Outcomes of Treatment for Melanoma Brain Metastases

Abstract

Background. Historically, melanoma with brain metastases has a poor prognosis. In this retrospective medical record review, we report basic clinicopathological parameters and the outcomes of patients with melanoma and brain metastases treated with different treatment modalities before the era of immunotherapy and modern radiotherapy technique. Methods. Patients with metastatic melanoma were treated with surgery, radiotherapy, and/or systemic therapy from 1998 to 2017. In our study, they were identified and stratified depending on treatment methods. Overall survival was defined as the time from the date of brain metastases to the death or last follow-up (2019 June 1st). Survival curves were estimated using the Kaplan–Meier method that was employed to calculate the hazard ratio. Results. Six (12%) of 50 patients are still alive as of the last follow-up. The median overall survival from the onset of brain metastases was 11 months. The longest survival time was observed in patients treated by surgery followed by radiotherapy, surgery followed by radiotherapy and systemic therapy, and also radiotherapy followed by systemic therapy. The shortest survival was observed in the best supportive care group and patients treated by systemic therapy only. Conclusions. Patients with brain metastases achieved better overall survival when treated by combined treatment modalities: surgery followed by radiotherapy (26.6 months overall survival), combining surgery, radiotherapy, and systemic therapy (18.7 months overall survival), and also radiotherapy followed by systemic therapy (13.8 months overall survival).

Mefloquine induces ER stress and apoptosis in BRAFi‐resistant A375‐BRAFV600E/NRASQ61K malignant melanoma cells targeting intracranial tumors in a bioluminescent murine model

“…Remarkably, feasibility of targeting intracranial melanoma upon systemic administration of MQ was demonstrated in a bioluminescent murine model, an important preclinical observation given the notoriously unsatisfactory clinical outcomes currently achieved using standard of care interventions in large patient populations afflicted by brain metastases (Figures 4 and 5). [10][11][12] Importantly, in the context of oral MQ targeting brain melanoma in a relevant murine model, it remains to be seen if MQ treatment may also impact molecular pathways involved in invasion and metastasis (such as regulation of epithelial-mesenchymal transition-related gene expression) blocking the occurrence of intracranial tumors, a topic of current research activities pursued in our laboratory. 34 Interestingly, molecular mechanisms of MQ-associated calcium dysregulation and ER-directed toxicity have been explored before in the context of MQ-induced neurotoxic symptoms observed in malaria patients, representing a well-documented adverse effect of this antimalarial intervention.…”

“…3,9 In addition to BRAFi-resistance compromising clinical outcomes in melanoma patients, an urgent need exists for the identification of molecular therapeutics that can target these drug-resistant cells at metastatic sites including the brain. [10][11][12] Indeed, brain metastases are a frequent complication in patients with metastatic melanoma. Up to 45% of patients develop clinically documented brain tumors during their lifetime, and it has been reported that brain lesions are observable in more than 70% of melanoma patients at autopsy.…”

“…Up to 45% of patients develop clinically documented brain tumors during their lifetime, and it has been reported that brain lesions are observable in more than 70% of melanoma patients at autopsy. 10,[12][13][14][15] The use of clinical antimalarials for the investigational treatment of malignant melanoma has shown moderate promise, attributed mostly to inhibition of lysosomal-autophagic adaptations of cancer cells. [16][17][18] Artemisinin-combination therapeutics (ACT) are now standard of care medications used as antimalarials worldwide.…”

“…In addition to BRAFi‐resistance compromising clinical outcomes in melanoma patients, an urgent need exists for the identification of molecular therapeutics that can target these drug‐resistant cells at metastatic sites including the brain 10–12 . Indeed, brain metastases are a frequent complication in patients with metastatic melanoma.…”

Site-Specific Metastasis and Survival in Papillary Thyroid Cancer: The Importance of Brain and Multi-Organ Disease

“…The treatment of brain metastatic lesions is further made challenging by the generally poor permeability of the blood-brain barrier to modern chemotherapeutics [ 44 ]. Surgery is the most effective method for patients with solitary CNS metastases [ 45 ].The National Comprehensive Cancer Network (NCCN) guideline recommended that surgical resection followed by whole brain radiation therapy (WBRT) or stereotactic radiation therapy (SRS) plus WBRT was appropriate for patients who had stable systemic disease or were newly diagnosed, while WBRT or SRS was advisable for patients who had multiple (>3) metastatic lesions [ 46 ]. Therefore, knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.…”