Frailty and Biomarkers in Head and Neck Cancer

Abstract

This thesis presents research that investigates the relation of frailty and rapidly available biomarkers such as sarcopenia and the neutrophil-to-lymphocyte ratio (NLR) in cancer patients In chapter 2 this thesis describes a review of the different measurement methods to diagnose sarcopenia, its predictive and prognostic value and its association with frailty. Chapter 3 of this thesis presents the association between sarcopenia, defined as reduced handgrip strength and loss of skeletal muscle mass, and the Geriatrics 8 (G8) screening tool for frailty. However, to investigate the potential value of sarcopenia as screening tool, the direct relation between sarcopenia and frailty had to be investigated. In chapter 4 the association between sarcopenia and frailty, diagnosed by the GA (based on the multiple deficit model of frailty, as recommend by the SIOG as the gold standard) and by the Fried criteria, and associations between sarcopenia and frailty screenings tests, such as the Groningen Frailty Indicator (GFI) were evaluated. In chapter 5 we investigated whether the specificity of the G8 could be improved (while maintaining good sensitivity) when combined with sarcopenia. Changes in the immunological system could be another pillar of developing frailty. The relation of frailty and several cytokines have been investigated and have been independently associated with frailty. One of the easiest available immunological biomarkers for frailty suggested in literature is the neutrophil-to-lymphocyte ratio (NLR). However, the relationship of NLR with frailty and sarcopenia in patients with HNC is not investigated. Therefore, in chapter 6 we investigated the relationships between NLR, sarcopenia, and frailty (defined by GA), and assess the potential of NLR for frailty screening in older patients with HNC. In conclusion the findings of this thesis show that biomarkers NLR and sarcopenia may be a component of frailty, but frailty is more multifaceted. The general concept of frailty goes beyond physical factors and encompasses social and psychological dimensions as well, including social support and cognitive function. Therefore, both biomarkers cannot be used as a tool for diagnosing frailty and it is recommended to still use the G8 for selecting HNC patients for CGA. However, the use of these biomarkers could contribute to improve the perioperative conditions of HNC patients who are ‘prefrail’ through prehabilitation.