BACKGROUND: Metastatic melanoma often involves the brain. Radiotherapy is an important treatment of melanoma brain metastases, although melanoma radiosensitivity is considered heterogeneous. Thus, identifying subsets with differential radiosensitivity is essential. MATERIALS AND METHODS: Patients with metastatic melanoma were identified in a prospective stereotactic radiosurgery (SRS) database. Tumor were tested for alterations in B-RAF, N-RAS, and c-KIT. Standardized imaging following SRS was reviewed for recurrence. Differences in local and distant failure were determined using modified Cox proportional hazards models. RESULTS: 102 patients and 1,028 brain metastases were included. N-RAS mutated patients were significantly less likely to develop local recurrence after SRS than wild type patients (HR 0.17, 95% CI 0.04-0.72, p=0.017). B-RAF and c-KIT mutations were not associated with altered rates of local recurrence. Lower local recurrence rates for N-RAS mutated tumors persisted on multivariate analysis (HR 0.18, 95% CI 0.04-0.84p=0.029). CONCLUSIONS: N-RAS mutation is associated with improved local control following SRS. Local recurrence is more common in wild type patients and those with B-RAF or c-KIT mutations. Further research is needed to validate these findings and integrate into practice.
BACKGROUND: Metastatic melanoma often involves the brain. Radiotherapy is an important treatment of melanoma brain metastases, although melanoma radiosensitivity is considered heterogeneous. Thus, identifying subsets with differential radiosensitivity is essential. MATERIALS AND METHODS: Patients with metastatic melanoma were identified in a prospective stereotactic radiosurgery (SRS) database. Tumor were tested for alterations in B-RAF, N-RAS, and c-KIT. Standardized imaging following SRS was reviewed for recurrence. Differences in local and distant failure were determined using modified Cox proportional hazards models. RESULTS: 102 patients and 1,028 brain metastases were included. N-RAS mutated patients were significantly less likely to develop local recurrence after SRS than wild type patients (HR 0.17, 95% CI 0.04-0.72, p=0.017). B-RAF and c-KIT mutations were not associated with altered rates of local recurrence. Lower local recurrence rates for N-RAS mutated tumors persisted on multivariate analysis (HR 0.18, 95% CI 0.04-0.84p=0.029). CONCLUSIONS: N-RAS mutation is associated with improved local control following SRS. Local recurrence is more common in wild type patients and those with B-RAF or c-KIT mutations. Further research is needed to validate these findings and integrate into practice.
Authors: Keith T Flaherty; Caroline Robert; Peter Hersey; Paul Nathan; Claus Garbe; Mohammed Milhem; Lev V Demidov; Jessica C Hassel; Piotr Rutkowski; Peter Mohr; Reinhard Dummer; Uwe Trefzer; James M G Larkin; Jochen Utikal; Brigitte Dreno; Marta Nyakas; Mark R Middleton; Jürgen C Becker; Michelle Casey; Laurie J Sherman; Frank S Wu; Daniele Ouellet; Anne-Marie Martin; Kiran Patel; Dirk Schadendorf Journal: N Engl J Med Date: 2012-06-04 Impact factor: 91.245
Authors: John A Jakob; Roland L Bassett; Chaan S Ng; Jonathan L Curry; Richard W Joseph; Gladys C Alvarado; Michelle L Rohlfs; Jessie Richard; Jeffrey E Gershenwald; Kevin B Kim; Alexander J Lazar; Patrick Hwu; Michael A Davies Journal: Cancer Date: 2011-12-16 Impact factor: 6.860
Authors: Esther Edlundh-Rose; Suzanne Egyházi; Katarina Omholt; Eva Månsson-Brahme; Anton Platz; Johan Hansson; Joakim Lundeberg Journal: Melanoma Res Date: 2006-12 Impact factor: 3.599
Authors: Vikas K Goel; Alexander J F Lazar; Carla L Warneke; Mark S Redston; Frank G Haluska Journal: J Invest Dermatol Date: 2006-01 Impact factor: 8.551
Authors: Brian J Blonigen; Ryan D Steinmetz; Linda Levin; Michael A Lamba; Ronald E Warnick; John C Breneman Journal: Int J Radiat Oncol Biol Phys Date: 2009-09-23 Impact factor: 7.038