title: Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis.
abstract: Salivary gland hypofunction is a common and permanent adverse effect of radiotherapy to the head and neck. Randomised trials of available treatment modalities have produced unclear results and offer little reliable guidance for clinicians to inform evidence-based therapy. We have undertaken this systematic review and meta-analysis to estimate the effectiveness of available interventions for radiotherapy-induced xerostomia and hyposalivation.
  
  
  
  We searched MEDLINE, Cochrane Central, EMBASE, AMED, and CINAHL database through July 2016 for randomised controlled trials comparing any topical or systemic intervention to active and/or non-active controls for the treatment of radiotherapy-induced xerostomia. The results of clinically and statistically homogenous studies were pooled and meta-analyzed.
  
  
  
  1732 patients from twenty studies were included in the systematic review. Interventions included systemic or topical pilocarpine, systemic cevimeline, saliva substitutes/mouthcare systems, hyperthermic humidification, acupuncture, acupuncture-like transcutaneous electrical nerve stimulation, low-level laser therapy and herbal medicine. Results from the meta-analysis, which included six studies, suggest that both cevimeline and pilocarpine can reduce xerostomia symptoms and increase salivary flow compared to placebo, although some aspects of the relevant effect size, duration of the benefit, and clinical meaningfulness remain unclear. With regard to interventions not included in the meta-analysis, we found no evidence, or very weak evidence, that they can reduce xerostomia symptoms or increase salivary flow in this population.
  
  
  
  Pilocarpine and cevimeline should represent the first line of therapy in head and neck cancer survivors with radiotherapy-induced xerostomia and hyposalivation. The use of other treatment modalities cannot be supported on the basis of current evidence.
authors.affiliation: University College London, UCL Eastman Dental Institute, London, UK. Electronic address: v.mercadante@ucl.ac.uk.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mercadante
authors.affiliation: Dental Services, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Arwa
authors.initials: A
authors.lastname: Al Hamad
authors.affiliation: University of Milan, Department of Biomedical, Surgical and Dental Sciences, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lodi
authors.affiliation: University College London, UCL Eastman Dental Institute, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Porter
authors.affiliation: University College London, UCL Eastman Dental Institute, London, UK; NIHR University College London Hospitals Biomedical Research Centre, London, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fedele
mesh_terms: D006801:Humans; D011878:Radiotherapy / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012472:Salivation / Q000528:radiation effects*; D014987:Xerostomia / Q000209:etiology*
keywords: Acupuncture; Radiotherapy; Saliva; Sialogogue; Xerostomia