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Purpose Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and a model of targeted molecular therapy. GIST depends on oncogenic KIT signaling and responds to the tyrosine kinase inhibitor imatinib. However, imatinib is rarely curative. We hypothesized that PLX3397, which inhibits KIT and CSF1R, would be more efficacious than imatinib in GIST by also depleting tumor-associated macrophages, which are generally thought to support tumor growth. Experimental Design We treated KitV558del/+ mice that develop GIST or mice with subcutaneous human GIST xenografts with imatinib or PLX3397 and analyzed tumor weight, cellular composition, histology, molecular signaling, and fibrosis. In vitro assays on human GIST cell lines were also performed. Results PLX3397 was more effective than imatinib in reducing tumor weight and cellularity in both KitV558del/+ murine GIST and human GIST xenografts. The superiority of PLX3397 did not depend on depletion of tumor-associated macrophages, since adding CSF1R inhibition did not improve the effects of imatinib. Instead, PLX3397 was a more potent KIT inhibitor than imatinib in vitro. PLX3397 therapy also induced substantial intratumoral fibrosis, which impaired the subsequent delivery of small molecules. Conclusions PLX3397 therapy has greater efficacy than imatinib in pre-clinical GIST models and warrants study in GIST patients. The resultant intratumoral fibrosis may represent one of the barriers to achieving complete tumor eradication.

Background In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. Methods Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self‐identified. Imaging, laboratory, and pathologic features were compared between Black and non‐Black cohorts. Results Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child‐Pugh score, Model of End‐Stage Liver Disease score, histology of nontumor tissue, and fibrosis‐4 (FIB‐4) score (all P < .05). FIB‐4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2‐6.2 cm] vs 3.1 cm [2.1‐5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1‐3 tumors] vs 1 tumor [1‐2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). Conclusions Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one‐third would not qualify for HCC screening using the common FIB‐4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.

Objective Latinos are a diverse population comprised of multiple countries of origin with varying cultural profiles. This study examines differences in colonoscopy completion across place of birth and migration-related factors in a sample of predominantly Dominican and Puerto Rican Latinos living in New York City after receiving a recommendation for colonoscopy screening and navigation services. Design The sample included 702 Latinos recruited for two cancer screening projects targeting Latinos eligible for colonoscopy who seek healthcare in New York City. Participants completed a survey that included sociodemographic, health-related questions, psychosocial assessments and cancer screening practices, in Spanish or English. Results Migration, acculturation, and language factors were found to predict colonoscopy completion. The results indicated that Latinos born in the Dominican Republic and Central America were more likely to complete a screening colonoscopy than their counterparts born in the US. Further, those who emigrated at an older age, who have resided in the US for less than 20 years, preferred Spanish and those with lower US acculturation levels were also more likely to complete a screening colonoscopy. Conclusion The findings suggest that Latinos who are less acculturated to the US are more likely to complete a screening colonoscopy after receiving a physician recommendation for colonoscopy screening. The results provide important information that can inform clinical practice and public health interventions. Continued attention to cultural and migration influences are important areas for cancer screening intervention development.

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