Patient-reported Symptom Outcomes and Microsatellite Instability in Patients With Metastatic Colorectal Cancer

In patients with metastatic colorectal cancer, microsatellite instability was associated with a greater symptom burden, and high levels of CpG island methylator subtype were associated with greater pain. The role of microsatellite instability associated tumor features, including histologic and immune features in potentially increasing the symptom burden in metastatic colorectal cancer warrants further investigation. Background: The survival of patients with metastatic colorectal cancer (mCRC) is influenced by the genetic and epigenetic changes that might influence the patient experience of symptom burden. Understanding the association of molecular changes with the symptom burden could help clinicians gain insight into the molecular basis of symptom burden and improve treatment tolerance. To date, no studies have compared the patient-reported symptom burden with these molecular subsets among patients with mCRC. Patients and Methods: We recruited patients with mCRC that was refractory to >= 1 line of therapy who had been enrolled in the Assessment of Targeted Therapies Against Colorectal Cancer trial at The University of Texas MD Anderson Cancer Center. All patients completed a baseline gastrointestinal symptom inventory MD Anderson Symptom Inventory, gastrointestinal). The symptom burden across key demographic variables and molecular changes, including CRC-associated mutations, microsatellite instability (MSI) status, and the CpG island methylator phenotype (CIMP) were compared using chi(2) tests. Association of the symptom burden with overall survival was examined using Cox regression models. Results: Patients with an MSI-high (MSI-H) phenotype reported greater pain (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.61-5.84), fatigue (OR, 2.78; 95% CI, 1.41-5.49), sleep (OR, 2.52; 95% CI, 1.32-4.08); and drowsiness (OR, 2.51; 95% CI, 1.32-4.78) compared with microsatellite stable patients. Patients with an MSI-H phenotype also had greater odds of overall symptom burden (OR, 2.48; 95% CI, 1.29-4.74) compared with microsatellite stable patients. The CIMP-high patients experienced greater odds of pain compared with the CIMP-negative patients (OR, 1.72; 95% CI, 1.06-2.80). A greater overall symptom burden was associated with poor overall survival (hazard ratio, 1.42; 95% CI, 0.98-2.06]), although the difference was not significant (P = .06). Conclusion: Correlation of MSI-H-associated tumor features with the symptom burden could help provide a better understanding of underlying mechanisms associated with our findings. (C) 2019 Elsevier Inc. All rights reserved.