The Photobiomodulation effect of 980 nm Diode Laser on Patients with Xerostomia.

PURPOSE: Xerostomia is not a disease in itself. This condition is associated with systemic diseases, medication use, and radiotherapy. Oral and general health suffer when the salivary gland´s function is reduced. The effectiveness of therapeutic methods in resolving this issue thus far has been inadequate. This study aimed to determine the photobiomodulation (PBM) effect of a 980 nm laser on xerostomia. METHODS: A quasi-experimental study was carried out using a 980 nm diode laser on 28 patients with xerostomia. A diode laser (980 nm) was used extortionally over the submandibular glands and parotids and it was used internally in the sublingual glands. The laser beam (extrorally 6 J, 300mW, 20 s, and introrally 4 J, 200mW, 20 s) was applied bilaterally every other day for 10 sessions. It should be noted that 8 points of the parotid, 2 points of the submandibular glands, and 2 points of the sublingual glands were irradiated. The saliva was collected each session using the Navazesh technique, 5 min before and after PBM. The Wilcoxon test was used to study the effect of laser therapy on saliva flow rate (volume and weight). The P < 0.05 level was considered a significant level. RESULTS: The volume (P < 0.0001) and the weight (P < 0.0001) of the saliva were increased by using a 980 nm diode laser. While, in smokers and diabetic patients with hypertension, no significant difference was observed in either saliva volume (P = 0.593, P = 0.092) or weight (P = 0.785, P = 0.089). CONCLUSION: In this study, the volume and weight of the unstimulated saliva in most patients with xerostomia increased with using PBM.

Photobiomodulation for the management of xerostomia and oral mucositis in patients with cancer: a randomized clinical trial.

To evaluate the applicability of photobiomodulation therapy (PBM-T) in the management of xerostomia and OM. Fifty-three patients with head and neck squamous cell carcinoma were randomized into two groups: Sham and PBM-T. The Sham group received artificial saliva and laser simulation, while the PBM-T group received artificial saliva and PBM-T. Xerostomia-related quality of life (QoL), the presence or absence of OM lesions, the decayed-missing-filled teeth (DMFT) index, and periodontal charts were evaluated. The results of the QoL questionnaire, DMFT index, and periodontal chart were analyzed with the Kruskal-Wallis test, followed by the Student-Newman-Keuls test, while OM findings were compared using the Mann-Whitney test. QoL scores significantly increased in the Sham group (p < 0.0001), denoting more severe xerostomia symptoms (p = 0.0074), and decreased in the PBM-T group, indicating no or very mild xerostomia. Higher grades of OM were found in the Sham group than the PBM-T group (p = 0.0001). There was no significant difference in DMFT index or periodontal charts between the groups (p > 0.05). PBM-T improved QoL in patients with head and neck cancer treated with radiotherapy, whether as radiation alone or as an adjunct to chemotherapy and surgery.

[State of art of photobiomodulation in the management of radiotherapy adverse events: Indications and level of evidence]. / État de l'art de la photobiomodulation dans la prise en charge des effets secondaires de la radiothérapie : indications et niveaux de preuve.

PURPOSE: To evaluate the current and potential indications of photobiomodulation (PBM) and their level of evidence in the prevention or management of radiation therapy-related side effects. MATERIALS AND METHODS: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that have assessed PBM in the prevention or management of radiotherapy-related side effects. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "hyposalivation"; "trismus"; "bone necrosis"; "osteoradionecrosis"; and "radiation induced fibrosis". Prospective studies were included, whereas retrospective cohorts and non-original articles were excluded from the analysis. RESULTS: PBM in the red or infrared spectrum has demonstrated efficacy in randomized controlled trials in the prevention and management of radiotherapy-related side effects, especially acute oral mucositis, acute radiation dermatitis, and upper extremity lymphedema. The level of evidence associated with PBM was heterogeneous, but overall was still moderate. The main shortcomings were the diversity and lack of detail in treatment protocols, which could have compromised efficiency and reproducibility of PBM results. CONCLUSION: The published data suggest that PBM may be considered as a full-fledged supportive care for patients treated with radiotherapy, or at least in the setting of a therapeutic clinical trial. However, until strong evidence has been published on its long-term safety, the use of PBM should be considered with caution, specifically when applied near areas with proven or potential tumors. The patient should be informed of the theoretical benefits and risks of PBM in order to obtain his informed consent before treatment.

Paciente con xerostomía posradioterapia por cáncer de cabeza y cuello tratado con células madre mesenquimales autólogas expandidas de tejido adiposo: una nueva oportunidad terapéutica / Radiation-induced xerostomia in a patient with head and neck cancer treated with Injection of autologous expanded adipose tissue-derived mesenchymal stem cells: A new therapeutic opportunity

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Evaluation of photobiomodulation in salivary production of patients with xerostomy induced by anti-hypertensive drugs: Study protocol clinical trial (SPIRIT compliant).

INTRODUCTION: Hypertension (systemic arterial hypertension [SAH]) is a systemic condition that affects about 30% of the world population, according to data from the World Health Organization (WHO). Drugs used to control this disease have the potential to induce xerostomia, an oral condition in which the decrease of the salivary flow is observed and whose presence leads to the increase of the index of caries, periodontal disease, loss of the teeth, dysgeusia, difficulty of mastication, dysphagia, bad breath and oral burning and impairment of prothesis installed in the buccal cavity, including retention of removable and total dentures. METHODS: This is a randomized, placebo-controlled, blind clinical protocol that aims to analyze the impact of phobiomodulation (PBM) on salivary glands of patients with antihypertensive drug induced xerostomia. Patients will be divided into 2 groups: G1: older adults with xerostomia induced by antihypertensive drugs and treatment with PBM (n = 30); G2: placebo PBM (n = 30). The irradiation will be made using a diode laser emitting at 808 nm with 100 mW and 40 seconds of exposure per site at the salivary glands. Twenty sites will be irradiated weekly for 4 weeks. Non-stimulated and stimulated salivary flow will be analyzed before and after the treatment. RESULTS: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. CONCLUSION: This protocol will determine the effectiveness of photodynamic therapy regarding the reduction of xerostomia in older adults using antihypertensive drugs. TRIAL REGISTRATION: Clinicaltrials.gov - NCT03632096.

Xerostomia and Clinical Outcomes in Definitive Intensity Modulated Radiotherapy (IMRT) Versus Three-dimensional Conformal Radiotherapy (3D-CRT) for Head and Neck Squamous Cell Carcinoma: A Meta-analysis.

BACKGROUND/AIM: Intensity modulated radiotherapy (IMRT) has been compared with three-dimensional conformal radiotherapy (3D-CRT) in randomized clinical trials for head and neck squamous cell carcinoma (HNSCC). The aim of this meta-analysis was to evaluate the efficacy and toxicity of IMRT and 3D-CRT and identify differences in grade ≥2 xerostomia incidence and clinical outcomes. MATERIALS AND METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement was applied. Random-effects models were used. Primary endpoint was xerostomia of grade 2 or worse. Secondary endpoints were overall survival (OS) and loco-regional control (LRC). RESULTS: Three randomized clinical trials representing 213 patients were identified. Global, grade ≥2 acute xerostomia and late xerostomia at 1 and 2 years after treatment were reduced with the IMRT technique (RR=0.71, 95%CI=0.59-0.86, RR=0.45, 95%CI=0.31-0.65 and RR=0.26, 95%CI=0.15-0.46, respectively). IMRT was not associated with significant OS and LRC improvement compared with 3D-CRT, with OR of 0.70 (95%CI=0.39-1.24; p=0.22) and 1.50 (95%CI=0.75-2.98; p=0.25). CONCLUSION: This meta-analysis explored the value of IMRT compared to 3D-CRT and confirmed the superiority of IMRT over 3D-CRT in terms of grade ≥2 xerostomia rates, but not on clinical outcomes. Its positive impact on tumor control and survival remains to be proven.

Photobiomodulation Therapy in the Treatment of Oral Mucositis, Dysphagia, Oral Dryness, Taste Alteration, and Burning Mouth Sensation Due to Cancer Therapy: A Case Series.

Oral complications of cancer therapy, such as oral dryness, dysphagia, and taste alteration, are associated with a negative impact in the quality of life of the patients. Few supportive care measures are available for such complications. This case series reveals the effectiveness of the photobiomodulation (PBM) therapy when used in a specific protocol and parameters, in the management of oral complications related to cancer therapy. Dysphagia was measured using the functional outcome swallowing scale for staging oropharyngeal dysphagia (FOSS). Oral mucositis was measured according to the National Cancer Institute scale. The quantity of the whole resting and stimulated saliva was measured in order to assess the oral dryness. In addition, the taste alteration was measured according to a protocol suggested by the International Standards organization (ISO). Sensation of burning mouth was measured using a visual analogue scale. These measurements were made before treatment, during, and at the end of the treatment. Diode laser 635 nm was used in 3 J/cm2. Five sessions interleaved with 24 h breaks were conducted for the dysphagia and oral dryness, and 10 sessions were conducted for the taste alteration and burning mouth sensation. Regardless of the limitations of this case series, PBM can be considered safe, time saving, and a promising approach for the management of the oral complications due to cancer therapy and the quality of life of cancer patients.

Oral Candida colonization in xerostomic postradiotherapy head and neck cancer patients.

OBJECTIVES: To evaluate (a) oral colonization of Candida species, especially for non-albicans Candida species (NACS), in xerostomic postradiotherapy head and neck cancer patients and (b) risk factors affecting their colonization. MATERIALS AND METHODS: Subjective and objective dry mouth scores, stimulated salivary flow rates, pH and buffering capacity were measured in 72 xerostomic postradiotherapy head and neck cancer patients. Candida counts and species identification were performed using oral rinse samples cultured in Candida Chromagar, followed by polymerase chain reaction and API 20C AUX system. RESULTS: Candida colonization was observed in 87.5% of subjects, with 80.6% and 48.6% of study population colonized by C. albicans and NACS, respectively. NACS was associated with high objective dry mouth scores, denture use, and females (p = .006, .009, and .036, respectively). In addition, Candida glabrata was detected more in females (p = .018) and denture wearers (p = .026), while Candida tropicalis was associated with high objective dry mouth scores (p = .022) and females (p = .027). Quantity of Candida colonization correlated positively with objective dry mouth scores (r = 0.599, p < .001) and negatively with salivary flow rates (r = -0.258, p = .041) and pH (r = -0.290, p = .022). CONCLUSION: NACS colonization was common in xerostomic head and neck cancer patients. Increased signs of dry mouth, female and dental prostheses may promote NACS colonization.

Comparison three-dimensional conformal radiotherapy versus intensity modulated radiation therapy in local control of head and neck cancer.

BACKGROUND: About 74% of head and neck cancer (HNC) patients need to undergo either definitive or postoperative radiation therapy because of aggressive nature of disease. The transition from two-dimensional conventional radiotherapy to three-dimensional conformal radiotherapy (3D-CRT) and further technological evolutions led to the successful clinical implementation of intensity modulated radiation therapy (IMRT), which constitutes an evolution of 3D-CRT. The IMRT technique gives the ability to create treatment fields with varying beam intensity using inverse planning and optimization algorithms to treat irregularly shaped target volumes with high precision. IMRT is in existence in clinical practice since 1995. Since then, presuming its clinical benefit a significant amount of patients has been treated by this technique. PARSPORT was the first multi-institutional prospective trial comparing IMRT with conventional RT in the treatment of HNC. It has shown a reduction in severe xerostomia but no difference in other toxicity and locoregional control after 24 months' follow or overall survival. Except for early T1, 2 N0 stages, the prognosis for patients with oral cavity cancer (OCC) is dismal than for carcinoma in other sites of the head and neck (HNC). AIM: The aim of this study was to assess the outcome of OCC following IMRT. MATERIALS AND METHODS: Between January 2013 and January 2015, 40 patients of carcinoma buccal mucosa and carcinoma alveolus were treated by postoperative (19) or definitive (21) radiation therapy by IMRT technique. Of these, 28 patients (70%) presented with locally advanced T3/4 or recurrent tumor. Total radiation doses delivered was between 60 and 70 Gray at 2 Gray/fraction. Of these 31 patients (78%) has received concurrent cisplatin-based chemotherapy. Another group of 42 similar patients treated by 3D-CRT as definitive or postoperative adjuvant treatment over the same period has been selected. Comparisons were performed between these two groups. STATISTICAL ANALYSIS: Data were entered into Excel spreadsheet and expressed as mean and standard deviation for deriving P value, and unpaired t-test was used to calculate 95% confidence interval. Local control (LC) was analyzed using Kaplan-Meier curve. Of all assessed treatment subgroups, LC rate was highest for patients treated with postoperative IMRT (89% LC at 2 years) followed by postoperative 3D-CRT patients (79% LC at 2 years); and finally, poorest LC rates (43% and 32% at 2 years) were seen in definitively irradiated patients with IMRT and 3D-CRT, respectively. LC rate for T1 stage (83%, n = 6) was significantly higher, than that for T2-4 (LC 55%, n = 76) as expected. CONCLUSION: Postoperative IMRT of carcinoma buccal mucosa and alveolus resulted in the highest LC rate of all the treatment subgroups assessed hence should be generously recommended in such cases especially ones with unfavorable features such as close resection margin, nodal involvement, locally advanced tumor (>T1N0), or recurrent disease, respectively. Despite definitive IMRT, locoregional control in carcinoma buccal mucosa and alveolus remain unsatisfactory, comparable to that following definitive 3D-CRT.

Murine Salivary Functional Assessment via Pilocarpine Stimulation Following Fractionated Radiation.

Hyposalivation is commonly observed in the autoimmune reaction of Sjögren's syndrome or following radiation injury to the major salivary glands. In these cases, questions remain regarding disease pathogenesis and effective interventions. An optimized technique that allows functional assessment of the salivary glands is invaluable for investigating exocrine gland biology, dysfunction, and therapeutics. Here, we present a step by step approach to performing pilocarpine stimulated saliva secretion, including tracheostomy and the dissection of the three major murine salivary glands. We also detail the appropriate murine head and neck anatomy accessed during these techniques. This approach is scalable, allowing for multiple mice to be processed simultaneously, thus improving the efficiency of the work flow. We aim to improve the reproducibility of these methods, each of which has further applications within the field. In addition to saliva collection, we discuss metrics for quantifying and normalizing functional capacity of these tissues. Representative data are included from submandibular glands with depressed salivary gland function 2 weeks following fractionated radiation (4 doses of 6.85 Gy).

Low-level laser therapy with 850 nm recovers salivary function via membrane redistribution of aquaporin 5 by reducing intracellular Ca2+ overload and ER stress during hyperglycemia.

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm2) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm2) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation.

Different Protocols of Photobiomodulation Therapy of Hyposalivation.

OBJECTIVE: Photobiomodulation (PBM) therapy has proved to be effective for a wide range of oral pathologies including oral dryness, but the literature still lacks reports of clinical trials and protocols. The purpose of our study was to evaluate the effects of different wavelengths of PBM on salivation in patients suffering from hyposalivation aiming at determination of optimal treatment protocol. MATERIALS AND METHODS: This study included 30 patients whose major salivary glands were treated with low-intensity diode laser BTL2000 (Medical Technologies, s.r.o., Czech Republic) during 10 consecutive days. Patients were randomly assigned into two groups, each of 15 patients, and treated with PBM of 830 nm and PBM of 685 nm, respectively. The whole unstimulated and stimulated saliva quantities were measured each day during 10 days, before and after laser treatment, and at 10th day after treatment was ended. RESULTS: Results have shown that the laser treatment significantly improves salivation (p < 0.0001) in both groups after 10 days treatment. The salivation also remains improved 10 days after the end of treatment. The patients treated with PBM of 830 nm have had continuously higher values of quantity of saliva. CONCLUSIONS: Our results have shown that both laser wavelengths were effective in increasing salivary flow rate, and the improvement in salivation was statistically significant. The effect of treatment could be observed 10 days after the completion of treatment, thus providing evidence not only of stimulative effect but also indicating regenerative potential of PBM therapy.

Impact of low-level laser therapy on hyposalivation, salivary pH, and quality of life in head and neck cancer patients post-radiotherapy.

Late effects of radiotherapy for head and neck cancer treatment have been increasingly investigated due to its impact on patients' quality of life. The purpose of this study was to evaluate the effect of low-level laser therapy on hyposalivation, low salivary pH, and quality of life in head and neck cancer patients post-radiotherapy. Twenty-nine patients with radiation-induced xerostomia received laser sessions twice a week, during 3 months (24 sessions). For this, a continuous wave Indium-Gallium-Aluminium-Phosphorus diode laser device was used punctually on the major salivary glands (808 nm, 0.75 W/cm2, 30 mW, illuminated area 0.04 cm2, 7.5 J/cm2, 10 s, 0.3 J). Six extraoral points were illuminated on each parotid gland and three on each submandibular gland, as well as two intraoral points on each sublingual gland. Stimulated and unstimulated salivary flow rate, pH (two scales with different gradations), and quality of life (University Of Washington Quality of Life Questionnaire for Patients with Head and Neck Cancer) were assessed at baseline and at the end of the treatment. There were significant increases in both mean salivary flow rates (unstimulated: p = 0.0012; stimulated: p < 0.0001), mean pH values (p = 0.0002 and p = 0.0004), and mean score from the quality of life questionnaire (p < 0.0001). Low-level laser therapy seems to be effective to mitigate salivary hypofunction and increase salivary pH of patients submitted to radiotherapy for head and neck cancer, thereby leading to an improvement in quality of life.

Low-level Laser Therapy: A Review of Its Applications in the Management of Oral Mucosal Disorders.

Due to its analgesic, anti-inflammatory, and biostimulating effects, low-level laser therapy (LLLT) has been widely used for oral disorders, such as oral lichen planus (OLP), xerostomia, recurrent aphthous stomatitis (RAS), herpes labialis, burning mouth syndrome (BMS), and oral mucositis (OM). The research team for the present study has reviewed the literature on the subject, with an emphasis on the applicability of LLLT in general and of its various clinical protocols for the management of those oral disorders. In lesions such as the ones occurring in OM, RAS, herpes labialis, and OLP, the course of wound healing and the pain have been shown to decrease, with a few, or most often, no adverse side effects. The literature shows that LLLT can also be effective in reducing symptoms in patients with BMS. For the treatment of hyposalivation and xerostomia, the use of LLLT has been described in the literature, but no consensus has resulted. Very few controlled clinical studies with well-established therapeutic protocols have occurred, except for OM, for which LLLT has been widely researched. Although information on the use of the laser for some lesions has already been consolidated, further research is needed, especially randomized, controlled clinical trials with long-term follow-up. Those studies will allow the safe use of LLLT, permitting the creation of care protocols for the management of oral disorders.

The Effectiveness of Low-Level Laser Therapy in Patients with Drug-Induced Hyposalivation: A Pilot Study.

OBJECTIVE: The aim of this study was to compare switched on and switched off (sham) low-level laser therapy (LLLT) in the treatment of drug-induced hyposalivation. BACKGROUND DATA: Hyposalivation is decreased salivary flow rate most frequently present in patients who take a lot of medication, suffer from Sjögren's syndrome, or were irradiated. Available therapies provide only short-term relief. MATERIALS AND METHODS: Forty-three participants (40 females and 3 males, average age 72.3 ± 8.9) participated in the study. Before therapy or after therapy, every participant fulfilled quality-of-life assessment scale (OHIP-CRO14). Unstimulated and stimulated salivary flow rates were measured before and after treatment. The LLLT was performed by the use of gallium-aluminum-arsenide (GaAlAs) laser (830 nm) on parotid, submandibular, and sublingual glands every day except during weekends for 14 days. RESULTS: Significant difference in unstimulated salivary flow rate after the treatment was found in the study group (p = 0.002) compared with the sham group. No significant difference in stimulated salivary flow rate after treatment was found in the laser group (p = 0.626) nor in the sham laser group (p = 0.233). No significant difference in patient's quality-of-life score was found after both treatments. CONCLUSIONS: The results of this study showed that the LLLT increased unstimulated salivary flow rate significantly. However, stimulated salivary flow rate did not increase significantly after the LLLT. In patients who underwent sham laser therapy, neither unstimulated nor stimulated salivary flow rate increased significantly.

Low-Level Laser for Mitigation of Low Salivary Flow Rate in Head and Neck Cancer Patients Undergoing Radiochemotherapy: A Prospective Longitudinal Study.

OBJECTIVE: The present study aimed to assess the impact of low-level laser (LLL) on low salivary flow rate in patients undergoing radiochemotherapy (RT-CT) for head and neck cancer. BACKGROUND DATA: LLL has shown efficiency in preventing hyposalivation in patients under different pathological conditions, including those undergoing RT-CT. METHODS: During all RT-CT, 17 patients received laser therapy and 10 received clinical care only. An Indium-Gallium-Aluminum-Phosphorus diode laser was punctually used for intraoral (660 nm, 40 mW, 10 J/cm(2), illuminated area 0.04 cm(2), 10 sec) and extraoral irradiation (780 nm, 15 mW, 3.8 J/cm(2), illuminated area 0.04 cm(2), 10 sec), three times a week and on alternate days, for a total of 21 sessions. Unstimulated salivary flow rate was assessed before the first RT session (N0), at the 15th RT session (N15), at the last RT session (Nf), and at 30 (N30) and 90 days after the end of the oncologic treatment (N90). RESULTS: At N15, Nf, and N30, patients treated with LLL showed significantly higher averages of salivary flow rate when compared with patients receiving clinical care only. CONCLUSIONS: LLL seems to be an efficient tool for mitigation of salivary hypofunction in patients undergoing RT for head and neck cancer.

Temporal Evolution of Parotid Volume and Parotid Apparent Diffusion Coefficient in Nasopharyngeal Carcinoma Patients Treated by Intensity-Modulated Radiotherapy Investigated by Magnetic Resonance Imaging: A Pilot Study.

PURPOSE: To concurrently quantify the radiation-induced changes and temporal evolutions of parotid volume and parotid apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiotherapy by using magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 11 NPC patients (9 men and 2 women; 48.7 ± 11.7 years, 22 parotid glands) were enrolled. Radiation dose, parotid sparing volume, severity of xerostomia, and radiation-to-MR interval (RMI) was recorded. MRI studies were acquired four times, including one before and three after radiotherapy. The parotid volume and the parotid ADC were measured. Statistical analysis was performed using SPSS and MedCalc. Bonferroni correction was applied for multiple comparisons. A P value less than 0.05 was considered as statistically significant. RESULTS: The parotid volume was 26.2 ± 8.0 cm(3) before radiotherapy. The parotid ADC was 0.8 ± 0.15 × 10(-3) mm(2)/sec before radiotherapy. The parotid glands received a radiation dose of 28.7 ± 4.1 Gy and a PSV of 44.1 ± 12.6%. The parotid volume was significantly smaller at MR stage 1 and stage 2 as compared to pre-RT stage (P < .005). The volume reduction ratio was 31.2 ± 13.0%, 26.1 ± 13.5%, and 17.1 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was significantly higher at all post-RT stages as compared to pre-RT stage reciprocally (P < .005 at stage 1 and 2, P < .05 at stage 3). The ADC increase ratio was 35.7 ± 17.4%, 27.0 ± 12.8%, and 20.2 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was negatively correlated to the parotid volume (R = -0.509; P < .001). The parotid ADC was positively associated with the radiation dose significantly (R(2) = 0.212; P = .0001) and was negatively associated with RMI significantly (R(2) = 0.203; P = .00096) significantly. Multiple regression analysis further showed that the post-RT parotid ADC was related to the radiation dose and RMI significantly (R(2) = 0.3580; P < .0001). At MR stage 3, the parotid volume was negatively associated with the dry mouth grade significantly (R(2) = 0.473; P < .0001), while the parotid ADC was positively associated with the dry mouth grade significantly (R(2) = 0.288; P = .015). CONCLUSION: Our pilot study successfully demonstrates the concurrent changes and temporal evolution of parotid volume and parotid ADC quantitatively in NPC patients treated by IMRT. Our results suggest that the reduction of parotid volume and increase of parotid ADC are dominated by the effect of acinar loss rather than edema at early to intermediate phases and the following recovery of parotid volume and ADC toward the baseline values might reflect the acinar regeneration of parotid glands.

Effect of low-level laser therapy on radiotherapy-induced hyposalivation and xerostomia: a pilot study.

OBJECTIVE: The present pilot study aimed to assess the effect of low-level laser therapy (LLLT) on hyposalivation and xerostomia as a consequence of head and neck radiotherapy. BACKGROUND DATA: The benefits of LLLT in salivary flow have been shown; however, there are no studies investigating its effects on patients who have already undergone radiotherapy and present hyposalivation and xerostomia as a sequela. METHODS: Twenty-three patients with a history of head and neck malignancy, who were treated by fractioned teletherapy (dosimetry ranging from 45 to 70 Gy) in the cervicofacial region were selected. They all presented with xerostomia and severe hyposalivation. Patients were randomly distributed into a laser group (n=12) and a control group (n=11). A GaAlAs laser (830 nm, 100 mW, illuminated area 0.028 cm2, 3.57 W/cm2, 20 sec, 2.0 J, 71 J/cm2) was used punctually in the major salivary glands, twice a week for 6 weeks, with a 12 session total. Stimulated and unstimulated salivary flow rate (SFR) were assessed, as well as the xerostomia and quality of life related to oral health (QLROH). RESULTS: The analysis did not show any significant difference between the groups with regards to the SFR and xerostomia, and the QLROH. However, at the end of the treatment, the xerostomia and the QLROH showed significant improvement in both groups compared with assessments performed at baseline, highlighting the importance of advice given to the irradiated patients, and their follow-up. CONCLUSIONS: With the parameters used, LLLT was not able to increase SFR or decrease xerostomia. The results may be associated with the late effects of radiotherapy on glandular structure, such as fibrosis and acinar atrophy.

Using multivariate regression model with least absolute shrinkage and selection operator (LASSO) to predict the incidence of Xerostomia after intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. METHODS AND MATERIALS: Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3(+) xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R(2), chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. RESULTS: Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R(2) was satisfactory and corresponded well with the expected values. CONCLUSIONS: Multivariate NTCP models with LASSO can be used to predict patient-rated xerostomia after IMRT.

[The effects of low-level laser therapy on xerostomia (mouth dryness)].

INTRODUCTION: Xerostomia is a subjective complaint of mouth/oral dryness, caused by a reduction in normal salivary secretion due to different causes. Even though there are many available treatment modalities to enhance salivary flow, the therapy often remains unsatisfactory. The low-level laser therapy (low-level laser irradiation, photo-biomodulation) has been extensively used as a new, non-invasive approach and advantageous tool for reduction of xerostomia. Therefore, the aim of this study is to give a systematic overview on the effects of low-level laser therapy on xerostomia. MATERIAL AND METHODS: A systematic review of published articles in PubMed database was carried out using keywords: "low-level laser therapy", "xerostomia", "mouth dryness". RESULTS: In all published articles, which were considered adequate for this overview, positive effects of low-level laser therapy were reported. Low-level laser therapy could significantly enhance salivary secretion and improve antimicrobial characteristics of secreted saliva (increased level of secretory immunoglobulin A; sIgA). Furthermore, low-level laser therapy could improve salivary flow and regeneration of salivary duct epithelial cells. CONCLUSION: The current literature suggests that low-level laser therapy can be safely and effectively used as an advanced treatment modality for reduction of xerostomia. Further in vivo, in vitro and clinical studies using different irradiation parameters are suggested to determine the best laser parameters to be used.