Surgical Resection Of Metastatic Melanoma Research Articles

Alterations in patient plasma microRNA expression profiles following resection of metastatic melanoma.

MicroRNAs (miRs) are noncoding RNAs that regulate protein translation and melanoma progression. Changes in plasma miR expression following surgical resection of metastatic melanoma are under-investigated. We hypothesize differences in miR expression exist following complete surgical resection of metastatic melanoma. Blood collection pre- and post-surgical resection was performed in six individuals with solitary melanoma metastases. miR expression in extracted RNA was quantified using the NanoString nCounter Digital Analyzer. Pre- and post-surgical plasma samples contained 216 miRs with expression above baseline. Comparison of postsurgical to preresection samples revealed differential expression of 25 miRs: miR-let-7a, miR-let7g, miR-15a, miR-16, miR-22, miR-30b, miR-126, miR-140, miR-145, miR-148a, miR-150-5p, miR-191, miR-378i, miR-449c, miR-494, miR-513b, miR-548aa, miR-571, miR-587, miR-891b, miR-1260a, miR 1268a, miR-1976, miR-4268, miR-4454 (P < 0.05). Utilizing P < 0.0046 as a cutoff to control for one false positive among the 216 miRs revealed that postsurgical melanoma plasma samples had upregulation of miR-1260a (P = 0.0007) and downregulation of miR-150-5p (P = 0.0026) relative to pre-surgical samples. Differential expression of miR-150-5p and miR-1260a is present in plasma following surgical resection of metastatic melanoma in this small sample (n = 6) of melanoma patients. Therefore, further investigation of these plasma miRs as noninvasive biomarkers for melanoma is warranted.

Surgical resection of metastatic melanoma in the era of immunotherapy and targeted therapy.

Melanoma is the deadliest form of skin cancer and one of the few malignancies whose incidence is on the rise. The treatment of metastatic melanoma continues to be quite challenging, although in recent years, there has been significant progress. Current National Comprehensive Cancer Network guidelines list immunotherapy, chemotherapy, surgery and clinical trials as potential options for patients with metastatic disease but do not clearly recommend which is superior. Additionally, when utilizing combined modality treatment there are no clear guidelines for the optimal timing of surgery in the treatment of metastatic melanoma. In this paper we sought to compile the current evidence and on-going trials in order to provide a comprehensive review of the different options available and underway in regards to the treatment of metastatic melanoma. It is clear that with the responses now seen with systemic immunotherapies and targeted therapies, an expanded role for surgery is the logical next step.

Preoperative peripheral blood lymphocyte/monocyte ratio and survival in patients with resected stage IV melanoma.

8600 Background: The prognosis of stage IV melanoma patients remains poor. Published results have suggested that components of the complete blood count have significant prognostic value in several malignancies. Among the most studied were the absolute lymphocyte count (ALC), and absolute monocyte count (AMC) on clinical outcomes of patients with lymphoid malignancies. Thus, we sought to investigate if the pre-operative ALC (ALC-PO), AMC (AMC-PO) and ALC/AMC ratio (ALC/AMC-PO) affects the risk of disease recurrence and survival after complete surgical resection of metastatic melanoma. Methods: We studied 66 stage IV, resected melanoma patients followed at Mayo Clinic from 2000 to 2010. Log rank chi-square analysis was used to determine the best cut-off values for each pre-operative variable, while proportional hazards models were used to compared survival. Results: The median follow-up of the cohort was 24 months (range: 2.3 – 117 months). ALC-PO, AMC-PO and ALC/AMC-PO, as continuous variables, were all identified as prognostic factors for both relapse-free survival (RFS) and overall survival (OS). The best cut-off values for ALC-PO, AMC-PO and ALC/AMC-PO were 1.9; 0.62; and 2.05, respectively. Using Kaplan-Meier analysis, patients with an ALC-PO ≥ 1.9 x 109/L experienced superior OS and RFS compared with ALC-PO &lt; 1.9 x 109/L patients [median OS of 58 months vs. 34 months, p &lt; 0.04; median RFS of 14 months vs. 5 months, p &lt; 0.009]. Conversely, a low AMC-PO (&lt;0.62 x 109/L) was associated with better OS and RFS compared with higher AMC-PO (≥ 0.62 x 109/L): [median OS of 47 months vs. 14 months, p &lt; 0.007; median RFS of 9 months vs. 5 months, p &lt; 0.02]. When the ALC-PO and AMC-PO were combined as an ALC/AMC ratio, the group with an ALC/AMC-PO ≥ 2.05 experienced a superior OS and RFS compared to patients with ALC/AMC-PO &lt; 2.05: [median OS of 49 months vs. 12 months, p &lt; 0.0001; median RFS of 10 months vs. 4 months, p &lt; 0.0001]. Multivariate analysis showed ALC/AMC-PO to be an independent prognostic factor for RFS and OS (HR = 0.32, p &lt; 0.003; HR = 0.23, p &lt; 0.002). Conclusions: Our study showed, that ALC/AMC-PO ratio is an independent prognostic factor for RFS and OS in patients undergoing resection of metastatic (stage IV) melanoma.

Contemporary surgical treatment of advanced-stage melanoma.

The clinical treatment of patients with stage IV melanoma according to criteria of the American Joint Committee on Cancer (AJCC) is controversial because the 5-year survival rate is approximately 5%. Specific clinicopathologic factors are predictive of survival following curative surgery. Cohort analysis of 1574 successive patients undergoing surgical resection of metastatic melanoma for a 29-year period. Patients received follow-up on a routine basis with serial examinations and radiographic studies. The median follow-up time was 19 months (range, 1-382 months). Tertiary cancer center. Surgical resection was performed in 1574 patients. The decision to perform surgery was individualized for each patient. The technique of surgical resection was based on the site of metastasis. Main Outcome Measure Computer-assisted database with statistical analyses using log-rank tests and Cox regression models. Of the 4426 patients with AJCC stage IV melanoma, 1574 (35%) underwent surgical resection; 970 (62%) were men, with a median age of 50 years. Of the primary melanomas, 46% arose on the trunk, and 56% were Clark level IV or V with a median thickness of 2.2 mm. We found 697 patients (44%) to have AJCC stage III melanoma (lymph node) prior to the development of stage IV metastases. The most common site for resection was the lung (42%), followed by the skin or lymph node (19%) and the alimentary tract (16%). Of our patients, 877 (56%) had melanoma at a single site. The 5-year survival rate was significantly (P<.001) better for patients with a solitary melanoma (mean +/- SD, 29% +/- 2%) than those with 4 or more metastases (n = 147; mean +/- SD, 11% +/- 3%). Skin and lymph node metastases had the most favorable survival rate (median, 35.1 months). Multivariate analyses identified an earlier primary tumor stage (I vs II) (P<.001), an absence of intervening stage III metastases (P =.02), solitary metastasis (P<.001), and a long (>36 months) disease-free interval from AJCC stage I or II to stage IV (P =.005) as predictive of survival. Our results demonstrate the benefit of surgical resection for advanced-stage melanoma. Patients with limited sites and numbers of metastases should be considered for curative resection regardless of the location of the disease.

Skin tests predict survival after autologous tumor cell vaccination in metastatic melanoma: Experience in 81 patients

Currently there is no standard adjuvant treatment following surgical resection of metastatic melanoma. We investigated whether surgery followed by autologous tumor cell-BCG vaccination was beneficial for malignant melanoma patients. In this study we focus on the prognostic value of DTH response following vaccination therapy. Eighty-one patients with AJCC stage III and IV melanoma were selected. Whenever feasible, radical metastasectomy was performed. ASI was initiated by the administration of three weekly intra-cutaneous vaccinations with 10(7) irradiated autologous tumor cells, starting four weeks after surgery. Depending on the size of DTH response to the first three injections, subsequent vaccinations were planned. The first two vaccines also contained 10(7) BCG organisms as an immune stimulatory adjuvant. Induration as well as erythema correlated strongly with survival (P < 0.0001 and P = 0.0004). After radical metastasectomy in stage III melanoma patients a five-year survival of 48% was observed. In stage IV disease, a five-year survival of 34% was seen, after radical surgery had been performed. When macroscopic disease was present at start of vaccination treatment, no clinical responses occurred. Apart from transient skin ulceration at the site of BCG-containing vaccinations, no serious side effects were observed. This study shows that large-scale preparation of autologous melanoma cell vaccines is feasible. while vaccination results in DTH responses that correlate significantly with survival. ASI seemed to be beneficial in stage III and stage IV melanoma when given in the adjuvant setting, while causing only very mild side effects.