BACKGROUND

Chemotherapy causes physiological, psychological, and social impairments in patients with cancer. Frailty reduces the effectiveness of chemotherapy and increases the toxicity associated with radiotherapy and chemotherapy, the possibility of chemotherapy failure, and adverse outcomes. However, factors affecting chemotherapy-related frailty in patients with cancer remain unclarified.

OBJECTIVE

This systematic review aimed to identify risk factors driving frailty progression during chemotherapy in patients with cancer.

METHODS

A comprehensive systematic search was conducted on PubMed, Web of Science, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP), and SinoMed for observational studies (cohort, cross-sectional, or case-control) on factors affecting the debility-of-chemotherapy stage in patients with cancers between the inception of the database and February 2025, with an updated search executed in May 2025. Literature screening, quality evaluation using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality checklist, and data extraction were conducted independently by 2 authors. Meta-analysis, effect size combination, sensitivity analysis, and publication bias analysis were performed using RevMan (version 5.4; The Cochrane Collaboration) and R (version 4.4.3; R Foundation).

RESULTS

The analysis comprised 14 studies (8 cross-sectional, 2 repeated cross-sectional, 3 cohort, and 1 mixed-design), including 3879 patients with cancer and 23 influencing factors. Methodological quality assessment using Agency for Healthcare Research and Quality (mean 8.8, SD 1.3, 95% CI 7.9-9.7; SE 0.4) and Newcastle-Ottawa Scale (mean 8.0, SD 1.0, 95% CI 6.7-9.3; SE 0.6) revealed 73% (8/11) of cross-sectional studies as high-quality. The meta-analysis showed a 35% (95% CI 22%-50%) prevalence of frailty during chemotherapy in these patients. Cancer stage (odds ratio 1.99, 95% CI 1.64-2.42), chemotherapy frequency (odds ratio 2.60, 95% CI 1.83-3.70), transfer (odds ratio 2.18, 95% CI 1.50-3.17), hemoglobin (odds ratio 0.29, 95% CI 0.18-0.47), white blood cell (odds ratio 0.37, 95% CI 0.21-0.65), comorbidity (odds ratio 1.93, 95% CI 1.30-2.86), and hypoproteinemia (odds ratio 1.74, 95% CI 1.31-2.30) were risk factors for frailty in patients at the chemotherapy stage.

CONCLUSIONS

Frailty during chemotherapy was strongly associated with advanced cancer stage, frequent treatment cycles, metastasis, anemia, leukopenia, comorbidities, and hypoproteinemia. Clinically actionable findings emphasized hemoglobin and albumin monitoring as preventive targets, while heterogeneity in assessment tools and population bias limited generalizability. The integration of frailty screening into chemotherapy workflows is urgent to mitigate treatment-related functional decline.