Healthy Happy Blog

by Richard Smith

Treatment of Melanoma Brain Metastases: A New Paradigm

Brain plays a very important role in body or in life or simply we say that without brain both sexes are not complete in society. And brain metastases are a common and serious problem of metastatic tumor. Approximately, up to 50% of patients develop brain metastases during the course of their illness, and approximately 20% of patients have them at first presentation with metastatic disease. In autopsy series, the rate is even higher at greater than 70%.4,5 Melanoma brain metastases are associated with a poor prognosis with a median survival of less than 6 months2,6-10 and contribute to death in up to 95% of patients who develop them.

Furthermore, the prognosis of patients with melanoma brain metastases has not changed between 1986 and 2007. Twelve Risk factors associated with development of melanoma brain metastasis include male sex, primaries located on the trunk, head and neck or mucosal surfaces, thick or ulcerated primary tumors, and histological findings of acral lentiginous or nodular lesions.

Many of these factors are not specific for the development of brain metastases but rather are markers of high-risk disease and for extensive visceral involvement. The presence of either a BRAF or NRAS mutation is associated with a higher risk of brain metastases at diagnosis with metastatic melanoma.

In 2 large case series of patients diagnosed with brain metastases, predictors of poor survival included increased number of brain metastases (hazard ratio [HR] for >3 metastases vs 1-3, 1.40; 95% confidence interval [CI], 1.11-1.78), the development of brain metastases after diagnosis of extracranial metastatic disease (HR for after extracranial disease vs at/before extracranial disease, 1.71; 95% CI, 1.31-3.22),2 elevated lactate dehydrogenase (HR, 2.7 [95% CI, 1.8-4.0] if 1-2 times normal and 7.3 [95% CI, 3.7-14.3] if >2 times normal),9 and the presence of bone metastases (HR, 1.7; 95% CI, 1.0-2.8).9 Despite the overall poor prognosis, patients with brain metastases are a heterogeneous group.

A small percentage of patients survive more than 3 years and are generally characterized by the presence of a locally treated (surgically or by stereotactic radiosurgery [SRS]) single brain metastasis in the absence of other visceral disease.11,15 In contrast, multiple brain metastases and extensive visceral disease are associated with a very poor survival of 1 to 2 months.16 To group patients with brain metastases into similar prognostic groups for comparison in clinical trials, the Radiation Therapy Oncology Group (RTOG) developed a recursive partition analysis (RPA) using pooled data from 3 consecutive prospective randomized trials.

The risk categories are based on 3 factors: Karnofsky Performance Score (KPS), status of extracranial disease, and patient age. Class 1 patients (age < 65 years, KPS ? 70, controlled primary, and no extracranial metastases) have the longest survival, class 2 (all others with KPS ? 70) have intermediate survival, and class 3 (KPS < 70) fare worst.17 The RPA was validated in 1 study of melanoma patients receiving whole-brain radiotherapy (WBRT) with survival rates of 151, 71, and 21 days in class 1, 2, and 3, respectively.18 However, in another study, the RPA was only significant by unvaried but not multivariate analysis.

Decisions regarding the use of specific treatment modalities for the management of melanoma brain metastases are dependent on a patient's performance status, the extent of both intracranial and extra cranial disease, and tumor BRAF mutation status. In addition to specific anticancer therapies, supportive measures including corticosteroids for cerebral edema-related symptoms, anticonvulsants, and analgesia play a critical in palliation of these patients. These have been recently reviewed elsewhere.

There are 3 treatment modalities used for the local management of brain metastases: surgery, SRS, and WBRT. Surgery and SRS are directed to the tumor volume only, whereas WBRT delivers lower-dose radiotherapy to the whole brain, including areas of no explicit tumor.

05 Oct 2017 author: Richard Smith