On demand Gamma-Knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases

Gaudy‐Marqueste, C.; Carron, Romain; Delsanti, Christine; Loundou, Anderson; Monestier, S.; Archier, E.; Richard, M.‐A.; Régis, Jean; Grob, Jean-Jacques

doi:10.1093/annonc/mdu266

Cited by 75 publications

(57 citation statements)

References 18 publications

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“…Scalp reactions as well as radiation recall dermatitis have been reported [18,[25][26][27]. However, larger series, such as the study from our group assessing concurrent vemurafenib with SRS, have failed to demonstrate an increased rate of skin toxicity [10,11]. Similarly, in our study with dabrafenib and trametinib administered either before, after, or concurrent with SRS, an increased rate of skin toxicity was not seen with one patient experiencing a grade 1 headache following SRS treatment.…”

Section: Discussioncontrasting

confidence: 45%

“…Recent clinical evidence from our group and others support the safety and efficacy of BRAFi therapy concurrent with radiation therapy in the management of melanoma BMs [10][11][12]. However, to our knowledge, the results of combined BRAF and MEK inhibition with radiation therapy for BRAF mutant melanoma patients with BMs has not been previously reported.…”

Section: Introductionmentioning

confidence: 86%

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Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases

et al. 2016

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The combined use of the BRAF inhibitor dabrafenib and MEK inhibitor trametinib has been found to improve survival over dabrafenib alone. The management of melanoma brain metastases continues to present challenges. In this study, we report our initial experience in the management of melanoma brain metastases with stereotactic radiosurgery (SRS) with the use of BRAF and MEK inhibitors. We identified six patients treated with SRS for 17 brain metastases within 3 months of BRAF and MEK inhibitor administration. The median planning target volume was 0.42 cm (range: 0.078-2.08 cm). The median treatment dose was 21 Gy (range 18-24 Gy). The median follow-up of all lesions from SRS was 10.6 months (range 5.8-28.5 months). One lesion was found to undergo local failure 21.7 months following SRS treatment. The median overall survival was 20.0 months (range 6.1-31.8 months) from the time of SRS treatment and 23.1 months (range: 12.1-30.9 months) from the date of BRAFi and MEKi administration. There was no evidence of increased nor unexpected toxicity with the two modalities combined. In this initial experience of melanoma brain metastases treated with BRAF and MEK inhibition with SRS, we find the two modalities can be combined safely. These outcomes should be assessed further in prospective evaluations.

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Section: Discussioncontrasting

confidence: 45%

Section: Introductionmentioning

confidence: 86%

Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases

et al. 2016

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“…Patel et al reported that BRAF inhibitors increase the rate of RN following SRS [24]. Multiple separate studies have failed to replicate these results, and current consensus guidelines recommend holding BRAF inhibitor therapy for 1 day before and after SRS [4,25].…”

Section: Targeted Therapiesmentioning

confidence: 99%

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

et al. 2017

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To investigate late toxicity among patients with newly-diagnosed brain metastases undergoing stereotactic radiosurgery (SRS) with concurrent systemic therapies with or without whole-brain radiation therapy (WBRT). Patients with newly-diagnosed brain metastasis who underwent SRS at a single tertiary-care institution from 1997 to 2015 were eligible for inclusion. The class and timing of all systemic therapies were collected for each patient. The primary outcome was the cumulative incidence of radiographic radiation necrosis (RN). Multivariable competing risks regression was used to adjust for confounding. During the study period, 1650 patients presented with 2843 intracranial metastases. Among these, 445 patients (27%) were treated with SRS and concurrent systemic therapy. Radiographic RN developed following treatment of 222 (8%) lesions, 120 (54%) of which were symptomatic. The 12-month cumulative incidences of RN among lesions treated with and without concurrent therapies were 6.6 and 5.3%, respectively (p = 0.14). Concurrent systemic therapy was associated with a significantly increased rate of RN among lesions treated with upfront SRS and WBRT (8.7 vs. 3.7%, p = 0.04). In particular, concurrent targeted therapies significantly increased the 12-month cumulative incidence of RN (8.8 vs. 5.3%, p < 0.01). Among these therapies, significantly increased rates of RN were observed with VEGFR tyrosine kinase inhibitors (TKIs) (14.3 vs. 6.6%, p = 0.04) and EGFR TKIs (15.6 vs. 6.0%, p = 0.04). Most classes of systemic therapies may be safely delivered concurrently with SRS in the management of newly-diagnosed brain metastases. However, the rate of radiographic RN is significantly increased with the addition of concurrent systemic therapies to SRS and WBRT.

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“…However, the radiosensitization effect of BRAF inhibitor also increased the risk of skin toxicities with radiation (133)(134)(135)(136). Due to the minimum skin dose from SRS, several studies that evaluated BRAF inhibitor with SRS for patients with brain metastases reported favorable outcome (137)(138)(139). Studies that directly compared outcomes of patients treated with SRS alone and SRS with BRAF inhibitor suggest that there indeed may be a survival benefit of combination therapy (140)(141)(142).…”

Section: Rt With Concomitant Agentsmentioning

confidence: 99%

Radiation Therapy for Melanoma

Shi

2017

Cutaneous Melanoma: Etiology and Therapy

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Although melanoma is a relative radioresistant tumor, radiation therapy (RT) remains a valid and effective treatment option for the management of melanoma. RT as a primary treatment is often offered in well-defined situations, such as medical inoperability, lentiginous melanoma, mucosal melanoma, and ocular melanoma. Adjuvant RT following lymphadenectomy in node-positive melanoma patients prevents local and regional recurrence; however, the role of adjuvant RT remains controversial and underutilized due to lack of overall survival benefit. On the other hand, RT is highly effective in providing symptom palliation for metastatic melanoma and is widely used. Advanced RT technologies such as stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) can achieve excellent local control with minimum toxicities. They are commonly used in the management of brain, lung, spine, and liver metastases. Most recently, it is under active investigation on combining RT with new systemic options, such as targeted therapy, or immunotherapy. The advancements in the treatment of patients with melanoma highlight the importance of multidisciplinary management in this disease. Radiation therapy will continue to be one of the key therapeutic options.

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On demand Gamma-Knife strategy can be safely combined with BRAF inhibitors for the treatment of melanoma brain metastases

Cited by 75 publications

References 18 publications

Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases

Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases

The risk of radiation necrosis following stereotactic radiosurgery with concurrent systemic therapies

Radiation Therapy for Melanoma

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