.gaudy@ap-hm.fr.
authors: C
authors: C
authors: Gaudy-Marqueste
authors: Department of Stereotaxic and Functional Neurosurgery, Gammaknife Unit, Inserm U751.
authors: R
authors: R
authors: Carron
authors: Department of Stereotaxic and Functional Neurosurgery, Gammaknife Unit, Inserm U751.
authors: C
authors: C
authors: Delsanti
authors: Department of Public Health, Aix-Marseille University, APHM, Marseille, France.
authors: A
authors: A
authors: Loundou
authors: Department of Dermatology and Skin Cancers, UMR911 CRO2.
authors: S
authors: S
authors: Monestier
authors: Department of Dermatology and Skin Cancers, UMR911 CRO2.
authors: E
authors: E
authors: Archier
authors: Department of Dermatology and Skin Cancers, UMR911 CRO2.
authors: M A
authors: MA
authors: Richard
authors: Department of Stereotaxic and Functional Neurosurgery, Gammaknife Unit, Inserm U751.
authors: J
authors: J
authors: Regis
authors: Department of Dermatology and Skin Cancers, UMR911 CRO2.
authors: J J
authors: JJ
authors: Grob
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary; D003131:Combined Modality Therapy; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects; D011859:Radiography; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011838:Radiation-Sensitizing Agents; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF inhibitors; Gamma-Knife radiosurgery; brain metastasis; metastatic melanoma; radiosensitization