Gabriel, Emmanuel

Background Recent studies have shown an increase in the incidence of gastric cancer (GC) among young adults in Asia and Latin America. However, it is unknown if a similar trend is happening in the United States. Methods A retrospective review of the National Cancer Database was conducted to identify patients diagnosed with gastric adenocarcinoma between the years of 2004 and 2013. Results A total of 93 734 patients were included. The two age groups below 40 did not see a change in GC incidence; however, age groups above 40 had increasing incidence. Patients aged 18 to 25 had the largest proportion of stage 4 disease and a poor survival (median 11.5 months), compared to older patients. Conclusion Despite the increasing trend of GC among individuals, the incidence of GC among young adults is not increasing. However, this subpopulation presents at more advanced stages (clinical stage 4) and thus has worse survival.

A negative sentinel lymph node biopsy (SLNB) for stage IB (T1b/T2a N0) melanoma would predict an excellent long-term prognosis. Combined with the concept of conditional survival, an “abbreviated” cancer surveillance strategy was implemented to reduce the number of visits and total length of follow-up. Retrospective review of all pathologic stage IB melanoma patients (negative SLNB) at a single institution between 2006 and 2008 after implementation of an “abbreviated” cancer surveillance; clinic visits every six months for five years followed by one annual visit (total follow-up six years). Patient demographics, tumor characteristics, and information regarding recurrences were obtained. Recurrence-free, disease-specific, and overall survival were calculated. Eighty-seven patients underwent the “abbreviated” cancer surveillance. Median age was 55.4 years and 50.6 per cent were male. Median Breslow thickness was 1.1 mm (range 0.5–2.0 mm) and 1.1 per cent were ulcerated. Primary tumor site was 49 per cent extremities, 39 per cent trunk, and 12 per cent head/ neck. Median follow-up was 68.6 months. Five-year recurrence-free, disease-specific, and overall survivals were 89, 95, and 88 per cent, respectively. During surveillance, 10 patients had concerning symptoms or physical findings prompting subsequent workup, all of which were negative for recurrence/metastases. There were only three true melanoma recurrences; all were distant metastases and presented symptomatically between scheduled follow-up visits. In light of the excellent prognosis for pathologic (SLNB negative) stage IB melanoma, an “abbreviated” cancer surveillance schedule based on conditional survival would reduce both direct and indirect costs in this cohort. The few recurrences were symptomatic and unlikely to have changed with more intensive surveillance.

e19047 Background: Colorectal cancer is one of the leading causes of cancer deaths in the US. Area of residence affects survival in many cancers, though largely unknown in colorectal cancer. The purpose of this study is to evaluate disparities between the metropolitan, urban and rural populations and the impact on survival in colorectal cancer. Methods: Data was obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal data sets. Patients (pts) were categorized by area of residence: metropolitan (MA), urban (UA), or rural (RA). Gender, race, insurance status, income, marital status, and tumor related data was collected. Univariate and multivariate analyses were performed to evaluate variables affecting overall survival (OS). Results: A total of 973,139 pts, spanning 2004-2013 were included in the study, 83% MA, 15% UA, 2% RA. RA and UA pts were more likely to be white than MA pts (92.7 v 91.4% v 83%). RA and UA were more likely to have lower income, with slightly lesser amounts of women and pts with no comorbidities. Uninsured rates were similar (3.3%). On univariate analysis, OS was worse for RA (HR 1.10) and UA (1.06) pts, as compared with MA. On multivariate analysis, small differences persisted with worse OS for RA (HR 1.02, p = .043) and UA (HR 1.01, p = .003). Black (HR 1.14) and native American (HR 1.17) pts had worse outcomes, while Asian (HR 0.8) pts had improved OS. Women (HR 0.88) and pts with higher incomes ( > 46K or 63K) had improved OS (HR 0.88). Conclusions: This study identifies socio-demographic disparities in colorectal cancer outcomes. Pts from rural and urban areas had worse OS, even though the proportion of minority pts with poor outcomes was lower. The difference in OS for RA and UA remained statistically significant in multivariate analysis, though it was largely corrected when adjusting for influencing variables. Part of this difference may be due to economic disparities, as lower income was linked to worse OS. This can independently limit access to care, especially for geographically isolated individuals. Additional research efforts are needed in order for us to better understand the key issues facing and the optimal means to improve outcomes in at risk populations.

Abstract Background Acral melanoma is the most common subtype of melanoma in Chinese patients and one of the least common in Caucasian patients. It has been unclear if outcomes differ between Chinese and Caucasian patients diagnosed with Acral Melanoma. This study investigated patient characteristics and survival differences between Chinese and Caucasian Acral Melanoma patients. Methods Two large institutional melanoma databases from Fudan University Shanghai Cancer Center (FUSCC) and Mayo Clinic enterprise, were retrospectively reviewed from 2009 to 2015. Clinicopathologic and survival data were collected and analyzed between the two groups. The primary outcome was disease-specific survival (DSS) and was calculated using the Kaplan Meier (KM) method. Results The Chinese group presented with more advanced disease compared with Caucasians: thicker Breslow depth (median 3.0 mm vs. 1.2 mm, p=0.003), more ulcerated disease (66.1% vs 29%; p<0.001), and advanced stages (stage II/III 84.3% vs. 37.1%; p<0.001). No significant difference was identified in terms of age at diagnosis, location, histologic subtypes, or node positive rate. The 5-year DSS rate was 68.4% and 73% (p=0.56) for Chinese and Caucasians, respectively. Male gender, Breslow thickness, ulceration, and positive sentinel lymph nodes predicted worse DSS on multivariate Cox regression analysis. Conclusions There appears to be no difference in stage-stratified survival between Chinese and Caucasians, supporting the implementation of clinical trials of AM that could include both Chinese and Caucasian patients.

Background: Gastric cancer is one of the leading causes of cancer-related mortality worldwide, accounting for 8.2% of cancer-related deaths. The purpose of this study was to investigate the geographic and sociodemographic disparities in gastric adenocarcinoma patients. Methods: We conducted a retrospective study in gastric adenocarcinoma patients between 2004 and 2013. Data were obtained from the National Cancer Data Base (NCDB). Univariate and multivariable analyses were performed to evaluate overall survival (OS). Socio-demographic factors, including the location of residence [metro area (MA) or rural area (RA)], gender, race, insurance status, and marital status, were analyzed. Results: A total of 88,246 [RA, N = 12,365; MA, N = 75,881] patients were included. Univariate and multivariable analysis showed that RA had worse OS (univariate HR = 1.08, p < 0.01; multivariate HR = 1.04; p < 0.01) compared to MA. When comparing different racial backgrounds, Native American and African American populations had poorer OS when compared to the white population; however, Asian patients had a better OS (multivariable HR = 0.68, p < 0.01). From a quality of care standpoint, MA patients had fewer median days to surgery (28 vs. 33; p < 0.01) with fewer positive margins (6.3% vs. 6.9%; p < 0.01) when compared to RA patients. When comparing the extent of lymph node dissection, 19.6% of MA patients underwent an extensive dissection (more than or equal to 15 lymph nodes) in comparison to 18.7% patients in RA (p = 0.03). Discussion: This study identifies socio-demographic disparities in gastric adenocarcinoma. Future health policy initiatives should focus on equitable allocation of resources to improve the outcomes.

Abstract Background: Immune checkpoint inhibitors (ICPIs) have led to dramatic improvement in outcome of several cancers. Program death ligand1 (PD-L1) staining and tumor mutational burden (TMB) have emerged as independent predictive biomarkers of ICPIs in lung cancer. Here we examine the landscape of TMB and PD-L1 expression in breast cancer and present a case of patient with high TMB and PD-L1 negative breast cancer with exceptional response to ICPIs. Methods: Hybrid-capture based comprehensive genomic profiling of 395 cancer related genes using the FoundationOne assay was performed on 14,867 breast carcinomas sequenced in the course of routine clinical care. Ventana (SP-263) PD-L1 status (n=1425) and hormone receptor status was available for a subset of patients. Subgroup analyses were performed based on histological type [invasive lobular carcinoma (ILC, n=740)], molecular subtypes [ER-positive (ER+; n= 1371), HER2-amplified (HER2+; n=1522), and TNBC (n=917)], patient age (≤45, 46-60, ≥61), and local vs. metastatic disease (n=5241 and 6710). Results: Consistent with previous reports, the rates of positive PD-L1 staining are highest in TNBC (14%) and lowest in HER2+, ILC, and ER+ disease (6.0%, 5.1%, 2.3%). Interestingly, the rate of PD-L1 positivity, defined as ≥1% tumor staining, was significantly lower in metastatic disease vs. local disease (6.3% vs. 11.1%; p = 0.005). The frequency of high TMB, defined as &gt;10 mutations/mb, was greatest in ILC and HER2+ disease (13.6% and 9.9%) and lowest in TNBC and ER+ disease (7.0% and 6.9%). Rates of high TMB were associated with increased patient age (3.7%, 9.3%, and 12.8% frequency in patients ≤45, 46-60, and ≥61) and were significantly higher in metastatic vs. local disease (11.1% vs 5.3%; p&lt;2E-23). PD-L1 positive and TMB high populations were not significantly co-occurrent (OR = 1.02, p = 0.87). Similar percentages of PD-L1 positivity were observed in both TMB low (9.3%) and TMB high (9.5%). However, among patients with very high TMB (&gt;20 mut/mb), there was a significant association between TMB and PD-L1 positivity (OR = 2.6, p = 0.023). Nevertheless, even with high cutoff, 79% of the TMB high samples were PD-L1 negative. We also report on a stage IIIb (T4, N2, M0) ER+ HER2- breast cancer patient with high TMB (40muts/mb) and negative PD-L1 IHC who previously progressed on aromatase inhibitor with CDK4/6 inhibitor and chemotherapy but achieved durable complete response of &gt; 1 year with nivolumab in combination with capecitabine. Conclusions: Predictive biomarkers for ICPIs are critical to identify a subset of breast cancer patients who may respond to immunotherapy. TMB high and PD-L1 positivity do not significantly co-occur and the majority of TMB high cases were PD-L1 negative. Nevertheless, this group of patients may still benefit with ICPIs. Further studies are needed to evaluate this subset of patients. Citation Format: Ethan Sokol, Lee Albacker, Aixa Soyano, Ricardo Parrondo, Brenda Ernst, Emmanuel Gabriel, Garrett Frampton, Jeffrey Ross, Siraj Ali, Jon Chung, Saranya Chumsri. Incidence of high tumor mutation burden (TMB) and PD-L1 positivity in breast cancers and potential response to immune checkpoint inhibitors (ICPIs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4894.

Background: External ear melanoma (EEM) is a rare condition with controversies in the literature. We analyzed patients with EEM in the United States compared to other head and neck melanomas (OHNMs). Methods: The National Cancer Database (NCDB) was used to select patients with head and neck melanoma from January 1, 2004 to December 31, 2015. Mann–Whitney and χ 2 tests were used to estimate statistical significance, and multivariate logistic regression to identify independent associations adjusted for confounders. Results: A total of 137,233 patients met the study criteria. Among them, 16,991 (12.4%) had EEM and 120,242 (87.6%) had OHNM. For patients with EEM, the mean (standard deviation) age was 66.26 (15.798) years. Most of the patients with EEM were men (85.5%), insured by Medicare (52.4%), and treated in Academic/Research Programs (47.7%) or Comprehensive Community Cancer Programs (32.3%). Most of the EEM tumors had invasive behavior (68.0%) were Stages 0 (30.3%) or I (40.3%), and were without ulceration (76.9%). Mean time to receive any treatment was 14.1 days for EEM compared with 14.6 days for OHNM (P < 0.001). We noticed a greater proportion of EEM in men (14.8%; adjusted odds ratio [aOR] 2.72 [2.605–2.852]; P < 0.001) compared to women (6.22%; reference). EEM was an independent factor for tumor Stage I (14.47%; aOR 1.61 [1.101–1.224], P < 0.001) and invasive behavior (13.86%; aOR 1.268 [1.15–1.389]; P < 0.001) compared to OHNM. Conclusion: EEM was associated with higher odds of invasive behavior compared to OHNM. Furthermore, men were found to have a higher likelihood to develop EEM compared to women.

Background: Eyelid melanoma (EM) is a rare condition that accounts for <1% of all cutaneous melanomas. In this analysis, patients diagnosed with EM in the United States were compared to those with other melanomas in the head and neck. Methods: The National Cancer Database was used to select patients with head and neck melanoma from 2004 to 2015. Results: A total of 137,233 patients met the criteria of the study. Among them, 2694 were diagnosed with EM (2%) and 134,539 in other head and neck locations (98%). Regarding the patients with EM, the mean age was 68.56 years (standard deviation 14.04). A greater number of them were treated in Academic/Research Programs (53.6%), insured by Medicare (55.7%), tumor in situ (52.2%), stage 0 (49%), and without ulceration (75.9%). The mean time to treatment commencement was 18.96 days for EM compared to 14.4 days for other melanoma in the head and neck regions (P < 0.001). There was a greater proportion of EM in female patients (odds ratio [OR] 2.371 [2.191–2.566], P < 0.001), compared to male; age greater than 80 years (OR 1.622 [1.360–1.934], P < 0.001) compared to 0 to 49 years. Moreover, EM was an independent predictor for treatment in Academic/Research Programs (OR 1.258 [1.160–1.365], P < 0.001) and diagnosis at autopsy (OR 1.414 [1.083–1.847], P = 0.011) compared to other melanoma in the head and neck region. Conclusion: These novel findings have the potential to guide clinical decision making in head and neck melanoma management.