Chemotoxicity and Associated Risk Factors in Colorectal Cancer: A Systematic Review and Meta-Analysis

Chemotoxicity in colorectal cancer (CRC) patients impacts treatment compliance, survival, and quality of life. While clinician-reported chemotoxicity predicts rehospitalization and survival, a comprehensive understanding is lacking. This systematic review and meta-analysis studied chemotoxicity in CRC patients. The study found that 45.7% of patients experienced overall moderate-to-severe toxicities, with gastrointestinal toxicity (22.9%) and neuropathy or neutropenia (17.9%) being the most common. Risk factors included malnutrition, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low quality of life. Age was linked to neutropenia and gastrointestinal toxicity. Older adults had higher overall and gastrointestinal toxicities but lower neutropenia than younger adults. The study underscores the need for close monitoring and management of chemotoxicity in CRC patients. Community contributions have been instrumental in raising awareness about these issues, advocating for patient support, and future research to improve treatment toxicities in CRC. Abstract Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (beta: -1.44) and GI toxicity (beta:1.85) (p-values < 0.01). Older adults (>65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (p-values < 0.05). Conclusions. Our findings highlight the importance of closely monitoring and managing chemotoxicity in CRC patients receiving chemotherapy.