Radiation-induced Xerostomia In Patients Research Articles

Marrow Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): Study Protocol for a Phase I Dose Escalation Trial of Patients with Xerostomia after Radiation Therapy for Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Xerostomia, or dry mouth, is a common side effect of head neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are a viable cell-based therapy for xerostomia. Adult stem cells are the ultimate source for replenishment of salivary gland tissue and the secretome of BM-MSCs may allow for the regeneration of salivary gland stem cells after radiation. We have undertaken FDA IND enabling studies demonstrating the phenotype, functionality, and secretome of interferon gamma (IFNγ) stimulated BM-MSCs taken from patients with head and neck cancer who have undergone radiation. Previous clinical trials with MSCs often required injection of MSCs rapidly after expansion, without cryopreservation. However this is unrealistic for patient care where patients are traveling for therapy or may require multiple injections of MSCs. Cryopreservation allows for a more inclusive therapy but can result in cellular injury or immune dysfunction. Stimulating the BM-MSCs with IFNγ prior to cryopreservation has been shown to prevent this. Here we present the protocol of MARSH, a first-in-human clinical trial of bone marrow derived, interferon gamma activated BM-MSCs for the treatment of radiation-induced xerostomia. <h3>Materials/Methods</h3> This single-center phase I dose-escalation with expansion cohort, study will assess the safety and tolerability of BM-MSCs for treatment of radiation-induced xerostomia in patients who had head and neck cancer. This is a 2-part trial. The first is a phase I trial of unilateral injection of MSCs into the submandibular gland of 6 patients to demonstrate safety. The second part is a phase I dose escalation study with a 3+3 design with staggered enrollment. A total of 21-30 subjects (9-18 in phase I study, 12 in expansion cohort) will be enrolled. The primary endpoint is determining the recommended phase 2 dose (RP2D) of interferon gamma stimulated BM-MSCs in order to conduct further studies on the efficacy of BM-MSCs. Patients will have their bone marrow aspirated, BM-MSCs expanded and stimulated with IFNγ, and then injected into the submandibular gland. The RP2D will be determined by dose limiting toxicities occurring within one month of BM-MSC injection. Secondary outcomes of salivary amounts, composition, ultrasound of salivary glands, and quality of life surveys will be taken at 3, 6, 12, and 24 month visits. <h3>Results</h3> Recruiting will start January 3, 2022. Subject accrual will occur over 2.5 years with the total duration of the trial expected to be approximately 4.5 years. <h3>Conclusion</h3> Autotransplantation of IFNγ-stimulated BM-MSCs in salivary glands post-radiation may provide an innovative remedy to treat xerostomia and restore quality of life.

Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): Study protocol for a phase 1 dose-escalation trial of patients with xerostomia after radiation therapy for head and neck cancer: MARSH: Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction

BackgroundXerostomia, or dry mouth, is a common side effect of head and neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Adult stem cells are the ultimate source for replenishment of salivary gland tissue. Bone marrow–derived mesenchymal stromal cells (BM-MSCs) are a viable cell-based therapy for xerostomia. We have undertaken studies enabling U.S. Food and Drug Administration Investigational New Drug status, demonstrating the normal phenotype, intact functionality, and pro-growth secretome of interferon-γ (IFNγ)-stimulated BM-MSCs taken from patients with head and neck cancer who have undergone radiation ± chemotherapy. Here we present the protocol of MARSH, a first-in-human clinical trial of bone marrow–derived, IFNγ-activated BM-MSCs for the treatment of radiation-induced xerostomia. MethodsThis single-center phase 1 dose-escalation with expansion cohort, non–placebo-controlled study will assess the safety and tolerability of BM-MSCs for the treatment of radiation-induced xerostomia in patients who had head and neck cancer. The phase 1 dose-escalation study will be a 3 + 3 design with staggered enrollment. A total of 21 to 30 subjects (9 to 18 in phase 1 study, 12 in expansion cohort) will be enrolled. The primary endpoint is determining the recommended phase 2 dose (RP2D) of IFNγ-stimulated BM-MSCs to enable further studies on the efficacy of BM-MSCs. Patients’ bone marrow will be aspirated, and BM-MSCs will be expanded, stimulated with IFNγ, and injected into the submandibular gland. The RP2D will be determined by dose-limiting toxicities occurring within 1 month of BM-MSC injection. Secondary outcomes of saliva amounts and composition, ultrasound of salivary glands, and quality of life surveys will be taken at 3-, 6-, 12-, and 24-month visits. DiscussionAutotransplantation of IFNγ-stimulated BM-MSCs in salivary glands after radiation therapy or chemoradiation therapy may provide an innovative remedy to treat xerostomia and restore quality of life. This is the first therapy for radiation-induced xerostomia that may be curative. Trial registrationWorld Health Organization International Clinical Trials Registry Platform: NCT04489732

Qualitative and dosimetric assessment of radiation-induced xerostomia in patients with oral cancers treated with 3DCRT versus IMRT: A prospective observational study

Background: Xerostomia is an important complication in patients with head-and-neck cancer treated with radiotherapy. It is caused by the radiation dose to the salivary glands situated in the lateral facial and submandibular regions, which are commonly included in or are close to the target volume.Objectives: Our primary objective was to evaluate xerostomia in patients treated with three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT). We also aimed to identify the risk factors for the development of xerostomia and the treatment-related and dosimetric parameters associated with xerostomia in patients with oral cancers receiving radiotherapy.Materials and Methods: We enrolled 100 patients with oral cancers between Sept 2015 and Apr 2018 who were planned for adjuvant radiotherapy. Patients were treated with unilateral portals in 3DCRT or IMRT. Xerostomia was assessed using the Wake Forest National Cancer Institute Community Oncology Research Program Research Base (WF NCORP RB) # 97115 Questionnaire at baseline, treatment completion, and at 1, 4, and 7 months following the completion of radiotherapy. Detailed salivary gland dosimetric parameters including the minimum (Dmin), maximum (Dmax), and mean dose (Dmean) and other dose and volume parameters (e.g., D25, D50, D75, and V10–V60) were assessed through cumulative dose volume histograms (DVH). Multivariate analysis was performed to determine the factors associated with the development of xerostomia and assess the correlation with dosimetric parameters.Results: At a median follow-up of 20 (95% confidence interval [CI], 8–32) months, the V20, V25, V30, V40, V45, V50, V60, Dmin, and Dmean received by the ipsilateral parotid gland were significantly lower in patients treated with IMRT compared to those treated with 3DCRT (P < 0.001). After the completion of radiotherapy, the mean xerostomia scores at each follow-up were significantly lower in the patients who had received IMRT, compared to 3DCRT. At 7 months of completion of treatment, the mean score of xerostomia in the 3DCRT arm was 44.4, compared to 33.8 in the IMRT arm (P = 0.023). On multivariate analysis, Dmin, V30, V40, V45, V60, history of substance abuse, advanced age, and lower body weight were found to be associated with higher chances of xerostomia.Conclusion: Compared to 3DCRT, IMRT results in lower rates of xerostomia based on dosimetric as well as subjective analysis.

18FDG positron emission tomography mining for metabolic imaging biomarkers of radiation-induced xerostomia in patients with oropharyngeal cancer

PurposeHead and neck cancers radiotherapy (RT) is associated with inevitable injury to parotid glands and subsequent xerostomia. We investigated the utility of SUV derived from 18FDG-PET to develop metabolic imaging biomarkers (MIBs) of RT-related parotid injury. MethodsData for oropharyngeal cancer (OPC) patients treated with RT at our institution between 2005 and 2015 with available planning computed tomography (CT), dose grid, pre- & first post-RT 18FDG-PET-CT scans, and physician-reported xerostomia assessment at 3–6 months post-RT (Xero 3–6 ms) per CTCAE, was retrieved, following an IRB approval. A CT-CT deformable image co-registration followed by voxel-by-voxel resampling of pre & post-RT 18FDG activity and dose grid were performed. Ipsilateral (Ipsi) and contralateral (contra) parotid glands were sub-segmented based on the received dose in 5 Gy increments, i.e. 0–5 Gy, 5–10 Gy sub-volumes, etc. Median and dose-weighted SUV were extracted from whole parotid volumes and sub-volumes on pre- & post-RT PET scans, using in-house code that runs on MATLAB. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test differences pre- and post-RT. Results432 parotid glands, belonging to 108 OPC patients treated with RT, were sub-segmented & analyzed. Xero 3–6 ms was reported as: non-severe (78.7%) and severe (21.3%). SUV- median values were significantly reduced post-RT, irrespective of laterality (p = 0.02). A similar pattern was observed in parotid sub-volumes, especially ipsi parotid gland sub-volumes receiving doses 10–50 Gy (p < 0.05). Kruskal-Wallis test showed a significantly higher mean RT dose in the contra parotid in the patients with more severe Xero 3-6mo (p = 0.03). Multiple logistic regression showed a combined clinical-dosimetric-metabolic imaging model could predict the severity of Xero 3-6mo; AUC = 0.78 (95%CI: 0.66–0.85; p < 0.0001). ConclusionWe sought to quantify pre- and post-RT 18FDG-PET metrics of parotid glands in patients with OPC. Temporal dynamics of PET-derived metrics can potentially serve as MIBs of RT-related xerostomia in concert with clinical and dosimetric variables.

A Risk Prediction Model by LASSO for Radiation-Induced Xerostomia in Patients With Nasopharyngeal Carcinoma Treated With Comprehensive Salivary Gland-Sparing Helical Tomotherapy Technique.

ObjectiveThis study aimed to develop a least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) model to predict radiation-induced xerostomia in patients with nasopharyngeal carcinoma (NPC) treated with comprehensive salivary gland–sparing helical tomotherapy technique.Methods and MaterialsLASSO with the extended bootstrapping technique was used to build multivariable NTCP models to predict factors of patient-reported xerostomia relieved by 50% and 80% compared with the level at the end of radiation therapy within 1 year and 2 years, R50-1year and R80-2years, in 203 patients with NPC. The model assessment was based on 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC).ResultsThe prediction model by LASSO with 10-fold cross-validation showed that radiation-induced xerostomia recovery could be predicted by prognostic factors of R50-1year (age, gender, T stage, UICC/AJCC stage, parotid Dmean, oral cavity Dmean, and treatment options) and R80-2years (age, gender, T stage, UICC/AJCC stage, oral cavity Dmean, N stage, and treatment options). These prediction models also demonstrated a good performance by the AUC.ConclusionThe prediction models of R50-1year and R80-2years by LASSO with 10-fold cross-validation were recommended to validate the NTCP model before comprehensive salivary gland–sparing radiation therapy in patients with NPC.

Effect of True and Sham Acupuncture on Radiation-Induced Xerostomia Among Patients With Head and Neck Cancer

Radiation-induced xerostomia (RIX) is a common, often debilitating, adverse effect of radiation therapy among patients with head and neck cancer. Quality of life can be severely affected, and current treatments have limited benefit. To determine if acupuncture can prevent RIX in patients with head and neck cancer undergoing radiation therapy. This 2-center, phase 3, randomized clinical trial compared a standard care control (SCC) with true acupuncture (TA) and sham acupuncture (SA) among patients with oropharyngeal or nasopharyngeal carcinoma who were undergoing radiation therapy in comprehensive cancer centers in the United States and China. Patients were enrolled between December 16, 2011, and July 7, 2015. Final follow-up was August 15, 2016. Analyses were conducted February 1 through 28, 2019. Either TA or SA using a validated acupuncture placebo device was performed 3 times per week during a 6- to 7-week course of radiation therapy. The primary end point was RIX, as determined by the Xerostomia Questionnaire in which a higher score indicates worse RIX, for combined institutions 1 year after radiation therapy ended. Secondary outcomes included incidence of clinically significant xerostomia (score >30), salivary flow, quality of life, salivary constituents, and role of baseline expectancy related to acupuncture on outcomes. Of 399 patients randomized, 339 were included in the final analysis (mean [SD] age, 51.3 [11.7] years; age range, 21-79 years; 258 [77.6%] men), including 112 patients in the TA group, 115 patients in the SA group, and 112 patients in the SCC group. For the primary aim, the adjusted least square mean (SD) xerostomia score in the TA group (26.6 [17.7]) was significantly lower than in the SCC group (34.8 [18.7]) (P = .001; effect size = -0.44) and marginally lower but not statistically significant different from the SA group (31.3 [18.6]) (P = .06; effect size = -0.26). Incidence of clinically significant xerostomia 1 year after radiation therapy ended followed a similar pattern, with 38 patients in the TA group (34.6%), 54 patients in the SA group (47.8%), and 60 patients in the SCC group (55.1%) experiencing clinically significant xerostomia (P = .009). Post hoc comparisons revealed a significant difference between the TA and SCC groups at both institutions, but TA was significantly different from SA only at Fudan University Cancer Center, Shanghai, China (estimated difference [SE]: TA vs SCC, -9.9 [2.5]; P < .001; SA vs SCC, -1.7 [2.5]; P = .50; TA vs SA, -8.2 [2.5]; P = .001), and SA was significantly different from SCC only at the University of Texas MD Anderson Cancer Center, Houston, Texas (estimated difference [SE]: TA vs SCC, -8.1 [3.4]; P = .016; SA vs SCC, -10.5 [3.3]; P = .002; TA vs SA, 2.4 [3.2]; P = .45). This randomized clinical trial found that TA resulted in significantly fewer and less severe RIX symptoms 1 year after treatment vs SCC. However, further studies are needed to confirm clinical relevance and generalizability of this finding and to evaluate inconsistencies in response to sham acupuncture between patients in the United States and China. ClinicalTrials.gov identifier: NCT01266044.

Relationship between radiation-induced xerostomia and the volume of parotid glands exposed in radiotherapy for nasopharyngeal carcinoma

Objective To evaluate the relationship between the volume of parotid glands and radiation-induced xerostomia in patients with nasopharyngeal carcinoma (NPC). Methods A total of 199 patients with NPC who were admitted to our hospital from 2015 to 2016 were enrolled as subjects. According to the initial volume of parotid glands, all patients were divided into large parotid group and small parotid group. The incidence of xerostomia after radiotherapy and dosimetric parameters were compared between the two groups. Comparison of categorical data was made by χ2 test. Comparison of continuous data was made by t-test or nonparametric test. Comparison of dose-volume histogram index was made by nonparametric test. Results There was no difference in the severity of xerostomia between the two groups at 3 and 6 months after radiotherapy. At one year after radiotherapy, the large parotid group had significantly milder xerostomia than the small parotid group (P=0.035). The small parotid group had a higher dose delivered to both parotid glands than the large parotid group. There was no difference in the mean dose to the submandibular gland between the two groups. Conclusions The initial volume of parotid glands is one of the influencing factors for the grade of xerostomia after radiotherapy. Patients with large parotid glands have better recovery from xerostomia after radiotherapy than those with small parotid glands. For patients with small parotid glands, more attention should be paid to reducing the dose to protect parotid glands. Key words: Nasopharyngeal neoplasms/intensity-modulated radiotherapy; Radiation-induce dxerostomia; Dosimetry

Experiences of xerostomia after radiotherapy in patients with head and neck cancer: A qualitative study.

To describe the experiences of radiation-induced xerostomia in patients with head and neck cancer. Xerostomia is the most commonly occurring complication during and following radiotherapy. It can persist for several months or years and can have a significant impact on patients' quality of life. This was a qualitative descriptive study. Semi-structured interviews were conducted with a sample of 20 participants. Inductive content analysis was used to analyse the qualitative data. Analysis of the manifest content identified five categories: communication problems, physical problems, psychosocial problems, treatment problems and relief strategies. The latent content was formulated into a theme: due to lack of information from professionals, the patients had to find their own solutions for their problems. Xerostomia is not only a biophysical symptom but also has a profound effect on the emotional, intellectual and sociocultural dimensions of life. The majority of patients continued to suffer from xerostomia and its associated symptoms after radiotherapy, in part, because of a lack of professional support, including the inability of nurses to provide oral health care. Nurses need to be knowledgeable about the effects of radiotherapy on oral mucosa and about appropriate interventions. The healthcare system requires a symptom management platform for radiation-induced complications, to help patients, their families and healthcare professionals obtain information about self-care, treatments and relief strategies.

Randomized Trial of Vitamin C/E Complex for Prevention of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer.

The present study was conducted to determine the preventive efficacy of vitamin C/E complex supplementation for radiotherapy (RT)-induced xerostomia in patients with head and neck cancer. Prospective, double-blinded, randomized, placebo-controlled study. A single tertiary referral institution. The trial group (n = 25) received antioxidant supplements (100 IU of vitamin E + 500 mg of vitamin C) twice per day during RT, while the control group (n = 20) received an identical placebo. Pre-RT and 1 and 6 months post-RT, patient-reported xerostomia questionnaires, observer-rated xerostomia score, and salivary scintigraphy were serially obtained to compare xerostomia severity between the 2 groups. The trial group showed greater improvements in xerostomia questionnaire and score at 6 months post-RT when compared with those at 1 month post-RT (P = .007 and .008, respectively). In contrast, the control group showed no changes between 1 and 6 months post-RT. By salivary scintigraphy, there was no difference in maximal accumulation or ejection fraction between the 2 groups. However, the trial group maintained significantly better oral indices at the prestimulatory (P = .01) and poststimulatory (P = .009) stages at 1 month post-RT, compared with the control group. At the final follow-up, there was no difference in overall survival and disease-free survival between the 2 groups. Our data suggest that short-term supplementation with an antioxidant vitamin E/C complex exerts a protective effect against RT-induced xerostomia.

Is Pilocarpine Effective in Preventing Radiation-Induced Xerostomia? A Systematic Review and Meta-analysis

To evaluate the efficacy of concomitant administration of pilocarpine on radiation-induced xerostomia in patients with head and neck cancers. The PubMed, Web of Science, Cochrane Library, and ClinicalTrials were searched to identify randomized, controlled trials studying the effect of concomitant administration of pilocarpine for radiation-induced xerostomia. Included trials were systematically reviewed, and quantifiable outcomes were pooled for meta-analysis. Outcomes of interest included salivary flow, clinician-rated xerostomia grade, patient-reported xerostomia scoring, quality of life, and adverse effects. Six prospective, randomized, controlled trials in 8 articles were included in this systematic review. The total number of patients was 369 in the pilocarpine group and 367 in the control group. Concomitant administration of pilocarpine during radiation could increase the unstimulated salivary flow rate in a period of 3 to 6 months after treatment, and also reduce the clinician-rated xerostomia grade. Patient-reported xerostomia was not significantly impacted by pilocarpine in the initial 3 months but was superior at 6 months. No significant difference of stimulated salivary flow rate could be confirmed between the 2 arms. Adverse effects of pilocarpine were mild and tolerable. The concomitant administration of pilocarpine during radiation increases unstimulated salivary flow rate and reduces clinician-rated xerostomia grade after radiation. It also relieves patients' xerostomia at 6 months and possibly at 12 months. However, pilocarpine has no effect on stimulated salivary flow rate.

Long-term effect of submandibular salivary gland transfer on radiation-induced xerostomia in patients with nasopharyngeal carcinoma

Objective:To investigate the long-term effect of submandibular salivary gland transfer on xerostomia induced by radiation in patients with nasopharyngeal carcinoma(NPC).Methods:A total of 70 eligible patients with NPC were divided into the test group(36 cases)and the control group(34 cases).In the test group,the submandibular salivary glands were transferred to the submental space before conventional radiotherapy (XRT)and shielded during XRT.Submandibular gland function and salivary fluid before and after radiotherapy, questionnaire of xerostomia at 60 months after XRT,and 5-year survival rate were compared between the two groups.Results:At 5 years after XRT,the trapping and excretion function of submandibular glands were significantly better in the test group(P=0.000 and P=0.000,respectively).The mean weight of saliva after XRT was greater in the test group than in the control group(1.65gvs.0.73g,P=0.000).Incidence of moderate to severe degree of xerostomia was significantly lower in the test group than in the control group (12.9%vs.78.6%,P=0.000).No significant difference was found in 5 year survival rate between the two groups(86.1%vs.82.4%,P0.05).Conclusion:Submandibular gland transfer procedure is safe for NPC patients. It can prevent XRT induced xerostomia and improve the quality of life of NPC patients.

Magnetic Resonance Sialography to Evaluate Radiation-Induced Xerostomia in Patients With Early-Stage Nasopharyngeal Carcinoma

To investigate the value of magnetic resonance sialography (MRS) as a noninvasive tool to evaluate radiation-induced xerostomia after intensity-modulated radiation therapy (IMRT) for patients with nasopharyngeal carcinoma(NPC), and to investigate the changes of oral health-related quality of life (QOL) in these patients.

The Preventive and Therapeutic Effect of Acupuncture for Radiation-Induced Xerostomia in Patients With Head and Neck Cancer

Methods currently available to prevent and manage xerostomia which caused by radiotherapy in patients with head and neck caner have limited efficacy. Some studies suggest that acupuncture may be beneficial. The authors evaluated the preventive and therapeutic effect of acupuncture for radiation-induced xerostomia among patients with head and neck cancer. PUBMED, EMBASE, Cochrane Library, CBM, CAJD, Wan Fang database, and VIP Database for Chinese Technical Periodicals were electronically searched, in conjunction with further manual search for relevant articles. Studies that met the inclusion criteria were systematically evaluated. Three randomized controlled trials (RCTs) investigating the therapeutic effect of acupuncture were included. One RCT on the preventive effect of acupuncture was found. Because of the considerable variation among included studies, meta-analysis was not possible. Two included RCTs used placebo controls, and both observed significant improvement in the salivary flow rates between acupuncture and control groups. However, no significant differences were found. Three included RCTs suggested that acupuncture for radiation-induced xerostomia can improve patients' subjective symptoms. The only study evaluating the preventive effect of acupuncture for radiation-induced xerostomia showed positive changes in salivary flow rates (both unstimulated and stimulated) and dry mouth -related symptoms. Acupuncture treatment was well tolerated by all patients and no severe adverse effects were seen. Insufficient evidence is available to judge whether acupuncture is safe and whether it is effective in preventing or treating radiation-induced xerostomia. Significant research remains to be done before acupuncture can be recommended for routine use in radiation-induced xerostomia.

Acupuncture for the prevention of radiation-induced xerostomia in patients with head and neck cancer

The aim of this study was to evaluate the effectiveness of acupuncture in minimizing the severity of radiation-induced xerostomia in patients with head and neck cancer. A total of 24 consecutive patients receiving > 5000 cGy radiotherapy (RT) involving the major salivary glands bilaterally were assigned to either the preventive acupuncture group (PA, n = 12), treated with acupuncture before and during RT, or the control group (CT, n = 12), treated with RT and not receiving acupuncture. After RT completion, clinical response was assessed in all patients by syalometry, measuring the resting (RSFR) and stimulated (SSFR) salivary flow rates, and by the visual analogue scale (VAS) regarding dry mouth-related symptoms. Statistical analyses were performed with repeated-measures using a mixed-effect modeling procedure and analysis of variance. An alpha level of 0.05 was accepted for statistical significance. Although all patients exhibited some degree of impairment in salivary gland functioning after RT, significant differences were found between the groups. Patients in the PA group showed improved salivary flow rates (RSFR, SSFR; p < 0.001) and decreased xerostomia-related symptoms (VAS, p < 0.05) compared with patients in the CT group. Although PA treatment did not prevent the oral sequelae of RT completely, it significantly minimized the severity of radiation-induced xerostomia. The results suggest that acupuncture focused in a preventive approach can be a useful therapy in the management of patients with head and neck cancer undergoing RT.

Submandibular salivary gland transfer for the prevention of radiation‐induced xerostomia in patients with nasopharyngeal carcinoma: 5‐Year outcomes

Our aim in this study was to investigate the value of the submandibular salivary gland transfer procedure in prevention of radiation-induced xerostomia in patients with nasopharyngeal carcinoma (NPC). In all, there were 70 patients, consisting of a test group (36 patients) and a control group (34 patients) in a nonrandomized fashion. In the test group, the submandibular salivary gland was transferred to submental space before radiotherapy (XRT) and shielded. Salivary gland functions were evaluated by the amount of saliva and a quality of life questionnaire before and after XRT and 3 and 60 months after XRT. At 5 years, the trapping and excretion functions of salivary gland were significantly better in the test group (p = .000 and p = .000). The mean weight of saliva after XRT was heavier (1.65 g vs 0.73 g, p = .000), and the incidence of xerostomia was lower in the test group, with no difference in 5-year survival and neck nodal recurrence between the 2 groups. Salivary gland transfer procedure prevents XRT-induced xerostomia and improves quality of life of patients with NPC.

Oral Symptom Intensity, Health-Related Quality of Life, and Correlative Salivary Cytokines in Adult Survivors of Hematopoietic Stem Cell Transplantation with Oral Chronic Graft-versus-Host Disease

Oral chronic graft-versus-host disease (cGVHD) is a frequent, clinically significant sequela of allogeneic hematopoietic stem cell transplantation (HSCT). This study was designed to elucidate relationships among clinical characteristics of oral cGVHD and related oral pain and oral dryness, salivary proinflammatory cytokine interleukin (IL)-6 and IL-1alpha concentrations, and health-related quality of life (HRQL). An understanding of the characteristics and correlates of oral cGVHD manifestations and related symptoms, such as oral dryness, is fundamental to the development of therapeutic interventions. Oral cGVHD severity was assessed with the Oral Mucositis Rating Scale (OMRS). Oral pain and perceived intensity of oral dryness were self-reported via a visual analog scale and a numeric rating scale, respectively. HRQL was assessed with the Functional Assessment of Cancer Therapy-General (FACT-G). Salivary IL-1alpha and IL-6 concentrations were measured by enzyme-linked immunosorbent assay. All 42 adult subjects (59% males) had clinician-assessed oral cGVHD by the OMRS scale (mean score, 18.38 +/- 12.99; range, 2-46). Oral dryness (in 43% of subjects; mean OMRS score, 2.56 +/- 3.45; range, 0-10) was more prevalent than oral pain (8%; mean score, 0.13 +/- 0.47). Salivary IL-6 was associated with oral cGVHD severity (r = 0.49; P < .01), oral ulceration (r = 0.38; P = .04), and erythema (r = 0.63; P < .01). FACT-G total score and physical and emotional well-being subscale scores were meaningfully lower than U.S. population normative values. Participants with more severe oral cGVHD manifestations had significantly inferior social/family well being (r = -0.49; P < .01). Oral dryness was associated with higher salivary IL-1alpha (r = 0.41; P = .04) and, controlling for cGVHD severity, with lower HRQL (r = -0.41; P = .03). Subjects with moderate to severe oral dryness tended to report the poorest overall HRQL. This study provides preliminary evidence of the relationship between oral dryness and HRQL, the contribution of oral cGVHD to inferior HRQL, and the association between IL-6 and oral cGVHD severity, ulceration, and erythema. The high prevalence of oral dryness and its relationship to HRQL in a sample of subjects with oral cGVHD underscores the importance of improving our evaluation and management of this symptom in long-term survivors of allogeneic HSCT. The positive associations between IL-6 and oral cGVHD severity and erythema, as well as the positive trend with oral ulceration, warrant further exploration of this cytokine as a potential biomarker of active oral cGVHD.

Acupuncture for radiation-induced xerostomia in patients with cancer: a pilot study

Acupuncture for radiation-induced xerostomia in patients with cancer: a pilot study

Acupuncture for radiation‐induced xerostomia in patients with cancer: A pilot study

This pilot study evaluated if acupuncture can alleviate radiation-induced xerostomia among patients with cancer. Secondary objectives were to assess the effects of acupuncture on salivary flow and quality of life (QOL). Nineteen patients received acupuncture twice a week for 4 weeks. Xerostomia inventory (XI) and patient benefit questionnaire (PBQ) scores were significantly better after acupuncture on weeks 4 and 8 than at baseline (XI: p = .0004 and .0001; PBQ: p = .0004 and .0011, respectively). For QOL at weeks 4 and 8, there was a significant difference for questions related to head/neck cancer (p = .04 and .006, respectively). At week 8, there was a significant difference in physical well-being (p = .04). At weeks 5 and 8, there were significant differences in the total score (p = .04 and .03, respectively). Acupuncture was effective for radiation-induced xerostomia in this small pilot study. Further research is needed.

Radiation-induced xerostomia in patients with head and neck cancer: pathogenesis, impact on quality of life, and management

Radiation-induced xerostomia in patients with head and neck cancer: pathogenesis, impact on quality of life, and management

Open-Label, Long-Term Safety Study of Cevimeline in the Treatment of Postirradiation Xerostomia

To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.