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CD8 T-cell infiltration of metastatic melanoma may be a useful biomarker for prediction of prognosis and response to therapy. The heterogeneous distribution of CD8 T cells within a single tumor, and across different tumors within a single patient, may complicate quantification of infiltration. However, the impact of heterogeneity has not been quantified sufficiently. To address this, we have assessed intratumoral heterogeneity of CD8 T-cell counts, as well as intertumoral heterogeneity for synchronous and metachronous metastases. In a tissue microarray containing 189 melanoma metastases from 147 patients, the density of CD8 T cells per sample was determined by immunohistochemistry. The mean density and coefficient of variation were calculated for each tumor and the rates of discordant values were determined. CD8 counts varied widely among different core samples of the same tumors (average coefficient of variation=0.77, 95% confidence interval: 0.70-0.85), with discordance occurring in 40% of tumors. CD8 densities were similar among pairs of simultaneous tumors; however, significant changes in CD8 densities were observed among 35 pairs of metachronous tumors. CD8 T-cell density is not well represented by a single 1 mm diameter sample. Differences in CD8 T-cell counts, observed in clinical trials, from pretreatment to post-treatment specimens may be explained by the spatial and temporal heterogeneity of CD8 distribution, especially if the assessed samples are small (i.e. 1 mm). A sufficiently large biopsy of one of several synchronous tumors may be representative of CD8 T-cell infiltration of a patient's disease.

Objective: The purpose of this study is to determine the comparative effectiveness of esophagectomy versus endoscopic mucosal resection followed by radiofrequency ablation (EMR-RFA) for the treatment of Barrett esophagus with high-grade dysplasia (HGD)., Background: HGD of the esophagus may be managed by surgical resection or EMR-RFA. National guidelines suggest that EMR-RFA is effective at eradicating HGD. The comparative effectiveness and cost-effectiveness of EMR-RFA versus esophagectomy for HGD remains unclear., Methods: A decision-analysis model was constructed to represent 3 management strategies for HGD: (1) esophagectomy, (2) EMR-RFA, and (3) endoscopic surveillance. Estimates for model variables were obtained from literature review, and costs were estimated from Medicare fee schedules. Costs and utilities were discounted at an annual rate of 3%. The baseline model was adjusted for alternative age groups and high-risk dysplastic variants. One-way and multivariable probabilistic sensitivity analyses were conducted., Results: For a 65-year-old patient, compared to esophagectomy, EMR-RFA yields equivalent utility (11.5 vs 11.4 discounted quality-adjusted life years) with lower total cost ($52.5K vs $74.3K) over the first 20 years. Dominance of EMR-RFA over esophagectomy persists for all age groups. Patients with diffuse or ulcerated HGD are more effectively treated with esophagectomy. Model outcomes are sensitive to estimated rates of disease progression and postintervention utility parameters., Conclusions: Existing evidence supports EMR-RFA over esophagectomy for the treatment of esophageal HGD. Long-term outcomes and more definitive quality-of-life studies for both interventions are crucial to better inform decision-making.

Objective: The purpose of this study was to assess regional recurrence rates of patients who underwent sentinel lymph node biopsy (SLNB) using radiocolloid guidance alone., Background: Isosulfan blue dye is commonly used along with Tc99-labeled radiocolloid localization in SLNB for melanoma. Blue dye has, however, been associated with allergic reactions, long-term staining of skin, and increased cost. We hypothesized that the rate of regional recurrence when SLNB is performed with radiocolloid alone would be comparable to established reports using both radiocolloid and blue dye., Methods: A prospectively collected database was retrospectively queried for patients who underwent SLNB for melanoma during the years 2005 through 2008. Data collected included patient demographics, primary lesion characteristics, operative details, and recurrence. The primary outcome was the rate of recurrence within the biopsied basin after negative SLNB's performed without isosulfan blue dye., Results: In 215 patients, 279 nodal basins were identified. All patients underwent successful radiocolloid localization, and positive sentinel nodes were found in 40 patients (18.6%). Six of 175 patients with a negative SLNB developed a regional node recurrence as the first site of metastasis (3.4%). Among all 215 patients, 44 experienced recurrence of any kind (20.5%). Higher mitotic rate and Breslow depth were significantly associated with likelihood of recurrence., Conclusions: Success rates, node positivity rates, and rates of regional recurrence after SLNB for melanoma using radiocolloid alone are acceptable and similar to those of prior reports using blue dye plus radiocolloid.

Objective: The objective of this study was to compare the long-term outcome of patients with metastatic melanoma vaccinated with 6MHP to that of a group of unvaccinated historical controls., Background: A multipeptide vaccine (6MHP), designed to induce helper T cells against melanocytic and cancer-testis antigens, has been shown to induce specific Th1-dominant CD4+ T cell responses., Methods: The 6MHP vaccine was administered to patients with metastatic melanoma. Circulating CD4+ T cell responses were measured by proliferation or direct IFN-gamma ELIspot assay. Overall survival of vaccinated patients was compared to a group of clinically comparable historical controls using multivariable Cox regression analysis and Kaplan-Meier survival analysis, taking into account age, metastatic site, and resection status., Results: Across 40 vaccinated patients and 87 controls, resection status (HR 0.54, P = 0.004) and vaccination (HR 0.24, P < 0.001) were associated with improved overall survival. Forty pairs of vaccinated patients and controls were matched by metastatic site, resection status, and age within 10 years. Median survival was significantly longer for vaccinated patients (5.4 vs 1.3 years, P < 0.001). Among the vaccinated patients, the development of a specific immune response after vaccination was associated with improved survival (HR 0.35, P = 0.040)., Conclusions: Helper peptide vaccination is associated with improved overall survival among patients with metastatic melanoma. These data support a randomized prospective trial of the 6MHP vaccine.