Prognostic value of hemoglobin-to-red cell distribution width ratio in cancer: a systematic review and meta-analysis

Plain language summary Hemoglobin and red cell distribution width are both widely available and routinely measured in blood tests. The hemoglobin-to-red cell distribution width ratio has recently been introduced as a new potential marker for predicting the clinical course and outcome in patients with various types of cancer. In the present meta-analysis of 11 studies representing 2985 cancer patients, the authors showed that cancer patients with a lower hemoglobin-to-red cell distribution width ratio were more likely to experience disease progression or relapse and had a greater mortality risk. Background: The hemoglobin-to-red cell distribution width ratio (HRR) has emerged as a novel integrative biomarker predictive of overall and disease-free survival in cancer patients. This study aimed to investigate the prognostic significance of HRR in the cancer population. Methods: A literature search was performed in PubMed/MEDLINE from inception to 1 July 2021, to collect studies assessing the prognostic value of HRR in cancer patients. The primary and secondary end points were all-cause mortality and occurrence of disease progression or relapse, respectively. A meta-analytic approach was employed to estimate the pooled hazard ratio with 95% CI by fitting random-effects models. Results: A total of 11 retrospective cohort studies representing 2985 cancer patients were included. Compared with patients with high HRR, patients with low HRR had a twofold risk of all-cause mortality (hazard ratio: 2.29; 95% CI: 1.76-2.98; p < 0.0001). There was substantial heterogeneity in the association of HRR with mortality across the studies (I-2: 66.8%; 95% CI: 35.3-82.9%; p = 0.0014). Similarly, low HRR was associated with a twofold risk of disease progression or relapse (hazard ratio: 2.19; 95% CI: 1.74-2.76; p < 0.0001). No significant heterogeneity was observed (I-2: 16.8%; 95% CI: 0.0-60.7%; p = 0.30). Conclusion: Low HRR was associated with mortality and disease progression or relapse in patients with cancer. Further studies are required to standardize the HRR cutoff value and investigate whether HRR can be incorporated into risk assessment models for predicting adverse prognosis in cancer patients.