Salivary Gland Hypofunction and/or Xerostomia Induced by Nonsurgical Cancer Therapies: ISOO/MASCC/ASCO Guideline

Abstract

PURPOSE To provide evidence-based recommendations for prevention and management of salivary gland hypofunction and xerostomia induced by nonsurgical cancer therapies. METHODS Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials published between January 2009 and June 2020. The guideline also incorporated two previous systematic reviews conducted by MASCC/ISOO, which included studies published from 1990 through 2008. RESULTS A total of 58 publications were identified: 46 addressed preventive interventions and 12 addressed therapeutic interventions. A majority of the evidence focused on the setting of radiation therapy for head and neck cancer. For the prevention of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer, there is high-quality evidence for tissue-sparing radiation modalities. Evidence is weaker or insufficient for other interventions. For the management of salivary gland hypofunction and/or xerostomia, intermediate-quality evidence supports the use of topical mucosal lubricants, saliva substitutes, and agents that stimulate the salivary reflex. RECOMMENDATIONS For patients who receive radiation therapy for head and neck cancer, tissue-sparing radiation modalities should be used when possible to reduce the risk of salivary gland hypofunction and xerostomia. Other risk-reducing interventions that may be offered during radiation therapy for head and neck cancer include bethanechol and acupuncture. For patients who develop salivary gland hypofunction and/or xerostomia, interventions include topical mucosal lubricants, saliva substitutes, and sugar-free lozenges or chewing gum. For patients with head and neck cancer, oral pilocarpine and oral cevimeline, acupuncture, or transcutaneous electrostimulation may be offered after radiation therapy. Additional information can be found at www.asco.org/supportive-care-guidelines .

Transient Activation of Hedgehog Signaling Inhibits Cellular Senescence and Inflammation in Radiated Swine Salivary Glands through Preserving Resident Macrophages

“…The consequent long-term dry mouth severely exacerbates dental caries and periodontal disease and causes problems related to taste, sleep, and speech that severely impair the patient's quality of life. Current treatments for radiation-induced salivary hypofunction, such as artificial saliva and salivasecretion stimulators, can only provide partial and temporary relief since they are often of short duration, lack the protective effects of saliva, or have potentially significant adverse effects [5] The only preventive measure strongly recommended by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology/American Society of Clinical Oncology (MASCC/ISOO/ASCO) is limiting the cumulative dose and the irradiated volume of SGs [6], which might be infeasible for some HNC patients due to cost or efficacy concerns.…”

Application of Diffusion Kurtosis Imaging in Evaluating Acute Xerostomia in Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy

“…Since RT targets overlap residence of the salivary glands, apoptosis of acinar cells of irradiated glands inevitably leads to ablation of saliva output and xerostomia ( 6 ), a prevalent and long-lasting adverse effect of RT ( 2 , 7 – 9 ). Acute xerostomia within 3 months after RT was the most serious and the most difficult period ( 10 ) for patients because of the limited efficacy of treatment ( 2 ).…”

“…The major salivary glands, including parotid (PG), submandibular (SMG), and sublingual glands (SLG), are in charge of more than 90% saliva production ( 9 , 14 ). PG produces approximately 50% of the total volume of stimulated whole saliva while the majority of saliva is secreted by SMG and SLG under resting conditions ( 9 ).…”

“…The major salivary glands, including parotid (PG), submandibular (SMG), and sublingual glands (SLG), are in charge of more than 90% saliva production ( 9 , 14 ). PG produces approximately 50% of the total volume of stimulated whole saliva while the majority of saliva is secreted by SMG and SLG under resting conditions ( 9 ). Limiting radiation dose of the major glands through intensity-modulated RT (IMRT) and sparing SMG techniques have demonstrated a reduction in salivary gland hypofunction and xerostomia ( 6 , 15 , 16 ).…”

Preventing collateral damage

“…Few interventions exist to stop this side effect from emerging, aside from technical refinements that limit the exposure of the glands to radiation ( Mercadante et al, 2021 ). Now, in eLife, Songlin Wang and colleagues at Capital Medical University – including Xiaoyu Feng and Zhifang Wu as joint first authors – report a remarkably simple measure that may protect salivary glands during radiation therapy ( Feng et al, 2021 ).…”