Austin Miller

Clinical characteristics of adenosquamous esophageal carcinoma

BACKGROUND Current published information of adenosquamous carcinoma (ASC) of the esophagus in the United States is limited to isolated case reports. We sought to study the clinical characteristics of this tumor using the Surveillance, Epidemiology and End Results (SEER) database. METHODS Relevant data of all patients with esophageal cancer in the SEER database diagnosed from 1998-2010 was obtained. Demographic, grade, stage, treatment and survival characteristics of patients with ASC were summarized and compared to those patients with adenocarcinoma (ACA) and squamous cell carcinoma (SqCC). Univariate analyses across comparison groups were performed using Wilcoxon rank sum test for continuous covariates and the Pearson Chi-square test for categorical covariates. To evaluate the association of selected covariates to survival by histology, unadjusted and adjusted proportional hazards models were generated for the entire study population. To further control for the difference in covariates among the histology groups, propensity weighted Cox regression modeling was performed using the inverse propensity to treat weighting (IPTW) approach. RESULTS Of 29,890 patients with the histological subgroups, only 284 patients had ASC (1%). Patients with ACA had a higher grade (72.9% with grade III/IV) and presented with advanced stage (48.2% distant disease) than their comparison group. Patients with ASC had worse overall survival compared to ACA but not SqCC in both univariate and multivariate analyses (OR =0.76; P<0.05 and OR =0.86; P<0.05 respectively). These results were further confirmed by the propensity weighted Cox regression analysis. Analysis of the ASC population alone demonstrated that decreasing stage, radiation therapy (OR =0.59; P<0.001) and surgery (OR =0.86; P<0.001) were associated with better overall survival, but grade was not. CONCLUSIONS ASC of the esophagus is a rare histological variant comprising 1% of esophageal ACA in the Unites States. This histological subtype presents in later stages, at a higher grade and portends a poorer survival than the more common ACA. Radiation therapy and surgical resection of appropriate stage patients provide the best chance of survival.

A phase II trial of pralatrexate (P) plus oxaliplatin (O) in advanced esophagogastric cancer (aEGC).

152 Background: Advanced EGC is an aggressive cancer with limited treatment (Rx) options. In preclinical studies P has demonstrated increased cellular uptake and polyglutamylation relative to other anti-folates plus is synergistic with platinum. We evaluated combination P plus O in aEGC and examined pharmacogenomics and tumor microRNA profiling to identify predictive signatures for response and toxicity. Here we report on clinical outcome data for the entire cohort. Methods: Objective response (OR) following P+O was assessed in an exact 2-stage design, including early stopping for futility and a safety lead-in cohort of 6 patients (pts) with provisions for dose de-escalation for dose limiting toxicity (DLT). Eligibility included metastatic/unresectable, therapy-naive EGC pts with adequate organ and functional status and < G2 neuropathy. Rx consisted of biweekly O (85mg/m2) plus P (Dose level [D] 1, 120mg/m2; dose level -1 [D-1] 100 mg/m2). O was stopped after 12 cycles. Secondary endpoints were toxicity, ...

Time trends in survival in young women with breast cancer in a population-based study: Are there estrogen receptor status differentials?

85 Background: As mammography is not generally recommended to women under 40, it is reasonable to conclude that documented outcome improvements over time are attributable to treatment advances with screening playing a less important role. In order to determine the contribution of screening and treatment to improvements, we evaluated the odds of presenting with more advanced disease by time-period and examined the time-trends in outcome in a population-based cohort ≤50. We evaluated whether any outcomes differentials existed by ER status. METHODS Patients in SEER diagnosed with breast cancer were divided into 4 by year of diagnosis (1990-1994, 1995-1999, 2000-2004, 2005-2008). Patients were categorized into 2 age-groups: <40 and 40-50 years. Odds ratios for presenting with more advanced disease over the 4 time-periods were calculated for the 2 age-groups. Multivariate analysis was done to investigate the association of survival with time-period for the 2 age-groups by ER status. RESULTS 110,629 patient records were included. Patients 40-50 who were diagnosed in the 3 later time-periods (1995-1999, 2000-2004, 2005-2008) were more likely to have small tumors (≤2cm) compared with patients diagnosed in 1990-1994. Similarly, these patients were less likely to have larger tumors (≥3cm) comparing the 3 time-periods relative to 1990-1994. Conversely, patients <40 years had a higher odds of presenting with larger tumors (≥3cm) when the 3 later time-periods were compared to 1990-1994. In the ER positive patients, multivariate analysis showed that being diagnosed in the 3 later time-periods relative to 1990-1994 was associated with improved survival irrespective of age. In the ER negative cohort, those 40-50 years had a higher risk of death in the 3 later time-periods relative to 1990-1994; while there was a no effect of time-period on mortality for the younger age group of <40. CONCLUSIONS Patients who are ER positive and between 40-50 years have had time-trend changes with improvements in breast cancer outcome and smaller tumors likely attributable to both screening and hormonal therapies. Patients who are <40 years and/or ER negative have not had improvements in breast cancer outcome.

Additional primary malignancies in patients with pancreatic cancer.

185 Background: Rates of second primary malignancy have been increasing with increased cancer survivorship. The published literature on second primaries in patients with pancreatic adenocarcinoma is sparse. We addressed this question utilizing the SEER database. METHODS 99,614 patients of primary pancreatic adenocarcinoma diagnosed between 1973-2006 were identified from SEER database. Of these, 8,889 (8.93%) had another primary diagnosed before pancreatic cancer (BPC) and 1813 (1.82%) a second primary diagnosed after pancreatic cancer (APC). SAS was used for statistical analysis and P-value <0.05 was determined to be significant. RESULTS The most common non-pancreatic primary identified were prostate, breast, lung, colorectal, and urinary bladder. The median age at presentation was 75 and 71 years in the BPC and APC groups respectively. APC patients had higher odds of developing primary cancers of embryonic gut origin (esophagus, stomach, small intestine, hepatobiliary, lung, and thyroid) compared to PBC patients (p<0.05). Patients of BPC compared to APC were more likely to be older than 70 yrs (70.5% vs. 65.3% p=0.01), less likely to undergo surgery for pancreatic cancer (11.2% vs.5.87% p=<0.05) and with decreased median survival (7 vs.3 months). With each passing decade, increasing second primaries were diagnosed, presumably reflecting better overall survival from cancer diagnosis. CONCLUSIONS Approximately 11% of pancreatic adenocarcinoma patients have another cancer in their life time. Identifying common genetic and risk factors in these patients with multiple malignancies may provide the new therapeutic opportunities for patients with pancreatic cancer.