Prevention Of Xerostomia Research Articles

Visceral flaps for oral cavity reconstruction and prevention of xerostomia in cancer patients: a case series and morphological study

Visceral flaps for oral cavity reconstruction and prevention of xerostomia in cancer patients: a case series and morphological study

Magnetic Resonance and CT Imaging Biomarkers for Prediction of Acute and Chronic Radiation-Induced Xerostomia

Xerostomia is a common adverse effect of radiation therapy at the head and neck area. Radiation-induced xerostomia can be severe and detrimental for the quality of life. Clinicians and radiologists have focused on the prevention of xerostomia as feasible, which has been significantly improved in the recent decades with the use of the contemporary radiation technology. However, radiation-induced xerostomia still remains one of the most devastating side effects of radiation therapy. Clinical risk factors have been identified, but the variation of its incidence and presentation has turned the focus on the investigation of parameters that would be able to predict the onset of acute or chronic xerostomia for each individual patient. Recently, potential imaging parameters and biomarkers are investigated in order for early prediction of the incidence and severity of xerostomia. Here, we compile the resulting imaging biomarkers as have been identified in the recent literature based on MRI and CT performed in correlation with radiation therapy. The identification of such biomarkers is very promising for the prevention and control of xerostomia in the head and neck radiation setting.

Effect of salivary gland cooling in 68Ga-PSMA uptake

Introduction: Techniques using PSMA radioligands have emerged as diagnostic and therapeutic alternatives in prostate cancer. Significant adverse events resulting from using beta-emitters such as 177Lu-PSMA for castration-resistant prostate cancer therapy include sialotoxicity and xerostomia. Sialotoxicity ranges from 8% mild to moderate up to 10% interruption of treatment, depending on the compound used, due to the physiological expression of PSMA in the salivary glands and consequent radioligand uptake. Cooling with icepacks emerged as a possible intervention to prevent this event. The rationale is that cold- induced vasoconstriction would lead to a reduction of the perfusion of the gland, similarly to scalp cooling applied in some chemotherapies. Although empirically used in European protocols, the efficacy of this technique was assessed in only one study, with no evidence of success. The objective of this work was to analyze the efficacy of salivary gland cooling in the reduction of PSMA radioligand uptake.Methodology: Unilateral cooling of the salivary glands was performed for 10 prostate cancer patients submitted to PET-CT with Ga68PSMA, a compound used for diagnostic purposes and validated mainly in biochemical recurrence scenario. For cooling, icepacks were coupled to a device that attached them to one of the patient's parotid gland. Cooling started 30 minutes before the injection of the radiopharmaceutical. The test was started 1h after the injection (acquisition t1), with an approximate duration of 30 minutes. A delayed image was made 4h after the injection (acquisition t4). The cooling was suspended just after the t1 acquisition. The packs were replaced every 30 minutes, and their temperature measured and recorded using infrared thermometers, for temperature standardization. Using OsiriX Dicom Viewer software, each of the glands (cooled parotid and control, cooled submandibular and control) was quantitatively assessed by the standardized maximum, mean and peak uptake values (SUVmax, SUVmean, and SUVpeak). The gland was delimited through an isocontour generated from a threshold of 10% of the SUVmax within a defined volume of interest (VOI). These four parameters were compared through the paired Student's T-test using R Commander software.Results: There was no statistically significant reduction in any of the SUV parameters in the cooled glands compared to contralateral controls, both in t1 in t4. Regarding the submandibular glands, there were also found no alterations of statistical relevance, but the means of the three SUV parameters were higher in the cooled glands that in the controls.Discussion: Results indicated no significant reduction of the radiation absorbed dose by cooled salivary glands. Despite the small sample size, that could reduce the ability to detect significant variations, results allow inferring that biological effects, if present, are probably small and of little clinical significance. Therefore, it was considered that results did not justify performing further exams since this is a high cost and complexity technique. The present findings corroborate with the other mentioned study.Conclusion: The cooling of the salivary glands does not significantly reduce their uptake of radiopharmaceuticals, and no evidence supports this technique for sialotoxicity and xerostomia prevention in clinical practice.

Efficacy of Zinc Sulphate and Amifostine in Prevention of Radiation Induced Salivary Gland Damage

Aim: Radiotherapy plays a significant role in the management of head and neck cancers. However, mucositis and xerostomia are the most common side effects in curative treatment. The aim of this prospective, randomized study is to compare the efficacy of zinc sulphate and amifostine in preventation of radiation induced salivary gland damage in head and neck cancer (HNC) patients using quantitative salivary gland scintigraphy (QSGS). Patients and Methods: Thirty patients with HNC who had received radio±chemotherapy were randomly assigned to receive either zinc sulfate or amifostine. All the patients were once a week during RT for oral mucositis using the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring criteria, and measurement of body weight. Before and 2 months after treatment, salivary gland scintigraphy was performed. Using the time–activity curves, changes in the maximum uptake (UR) and relative saliva excretion rate (ER) between pre- and post- treatment were calculated. The measurements were statistically compared using paired Mann-Whitney U test. Statistical significance was defined as p < 0.05. Results: The protective effect of zinc sulphate on the salivary glands was similar to amifostine and there were no statistically significant difference in UR, ER results at QSGS, oral mucositis or weight loss between the two groups. Conclusion: The effectiveness of both support therapy was compared and there was no significant difference in efficacy. However, because of the cost difference, the use of the zinc sulphate can be an alternative to amifostine for prevention of xerostomia, oral mucositis and other toxic effects. Further studies with more patients and follow-up are suggested in this regard.

Role of current strategies for preventing xerostomia in oropharyngeal cancer patients: A literature review

Xerostomia occurring as sequelae of radiation therapy results in oral complications, i.e., acid erosion, dysphagia, dysgeusia, periodontal diseases, taste disturbance, and dental caries. The best strategy should be to prevent damage of any salivary acini during the course of radiotherapy; therefore, we planned to look for all the strategies for its prevention. We searched PubMed, Google Scholar, and Oral and Dentistry database thoroughly and included all the relevant articles published in the past 12 years (2005–2017). We found the following strategies for the prevention of xerostomia during radiation therapy: amifostine, pilocarpine, Vitamin C, and Vitamin E, acupuncture, bethanechol, botulism toxin, histamine, insulin growth factor, submandibular gland transfer, intensity-modulated radiation therapy, radiation stents, stem cell transplantation, intravenous injection of adipose stem cells, lasers, and lidocaine HCL. These preventive methods not only maintain the morphology and function of salivary glands but also reduces the need for saliva-enhancing therapies later.

Assessment of the Preventive Effect of Pilocarpine on Radiotherapy-Induced Xerostomia in Patients with Head and Neck Cancers

Introduction Xerostomia is one of side-effects of radiotherapy for head and neck cancers. No definitive method has been proposed for the treatment of this condition. However, pilocarpine is considered effective for the management of chronic xerostomia. The purpose of the present study was to assess the preventive effect of pilocarpine. Materials and Methods This study was performed on 34 patients with head and neck cancers, undergoing radiation therapy (5000 cGy). The patients were randomly divided into two groups. The case group was administered 16 drops of pilocarpine (2%) eye drops per day, while the control group received normal saline; the treatment plan continued for four weeks. Unstimulated whole saliva flow rate was measured at four stages: two weeks before radiotherapy (baseline), the first day of radiotherapy, and two and four weeks after the initiation of radiotherapy. Results At baseline and the first day of radiotherapy, no significant differences were observed in the amount of saliva between the case and control groups (PConclusion According to the findings, pilocarpine was found to be effective for the prevention of xerostomia. Moreover, it could restrain the decline in the amount of saliva and reduce the rate of xerostomia.

Phase II Randomized Trial of Acupuncture-Like Transcutaneous Electrical Nerve Stimulation to Prevent Radiation-Induced Xerostomia in Head and Neck Cancer Patients.

Current evidence indicates that acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) can provide sustained benefit for established radiation-induced xerostomia (RIX) symptoms. This is further being evaluated by comparing it with standard treatment (pilocarpine) in a randomized controlled trial. This report studies the potential effectiveness of xerostomia prevention using ALTENS delivered concomitantly with radiotherapy administered to head and neck cancer patients. Sixty patients were randomized to either the treatment group (n = 30) that received ALTENS daily with radiotherapy or the control group (n = 26) that had standard mouth care only. Stimulated and basal unstimulated whole saliva production (WSP) plus RIX symptoms visual analogue score (RIXVAS) were assessed at specific time points. Generalized linear models and generalized estimating equations were used for analysis. RIXVAS at 3 months follow-up after therapy completion was used as the primary study endpoint. The mean RIXVAS for the ALTENS intervention at 3 months was 39.8, which was not significantly different from the control arm value of 40.5. There were no statistically significant differences between the two groups for their mean RIXVAS and WSP at all assessment time points. In conclusion, there was no significant difference in mean WSP and RIXVAS between the two groups, so ALTENS is not recommended as a prophylactic intervention.

The Use of Xylitol for the Prevention of Xerostomia in Patients Receiving Intensity Modulated Radiation Therapy for Head and Neck Cancers

The Use of Xylitol for the Prevention of Xerostomia in Patients Receiving Intensity Modulated Radiation Therapy for Head and Neck Cancers

Clinical observation of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma: a prospective randomized controlled study of 32 cases

BackgroundThe aim of this study was to evaluate the clinical efficacy of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma.MethodsUsing the randomized controlled clinical research method, 65 patients with nasopharyngeal carcinoma were randomly divided into an experimental group consisting of 32 patients and a control group consisting of 33 patients. The submandibular glands were averted to the submental region in 32 patients with nasopharyngeal carcinoma before they received conventional radiotherapy; a lead block was used to shield the submental region during therapy. Prior to radiotherapy, the function of the submandibular glands was assessed using imaging. Submandibular gland function was measured using 99mTc radionuclide scanning at 60 months after radiotherapy. The data in the questionnaire regarding the degree of xerostomia were investigated and saliva secretion was measured at 3, 6, 12, and 60 months after radiotherapy. In addition, the 5-year survival rate was calculated.ResultsAfter follow-up for 3, 6, and 12 months, the incidence of moderate to severe xerostomia was significantly lower in the experimental group than in the control group. The average amount of saliva produced by the experimental and control groups was 1.60 g and 0.68 g, respectively (P < 0.001). After follow-up for 60 months, the uptake and secretion functions of the submandibular glands in the experimental group were found to be significantly higher than in the control group (P < 0.001 and P < 0.001, respectively). The incidence of moderate or severe xerostomia was significantly lower than in the control group (15.4% and 76.9%, respectively; P < 0.001). The 5-year survival rates of the experimental group and the control group were 81.3% and 78.8%, respectively, and there was no significant difference between the two groups (P = 0.806).ConclusionsAfter a 5 year follow-up period involving 32 patients who had their submandibular glands transferred for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma, we found that clinical efficacy was good. This approach could improve the quality of life of nasopharyngeal carcinoma patients after radiotherapy and would not affect long-term treatment efficacy.

Technologic Advances in External Beam Radiotherapy for Head and Neck Cancer

Purpose:Radiotherapy (RT) has evolved substantially since its first clinical use in 1896. Most recently, the introduction of the computed tomography (CT) scan in the 1980s launched 2 decades of technologic (r)evolution. In this article we will give an overview of the recent technical advances in external beam RT for head and neck cancer (HNC).Discussion:In HNC, intensity-modulated RT (IMRT) has become standard of care as it has shown superiority over 3D conformal RT in terms of prevention of xerostomia. Other treatment options are fractionated stereotactic RT as a boost and the use of particle therapy with its interesting ballistic capacities. Carbon ions will be mainly used for radio-resistant cancers because of the supplementary higher biologic effect. Adaptive RT is promising but needs much more evolution before it can be optimally used. All these new techniques require a high level of image guidance in order to reach their maximal capacities. Rigorous quality assurance of all the different steps in the irradiation process is essential to deliver the right dose exactly at the right place.Conclusion:The recent rapid technologic evolution in RT is particularly interesting for HNC as it permits better sparing of the many radiosensitive organs in close vicinity to these aggressive tumors.

The Groningen Radiotherapy-Induced Xerostomia questionnaire: Development and validation of a new questionnaire

Purpose The purpose of this study was to develop and validate a questionnaire (Groningen Radiotherapy-Induced Xerostomia (GRIX) questionnaire) that has the ability to distinguish between patient-rated xerostomia during day and night and can be used to evaluate the impact of emerging radiation delivery techniques aiming at prevention of xerostomia in more detail. Materials and methods All questions in the GRIX were generated from an exhaustive list of relevant questions according to xerostomia as reported in the literature and reported by patients and health care providers. Finally the GRIX was reduced from 56 questions to a 14-item questionnaire, with four subscales; xerostomia during day and night and sticky saliva during day and night. 315 patients filled out 2936 questionnaires and the GRIX was evaluated by calculating Crohnbach’s α for all subscales. Criterion validity was evaluated to compare the GRIX with patient-rated xerostomia scored with the EORTC QLQ-HN35 and physician-rated xerostomia, test–retest analysis and responsiveness were also tested. Results Crohnbach’s α varied for all subscales between 0.88 and 0.94. The GRIX scored well for criterion-related validity on all subscales with high correlations with the EORTC QLQ-HN35 xerostomia and sticky saliva scale as well with physician-rated toxicity scoring. No significant differences were found between test and retest score and the GRIX showed good responsiveness with different time points for all subscales. Conclusion The GRIX is a validated questionnaire which can be used in future research focusing on patient-rated xerostomia and sticky saliva during day and night in relation with the impact of emerging radiation delivery techniques aiming at reduction of xerostomia.

Treatment of Head and Neck Cancers: Issues for Clinical Pharmacists

Head and neck cancers are a heterogeneous group of diseases involving the oral cavity, pharyngeal tube, and larynx. Given the drug therapy options available, clinical pharmacists can play an important role in the care of this patient population. They can recommend a regimen based on efficacy, toxicity, and patient-specific factors; ensure that the prescribed regimen has been studied and reported in the literature; verify dosages; and monitor and counsel patients about adverse effects. Chemotherapy plus radiation (chemoradiation) is often the standard treatment for patients with stage III or nonmetastatic stage IV head and neck cancer. Cisplatin-based regimens are preferred, although carboplatin may be appropriate in some circumstances. Induction therapy with a docetaxel-based regimen is recommended for some patients; however, this therapy has been associated with a high frequency of grade 3 and 4 neutropenia and febrile neutropenia. Cetuximab, an epidermal growth factor receptor inhibitor, is the newest agent approved for treatment of head and neck cancer. Although evidence supports cetuximab combined with cisplatin versus cisplatin alone for patients with metastatic disease, the role of combination therapy is less clear in patients undergoing chemoradiation. Patients with head and neck cancer may experience swallowing difficulties or mouth pain, possibly interfering with drug administration and adherence; thus, pharmacists in all practice settings should be knowledgeable about different regimens and alternative routes of administration. Xerostomia and mucositis are common adverse effects of radiation therapy, and it is critical that good oral hygiene practices are maintained. Patients may achieve symptomatic relief from xerostomia with saliva substitutes, and clinical experience suggests that use of pilocarpine is worthwhile. Until more evidence becomes available, prevention of xerostomia and mucositis with amifostine is still controversial. Salt-water rinses, bioadherent oral gel, and honey are relatively inexpensive and nontoxic agents for managing mucositis. Because of the expense of palifermin, it is best reserved for refractory cases. Skin toxicities are common with radiation. Rash is also a common adverse effect of cetuximab. When used together, they may produce complicated skin toxicities. It is important to become familiar with the grading of these rashes so that appropriate therapy can be recommended. As pharmacotherapy for head and neck cancers continues to evolve, clinical pharmacists will continue to have an important role in optimizing treatment for patients by balancing efficacy and toxicity.

Submandibular Gland Transfer for Xerostomia Prevention in Patients Undergoing Chemotherapy and Radiation Therapy

Submandibular Gland Transfer for Xerostomia Prevention in Patients Undergoing Chemotherapy and Radiation Therapy

Systemic pilocarpine for treatment of xerostomia

Background: Xerostomia is the feeling of dryness in the mouth, usually owing to hypofunctioning of the salivary glands. Causes of xerostomia include medications, the effects of radiation therapy on the salivary glands during the treatment of head and neck cancer or thyroid cancer, and autoimmune diseases such as Sjögren's syndrome. The primary treatment to reduce xerostomia is oral pilocarpine. Objective: This review discusses the randomized trials available on the efficacy and tolerability of oral pilocarpine for the treatment of xerostomia. Methods: The randomized trials of pilocarpine for xerostomia available in the medical literature are reviewed. Results/conclusion: Pilocarpine has some efficacy in the treatment of xerostomia from radiation therapy, graft-versus-host disease and Sjögren's syndrome. It has limited activity for the prevention of xerostomia during radiation therapy. It may have increased efficacy in combination with newer forms of radiation therapy.

Impact of Radiation-Induced Xerostomia on Quality of Life After Primary Radiotherapy Among Patients With Head and Neck Cancer

To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy. A total of 288 patients with Stage I-IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy. A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001). A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18-65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia. The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade > or =2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia.

Evaluation, prevention and management of radiotherapy-induced xerostomia in head and neck cancer patients

As part of the multidisciplinary approach to head and neck cancer patients, radiation therapy plays an essential role, improving locoregional control. Radiation therapy-induced xerostomia is a late side-effect that increases the risk for developing dental caries and compromises oral mucosal integrity, resulting in oral pain, loss of taste, difficulties with swallowing and chewing, sleep disorders and worse quality of life. This review focuses on evaluation, prevention and management of radiation therapy-induced xerostomia. In terms of xerostomia prevention, some clinical trials evaluating amifostine and intensity-modulated radiation therapy have shown positive results. Pilocarpine is a useful agent as a treatment of radiation-induced xerostomia in head and neck cancer patients. Despite some advances in radiation therapy-induced xerostomia prevention, its treatment is an area in which advances are urgently needed.

Kinetics of Tempol for Prevention of Xerostomia Following Head and Neck Irradiation in a Mouse Model

Radiotherapy is commonly used to treat the majority of patients with head and neck cancers. Salivary glands in the radiation field are dramatically affected by this procedure. The purpose of this study was to examine pharmacokinetic characteristics of the stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) with respect to radioprotection of the salivary glands. To evaluate the effect of different doses and times of administration, the heads of C3H mice were exposed to a single irradiation dose of 15 Gy, with i.p. tempol injection. To analyze other routes of administration, we injected 275 mg/kg tempol by an i.m., i.v., or s.c. route, 10 minutes before irradiation. We also tested whether oral administration of tempol in a topical form (either in a mouthwash or gel) provided any salivary gland protection. Tempol treatment (137.5 or 275 mg/kg, i.p., 10 minutes before irradiation) significantly reduced irradiation-induced salivary hypofunction (approximately 50-60%). I.v. or s.c. administration of tempol also showed significant radioprotection, whereas i.m. administration proved to be ineffective. Topical use of tempol, either as a mouthwash or gel, also was radioprotective. Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers.

Submandibular Gland Transfer for Prevention of Xerostomia After Radiation Therapy: Swallowing Outcomes

To assess swallowing outcomes in patients with oropharyngeal carcinoma in relation to the Seikaly-Jha procedure for submandibular gland transfer (SJP). The SJP has recently been described as beneficial in the prevention of xerostomia induced by radiation therapy in patients with head and neck cancer. Inception cohort. University-affiliated primary care center. A phase 2 clinical trial was conducted from February 1, 1999, through February 28, 2002, to evaluate SJP in patients with head and neck cancer. During that period, a consecutive sample of 51 patients who underwent surgical resection and reconstruction with a radial forearm free flap for oropharyngeal carcinoma were referred for functional assessment of swallowing after completion of adjuvant radiation therapy. At 6 months after surgery, swallowing assessments for 24 patients were available. The cohort of 24 patients included 13 who had preservation of 1 submandibular gland (SJP group) and 11 who did not (control group). Quantitative and qualitative aspects of swallowing were obtained to determine whether patients in the SJP group performed more optimally than those in the control group. Baseline and stimulated salivary flow rates were significantly different between groups. Patients in the SJP group were able to move the bolus through the oral cavity and into the pharynx faster than those in the control group. In addition, patients in the SJP group swallowed less often per bolus than patients in the control group. The complete swallowing sequence was twice as long in controls. The SJP for submandibular gland transfer appears to be beneficial in promoting more time-efficient swallowing behaviors. This efficiency has implications for the overall well-being and nutritional status of patients with head and neck cancer.

721 poster Amifostine (A) in the prevention of xerostomia of irradiated head & neck tumors (HNT): results at 1 year of a multicentric outcome study

721 poster Amifostine (A) in the prevention of xerostomia of irradiated head & neck tumors (HNT): results at 1 year of a multicentric outcome study

Preclinical modeling of improved amifostine (ethyol) use in radiation therapy

Amifostine (Ethyol) has been evaluated clinically as a radioprotective agent for the prevention of xerostomia and mucositis for patients receiving radiotherapy (RT). Currently, amifostine is approved for the prevention of xerostomia in head and neck cancer patients receiving RT when administered intravenously (IV) before RT. For the clinician, there would be several advantages to administering the drug subcutaneously and to being able to show its protective effects on mucositis. The authors have developed a rat RT model to examine the protective effects of amifostine after IV and subcutaneous (SC) administration in a mucositis model. Rats (5 per group) were given 200 mg/kg (human dose equivalent of approximately 1,300 mg/m(2)) of amifostine either IV or SC, and their head and neck regions were exposed to 15.3 Gy of gamma radiation 0.5, 2, 4, and 8 hours after amifostine administration. For 10 days after treatment, the oral cavities of the rats were examined for signs of mucositis. Mucosal erythema and mucosal edema were scored according to 0 through 5 and 0 through 2 scales, respectively, with the scores added to indicate overall mucositis. The average mucositis score for the untreated animals was 3.5. Rats were protected from mucositis up to 4 hours when given amifostine either IV or SC. Rats that received amifostine SC, but not IV, were protected from mucositis 8 hours after administration. Preliminary pharmacokinetic data have revealed slightly higher active metabolite (WR-1065) levels in the parotid gland and small intestine in the rats given amifostine SC compared with IV and equivalent levels in the plasma and kidney. The data showed that SC administration of amifostine gave radioprotection comparable to IV administration up to 4 hours before RT and may be more effective than IV administration at longer pretreatment intervals.