A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life.

PURPOSE: This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article. RESULTS: The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy. CONCLUSIONS: Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact.

PURPOSE: This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. RESULTS: Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. CONCLUSIONS: There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

Incidence of fever following invasive oral interventions in the myelosuppressed cancer patient.

Oral complications in cancer patients with chemotherapy-induced myelosuppression contribute to morbidity and mortality. However, guidelines for oral care to prevent such complications, including disorders involving the periodontium, are not clear. This study specifically analyzed the impact of a noninvasive oral examination versus invasive oral interventions (periodontal probing, dental scaling) prior to chemotherapy on subsequent development of fever and/or bacteremia in these patients. Medical and dental records were reviewed for 100 patients who had been assigned to receive either the invasive or noninvasive procedures prior to chemotherapy. Temperature values immediately before and up to 48 h after the oral intervention were recorded, and the occurrence of fever and/or bacteremia was documented for each group. There was no statistically significant difference in the incidence of fever and/or bacteremia between the two groups of patients. Although periodontal probing and dental scaling are procedures that invade mucosal barriers, such interventions did not appear significantly to affect the incidence of fever or bacteremia among persons in this study.

Periodontal disease and oral microbial successions during myelosuppressive cancer chemotherapy.

Factors contributing to the succession of opportunistic pathogens at oral sites, including the periodontium, during myelosuppressive chemotherapy are poorly understood. This study examined the relation of periodontal disease to qualitative and proportional shifts in the oral microflora of 21 acute nonlymphocytic leukemia patients (7 male and 14 female, mean age (range) = 51.0 (25-81 years) observed during standardized myelosuppressive regimens. Supra- and subgingival microbial plaque specimens were individually collected from 2 contralateral oral sites (distobuccal of teeth 1-6 and 3-6) in each participant at hospital admission (day 1) and during point of maximal myelosuppression (day 14). Periodontal disease indices obtained at day 1 included site-specific measures of attachment loss and clinical assessment of disease status. Using a residualized change score analysis, periodontal disease status and attachment loss were positively correlated with increases in the proportional recovery of Staphylococcus sp. from supragingival sites and total yeast from supra- and subgingival sites. When age-related covariation in the microbial shifts was controlled in the analysis, periodontal disease status and attachment loss demonstrated no significant correlation with increases in total yeast at supragingival sites. These findings suggest that host factors such as periodontal disease may contribute to patterns of oral microbial successions during cancer chemotherapy.

Effect of granulocytopenia on oral microbial relationships in patients with acute leukemia.

Risk for acute infection increases as granulocyte levels decrease secondary to myelosuppressive chemotherapy in patients with acute nonlymphocytic leukemia (ANLL). Acute exacerbations of concomitant inflammatory periodontal diseases can result in systemic infections in these patients. However, host-oral bacterial relationships in the periodontium in patients with ANLL are not well understood. Twenty-one adult patients with ANLL with periodontal disease ranging from gingivitis to severe periodontitis were studied. Supragingival and subgingival plaque specimens were collected before chemotherapy (prechemotherapy), and at a defined midpoint of myelosuppression (midchemotherapy; day 14). All specimens were extensively cultured both aerobically and anaerobically. Data were submitted to a partial correlational analysis, controlling for covariation relation to oral hygiene intervention and antibiotic administration. Levels of total yeast exhibited a significant association with Staphylococcus sp. at supragingival sites midchemotherapy (r = 0.68, p less than or equal to 0.05). Levels of total yeast also correlated positively with Pseudomonas aeruginosa at subgingival sites both prechemotherapy (r = 0.70, p less than or equal to 0.01) and midchemotherapy (r = 0.61, p less than or equal to 0.05). Significant correlations of levels of Veillonella sp. with Neisseria sp. and gram-negative enteric bacilli were observed in both supragingival (r = 0.95, 0.77, p values less than or equal to 0.01) and subgingival (r = 0.69, 0.61, p values less than or equal to 0.05) plaque specimens midchemotherapy but not prechemotherapy. These data suggest that potentially pathogenic bacteria occur in plaque simultaneous with granulocytopenia in these patients. Multiple mechanisms, including intergeneric coaggregation and other symbiotic relationships, may influence infectivity of the mixed plaque flora and thus contribute to the oral ecology observed in these patients.