Rationale: Malignant melanoma (MM) is the cutaneous neoplasia with the greatest mortality rates and one of the malignancies with the highest potential of dissemination.,The prognosis of patients with metastatic MM is grim, with a 5-years survival rate between 5-19%, and is dictated by the location and the number of metastases.,Objective: We aimed to estimate the survival of patients with metastatic MM from our study and find out if the metastasis’ location influences survival.,Methods and results: Between 2008 and 2013, 155 patients with cutaneous MM were diagnosed in our clinic.,All the patients were staged according to 2009 AJCC staging system.,The median follow-up period was of 24 months.,Survival was calculated by using the Kaplan-Meier method with a confidence level of 95%.,40.5% of the patients developed metastases in different organs, especially the brain.,80.6% of those with metastases died during the study.,The median overall survival, estimated for the entire group of patients who developed metastases, was of 5.3 months.,Discussion: The influence of metastases distribution on the overall survival was examined and it was noticed that there were statistically significant differences between the risks of death of various groups of patients, depending on metastasis topography.,Thus, the death probability of a patient with brain metastases is twice that of a patient with digestive metastasis, about 7 times higher than that of a patient with lung metastasis (p = 0.0004) and 12 times higher than the death risk of a patient with extra-regional lymph nodes or subcutaneous metastasis (p = 0.0000).
Current therapeutic regimens attempt to eliminate all malignant cells of a melanoma lesion.,Pre-clinical data, however, indicate that melanoma is maintained by a minor subset of cancer cells, which are characterized by CD20 expression.,We attempted to eliminate those cells in a progressing, chemotherapy-refractory metastatic melanoma patient by lesional injections of the anti-CD20 therapeutic antibody rituximab and concomitant dacarbazine treatment, which was ineffective as monotherapy.,Although the frequency of CD20+ melanoma cells within the tumor lesions was initially about 2% and the bulk of tumor cells did not express CD20, rituximab treatment produced lasting remission accompanied by a decline of the melanoma serum marker S-100 to physiological levels.,Detailed in-depth-analyses revealed a switch of serum cytokines from a T helper-2 to a pro-inflammatory T helper-1 cell profile.,Apart from B cell elimination and decline in gammaglobulin levels, no grade 3/4 toxicity related to treatment was observed.,Data provide the first clinical evidence that targeting the minor subset of CD20+ “melanoma sustaining cells” produces regression of chemotherapy-refractory melanoma and highlight the potency of selective cancer cell targeting in the treatment of melanoma.