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

Clin Colorectal Cancer. 2020 Mar;19(1):48-56.e2. doi: 10.1016/j.clcc.2019.10.006. Epub 2019 Oct 23.

Abstract

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 χ2 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.

Keywords: Epigenetics; Microsatellite instability; Patient reported outcomes; Survivorship; Symptom burden.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • CpG Islands / genetics
  • DNA Methylation
  • Drug Resistance, Neoplasm / genetics
  • Epigenesis, Genetic
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Mutation
  • Patient Reported Outcome Measures*
  • Severity of Illness Index*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor