Deborah Hurley

BACKGROUND: Survival from metastatic cutaneous melanoma is substantially lower than for localized disease. Treatments for metastatic melanoma have been limited, but remarkable clinical improvements have been reported in clinical trials in the last decade. We described the characteristics of US patients diagnosed with cutaneous melanoma during 2001-2013 and assessed trends in short-term survival for distant-stage disease. METHODS: Trends in 1-year net survival were estimated using the Pohar Perme estimator, controlling for background mortality with life tables of all-cause mortality rates by county of residence, single year of age, sex, and race for each year 2001-2013. We fitted a flexible parametric survival model on the log-hazard scale to estimate the effect of race on the hazard of death because of melanoma and estimated 1-year net survival by race. RESULTS: Only 4.4% of the 425 915 melanomas were diagnosed at a distant stage, cases diagnosed at a distant stage are more commonly men, older patients, and African Americans. Age-standardized, 1-year net survival for distant-stage disease was stable at approximately 43% during 2001-2010. From 2010 onward, survival improved rapidly, reaching 58.9% (95% confidence interval = 56.6% to 61.2%) for patients diagnosed in 2013. Younger patients experienced the largest improvement. Survival for distant-stage disease increased in both Blacks and Whites but was consistently lower in Blacks. CONCLUSIONS: One-year survival for distant-stage melanoma improved during 2001-2013, particularly in younger patients and those diagnosed since 2010. This improvement may be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. Persistent survival inequalities exist between Blacks and Whites, suggesting differential access to treatment.

BACKGROUND: Comparisons of incidence and mortality rates are the metrics used most commonly to define cancer-related racial disparities. In the US, and particularly in South Carolina, these largely disfavor African Americans (AAs). Computed from readily available data sources, the mortality-to-incidence rate ratio (MIR) provides a population-based indicator of survival. METHODS: South Carolina Central Cancer Registry incidence data and Vital Registry death data were used to construct MIRs. ArcGIS 9.2 mapping software was used to map cancer MIRs by sex and race for 8 Health Regions within South Carolina for all cancers combined and for breast, cervical, colorectal, lung, oral, and prostate cancers. RESULTS: Racial differences in cancer MIRs were observed for both sexes for all cancers combined and for most individual sites. The largest racial differences were observed for female breast, prostate, and oral cancers, and AAs had MIRs nearly twice those of European Americans (EAs). CONCLUSIONS: Comparing and mapping race- and sex-specific cancer MIRs provides a powerful way to observe the scope of the cancer problem. By using these methods, in the current study, AAs had much higher cancer MIRs compared with EAs for most cancer sites in nearly all regions of South Carolina. Future work must be directed at explaining and addressing the underlying differences in cancer outcomes by region and race. MIR mapping allows for pinpointing areas where future research has the greatest likelihood of identifying the causes of large, persistent, cancer-related disparities. Other regions with access to high-quality data may find it useful to compare MIRs and conduct MIR mapping.

BACKGROUND: The objective of this study was to evaluate racial cancer disparities in Georgia by calculating and comparing mortality-to-incidence ratios (MIRs) by health district and in relation to geographic factors. METHODS: Data sources included cancer incidence (Georgia Comprehensive Cancer Registry), cancer mortality (Georgia Vital Records), and health factor (County Health Rankings) data. Age-adjusted incidence and mortality rates were calculated by cancer site (all sites combined, lung, colorectal, prostate, breast, oral, and cervical) for 2003-2007. MIRs and 95% confidence intervals were calculated overall and by district for each cancer site, race, and sex. MIRs were mapped by district and compared with geographic health factors. RESULTS: In total, 186,419 incident cases and 71,533 deaths were identified. Blacks had higher MIRs than whites for every cancer site evaluated, and especially large differentials were observed for prostate, cervical, and oral cancer in men. Large geographic disparities were detected, with larger MIRs, chiefly among blacks, in Georgia compared with national data. The highest MIRs were detected in west and east central Georgia, and the lowest MIRs were detected in and around Atlanta. Districts with better health behavior, clinical care, and social/economic factors had lower MIRs, especially among whites. CONCLUSIONS: More fatal cancers, particularly prostate, cervical, and oral cancer in men were detected among blacks, especially in central Georgia, where health behavior and social/economic factors were worse. MIRs are an efficient indicator of survival and provide insight into racial cancer disparities. Additional examination of geographic determinants of cancer fatality in Georgia as indicated by MIRs is warranted.

Polyploid giant cancer cells (PGCC) represent a poorly understood, small subpopulation of tumor cells that are increasingly being recognized for their critical role in therapy resistance, metastasis, and cancer recurrence. PGCC have the potential to generate progeny through primitive or cleavage-like division, which allows them to evade antimitotic insults. We recently demonstrated that the sphingolipid enzyme acid ceramidase (ASAH1) is required for this process. Since specific ASAH1 inhibitors are not clinically available, we investigated whether tamoxifen, which interferes with ASAH1 function via off-target effects, has a potential clinical benefit independent of estrogen signaling. Our results show that tamoxifen inhibits generation of PGCC offspring in prostate cancer, glioblastoma, and melanoma cells. Analysis of two state-level cancer registries revealed that tamoxifen improves survival outcomes for second, nonbreast cancers that develop in women with early stage breast cancer. Our results suggest that tamoxifen may have a clinical benefit in a variety of cancers that is independent of estrogen signaling and could be due to its inhibition of acid ceramidase. Thus the distinct application of tamoxifen as potentially a first-in-class therapeutic that inhibits the generation of PGCC offspring should be considered in future clinical trials.

South Carolina (SC) has some of the largest health disparities in the nation, in particular cancer mortality rates that disfavor African Americans (AA) in comparison to European Americans (EA) with 37% higher incidence and 61% higher mortality rates for AA women compared to EA women. Consequently, the purpose of this investigation was to examine and compare the impact of race on survival among cervical cancer patients in SC. Data from the SC Central Cancer Registry on all AA and EA cervical cancer patients in SC were analyzed for this investigation. All women greater than 19 years of age with a histopathologically-confirmed cervical neoplasm were included. Kaplan Meier survival curves were calculated and compared for each racial group using the log rank test statistic. Significant differences between races were noted for alcohol use, grade, histology, marital status, and vital status. AA women with cervical cancer had significantly decreased survival compared to EA women (49% vs. 66%, p < 0.01). This same trend was noted for all grade, histology, and stage types. We found significantly decreased survival among AA women with cervical cancer compared to EA women, which persisted even among AA and EA women with the same disease stage, grade, or histology. The causes of these disparities are most likely multi-faceted and interdependent. These findings emphasize the need for intervention into the myriad of factors ranging from the biological and genetic to the environmental and structural barriers impacting cervical cancer mortality.