Local Control After Stereotactic Radiosurgery (SRS) for Brain Metastases (BM) in Melanoma Patients With and Without BRAF Mutation and Treatment

Abstract PURPOSE/OBJECTIVE(S): Melanoma commonly metastasizes to the brain and is radioresistant. Stereotactic radiosurgery (SRS) confers durable local control of brain metastases (BM) while maintaining neurocognitive function. These advantages are increasingly important as survival among these patients improves secondary to advances in systemic therapies. This study investigated the local control (LC), intracranial PFS (iPFS), freedom from radionecrosis (FFRN), and overall survival (OS) among melanoma patients receiving SRS for BM. MATERIALS/METHODS: We retrospectively reviewed clinical outcomes of melanoma patients with brain metastases treated with SRS between October 2008 and January 2017 in a large academic centre. Post-SRS, patients were followed in a multidisciplinary clinic with clinical examination and brain MRI every 3 months. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: In total, 97 patients with 283 brain metastases (including 12 surgical cavities) treated with SRS were identified. Median age was 60.5 (24.4–90.7). Median follow-up was 9.6 (2.2–74.7) months after first SRS. Median prescription dose was 21 (10–24) Gy delivered in a single fraction. Thirty (30.9%) patients had WBRT post-SRS, 36 (37.1%) patients had BRAF-positive disease. Per lesion (N=283), 1-year LC and FFRN were 84.4%, and 90.1%, respectively; medians were not achieved for either LC or FFRN. Radionecrosis (RN) occurred in 20 (7.1%) lesions. Per patient (N=97), median OS and iPFS were 16.0 and 5.3 months, respectively; 1-year OS and iPFS rates were 62.0%, and 30.1%, respectively. CONCLUSION: SRS resulted in excellent rates of LC, with a low risk of RN. However, most patients developed intracranial progression within 1 year. Further analyses to establish correlates (lesion size, SRS dose, and molecular status) to LC, FFRN, OS, and iPFS will be performed prior to the final presentation.

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Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases under Simultaneous Anti-PD-1 Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms19092653 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2653 ◽

Cited By ~ 11

Author(s):

Maike Trommer-Nestler ◽

Simone Marnitz ◽

Martin Kocher ◽

Daniel Rueß ◽

Max Schlaak ◽

...

Keyword(s):

Acute Toxicity ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Local Control ◽

Lesion Size ◽

Simultaneous Treatment ◽

Volumetric Assessment ◽

Programmed Death ◽

Programmed Death 1 ◽

Melanoma Patients

Combination concepts of radiotherapy and immune checkpoint inhibition are currently of high interest. We examined imaging findings, acute toxicity, and local control in patients with melanoma brain metastases receiving programmed death 1 (PD-1) inhibitors and/or robotic stereotactic radiosurgery (SRS). Twenty-six patients treated with SRS alone (n = 13; 20 lesions) or in combination with anti-PD-1 therapy (n = 13; 28 lesions) were analyzed. Lesion size was evaluated three and six months after SRS using a volumetric assessment based on cranial magnetic resonance imaging (cMRI) and acute toxicity after 12 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE). Local control after six months was comparable (86%, SRS + anti-PD-1, and 80%, SRS). All toxicities reported were less than or equal to grade 2. One metastasis (5%) in the SRS group and six (21%) in the SRS + anti-PD-1 group increased after three months, whereas four (14%) of the six regressed during further follow-ups. This was rated as pseudoprogression (PsP). Three patients (23%) in the SRS + anti-PD-1 group showed characteristics of PsP. Treatment with SRS and anti-PD-1 antibodies can be combined safely in melanoma patients with cerebral metastases. Early volumetric progression of lesions under simultaneous treatment may be related to PsP; thus, the evaluation of combined radioimmunotherapy remains challenging and requires experienced teams.

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