Optimal Threshold of Pre-Treatment Hemoglobin Level as a Prognostic Biomarker for Survival Outcome in Patients with Head and Neck Cancer in the Era of Human Papillomavirus

Abstract

<h3>Purpose/Objective(s)</h3> Recent systematic reviews suggested that hemoglobin (Hgb) level may play a role as biomarker for survival outcome among patients with head and neck cancer. However, the optimal threshold for anemia and its role in a current human papillomavirus (HPV) era remain unclear. To address this knowledge gap, we performed an observational cohort study to investigate pre-treatment Hgb and its association with survival outcomes in patients with head and neck cancer treated with radiation therapy. <h3>Materials/Methods</h3> A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent radiation therapy from January 2005 to April 2021. Pre-radiation Hgb was evaluated as a continuous variable using restricted cubic splines (RCS), and the model-derived threshold was used to stratify patients into low and high Hgb. Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze overall survival (OS) and disease-specific survival (DSS). Logistic MVA was performed to identify variables associated with low Hgb level. Propensity score matching was used to construct matched pairs. A subgroup analysis was also performed among patients with available HPV data. <h3>Results</h3> Among a total of 753 patients, median follow up was 29.7 months (interquartile range 17.8-57.8). Cox MVA based on RCS showed a threshold of Hgb at 12.96, with worsening survival in a continuous fashion without plateau as Hgb decreases. Low Hgb was associated with worse OS (aHR 1.55, 95% CI 1.17-2.05, p=0.002) and DSS (aHR 1.79, 95% CI 1.28-2.51, p<0.001). Similar findings were observed in 178 matched pairs (OS: HR 1.47, 95% CI 1.05-2.06, p=0.03; DSS: HR 1.82, 95% CI 1.19-2.78, p=0.006). On logistic MVA, patients were more likely to have low Hgb if they were female, had a higher T staging, underwent induction chemotherapy or surgery prior to radiation therapy, and had feeding tubes placed. They were less likely to have low Hgb if they had a good performance status and HPV-associated head and neck cancer. Among 466 patients with available HPV data, low Hgb was associated with DSS (aHR 1.84, 95% CI 1.30-2.61, p<0.001), but not OS (aHR 1.32, 95% CI 0.89-1.95, p=0.16). <h3>Conclusion</h3> In this study, low Hgb was associated with worse survival outcomes even among those with available HPV data. Patients with significant primary disease burden, feeding tube placement, and poor performance status who underwent either induction chemotherapy or surgery were more likely to have low Hgb. Further studies would be warranted to investigate the role of Hgb to identify patients early with poor prognosis and tailor treatments based on their risk factors.