Incidence Of Xerostomia Research Articles

Dose–volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy

We investigated the factors that affect salivary function after head-and-neck radiotherapy (RT), including parotid gland dose-volume effects, potential compensation by less-irradiated gland tissue, and functional recovery over time. Sixty-five patients with head-and-neck tumors were enrolled in a prospective salivary function study. RT was delivered using intensity-modulated RT (n = 45), forward-planning three-dimensional conformal RT (n = 14), or three-dimensional conformal RT with an intensity-modulated RT boost (n = 6). Whole salivary flow was measured before therapy and at 6 months (n = 61) and 12 months (n = 31) after RT. A wide variety of dose-volume models to predict post-RT salivary function were tested. Xerostomia was defined according to the subjective, objective, management, analytic (SOMA) criteria as occurring when posttreatment salivary function was < 25% of the pretreatment function. Multivariate logistic regression analysis was used to assess the combined effect of dose-volume, patient-, and treatment-related factors. A significant correlation was observed between the relative quality-of-life scores and relative stimulated saliva values at 6 months after RT (Spearman's correlation coefficient [R(s)] = 0.46, p < 0.001). The dose-volume factors were by far the strongest correlates with stimulated saliva flow, although other factors showed modest significance in multimetric models (chemotherapy, gender, and Karnofsky performance status). Several fitted dose-volume models provided a good mathematical description of the data. Significant noise in the salivary measurements (repeated measurement coefficient of variation was 27% in normal subjects) precluded selection of any one of the models presented solely on the basis of the objective fit criteria. Nevertheless, the mean dose-exponential model, in which each parotid gland's relative salivary gland function equaled exp(-A x mean gland dose), with A equal to 0.054/Gy (68% confidence interval 0.052-0.059), provided a good representation of the data and was incorporated into our multimetric analysis. Using that model, we estimated that a mean parotid dose of 25.8 Gy, on average, was likely to reduce a single parotid gland's flow to 25% of its pretreatment value, regardless of the treatment delivery method. Significant correlations were observed between a logistic multivariate model (incorporating the mean dose-exponential equation, gender, and Karnofsky performance status) and stimulated saliva flow at 6 months (R(s) = 0.73), stimulated saliva flow at 12 months (R(s) = 0.54), and quality-of-life score at 6 months (R(s) = 0.35) after RT. Stimulated parotid salivary gland dose-volume models strongly correlated with both stimulated salivary function and quality-of-life scores at 6 months after RT. The mean stimulated saliva flow rates improved from 6 to 12 months after RT. Salivary function, in each gland, appeared to be lost exponentially at a rate of approximately 5%/1 Gy of mean dose. Additional research is necessary to distinguish among the models for use in treatment planning. The incidence of xerostomia was significantly decreased when the mean dose of at least one parotid gland was kept to < 25.8 Gy with conventional fractionation. However, even lower mean doses imply increased late salivary function.

Intensity-modulated radiotherapy: Is xerostomia still prevalent?

Conformal radiation with intensity-modulated radiotherapy (IMRT) is a technique that potentially can minimize the dose to salivary glands and thereby decrease the incidence of xerostomia. Precise target determination and delineation is most important when using salivary gland-sparing techniques of IMRT. Reduction of xerostomia can be achieved by sparing the salivary glands on the uninvolved oral cavity and keeping the mean parotid gland dose of less than 26 to 30 Gy as a planning criterion if the treatment of disease is not compromised and parotid function preservation is desired.

A forward-planned treatment technique using multisegments in the treatment of head-and-neck cancer

Purpose To describe in detail a forward-planned multisegment technique (FPMS) as an alternative treatment method for patients who are not suitable for inverse-planned intensity-modulated radiation therapy (IP-IMRT), or for situations where IP-IMRT is not available in a medical clinic. Methods and materials Between April 1995 and February 2002, 38 primary head-and-neck patients were treated using the FPMS technique, which has evolved over the past 7 years at our medical center. In the most recent version of the FPMS technique, which includes 5 patients examined in this analysis, the primary tumor and the upper neck nodes were treated with 7 gantry angles, including an anterior, 2 lateral, 2 anterior oblique, and 2 posterior oblique beams with a total of 13 beam shapes formed by multileaf collimators (MLC), called MLC segments. The shape of each MLC segment was carefully designed, and the associated weights were optimized through manual iterations. The lower neck nodes and the supraclavicular nodes were treated with a split-beam anterior field, matched to the inferior border of the FPMS plan at the isocenter. With an autosequencing delivery system, all fields, including dynamic wedges, can be automatically treated. The dosimetric accuracy of this technique was verified with a phantom plan and measured with an ionization chamber, as well as film dosimetry. A sample FPMS plan is described in detail, and the average results for the 5 patients treated with FPMS are retrospectively compared to results for similar patients treated with IP-IMRT. Results The gross tumor volume was prescribed to 70 Gy (2.12 Gy/fraction) at the 88% isodose line, whereas the clinical target volume received a dose of 59.4 Gy (1.8 Gy/fraction) at the 75% isodose line. The maximum dose to the brainstem and spinal cord was below 54 and 45 Gy, respectively, comparable to IP-IMRT. The mean dose to the parotid glands was 32 Gy with FPMS vs. 26 Gy with IP-IMRT. Average delivery time was shorter for FPMS (15 min) than IP-IMRT (30 min), whereas the planning time depended on the expertise of the planner. Dosimetric accuracy for FPMS and IP-IMRT plans using phantom measurements was similar, within 1% of the phantom plan. With a median follow-up of 31 months, there was no local-regional recurrence, and the incidence of xerostomia is reduced compared to conventional techniques. Conclusion FPMS achieved plans comparable to those for IP-IMRT and is an ideal alternative treatment technique for a center without the capabilities of IP-IMRT or for a patient who is not a suitable candidate, because of prolonged treatment time. The treatment outcomes from our clinical experience indicate that FPMS can achieve excellent local freedom from progression rates without causing excessive toxicity. Lastly, IP-IMRT plans should be comparable to, if not better than, FPMS plans in the treatment of head-and-neck cancer.

Salivary gland dysfunction: A review of systemic therapies

Xerostomia may result from salivary dysfunction secondary to a variety of conditions, including medications, autoimmune disease, and tumoricidal therapy. As the geriatric population increases, the incidence of xerostomia will increase and the oral manifestations will continue to be a challenge to the clinician. Common oral manifestations resulting from decreased salivary flow include increased dental caries, fungal infections, and dysphagia. Treatment for salivary gland dysfunction is currently limited because of a lack of controlled clinical trials. Medications that have been studied in clinical trials are emphasized in this article. The aim of this article is to briefly review salivary gland physiology and to summarize the suggested systemic treatment modalities for xerostomia that emphasize controlled clinical trials. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:156-62)

Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours.

Salivary gland scintigraphy with technetium-99m pertechnetate was used to follow changes in the excretion and uptake function of the major salivary glands until 1 year after irradiation. Twenty-five patients who received radiotherapy for head and neck tumours were included in the study. Seventy-nine salivary glands (39 parotid and 40 submandibular) were evaluated in relation to the average received radiation dose. Salivary gland scintigraphy was performed before and 1, 6 and 12 months after radiotherapy. For each gland the excretion response to carbachol, evaluated by calculation of the salivary excretion fraction (SEF), the cumulative gland uptake (CGU) and the absolute excreted activity (AEA) at various intervals after radiotherapy were compared with the baseline values. The excretion response decreased in 20 of 25 patients at 1 month after radiotherapy. One month after radiotherapy both SEF and AEA decreased significantly in relation to the radiation dose. These decreases in excretion parameters persisted during the follow-up period. Parotid excretion was affected significantly more than submandibular excretion. CGU values did not change significantly until 6 months after radiotherapy, but at 12 months a significant decrease related to radiation dose was observed. Xerostomia was assessed during radiotherapy and on the days of the scintigraphic tests. The incidence of xerostomia did not correspond to the effects observed in the scintigraphic studies. It is concluded that radiotherapy induces early and persistent impairment of salivary gland excretion, related to the radiation dose. This impairment is stronger in parotid glands than in submandibular glands.

A study on the effect of aging on salivary glands and xerostomia

To elucidate the effect of aging on salivary gland, age-related histological changes of parotid gland and age-related changes in the volume of total saliva at rest were evaluated. Histopath- ological investigation of parotid gland and sialometric analysis were also performed in subjects with xerostomia to elucidate the effect of aging on pathogenesis of xerostomia. Decrease in the number of acinus was histopathologically studied in several microscopic fields, and the rate of remaining acinus was evaluated as residual rate. Residual rate of acinus in parotid gland in normal subjects aged 11-40 (N=9) and in those aged 51-80 (N=15) without apparent signs and symptoms of abnormalities of salivary gland were 88.4±7.1% and 67.9±16.9% respectively.Aging caused statistically significant atrophy of parotid parenchym (P〈0.05). Total saliva at rest in the male and the female subjects aged 11-40 were 3.3±2.5 (N=75) and 3.0±2.1 (N=75) respectively and were 2.8±2.0 (N=75) and 1.6±1.5 (N=75) in the male and the female subjects aged 51-80 respectively. Aging caused significant decrease of the volume of total saliva at rest only in female subjects (P〈0.05). Apparent sex and age differences were observed in incidence of xerostomia due to atrophy of salivary parenchym which showed significant age-related increase only in female subjects after menopause. Histopathological findings of parotid gland in these patients were characterized by decreased number of acinus with concomitant increase of fat tissue.Residual rate of acinus in parotid gland (N=13) ranged between 28 and 59% (46.2±9.3). Electronmicroscopically fat droplets, lipofuscin granules and vacuoles were occasionally observed in cytoplasm of remaining acinus cells and peripheral duct epithelial cells. However these degenerative changes were generally mild and majority of individual remaining acinus was assumed ultrastructurally to restore normal function. Pathogenesis of xerostomia due to parenchymal atrophy of salivary gland is related closely with the effect of aging not only on salivary gland but also probably on reproductive hormonal system.Incidence of drug-induced xerostomia also showed age-related increase in female subjects. Residual rate of acinus in parotid gland of these patients (N=14) ranged between 18 and 70% (50.4±15.3). Incidence of various systemic diseases which require medications increase with aging. In many patients with drug-induced xerostomia, salivary gland had undergone various degree of age-related parenchymal atrophy. In these subjects mild secretory suppression induced by medication is assumed to result in sufficient decrease of salivary secretion to cause clinical symptoms.