Faculty Bibliography

BACKGROUND:Patients with thick primary melanomas (≥4 mm) have highly variable survival outcomes. Cell proliferation marker Ki-67 has been identified as promising biomarker in thick melanoma but has not been evaluated since the wide spread adoption of sentinel lymph node biopsy. We revisit its prognostic relevance in the sentinel node era. METHODS:We studied patients with thick (≥4 mm) primary melanoma prospectively enrolled in a clinicopathological biospecimen database from 2002 to 2015, and evaluated the prognostic value of Ki-67 expression while controlling for features included in the existing staging criteria. RESULTS:We analyzed 68 patients who underwent lymph node sampling and who had an available tumor for Ki-67 immunohistochemical (IHC) staining. The median tumor thickness was 6.0 mm; the median follow-up was 2.6 years. In multivariable analysis including nodal status and primary tumor ulceration, Ki-67 expression was an independent predictor of worse recurrence-free survival (HR 2.19, P = 0.024) and overall survival (HR 2.49, P = 0.028). Natural log-transformed tumor thickness (ln [thickness]) was also significantly associated with worse OS (HR 2.39, P = 0.010). CONCLUSION/CONCLUSIONS:We identify Ki-67 and ln (thickness) as potential biomarkers for patients with thick melanoma who have undergone nodal staging. If validated in additional studies, these biomarkers could be integrated into the staging criteria to improve risk-stratification.

BACKGROUND:Cancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls. METHODS:All melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort. All such patients with stage III melanoma were subsequently compared to historical control patients identified via a prospective institutional database with protocol-driven follow-up. Survival times were calculated using the Kaplan-Meier method, and Cox proportional hazard models were employed to identify significant prognostic factors and control for confounding variables. RESULTS:A total of 91 patients were treated with an NY-ESO-1 vaccine for the treatment of high-risk resected melanoma. Of this group, 67 patients were stage III and were selected for comparative analysis with 123 historical control patients with resected stage III melanoma who received no adjuvant therapy. Among the pooled vaccine cohort (median follow-up 61 months), the estimated median recurrence-free survival was 45 months, while the median overall survival was not yet reached. In the control cohort of 123 patients (median follow-up 30 months), the estimated median recurrence-free and overall survival were 22 and 58 months, respectively. Within the retrospective stage III cohort, NY-ESO-1 vaccine was associated with decreased risk of recurrence (HR = 0.56, p < 0.01) and death (HR = 0.51, p = 0.01). Upon controlling for sub-stage, the adjuvant NY-ESO-1 clinical trial cohort continued to exhibit decreased risk of recurrence (HR = 0.45, p < 0.01) and death (HR = 0.40, p < 0.01). CONCLUSIONS:In this small retrospective cohort of resected stage III melanoma patients, adjuvant NY-ESO-1 vaccine immunotherapy was associated with longer recurrence-free and overall survival relative to historical controls. These data support the continued investigation of adjuvant NY-ESO-1 based immunotherapy regimens in melanoma.

BACKGROUND:The ability to provide optimal care to cancer patients depends on awareness of current evidence-based practices emanating from research or involvement in research where circumstances permit. The significant global variations in cancer-related research activity and its correlation to cancer-specific outcomes may have an influence on the care provided to cancer patients and their outcomes. The aim of this project is to develop a global curriculum in research literacy for the surgical oncologist. MATERIALS AND METHODS/METHODS:The leadership of the Society of Surgical Oncology and European Society of Surgical Oncology convened a global curriculum committee to develop a global curriculum in research literacy for the Surgical Oncologist. RESULTS:A global curriculum in research literacy is developed to incorporate the required domains considered to be essential to interpret the published research or become involved in research activity where circumstances permit. The purpose of this curriculum is to promote research literacy for the surgical oncologist, wherever they are based. It does not mandate direct research participation which may not be feasible due to restrictions within the local health-care delivery environment, socio-economic priorities and the educational environment of the individual institution where they work. CONCLUSIONS:A global curriculum in research literacy is proposed which may promote research literacy or encourage involvement in research activity where circumstances permit. It is hoped that this will enhance cancer-related research activity, promote awareness of optimal evidence-based practices and improve outcomes for cancer patients globally.

INTRODUCTION/BACKGROUND:The aim of this study was to analyze global variations in the level of cancer-related research activity and correlate this with cancer-specific mortality. METHODS:The SCOPUS database was explored to obtain data relating to the number of cancer-related publications per country. Cancer-specific mortality rates were obtained from the World Health Organization. Global variations in the level of scholarly activity were analyzed and correlated with variations in cancer-specific mortality. RESULTS:Data for 142 countries were obtained and significant variations in the level of research activity was noted. The level of research activity increased with rising socio-economic status. The United States was the most prolific country with 222,300 publications followed by Japan and Germany. Several countries in different regions of the world had a low level of research activity. An inverse relationship between the level of research activity and cancer-specific mortality was noted. This relationship persisted even in countries with a low level of research activity. The socioeconomic status of a nation and geographic location (continent) had a mixed influence with an overall apparent correlation with cancer-related research activity. CONCLUSION/CONCLUSIONS:This study demonstrates significant global variation in the level of cancer-related research activity and a correlation with cancer-specific mortality. The presence of a minimum set of standards for research literacy, as proposed by the European Society of Surgical Oncology and the Society of Surgical Oncology may contribute to enhanced research activity and improve outcomes for cancer patients worldwide.

INTRODUCTION: This study compares NBME surgical clerkship scores of students who completed their medicine clerkship before their surgical clerkship with the performance of those who had not previously completed their medical clerkship. METHODS: The study included 815 New York University School of Medicine students from the years 2014-2018 (571 students took medicine first, while 244 took surgery first). Performance on the surgical clerkship was assessed using the NBME SHELF examination. Statistical comparisons were performed via 2-tailed, independent-samples, unequal-variance t-tests. RESULTS: Mean NBME surgical SHELF scores of the students who had previously taken medicine were significantly higher than students who had not (mean 78.6 vs. 73.5, p < 0.001). Students who had solely medicine (as their first clerkship) before surgery also performed significantly better (mean 78.8 vs. 73.5, p < 0.001). Students who completed surgery later in the year did not perform better on the surgical SHELF, so long as both surgical clerkship cohorts had completed medicine. CONCLUSION: Students who completed their core medical clerkship prior to their surgical clerkship scored significantly better on the NBME surgical SHELF examination.

INTRODUCTION/BACKGROUND:The aim of this study was to analyze global variations in the level of cancer-related research activity and correlate this with cancer-specific mortality. METHODS:The SCOPUS database was explored to obtain data relating to the number of cancer-related publications per country. Cancer-specific mortality rates were obtained from the World Health Organization. Global variations in the level of scholarly activity were analyzed and correlated with variations in cancer-specific mortality. RESULTS:Data for 142 countries were obtained and significant variations in the level of research activity was noted. The level of research activity increased with rising socio-economic status. The United States was the most prolific country with 222,300 publications followed by Japan and Germany. Several countries in different regions of the world had a low level of research activity. An inverse relationship between the level of research activity and cancer-specific mortality was noted. This relationship persisted even in countries with a low level of research activity. The socioeconomic status of a nation and geographic location (continent) had a mixed influence with an overall apparent correlation with cancer-related research activity. CONCLUSION/CONCLUSIONS:This study demonstrates significant global variation in the level of cancer-related research activity and a correlation with cancer-specific mortality. The presence of a minimum set of standards for research literacy, as proposed by the European Society of Surgical Oncology and the Society of Surgical Oncology may contribute to enhanced research activity and improve outcomes for cancer patients worldwide.

BACKGROUND:The ability to provide optimal care to cancer patients depends on awareness of current evidence-based practices emanating from research or involvement in research where circumstances permit. The significant global variations in cancer-related research activity and its correlation to cancer-specific outcomes may have an influence on the care provided to cancer patients and their outcomes. The aim of this project is to develop a global curriculum in research literacy for the surgical oncologist. MATERIALS AND METHODS/METHODS:The leadership of the Society of Surgical Oncology and European Society of Surgical Oncology convened a global curriculum committee to develop a global curriculum in research literacy for the Surgical Oncologist. RESULTS:A global curriculum in research literacy is developed to incorporate the required domains considered to be essential to interpret the published research or become involved in research activity where circumstances permit. The purpose of this curriculum is to promote research literacy for the surgical oncologist, wherever they are based. It does not mandate direct research participation which may not be feasible due to restrictions within the local health-care delivery environment, socio-economic priorities and the educational environment of the individual institution where they work. CONCLUSIONS:A global curriculum in research literacy is proposed which may promote research literacy or encourage involvement in research activity where circumstances permit. It is hoped that this will enhance cancer-related research activity, promote awareness of optimal evidence-based practices and improve outcomes for cancer patients globally.

BACKGROUND:Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal gene expression enacted by tumors nor the extent to which altered stromal gene expression penetrates the stromal tissue. Presently, post-surgical "tumor-free" stromal tissue is determined to be cancer-free based on solely on morphological normality-a criteria that has not changed in more than 100 years despite the existence of sophisticated gene expression data to the contrary. We therefore investigated the extent to which breast tumors alter stromal gene expression in three dimensions in women undergoing mastectomy with the intent of providing a genomic determination for development of future risk of recurrence criteria, and to inform the need for adjuvant full-breast irradiation. METHODS AND FINDINGS/RESULTS:Genome-wide gene expression changes were determined in histopathologically normal breast tissue in 33 women undergoing mastectomy for stage II and III primary invasive ductal carcinoma at serial distances in three dimensions from the tumor. Gene expression was determined by genome-wide mRNA analysis and subjected to metagene mRNA characterization. Tumor-like gene expression signatures in stroma were identified that surprisingly transitioned to a plastic, normalizing homeostatic signature with distance from tumor. Stroma closest to tumor displayed a pronounced tumor-like signature enriched in cancer-promoting pathways involved in disruption of basement membrane, cell migration and invasion, WNT signaling and angiogenesis. By 2 cm from tumor in all dimensions, stromal tissues were in transition, displaying homeostatic and tumor suppressing gene activity, while also expressing cancer supporting pathways. CONCLUSIONS:The dynamics of gene expression in the post-tumor breast stroma likely co-determines disease outcome: reversion to normality or transition to transformation in morphologically normal tissue. Our stromal genomic signature may be important for personalizing surgical and adjuvant therapeutic decisions and risk of recurrence.

BACKGROUND: Perioperative chemotherapy in gastric cancer is increasingly used since the "MAGIC" trial, while clinical practice data outside of trials remain limited. We sought to evaluate the predictors and prognostic implications of perioperative chemotherapy completion in patients undergoing curative-intent gastrectomy across multiple US institutions. METHODS: Patients who underwent curative-intent resection of gastric adenocarcinoma between 2000 and 2012 in eight institutions of the US Gastric Cancer Collaborative were identified. Patients who received preoperative chemotherapy were included, while those who died within 90 days or with unknown adjuvant chemotherapy status were excluded. Predictors of chemotherapy completion and survival were identified using multivariable logistic regression and Cox proportional hazards. RESULTS: One hundred sixty three patients were included (median age 63.3, 36.8% female). The postoperative component of perioperative chemotherapy was administered in 112 (68.7%) patients. Factors independently associated with receipt of adjuvant chemotherapy were younger age (odds ratio (OR) 2.73, P = 0.03), T3 tumors (OR 14.3, P = 0.04), lymph node metastasis (OR 5.82, P = 0.03), and D2 lymphadenectomy (OR 4.12, P = 0.007), and, inversely, postoperative complications (OR 0.25, P = 0.008). Median overall survival (OS) was 25.1 months and 5-year OS was 36.5%. Predictors of OS were preexisting cardiac disease (hazard ratio (HR) 2.7, 95% CI 1.13-6.46), concurrent splenectomy (HR 4.11, 95% CI 1.68-10.0), tumor stage (reference stage I; stage II HR 2.62; 95% CI 0.99-6.94; stage III HR 4.86, 95% CI 1.81-13.02), and D2 lymphadenectomy (HR 0.43, 95% CI 0.19-0.95). After accounting for these factors, adjuvant chemotherapy administration was associated with improved OS (HR 0.33, 95% CI 0.14-0.82). CONCLUSION: Completion of perioperative chemotherapy was successful in two thirds of patients with gastric cancer and was independently associated with improved survival.