PurposeTo analyze differences in esophageal cancer survival by geographic region of the U.S. from the 1970s to the 2000s, and attribute the causes of these discrepancies.MethodsRaw data were obtained from the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute. Patients were stratified by decade of diagnosis and by geographic region (East, Hawaii/Alaska, Midwest, Southwest, and West), containing SEER registries. The Kaplan-Meier method with the log-rank test was used to compare the overall survival (OS) among these geographic groups. A multivariate Cox Proportional Hazard analysis was conducted to evaluate the impact of the following factors on differences in survival: patient age, gender, race, tumor stage, site, histology, treatment method, and metropolitan size.ResultsA total of 87,834 patients were identified. OS has increased significantly since 1973, with five-year OS improving from 4.9% (the 1970s) to 15.3% (2000s) (P<0.001). Residence in the East was prognostic for higher OS compared to all the other regions, with a median OS of six months in the 1970s and 12 months in the 2000s (P<0.001). The multivariate analysis revealed increased age, African American race, distant disease, non-distal tumor location, squamous cell histology, and no radiation therapy were associated with worse OS. The West and East had the highest amount of cancer centers (12 and seven, respectively). And the East had the highest number of cancer centers per person (5.7E-07) while the South had the lowest (1.6E-07).ConclusionsThere are disparities in esophageal cancer survival and quality of care through different geographic regions of the U.S., which may be attributed to a combination of the unbalanced distribution of medical resources, the regional differences in cancer biology, and other lifestyle and socioeconomic factors. More research should be conducted to further characterize regional differences and guide the implementation of improvements in survival.

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the developing brain through loss of function studies, using morpholinos targeting Praja1 in embryonic zebrafish, and observed that Praja1 is expressed prominently in regions enriched with neural precursor cell subtypes. Antisense Praja morpholinos resulted in multiple embryonic defects including delayed neural development likely through increased apoptosis. Further studies revealed high levels of Cdk1 with loss of Praja1 in TGF-β or insulin treated cells, supporting the link between Praja1 and cell cycle regulation. In summary, these studies underscore Praja's role in mammalian brain development and Praja1 deregulation may lead to gliomas possibly through the regulation of cell cycle and/or apoptosis.

In the SEER database, there appears to be both a CSM and ACM benefit to adding surgery following radiation for Stage IIIB NSCLC.

Purpose/Objective(s): Traditionally, stage IIIB non-small cell lung cancer (NSCLC) has been considered to be a surgically unresectable disease. Chemoradiation has become a standard treatment approach. However, in select patients, neoadjuvant treatment has been able to convert unresectable disease to resectable disease. Limited work, either retrospective or prospective, has been done to investigate whether or not there is a causespecific mortality (CSM) or all-cause mortality (ACM) benefit to adding surgery following neoadjuvant treatment for stage IIIB NSCLC. Materials/Methods: We extracted patients with Stage IIIB NSCLC from the Survival, Epidemiology, and End Results Program (SEER) database treated from 2004-2012 with either radiation alone or radiation followed by surgery. Potentially confounding variables which were extracted from the database included age, sex, race, and tumor location. The impact of patient and treatment variables on CSM and ACM was explored using Cox multivariable regression analysis-the potentially confounding factors listed above were included in the multivariable analysis. Results: 14,065 patients were extracted from the SEER database. 42.2% of patients were age 64. 39.7% of patients were female, while 60.3% were male. 79.0% of patients were white, 15.0% were black, and 6.0% were other. On multivariable analysis, even after adjustment for age, gender, race, and site, radiation followed by surgery was associated with a reduction in cause-specific mortality compared to radiation alone (adjusted HR Z 0.46; 95% CI Z 0.41, 0.52; P<0.0001). Median overall survival was 11 months in the radiation therapy alone arm versus 21 months in the radiation therapy plus surgery arm (P<0.0001 by log-rank test). After adjustment for these same factors, radiation followed by surgery was also associated with a reduction in allcause mortality compared to radiation alone (adjusted HR Z 0.47; 95% CI Z 0.42, 0.52; P<0.0001). Median cause-specific survival was 12 months in the radiation therapy alone arm versus 33 months in the radiation therapy plus surgery arm (P<0.0001 by log-rank test). Conclusion: In this population based analysis, there appears to be both a CSM and ACM benefit to adding surgery following radiation for Stage IIIB NSCLC. There are several limitations to this study including lack of chemotherapy data and the lack of data on medical co-morbidities. Indeed, our results are hypothesis generating, and would best be verified by a randomized clinical trial.