BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/Microsatellite High Colorectal Cancer.

BACKGROUND: Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC. MATERIALS/METHODS: This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type. RESULTS: There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis. CONCLUSION: BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.

Immune checkpoint inhibitors in gastrointestinal malignancies: what can we learn from experience with other tumors?

Gastrointestinal (GI) malignancies are some of the most common cancers worldwide with high rates of morbidity and mortality. Immune checkpoint inhibitors have afforded additional treatment options for patients, but their success has been limited. Conversely, in other tumor types such as lung cancer, melanoma and renal cell carcinoma, treatment strategies with immune checkpoint inhibitors have propelled those agents into the front lines of treatment. Strategies utilized include combining immune checkpoint inhibitors with chemotherapy, other checkpoint inhibitors, and targeted therapy. In this review, we analyze combination strategies employed in other tumor types to help identify current and future approaches toward improving outcomes with immunotherapy in GI malignancies.

Temporal trends from 1986 to 2008 in overall survival of small cell lung cancer patients.

OBJECTIVES: An assessment of temporal trends in patient survival is important to determine the progress toward patient outcomes and to reveal where advancements must be made. This study assessed temporal changes spanning 22years in demographics, clinical characteristics, and overall survival of small cell lung cancer (SCLC) patients. MATERIALS AND METHODS: This analysis included 1032 SCLC patients spanning two time-periods from the H. Lee Moffitt Cancer Center and Research Institute: 1986-1999 (N=410) and 2000-2008 (N=622). Kaplan-Meier survival curves and log-rank statistics were used to assess survival rates across the two time-periods and multivariable Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The overall 5-year survival rate significantly increased from 8.3% for the 1986-1999 time-period to 11.0% (P<0.001) for the 2000-2008 time-period, and the median survival time increased from 11.3months (95% CI 10.5-12.7) to 15.2months (95% CI 13.6-16.6). We also observed significant increases in stage-specific median survival times and survival rates across the two time-periods. A multivariable Cox proportional hazards model for the entire cohort revealed significant increased risk of death for patients diagnosed in 1986-1999 (HR=1.29; 95% CI 1.11-1.49), patients diagnosed between 60 and 69years of age (HR=1.33; 95% CI 1.04-1.49) and over 70years of age (HR=1.63; 95% CI 1.26-2.11), men (HR=1.33; 95% CI 1.16-1.53), patients with no first course treatment (HR=2.17; 95% CI 1.57-3.00) and extensive stage SCLC (HR=2.79; 95% CI 2.35-3.30). CONCLUSION: This analysis demonstrated significant improvements in overall and stage-specific median survival times and survival rates of SCLC patients treated at the Moffitt Cancer Center from 1986 to 2008.