Commentary: Comparative efficacy and safety of non-pharmacological interventions on treatment induced xerostomia in head and neck cancer patients: a systematic review and network meta-analysis

Abstract

I read with interest the recently published network meta-analysis evaluating interventions for treating radiation-induced xerostomia in head and neck cancer patients (1). The authors are to be congratulated for embarking on a methodologically intensive synthesis of comparative interventions aimed at this clinically burdensome sequela of radiotherapy. Because xerostomia considerably impairs patients' quality of life and adherence to oncologic treatment regimens, systematic efforts toward identifying optimal interventions are of utmost relevance. On close scrutiny, however, several important issues arise with respect to heterogeneity among included interventions While some of these issues were acknowledged as limitations in the original article, their methodological and clinical implications warrant further elaboration, particularly given the reliance on SUCRA-based hierarchies for informing practice. With explicit inclusion criteria of patient developing xerostomia post radiation in the study (1), trials investigating both preventive (2-4) , and therapeutic modalities were included in the network metaanalysis (NMA) without specification of their mechanistic or clinical intent. For example, photobiomodulation, pilocarpine, and acupuncture may have been administered as prophylaxis before or during radiotherapy or as treatment for established xerostomia. Such conflation undermines the internal validity of pooled estimates, as these strategies target divergent pathophysiological windows: prophylaxis targets the prevention of insult to the salivary glands, while treatment involves the modulation of residual gland function or neurostimulation following injury. Additional methodological concern in this meta-analysis is the inclusion of studies evaluating xerostomia of other etiologies rather than radiation, introducing significant clinical and pathophysiological heterogeneity. For instance, Aagaard et al. (5)