Viviana Avila-Gnau General Dentist
Head and neck cancer treatments induce salivary gland hypofunction and xerostomia; reducing the radiation dose to the salivary glands can minimize effects on oral tissues. In particular, new/optimized approaches can be used to further reduce the dose to the parotid glands as well as the submandibular and minor salivary glands, all of which are major contributors to moistening of oral tissues.
Minimizing salivary gland exposure to common treatments for head and neck cancer treatment is a must, since the xerostomia and salivary gland hypofunction that may result will negatively impact oral health.
In patients undergoing various head and neck cancer therapies, what is the impact of the treatment on salivary gland hypofunction prevalence and severity, xerostomia prevalence and severity, and patient oral health-related quality of life (QoL)?
The authors searched two databases for articles published in English between 1990 and 2008. They included studies containing original data on prevalence of salivary gland hypofunction and/or xerostomia as well as the economic burden, impact on oral health-related QoL, or management strategies of salivary gland hypofunction and/or xerostomia in patients with cancer who were undergoing head and neck radiotherapy, chemotherapy, or combined treatment modalities. The authors excluded systematic and non-systematic reviews, studies that did not report actual data on xerostomia/salivary gland hypofunction, studies that reported data from previous publications or with a relevant follow-up publication, phase I and II studies, opinion papers, case reports, or articles from the 1990 NCI monographs based on the 1989 NIH development Consensus Conference on oral complications. Two independent reviewers (from a pool of 23 expert reviewers) evaluated each article, judging data quality based on sources of bias, representativeness, scale validity, and sample size. There is a companion citation (reference 14 in the systematic review) that describes the quality of the literature, the details of which are not available herein.
The authors found 184 articles that satisfied the inclusion criteria, which covered salivary gland hypofunction and xerostomia induced by conventional, 3-D conformal radiotherapy or intensity-modulated radiotherapy (IMRT) in patients with head and neck cancer, or those undergoing cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment and immunotherapy. The included study designs were two randomized controlled trials, 141 cohort studies, three case control studies, and 41 cross-sectional studies. Xerostomia is the most common and permanent complaint after conventional radiotherapy. Decreased salivary flow rates were seen within the first week of radiation treatment, and a further decrease in secretion was sometimes noted after completion of radiation therapy, with no recovery after a high dose of 60 gray units (Gy) to the salivary glands. Also, after IMRT, researchers observed an initial post-radiation decline in salivary secretion and xerostomia that lasted 1 to 3 months after treatment; however, some studies indicated potential gradual recovery over time (1 to 2 years). The weighted prevalence of xerostomia across all studies before, 1-3 months after, and >2 years after radiation therapy was 6.0% (95%CI = 0-3.9), 73.6% (95%CI = 58.9-88.4), and 85.3% (95%CI = 77.6-93.0), respectively. Incomplete improvement in xerostomia with parotid-sparing IMRT emphasizes the need to enhance protection of the submandibular glands, the greatest contributors to whole saliva during rest. Approximately 4-12 years after bone marrow transplantation, normal stimulated whole saliva secretion has been reported in children conditioned with chemotherapy, while conditioning regimens that include total body irradiation may result in a permanent reduction. Although the authors discussed various cancer therapies in addition to radiation therapy, the radiation therapy data are the most relevant.
The authors found no studies that assessed QoL in relation to salivary gland hypofunction or xerostomia as sequelae of cancer chemotherapy, conditioning total body irradiation/chemotherapy and hematopoietic stem cell transplantation, radioactive iodine treatment, or cancer therapies in children/adolescents.
Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck, depending on cumulative dose to the salivary gland tissue. Treatment focus should be on reducing the radiation dose to all of the salivary glands to minimize xerostomia and the detrimental effects on the oral tissues. The adverse effects of other radiation regimens (e.g., interstitional radiotherapy, radioactive iodine) and chemotherapy on salivary gland function was found to be much less severe, and chemotherapy-induced xerostomia found to be reversible after the end of treatment.
Source of Funding:
No support statement is provided in the paper.
Importance and Context:
Saliva facilitates tooth integrity, dilution of food detritus and bacteria, mechanical cleansing, antimicrobial activity, taste perception, formation of food bolus, mastication, swallowing, and speech as well as lubrication of mucosa. Hypofunction (objective evidence of reduced saliva) and xerostomia (subjective feeling of dry mouth) are significant during and following radiotherapy involving exposure of the major and minor salivary glands. Because the salivary glands are superficially located compared with most head and neck tumors, the ionization radiation affects them en route to treating the targeted tumor.
The authors reference a commonly accepted definition of “hyposalivation” as “pathological low saliva secretion with a resting whole saliva flow rate of no more than 0.1ml/min and/or a stimulated whole saliva flow rate of no more than 0.5 ml/min” (Sreebny LM (2000) Saliva in health and disease: an appraisal and update. Int Dent J 50:140-161). Patients with salivary gland hypofunction experience a direct impact on their daily activities and social interactions. Dry mouth also significantly increases caries risk, risk of developing oral infections, and oral mucosa discomfort and pain, and influences the ability to receive proper nutrition.
Strengths and Weaknesses of the Systematic Review:
The question that the authors set out to answer was quite broad, and while the types of studies that were excluded were clearly stated, the information about the studies that they included was limited to search words and main topics. The authors, who conducted the reviews, included 23 experts in relevant disciplines; they used calibration sessions to ensure uniformity, though their article search was limited to English, which could be considered a potential source of bias. The heterogeneity of diagnoses and treatment parameters and number of variables within studies resulted in difficulties in interpretation of the outcomes, so genuine differences in effects may have been obscured.
Strengths and Weaknesses of the Evidence:
The authors did not report quality or methods in this systematic review, but those details are available in the companion paper listed as reference 14 in the systematic review (Brennan MT, Elting LS, Spijkervet FKL (2010) Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO: Methodology and quality of the literature. Support Care Center (in press)). Based on a preponderance of prospective cohort studies with reasonable follow-up as appropriate for prognostic questions, the quality of evidence was generally good in accordance with SORT criteria, although the authors identified some confusion in the literature regarding the definitions of “salivary gland hypofunction” and “xerostomia”. They found that “xerostomia,” the subjective feeling of dry mouth, was often confused with and/or used as a synonym of “salivary gland hypofunction” or “hyposalivation,” the objective measure of decreased salivary secretion. Additionally, the authors noted substantial variation among studies regarding, for example, data reporting, saliva collection procedures, techniques to stimulate saliva flow, and timeframes during and after cancer treatment. Within studies, the authors found heterogeneity of cancer diagnoses and cancer treatment regimes.
Implications for Dental Practice:
As oral health professionals, we need to be able to provide care and manage the conditions that our patients who are undergoing cancer therapies face. Dentists should convey to other health professionals and personnel involved in cancer therapy delivery the importance of lowering the exposure to salivary glands when possible. There is also a need to develop neoplasm-focused delivery of specific radiation dosages with sparing of the normal tissue, which can reduce the cumulative effects of radiotherapy on the major and minor salivary glands and thus also reduce the prevalence and severity of hypofunction and xerostomia.