stage-IV Melanoma Research Articles

Enrollment in Clinical Trials Correlates with Improved Survival in Metastatic Melanoma

Background: Although the current median survival time of stage-IV melanoma patients is less than 12 months, there is a subset of patients who experience long-term survival. Due to poor response rates to standard cytotoxic agents in metastatic melanoma, patients are encouraged to participate in clinical trials, the overall impact of which has not been studied, however. The aim of our study was to identify the factors associated with long-term survival and to determine the impact of clinical trial enrollment on patient outcome. Methods: We studied stage-IV melanoma patients prospectively enrolled at New York University Medical Center from 2002–2008. Associations between clinicopathologic variables and overall post-stage-IV survival were examined. Kaplan-Meier survival analysis was used to identify univariate predictors of post-stage-IV survival and the independent effect of these variables was assessed in a multivariate Cox proportional hazards regression model. The associations between clinicopathologic variables and long-term survival status (≧2 vs. <2 years) were examined by χ² analysis and the independent effect of these variables on the latter was assessed in a multivariate logistic regression model. Results: Site of metastasis, treatment (systemic vs. localized) and pretreatment lactate dehydrogenase (LDH) level independently correlated with post-stage-IV survival. Participation in clinical trials and normal LDH levels were associated with a long-term survival of ≧2 years. Conclusion: Our data suggest that enrollment in clinical trials independently correlates with prolonged survival after a diagnosis of stage IV melanoma.

Low back pain as the presenting sign in a patient with primary extradural melanoma of the thoracic spine - A metastatic disease 17 Years after complete surgical resection

Primary spinal melanomas are extremely rare lesions. In 1906, Hirschberg reported the first primary spinal melanoma, and since then only 40 new cases have been reported. A 47-year-old man was admitted suffering from low back pain, fatigue and loss of body weight persisting for three months. He had a 17-year-old history of an operated primary spinal melanoma from T7-T9, which had remained stable for these 17 years. Routine laboratory findings and clinical symptoms aroused suspicion of a metastatic disease. Multislice computed tomography and magnetic resonance imaging revealed stage-IV melanoma with thoracic, abdominal and skeletal metastases without the recurrence of the primary process. Transiliac crest core bone biopsy confirmed the diagnosis of metastatic melanoma. It is important to know that in all cases of back ore skeletal pain and unexplained weight loss, malignancy must always be considered in the differential diagnosis, especially in the subjects with a positive medical history. Patients who have back, skeletal, or joint pain that is unresponsive to a few weeks of conservative treatment or have known risk factors with or without serious etiology, are candidates for imaging studies. The present case demonstrates that complete surgical resection alone may result in a favourable outcome, but regular medical follow-up for an extended period, with the purpose of an early detection of a metastatic disease, is highly recommended.

Stage-IV Melanoma and Pulmonary Metastases: Factors Predictive of Survival

We reviewed a contemporary, single-institution experience to evaluate the natural history of stage-IV melanoma metastatic to the lung and identify factors predictive of survival. A search of our prospective database was performed to identify patients with stage-IV melanoma and pulmonary metastases as the initial disease site; only patients seen at our institution prior to developing stage-IV disease and in whom treatment response was available were included. Patients' demographic, clinical, and treatment variables were recorded. Cox regression was used to identify factors independently predictive of survival. The study cohort was comprised of 122 patients. Median survival was 14 months (5-year survival of 8%). Clinical factors at time of diagnosis of stage IV independently predictive of survival were a solitary pulmonary metastasis (HR 2.7, CI 1.6-4.4, P<0.0005) and absence of extra-pulmonary disease (HR 1.9, CI 1.2-3.1, P = 0.01). Among treatment factors, only metastasectomy was independently predictive of survival (HR 0.42, CI 0.21-0.87, P = 0.02). Of the patients, 26 (21%) underwent metastasectomy, with a median survival of 40 months compared with 13 months in patients not selected for surgical treatment. Of these 26, 23 (88%) experienced recurrence at a median of 5 months after the procedure. No survival difference was seen between responders and non-responders to systemic therapy (P = 0.55). In stage-IV melanoma with pulmonary metastases, a solitary metastasis and absence of extra-pulmonary disease are predictive of survival. While these factors are often present in patients selected for pulmonary metastasectomy, this independently predicts survival. However, response to systemic therapy does not correlate with a survival difference.

High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: implications for protocol design of therapeutic antigen-specific vaccination strategies.

Human melanoma cells express several antigens which are recognized by autologous and specific CTL clones in association with HLA-class-I molecules. Many of these antigens represent suitable targets for tumor immunotherapy, since their expression in human melanoma cells is common and highly specific. In order to achieve real clinical success with therapeutic vaccination strategies, one important requirement is the expression of the target antigen by all the tumor lesions of a patient. We have studied this issue by assessing, through an RT-PCR approach, the expression of MAGE-1, MAGE-2, MAGE-3, BAGE, GAGE-1/2, Tyrosinase and Melan-A/MART-1 genes in 17 clusters of simultaneous in-transit or regional lymph-node metastases collected from 15 stage-III and 1 stage-IV (AJCC/UICC pTNM system) melanoma patients. In 14 out of 17 clusters of simultaneous metastatic lesions (82%), the homogeneity in the pattern of gene expression within the cluster was complete. Heterogeneity within the same cluster was observed in only 3 out of 17 clusters (18%) and represented only minor features. Our data reveal that, in AJCC-stage-III melanoma patients, different but simultaneous metastatic lesions express the same pattern of antigen-coding genes. These observations have 2 main clinical implications: (i) the antigenic characterization of one single and easily accessible lesion allows identification of optimal targets for an active antigen-specific immunotherapy treatment; (ii) almost all the metastatic lesions are expected to be hit by the immune response eventually induced against the tumor antigen. Moreover, these data suggest that active specific immunotherapy directed against MAGE-1, MAGE-3, BAGE, GAGE-1/2, Melan-A/MART-1 and Tyrosinase antigens could be exploited as an adjuvant treatment to surgery in high-risk AJCC-stage-III-melanoma patients.