S Farley

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.

ABSTRACT Xenografting human cancer tissues into mice to test new cures against cancers is critical for understanding and treating the disease. However, only a few inbred strains of mice are used to study cancers, and derivatives of mainly one strain, mostly NOD/ShiLtJ, are used for therapy efficacy studies. As it has been demonstrated when human cancer cell lines or patient-derived tissues (PDX) are xenografted into mice, the neoplastic cells are human but the supporting cells that comprise the tumor (the stroma) are from the mouse. Therefore, results of studies of xenografted tissues are influenced by the host strain. We previously published that when the same neoplastic cells are xenografted into different mouse strains, the pattern of tumor growth, histology of the tumor, number of immune cells infiltrating the tumor, and types of circulating cytokines differ depending on the strain. Therefore, to better comprehend the behavior of cancer in vivo , one must xenograft multiple mouse strains. Here we describe and report a series of methods that we used to reveal the genes and proteins expressed when the same cancer cell line, MDA-MB-231, is xenografted in different hosts. First, using proteomic analysis, we show how to use the same cell line in vivo to reveal the protein changes in the neoplastic cell that help it adapt to its host. Then, we show how different hosts respond molecularly to the same cell line. We also find that using multiple strains can reveal a more suitable host than those traditionally used for a “difficult to xenograft” PDX. In addition, using complex trait genetics, we illustrate a feasible method for uncovering the alleles of the host that support tumor growth. Finally, we demonstrate that Diversity Outbred mice, the epitome of a model of mouse-strain genetic diversity, can be xenografted with human cell lines or PDX using 2-deoxy-D-glucose treatment.