Treatment Of Radiation-induced Xerostomia Research Articles

A real-life experience of long-term use of pilocarpine in irradiated head and neck cancer patients.

To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.

Abstract 3152: IFN-gamma stimulated cryopreserved mesenchymal stromal cells for treatment of radiation induced xerostomia

Abstract Purpose/Objectives: There is a critical need for a treatment that will safely and effectively alleviate radiation-induced xerostomia (RIX). Head and neck radiation results in hyposalivation and altered sialochemistry which patients experience as xerostomia. We performed a preclinical and a pilot clinical study to determine if IFN-ɣ stimulated marrow-derived mesenchymal stromal cells (MSC(M)) from HNC patients could function as a source of autologous cells for the treatment of RIX and as a tool in preclinical murine studies of RIX. Materials/Methods: Bone marrow aspirates from HNC patients previously treated with chemoradiation were obtained (IRB #2019-0497, NCT 04007081). MSC(M)s were isolated from bone marrow. MSC(M) were expanded in culture, surface marker expression was confirmed via flow cytometry, stimulated with IFN-ɣ, and cryopreserved. Thawed MSC(M)s were profiled to evaluate their functionality after cryorecovery. Cells were tested for their ability to stimulate salivary production in a murine model of RIX by injecting 1x106 cells into the submandibular gland (SMG) one week after a single 15 Gy fraction of radiation. Efficacy was evaluated by saliva production and histology. Results: MSC(M)s from six patients were expanded to >20x106 cells (median 15.5, range of 8-20 days). Post-thaw cultures demonstrated robust growth, with a median doubling time of 3.1 days. Cultured cells showed an MSC(M) phenotype, positive for CD73, CD90, and CD105 and negative for CD14, CD20, CD34, or CD45. IFN-ɣ stimulated MSC(M)s had immunomodulatory potential based on increased expression of IDO, ICAM-1, PD-L1, MHC I and MHC II expression compared with non-stimulated MSC(M)s (391%, 263%, 114%, 70% and 196% percent increase respectively). In a murine model of RIX, radiation resulted in structural changes to the gland as evidenced by increased fibrosis, decreased acinar size, and immune cell infiltration. Injection of MSC(M)s to the SMG following radiation resulted in improved saliva production, a reduction in fibrosis, and an increase in the size and density of acini within the tissue compared to control. Conclusions: These data strongly support the feasibility of a first-in-human clinical trial of autologous IFN-ɣ stimulated MSC(M)s to treat RIX and the potential of using human-derived MSC(M)s in future murine studies of RIX. Citation Format: Cristina Paz, Grace Blitzer, Annemarie Glassey, Kwangok P. Nickel, Jayeeta Giri, Andrea Pennati, Daniel Robbins, Tadeas Lunga, Susan Thibeault, Jacques Galipeau, Randall Kimple. IFN-gamma stimulated cryopreserved mesenchymal stromal cells for treatment of radiation induced xerostomia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3152.

Treatment of Radiation-Induced Xerostomia with INF-g Pre-Licensed Mesenchymal Stromal Cells (MSCs)

<h3>Purpose/Objective(s)</h3> There is a <b>critical need</b> for a treatment that will safely and effectively alleviate radiation-induced xerostomia (RIX). Head and neck radiation results in hyposalivation and altered sialochemistry which patients experience as xerostomia. We preformed preclinical and a pilot clinical study to determine if IFN-ɣ stimulated marrow-derived mesenchymal stromal cells (MSC(M)) from HNC patients could function as a source of autologous cells for the treatment of RIX. <h3>Materials/Methods</h3> Bone marrow aspirates from HNC patients previously treated with chemoradiation were obtained (IRB #2019-0497, NCT 04007081). MSC(M)s were isolated from bone marrow, expanded in culture, surface marker expression confirmed via flow cytometry, stimulated with IFN-ɣ, and cryopreserved. Thawed MSC(M)s were profiled to evaluate their functionality after cryorecovery. Cells were tested for their ability to stimulate salivary production in a murine model of RIX by injecting 1 × 10⁶ cells into the submandibular gland (SMG) one week after delivery of a 15 Gy dose of radiation. Efficacy was evaluated by histology and saliva production. <h3>Results</h3> MSC(M)s from six patients were expanded to >20 × 10⁶ cells (median 15.5, range of 8-20 days). Post-thaw cultures demonstrated robust growth, with a median doubling time of 3.1 days. Cultured cells showed an MSC(M) phenotype, positive for CD73, CD90, and CD105 and negative for CD14, CD20, CD34, or CD45. IFN-ɣ stimulated MSC(M)s had immunomodulatory potential based on increased expression of IDO, ICAM-1, PD-L1, MHC I and MHC II expression compared with non-stimulated MSC(M)s (391%, 263%, 114%, 70% and 196% percent increase respectively). In a murine model of RIX, delivery of a single 15 Gy dose to the SMG resulted in decreased saliva production, structural changes evidenced by decreased acinar size, increased fibrosis, and immune cell infiltration. Injection of MSC(M)s to the SMG following radiation resulted in improved saliva production, a reduction in fibrosis, and an increase in the size and density of acini within the tissue compared to control. <h3>Conclusion</h3> These data strongly support the feasibility of a first-in-human clinical trial of autologous IFN-ɣ stimulated MSC(M)s to treat RIX and the potential of using human-derived MSC(M)s in future murine studies of RIX.

Accupuncture-like transcutaneous electrical nerve stimulation therapy success using a commercially available unit 8 years post-radiation for xerostomia: a case report.

BackgroundAccupuncture-like transcutaneous electrical nerve stimulation (ALTENS) therapy has been shown in prospective studies to be effective in the treatment of radiation-induced xerostomia. Those studies treated patients within 27 months from end of radiation with ALTENS delivered in the clinic using a Codetron unit. However, that unit is no longer produced and there is limited data on success of ALTENS when delivered at home.MethodsA 50-year old man with xerostomia, 8 years post-radiation for T4N1 squamous cell carcinoma of the tonsillar fossa, was given ALTENS with a currently commercially available unit from Girish Surgical. He used the unit at home, 20 minutes daily for 8 weeks.ResultsAfter 8 weeks of ALTENS therapy the patient saw a reduction in the Self-Reported University of Michigan Xerostomia-Related Quality of Life Scale from 20 to 1.ConclusionThis case report demonstrates (1) the Girish Surgical unit is effective, (2) self-administration of ALTENS in patients who cannot come to clinic regularly may be practical and (3) ALTENS can still offer durable benefit to patients even 8 years after chemoradiation therapy.

The effectiveness of thyme honey for the management of treatment-induced xerostomia in head and neck cancer patients: Afeasibility randomized control trial.

Radiation-induced xerostomia is one of the most common side effects that head and neck cancer patients experience during and after treatment. Despite the various methods for the prevention and treatment of radiation-induced xerostomia, it remains highly prevalent among patients treated for head and neck cancers negatively influencing their lives. The purpose of this study was to evaluate the effectiveness of thyme honey as a means for managing radiation-induced xerostomia. This was a parallel randomised controlled trial with two equal arms, the experimental arm (thyme honey) and the control arm (saline). 72 head and neck cancer patients receiving radiotherapy or/and chemotherapy or/and surgery were recruited in a specialised cancer centre. Patients in both arms followed the same administration protocol with thyme honey and saline respectively. Identical assessments at baseline, 1 month and 6 months following completion of the intervention were performed in both arms including the National Cancer Institute (NCI) xerostomia scale and the Xerostomia Questionnaire (XQ) additionally to weekly oral clinical assessments. The ClinicalTrials.gov Identifier for this study is NCT01465308. Linear Mixed Models revealed the statistically significant effect of the intervention on xerostomia (F=8.474 p<0.001) and overall quality of life (F=13.158 p<0.001). Moreover, Generalised Estimating Equations revealed a statistically significant effect on strong and unbearable pain (F=10.524 p<0.001) and dysphagia (F=4.525 p=0.033). The study has demonstrated the safety and efficacy findings of Thyme honey in head and neck cancer patients for the management of treatment induced xerostomia.

Parasympathomimetic drugs for dry mouth due to radiotherapy.

Data sourcesCochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase and CINAHL databases. Reference lists of identified articles were checked and experts in the field and relevant pharmaceutical companies were contacted.Study selectionRandomised controlled trials, including parallel and crossover, carried out in any setting on any patient population with radiation-induced salivary dysfunction using parasympathomimetics drugs.Data extraction and synthesisThe two authors independently assessed for inclusion, established the risk of bias and abstracted data. The primary outcome was level of xerostomia. The authors intended to report risk ratio, odds ratio, risk difference and NNT for dichotomous data and mean difference and standard mean difference for continuous data.ResultsOf the three included studies, one (n=20) reported mean improvement on the VAS (22.5 mm on a 100 mm scale). The other two studies considered a change in 25 mm on the VAS a positive response. Of those one (n=207) reported positive response in 51% of subjects on 5mg of pilocapine TID and 47% for 10mg TID. The second (n= 162) reported a 42% positive response with a titrated dose regimen. The side effects rate was high,and the main reason for discontinuation.ConclusionsThere is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Acupuncture-like transcutaneous nerve stimulation therapy success after 5 years post-radiation-induced xerostomia: a case report

AbstractBackgroundSuccess with acupuncture-like transcutaneous nerve stimulation (ALTENS) in the treatment of radiation-induced xerostomia has not been reported after an extended time.MethodsWe report a case of successful ALTENS therapy 5 years after radiation treatment.ResultsThe patient discontinued treatments in a second course due to complete resolution of symptoms.ConclusionThis case report demonstrates a potential for offering ALTENS to those long suffering from radiation-induced xerostomia.

Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy.

This is an updated version of the original Cochrane review on parasympathomimetic drugs for the treatment of salivary gland dysfunction due to radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition. To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction (specifically radiation-induced xerostomia). For this update, we ran searches of the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July 2015. We checked the reference lists of retrieved articles for additional studies, contacted experts in the field for unpublished and ongoing trials, and contacted relevant pharmaceutical companies for unpublished and ongoing trials. The selection criteria for the review were: 1) randomised controlled trials; 2) people suffering from radiation-induced salivary gland dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measure. The two review authors independently collected data from the full-text version of relevant papers including: 1) citation details; 2) participants; 3) interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and 6) quality issues.Due to a lack of appropriate data, we were unable to perform a meta-analysis. In the original review, three studies, including a total of 298 participants, fulfilled the inclusion criteria. All three studies involved the use of pilocarpine hydrochloride. We have included no additional studies in the update of the review; we have excluded eight additional studies.The data suggest that pilocarpine hydrochloride is more effective than placebo and at least as effective as artificial saliva. The response rate was 42% to 51%. The time to response was up to 12 weeks. The overall side effect rate was high, and side effects were the main reason for withdrawal (6% to 15% of participants taking 5 mg three times a day had to withdraw). The side effects were usually the result of generalised parasympathomimetic stimulation (for example sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent. There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced xerostomia. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of radiation-induced xerostomia. Available studies suggest that approximately half of patients will respond, but side effects can be problematic. The conclusions of the update are the same as the conclusions of the original review, since no new relevant studies have been published in the interim.

Research progress of radiation-induced xerostomia in nasopharyngeal carcinoma

Radiation-induced xerostomia is the common radiotherapy-related complication of nasopharyngeal cancer and other head and neck cancers.The cause is that the radioactive rays damage salivary gland acini,ducts,blood vessels and nerves at different levels,resulting in dry mouth,mucositis,sialadenitis,and even dysphagia,trismus and other symptoms.In addition,radiation-induced xerostomia has a close relation to the radiation effect on the genes.Reasonable application of cytoprotective agents and sialagogues is the main treatment means.Chinese medicine also plays a crucial role in the prevention and treatment of radiation-induced xerostomia in recent years. Key words: Nasopharyngeal neoplasms ; Radiation-induced xerostomia ;

Improvement of radiation-induced xerostomia with acupuncture: A retrospective analysis

ObjectiveOur previous case study introduced combination acupuncture (manual, auricular and electro-acupuncture) as a treatment for radiation-induced xerostomia. The present retrospective study evaluates the effect of combination acupuncture on the severity of dry mouth and activities of daily living as related to radiation-induced xerostomia. DesignData was retrospectively collected from twenty-two patients with xerostomia related to radiotherapy for head and neck cancer (HNC). Sixteen patients who met the inclusion and exclusion criteria were analyzed for this report. The intervention was weekly 20min sessions of combination acupuncture. Upon reaching a plateau in symptom improvement the length in time between treatments was increased as tolerated without return of symptoms. Outcome measures included a self-reported quality of life xerostomia questionnaire completed prior to each acupuncture session and quantitative data from documented Modified Schirmer's tests. ResultsSignificant improvement in dry mouth and pain occurred during the initial six weeks of treatment (p<0.05). During this period, the mean severity of dry mouth and pain decreased by 35% and 50%, respectively (p<0.001). After six weeks, the improvement in dry mouth and pain symptoms plateaued. This effect was maintained with intermittent acupuncture treatments. ConclusionsCombination acupuncture significantly decreases the severity of dry mouth and pain with long lasting effects, up to six months (at the end of data collection), in patients with radiation-induced xerostomia.

Stimulating neuronal processes that benefit patients and our profession

Stimulating neuronal processes that benefit patients and our profession

Organ-sparing radiation therapy for head and neck cancer

To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.

Radiation‐induced xerostomia

Radiation-induced xerostomia is a frequent and usually permanent side effect of radiation therapy for head and neck cancer. We summarize recent developments in the prevention and treatment of radiation-induced xerostomia. The Medline database was searched for articles published within the past 10 years on the prevention and treatment of postirradiation xerostomia. Proceedings of recent important national meetings and government Web registries of clinical trials and therapeutic agents were also consulted. Priority was given to randomized controlled trials but, because of the scarcity of such trials, small open trials were included in this review. No other predetermined selection criteria were used, although articles exploring the effects of xerostomia and its treatment on quality of life were considered of special interest. A variety of preventive approaches for postirradiation xerostomia exist, involving more conformal radiation delivery technology, radioprotective agents, and even preirradiation surgical techniques. Therapeutic interventions include supportive care, saliva supplementation, and the use of pro-cholinergic salivary secretagogues. Radiation-induced xerostomia constitutes a significant morbidity after orofacial irradiation. Careful preventive techniques, meticulous supportive care, and new preventive and therapeutic agents may prove useful in combination.

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.

Two phase III clinical studies of cevimeline for post-radiation xerostomia in patients with head and neck cancer

5503 Background: Xerostomia is a frequent debilitating complication of head and neck cancer radiotherapy. Morbidities include dental caries, oral infections, and impaired quality of life. Methods: Two multicenter double-blind trials were conducted to assess the efficacy and safety of cevimeline in the treatment of radiation-induced xerostomia. Each trial enrolled subjects ≥18 years of age with head and neck cancer who had received >4000 cGy of radiation ≥4 months before entry and had clinically significant salivary gland dysfunction. Subjects were randomized to cevimeline 30 mg TID or placebo for 12 weeks, with escalation to 45 mg TID or placebo equivalent at 6 weeks if no improvement was reported. Subjects experiencing side effects after dose escalation could de-escalate to 30 mg TID. The primary efficacy endpoint was global evaluation of oral dryness, with a secondary endpoint being change in unstimulated salivary flow. Results: A total of 570 subjects (284 in the 003 and 286 in the 004 study) were randomized. In the final (visit 5) global evaluation of dry mouth in the intention-to-treat (ITT) analysis, improvement was reported by a greater percentage of subjects treated with cevimeline compared with placebo recipients (47.4% vs 33.3%, P=0.0162) in the 003 study; differences between groups were significant at visits 3 through 5 (P≤0.0162). Differences of global evaluation of oral dryness between the treatment and placebo groups were not statistically significant in the 004 study, although a high placebo response rate was observed (48.9% vs 47.6%, P=0.9565). In both studies, cevimeline-treated patients had significantly greater mean increases in unstimulated salivary flow than placebo treated patients at the final visit (ITT, P=0.0093 [003] and P=0.0215 [004]). Cevimeline was well tolerated in both studies. Adverse event frequency was comparable in the placebo and cevimeline groups, with the exception of increased sweating in the cevimeline group. Conclusions: Cevimeline 30 to 45 mg TID increased mean unstimulated salivary flow in both studies and in one study improved subjective dry mouth sensation in subjects with xerostomia following radiation therapy for head and neck cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi

PD.3 Oral pilocarpine as preventive treatment forradiation-induced xerostomia. Preliminary report

PD.3 Oral pilocarpine as preventive treatment forradiation-induced xerostomia. Preliminary report

Hyperbaric oxygen for radiation-induced xerostomia

HBO2 is currently used to treat the sequelae of radiation injury such as ORN of the mandible and laryngeal STRN, but it also has the potential to be used as a novel treatment for radiation-induced xerostomia.

A Phase I–II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy

Purpose Recent studies have suggested that acupuncture may improve radiation-induced xerostomia with an increase in the median salivary flow rate and sustained symptom relief. An acupuncture-like transcutaneous nerve stimulation method (Codetron) without invasive needles was developed to mimic acupuncture treatment. This Phase I–II study examined the effectiveness of Codetron in treating radiation-induced xerostomia. Methods and materials Patients with symptomatic xerostomia after radical radiotherapy for head-and-neck cancer but with evidence of residual salivary function were recruited into the study. Two 6-week courses of Codetron treatment of acupuncture points preselected according to traditional Chinese medicine principles were given with a 2-week break between each course. Basal and citric acid-primed whole saliva production were measured at baseline and up to 1 year after treatment completion. Xerostomia symptoms were assessed by a five-item xerostomia symptom questionnaire with a visual analog scale and quality of life was evaluated using the Head and Neck Radiotherapy Questionnaire. Results We enrolled 46 patients in the study. All patients had received radiotherapy doses of ≥50 Gy to bilateral head-and-neck fields, including the parotid glands. Of the 46 patients, 37 completed the follow-up assessments at 3 and 6 months after treatment completion. No Codetron treatment-related complications occurred. Improvement in xerostomia symptoms was noted, with a mean increase in the visual analog scale score of 86 ( p < 0.0005) and 77 ( p < 0.0001) at 3 and 6 months after treatment completion, respectively. For all patients, the increase in the mean basal and citric acid-primed whole saliva production at 3 and 6 months after treatment completion was also statistically significant ( p < 0.001 and p < 0.0001, respectively). No statistically significant change in the quality-of-life evaluation compared with baseline was observed. Conclusion The results suggest that Codetron treatment improves whole saliva production and related symptoms in patients with radiation-induced xerostomia. The treatment effects were sustained for at least 6 months after Codetron treatment completion. A prospective randomized Phase III trial with appropriate controls is being planned.

60 The use of acupuncture-like transcutaneous nerve stimulation (codetron) in the treatment of radiation-induced xerostomia in head and neck caner patients treated with radical radiotherapy

60 The use of acupuncture-like transcutaneous nerve stimulation (codetron) in the treatment of radiation-induced xerostomia in head and neck caner patients treated with radical radiotherapy

Tissue Engineering of Human Salivary Gland Organoids

Radiation therapy for malignant head and neck tumours is mainly responsible for inadvertent damage of the salivary glands. Xerostomia is the major symptom of this condition, with consequent mucositis, dental caries, dysphagia and nutritional deficits. At present there is no routine treatment for radiation-induced salivary dysfunction. Based on the principles of tissue engineering, this study presents a new experimental concept for reconstituting salivary gland function after radiation therapy for head and neck cancer. Human parotid cells were cultured with two different types of commercially available microcarriers - Cytodex 3 and Cytopore 1 - for up to 3 weeks in vitro . Cultures were controlled daily by means of inverted microscopy. Medium samples were tested for alpha-amylase, tissue polypeptide antigen (TPA) and S100 in order to control parotid cell function in vitro . The vitality of the cells was investigated by in vitro staining with erythrosine. Immunocytochemical analysis for amylase and cytokeratin was performed in order to confirm epithelial character and maintain acinar cell type. Parotid gland cells could be cultured in a differentiated and vital state on both types of microcarriers for up to 3 weeks. Almost all of the cultured cells exhibited immunoreactivity for cytokeratin. High concentrations of TPA, a specific marker for salivary duct epithelium, indicated persistent differentiation of this cell type in vitro . Positivity for amylase was detectable in 20-45% of cells growing on the microcarriers, and especially on Cytodex 3. Decreasing amylase levels in the culture medium indicated functional deficiencies of the remaining acinar cells. Tissue engineering of human salivary gland organoids on microcarriers is a new approach for potential causative treatment of radiation-induced xerostomia. Before clinical application can be considered significant improvements in the in vitro cultivation of salivary gland tissue and scaffold design have to be realized.