NRAS mutation status is an independent prognostic factor in metastatic melanoma.

BACKGROUND: There is a need for improved prognostic markers in melanoma. In this study, the authors tested the prognostic significance and clinicopathologic correlations of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutations in patients with metastatic melanoma. METHODS: Clinical and pathologic data were collected retrospectively on melanoma patients who were clinically tested for BRAF (exon 15) and NRAS (exons 1 and 2) mutations at The University of Texas M. D. Anderson Cancer Center. Analyses were performed to identify significant associations of mutations with tumor and patient characteristics and with survival from the diagnosis of stage IV disease. RESULTS: The genotypes of the full cohort (n = 677) were 47% BRAF mutation, 20% NRAS mutation, and 32% wild-type for BRAF and NRAS ("WT"). Tumor mutation status was associated (P = .008) with the risk of central nervous system involvement at the diagnosis of stage IV disease, with a higher prevalence observed in BRAF-mutant (24%) and NRAS-mutant (23%) patients than in WT patients (12%). Among patients with nonuveal melanoma who underwent mutation testing within 6 months of stage IV diagnosis (n = 313), patients with NRAS mutations had a median survival of 8.2 months from stage IV diagnosis, which was shorter than the median survival of WT patients (15.1 months; P = .004). Multivariate analysis of this population incorporating age, sex, metastases (M1) category, serum lactate dehydrogenase level, and mutation status confirmed that NRAS mutations are associated independently with decreased overall survival (vs WT; P = .005; hazard ratio, 2.05). CONCLUSIONS: Patients with BRAF or NRAS mutations were more likely than WT patients to have central nervous system involvement at the time they were diagnosed with distant metastatic disease. NRAS mutation status was identified as an independent predictor of shorter survival after a diagnosis of stage IV melanoma.

Pelvic computed tomography scans for surveillance in patients with primary melanoma in the head and neck.

Although pelvic computed tomography (CT) scans are frequently performed as a part of routine surveillance, the evidence for or against the routine use of these scans in patients with primary melanoma in the head and neck is weak. We conducted a retrospective study to evaluate the value of pelvic CT scans as routine surveillance in patients with primary melanoma in the head and neck. We identified 146 patients with either primary or mucosal primary melanoma who had adequate follow-up evaluation for at least 5 years at our institution. Among them, 33 patients (23%) had stage III melanoma, and four (3%) had stage IV melanoma at the time of diagnosis. At a median follow-up duration of 49 months, 110 patients (75%) had developed recurrences, and the median time to the first recurrence was 13 months. A total of 82 (56%) patients had eventually developed distant metastases, but only 10 (7%) had developed metastases in the pelvis, and none had developed pelvic metastases as the first and the only site of recurrence. If the true rate of finding the pelvic metastasis as the first and the only recurrence was at least 3%, the probability of seeing 0 events of the 146 patients was 1.17%. This study, which is the largest series to evaluate the value of pelvic CT scans in this patient population to date, suggests that the routine use of a pelvic CT scan as a surveillance method does not have any impact on the management in patients with primary melanoma in the head and neck.

The clinical efficacy of combination of docetaxel and temozolomide in previously treated patients with stage IV melanoma.

No standard therapy exists for patients with metastatic melanoma whose disease failed to respond to first-line systemic treatment. We conducted a retrospective study to evaluate the clinical efficacy of the combination of docetaxel and temozolomide in previously treated patients. We searched our institution's patient and pharmacy databases for patients with metastatic melanoma who received docetaxel-tamozolomide and reviewed their medical records. We identified 38 patients who received docetaxel-temozolomide between February 2002 and January 2007 for resistant or refractory melanoma to a first-line therapy. The median age was 50 years, and all patients had stage IV melanoma (M1c, 87%) including 16 (42%) with brain metastases. All patients had received the same combination regimen: 80 mg/m docetaxel intravenously on day 1 and 150 mg/m temozolomide orally on days 1-5 every 28 days. Five patients (13%) had a partial response, and five (13%) had stable disease. The median time to disease progression was 8 weeks, and the overall survival duration was 26 weeks. Among the 10 patients who had a clinical benefit, the median time to disease progression was 51 weeks. Among 16 patients with brain metastases, none had confirmed clinical response in the brain. The regimen was generally well tolerated, with less than or equal to 8% of patients experiencing grade III or IV neutropenia or thrombocytopenia. Within the limitation of being a retrospective study with a potential patient selection bias, the docetaxel-temozolomide combination has modest activity, and is a reasonable option for previously treated patients with metastatic melanoma.