Age-dependent prognostic value of KRAS mutation in metastatic colorectal cancer.

Background: The age-dependent prognostic impact of KRAS status in metastatic colorectal cancer (mCRC) is unknown. Materials & Methods: We used the National Cancer Database to evaluate the survival by KRAS status for age-groups <50, 50-69 and ≥70, adjusting for relevant patient and tumor characteristics. Results: mCRC patients (n = 26,095; 33.5%) had KRAS status reported, and 11,338 of these patients (43.4%) had mutations in the KRAS gene. Patients with KRAS mutations had worse overall survival than wild-type KRAS patients. In age-groups <50 years (23 vs 29 months; p < 0.001) and 50-69 (21 vs 23.4 months; p < 0.001), KRAS mutations were significantly associated with worse survival, whereas in the ≥70-year age-group, there was no significant association (14 vs 14 months; p = 0.34). Conclusion: We conclude that the age of patients influences the prognostic value of KRAS mutation in metastatic colorectal cancer.

Financial Conflicts of Interest: Payment at the Expense of Patients?

This provocative editorial proposes four steps that can be immediately implemented to reduce the impact of financial conflicts of interest in oncology without stifling collaboration.

Ablative Radiation Therapy in Oligometastatic Pancreatic Cancer to Delay Polyprogression, Limit Chemotherapy, and Improve Outcomes.

PURPOSE: The oligometastatic state is observed in patients across many malignancies, with increased recognition regarding improved outcomes after local therapies. However, there is limited data specifically regarding pancreatic ductal adenocarcinoma. We hypothesized that an oligometastatic pancreatic ductal adenocarcinoma (OPanc) phenotype would benefit from stereotactic ablative radiation therapy (SABR) to all active metastatic sites. Here, we report our institutional experience of SABR-treated OPanc to evaluate the feasibility of the approach. METHODS AND MATERIALS: A retrospective review of patients with synchronous or metachronous OPanc (1 to 5 metastases) who received SABR to all active metastatic sites was performed. We identified a comparable group of patients with similar metastatic burden, range of CA19-9 levels, and no progression for at least 5 months who did not receive SABR. We compared overall survival as the primary outcome, and polyprogression-free survival and time off chemotherapy as the secondary exploratory assessments. A third group presenting with stage IV pancreatic ductal adenocarcinoma and more than 5 distant lesions (polymetastatic) was identified to help define expected outcomes after polyprogression. RESULTS: Our study included 20 patients with OPanc receiving SABR and 21 who did not. SABR was delivered to 38 metastatic tumors. Out of the 20 SABR-treated OPanc patients, 17 (85%) had 6 or more months of time off chemotherapy, compared with 7 patients (33.3%) among the chemotherapy-treated group. Median polyprogression-free survival was 40 and 14 months (hazard ratio = 0.2; 95% confidence interval, 0.07-0.54; P = .0009), and overall survival was 42 and 18 months (hazard ratio = 0.21; 95% confidence interval, 0.08-0.53; P = .0003), for SABR- and chemotherapy-treated cohorts, respectively. CONCLUSIONS: Management of OPanc with SABR as local regional therapy could improve outcomes in a selected population and warrants prospective evaluation.

Distinct Clinical Characteristics in Young-Onset Pancreatic Neuroendocrine Tumor.

BACKGROUND: We aimed to study the effect of socioeconomic differences and molecular characteristics on survival in patients with young-onset pancreatic neuroendocrine tumors (YOPNET) and typical-onset PNET (TOPNET). METHODS: We identified the patients with YOPNET (<50 years) and TOPNET (≥50 years) who underwent definitive surgery diagnosed between 2004 and 2016 using the National Cancer Database. We evaluated overall survival (OS) using the Kaplan-Meier and Cox regression methods before and after propensity score matching. A publicly available genomic dataset was used to compare mutation frequencies among the two groups. RESULTS: A total of 6259 patients with PNET were included, of which 27% were YOPNET. Patients with YOPNET were more likely to be Black, Hispanic, female, and have private insurance versus patients with TOPNET (all p < 0.001). Patients with YOPNET had a lower comorbidity score, but higher stage and tumor size (all p < 0.001). YOPNET was associated with a greater improved OS than TOPNET before and after propensity score matching (p < 0.001). On multivariable analysis, this survival difference persisted for YOPNET as an independent prognostic factor (unmatched p = 0.008; matched p = 0.01). For genomic analysis, patients with YOPNET had a lower rate of multiple endocrine neoplasia type-1 (MEN-1) mutation than patients with TOPNET (26% vs. 56%, p < 0.001). CONCLUSIONS: YOPNET represents a disease with distinct clinical features. Patients with YOPNET who underwent definitive surgery had better OS than patients with TOPNET despite having higher stage and tumor size. YOPNET also had lower rate of MEN-1 mutation.

Racial/Ethnic Disparities and Survival Characteristics in Non-Pancreatic Gastrointestinal Tract Neuroendocrine Tumors.

Background: We studied the effect of race and ethnicity on disease characteristics and survival in gastrointestinal neuroendocrine tumors. Methods: The Surveillance, Epidemiology, and End Results database was used to select patients with non-pancreatic gastrointestinal neuroendocrine tumors diagnosed between 2004 and 2015. Trends in survival were evaluated among three groups: Hispanic, non-Hispanic White, and non-Hispanic Black. Kaplan-Meier and Cox regression methods were performed to calculate overall survival and cause-specific survival after adjusting for patient and tumor characteristics. Results: A total of 26,399 patients were included in the study: 65.1% were non-Hispanic White, 19.9% were non-Hispanic Black, and 15% were Hispanic. Non-Hispanic White patients were more likely to be male (50.0%, p < 0.001), older than 60 years (48.0%, p < 0.001), and present with metastatic disease (17.7%, p < 0.001). Non-Hispanic White patients had small intestine neuroendocrine tumors, while Hispanic and non-Hispanic Black patients had rectum neuroendocrine tumors as the most common primary site. Hispanic patients had better overall survival, while non-Hispanic Black patients had better cause-specific survival versus non-Hispanic White patients. This finding was confirmed on multivariable analysis where Hispanic patients had improved overall survival compared to non-Hispanic White patients (Hazard ratio (HR): 0.89 (0.81-0.97)), whereas non-Hispanic Black patients had better cause-specific survival compared to non-Hispanic White patients (HR: 0.89 (0.80-0.98)). Conclusions: Race/ethnicity is an independent prognostic factor in patients with gastrointestinal neuroendocrine tumors.