Electromyography findings in radiation-induced unilateral tongue immobility.

BACKGROUND: We used electromyography to characterize hypoglossal nerve function among radiation-treated head and neck cancer survivors with later onset unilateral tongue immobility. METHODS: Patients with unilateral tongue immobility without evidence of recurrent cancer were seen at a tertiary academic institution between February and September 2021. All patients were at least 2 years post-treatment with radiation therapy for head and neck squamous cell carcinoma. Participants were under annual surveillance and displayed no evidence of operative injury to the hypoglossal nerve. RESULTS: The median symptom-free interval for the 10 patients included in this study was 13.2 years (range 2-25 years). Myokymia alone was present in 3 of 10 patients, fibrillation potentials alone were present in 3 of 10 patients, and 1 subject displayed both fibrillation and myokymia. Three out of 10 patients had normal hypoglossal nerve function. DISCUSSION: These findings highlight how disparate mechanisms may underlie similar clinical presentations of radiation-induced neuromuscular dysfunction.

Locally administered heparin-binding epidermal growth factor-like growth factor reduces radiation-induced oral mucositis in mice.

Oral mucositis refers to lesions of the oral mucosa observed in patients with cancer being treated with radiation with or without chemotherapy, and can significantly affect quality of life. There is a large unmet medical need to prevent oral mucositis that can occur with radiation either alone or in combination with chemotherapy. We investigated the efficacy of locally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent epithelial proliferation and migration stimulator of the oral mucosa as a potential therapy to prevent radiation induced oral mucositis. Using a single dose (20 Gy) of radiation to the oral cavity of female C57BL/6 J mice, we evaluated the efficacy of HB-EGF treatment (5 µl of 10 µg/ml) solution. The results show that HB-EGF delivered post radiation, significantly increased the area of epithelial thickness on the tongue (dorsal tongue (42,106 vs 53,493 µm2, p < 0.01), ventral tongue (30,793 vs 39,095 µm2, *p < 0.05)) compared to vehicle control, enhanced new epithelial cell division, and increased the quality and quantity of desmosomes in the oral mucosa measured in the tongue and buccal mucosa. This data provides the proof of concept that local administration of HB-EGF has the potential to be developed as a topical treatment to mitigate oral mucositis following radiation.

Characterization of very late dysphagia after chemoradiation for oropharyngeal squamous cell carcinoma.

OBJECTIVES: Improved prognosis for p16+ oropharyngeal squamous cell carcinoma (OPSCC) has led to efforts to mitigate long-term complications of treatment, which remains poorly defined in late survivors. Here we characterize very late dysphagia in OPSCC. MATERIALS AND METHODS: Long-term review of 93 p16+ OPSCC patients treated with chemoradiation was performed. We scored videofluoroscopic swallow studies (VFSS) according to the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Very late dysphagia was defined >2.5 years from end of treatment. Fine-Gray regression models were used to assess dysphagia with competing risk of death. RESULTS: Median follow up was 10.5 years. 402 total VFSS were assessed (median 4 per patient, range 0-8). 15.1% of patients had a DIGEST score ≥2 very late after treatment. Very late DIGEST score ≥2 correlated with T-stage (HR 1.7, p = 0.049), second cancer (HR 6.5, p = 0.004), superior pharyngeal constrictor dose (HR 1.11, p = 0.050), total tongue dose (HR 1.07, p = 0.045), but not hypoglossal nerve dose (p > 0.2). Seven patients (7.5%) had late progressive dysphagia, defined as DIGEST score that increased by ≥2 beyond one year after treatment, and this correlated with higher ipsilateral hypoglossal nerve D1cc dose (75 vs 72 Gy, p = 0.037). CONCLUSION: In p16+ OPSCC patients treated with definitive chemoradiation, at least 7.5% developed late progressive dysphagia, and 15.1% experienced moderate dysphagia >2.5 years from treatment. Our study suggests that dose to tongue musculature may be associated with very late dysphagia, and hypoglossal nerve dose may be associated with late progressive dysphagia. More intensive long-term dysphagia survivorship monitoring is suggested.

Photobiomodulation by low-level laser therapy in patients with obstructive sleep apnea: Study protocol clinical trial (SPIRIT compliant).

Obstructive sleep apnea (OSA) increases morbidity and mortality and it is associated with an increased cardiovascular risk. The gold standard treatment for OSA is positive airway pressure therapy (CPAP). However, it is an expensive treatment and several patients do not adapt to CPAP. GOAL: The researchers will verify the effects of low-level laser therapy (LLLT) on OSA, when applied to the soft palate and on the tongue base. METHODS: The researchers will select individuals of both sexes aged 30 to 60 years old who are sedentary and that present a high risk of OSA by the Berlin questionnaire. The evaluations pre and post interventions will be polysomnography; anthropometric and body composition measurements (Bioimpedance); metabolic syndrome risk factors (International Diabetes Federation); physical capacity (VO2 peak at the cardiopulmonary exercise test, CPET); endothelial function (flow-mediated dilatation, FMD); autonomic control (heart rate variability and sympathovagal balance). Those diagnosed with moderate and severe OSA (apnea/hypopnea index, AHI ≥15 events/h) will be invited to participate in the study and they will be randomized into 2 groups: LLLT treatment or placebo (C). The LLLT group will receive applications at 8 points on the soft palate and on the base of the tongue for 8 seconds for each point. The applications of LLLT will occur twice a week, with a minimum interval of 2 days between the applications for 2 months, when using a Therapy Plus NS 13678 Laser. The C group will have similar applications, but with the device turned off. EXPECTED RESULTS: In the individuals with OSA, photobiomodulation through LLLT will decrease the AHI. Additionally, when LLLT is applied in the oral cavity, a highly vascularized region, this may cause improvements in the vascular function and in the autonomic and hemodynamic control. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committee of the Nove de Julho University, São Paulo, Brazil, on the date of March 11, 2019 (CAAE: 06025618.2.0000.5511 - Acceptance Number: 3.191.077). This trial has been registered with the Brazilian Registry of Clinical Trials (REBEC TRIAL RBR-42v548). This study is not yet recruiting. Issue date: November 4, 2019.

Decreased Tongue Volume Post Radiation.

OBJECTIVES: To evaluate volume changes within the tongue post chemoradiation therapy (CRT). STUDY DESIGN: Retrospective review. SETTING: Academic Medical Center. SUBJECTS AND METHODS: Subjects included 19 patients that received CRT as the primary treatment for tonsillar or hypopharynx squamous cell carcinoma. Tongue volumes were calculated by three raters from thin slice computed tomography images collected before treatment and up to 29 months post-CRT. Body mass index (BMI) was also collected at each time point. RESULTS: Inter-rater reliability was high with an ICC of 0.849 (95% CI = 0.773, 0.905). Linear mixed effects modeling showed a mean decrease of 0.45 cm3 (standard error of the mean [SEM] = 0.11) in tongue volume per month post-CRT (P < .001). However, the addition of BMI to the model was significant (χ2 (4) = 25.0, P < .001), indicating that BMI was a strong predictor of tongue volume, with a mean decrease of 1.75 cm3 (SEM = 0.49) in tongue volume per unit decrease in BMI (P < .001) and reducing the post-CRT effect on tongue volume decrease per month to 0.23 cm3 (P = .02). BMI significantly (P < .001) decreased by 0.11 units (SEM = 0.02) per month post radiation. CONCLUSION: Tongue dysfunction and decreased tongue strength are significant contributors to the dysphagia that patients experience after receiving CRT. In this study, both tongue volume and BMI decreased post-CRT; therefore, BMI could potentially be used as a predictor of tongue volume post-CRT.

Targeted Intervention to Improve the Quality of Head and Neck Radiation Therapy Treatment Planning in the Netherlands: Short and Long-Term Impact.

PURPOSE: To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed. METHODS AND MATERIALS: A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases. RESULTS: Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable. CONCLUSIONS: Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols.

Development of a semi-customized tongue displacement device using a 3D printer for head and neck IMRT.

PURPOSE: To reduce radiation doses to the tongue, a patient-specific semi-customized tongue displacement device (SCTDD) was developed using a 3D printer (3DP) for head and neck (H&N) radiation therapy (RT). Dosimetric characteristics of the SCTDD were compared with those of a standard mouthpiece (SMP). MATERIALS AND METHODS: The SCTDD consists of three parts: a mouthpiece, connector with an immobilization mask, and tongue displacer, which can displace the tongue to the contralateral side of the planning target volume. Semi-customization was enabled by changing the thickness and length of the SCTDD. The instrument was printed using a 3DP with a biocompatible material. With the SCTDD and SMP, two sets of planning computed tomography (CT) and tomotherapy plans were obtained for seven H&N cancer patients. Dosimetric and geometric characteristics were compared. RESULTS: Using the SCTDD, the tongue was effectively displaced from the planning target volume without significant tongue volume change compared to the SMP. The median tongue dose was significantly reduced (29.6 Gy vs. 34.3 Gy). The volumes of the tongue receiving a dose of 15 Gy, 30 Gy, 35 Gy, 45 Gy, and 60 Gy were significantly lower than using the SMP. CONCLUSION: The SCTDD significantly decreased the radiation dose to the tongue compared to the SMP, which may potentially reduce RT-related tongue toxicity.

Evolution of self-perceived swallowing function, tongue strength and swallow-related quality of life during radiotherapy in head and neck cancer patients.

BACKGROUND: Radiation-associated-dysphagia is a serious side effect of radiotherapy (RT) for head and neck cancer (HNC). METHODS: Seventy-six patients had a weekly prospective follow-up from baseline until one week post-RT. Combined mixed model analysis (n = 43) determined the evolution of self-perceived swallowing function, isometric tongue strength (MIP), tongue strength (TS) during swallowing (Pswal), and quality of life (QoL) in these patients during RT. RESULTS: Swallowing deteriorated from the third week on, resulting in an increase of tube dependency from 10% at baseline toward 31% post-RT. Both MIP and Pswal are reduced, with anterior MIP decreasing in 29% of patients and posterior MIP in 17%. Pswal decreases for saliva and a bolus swallow. All QoL subscales except "sleep" were affected during RT. CONCLUSIONS: Self-perceived swallowing function, TS and QoL decrease during RT for HNC. Current findings highlight the need for early monitoring of these parameters.

Functional Swallowing Units (FSUs) as organs-at-risk for radiotherapy. PART 1: Physiology and anatomy.

BACKGROUND AND PURPOSE: When optimising radiotherapy treatments today, the pharyngeal constrictor muscles and the larynx are usually regarded as the swallowing organs at risk (SWOARs). The purpose of this study was to identify and describe additional, previously undefined groups of muscles (functional units) involved in crucial components of swallowing (hyolaryngeal elevation (HLE), tongue base retraction (TBR) and tongue motion), and to emphasise their relevance in radiation-induced dysphagia. MATERIAL AND METHODS: Based on available literature on human anatomy and swallowing physiology, the functional units of muscles involved in HLE, TBR and tongue motion have been identified and described. RESULTS AND CONCLUSION: Functional swallowing units (FSUs) were defined as groups of swallowing muscles sharing their function, that are in close proximity to each other. Seven FSUs involved in HLE, TBR and tongue motion were identified: floor of mouth, thyrohyoid muscles, posterior digastric/stylohyoid muscles complex, longitudinal pharyngeal muscles, hyoglossus/styloglossus muscles complex, genioglossus muscles, intrinsic tongue muscles. The swallowing physiology and anatomy of the FSUs described in this paper will lead to a greater understanding of radiation-induced dysphagia mechanisms and, consequently, to an improvement in the development of swallowing sparing strategies. This article (PART 1) serves as the theoretical foundation for a subsequent article (PART 2), which provides detailed delineation guidelines for FSUs.

Temperature and depth evaluation of the in vitro effects of femtosecond laser on oral soft tissue, with or without air-cooling.

Femtosecond laser is an effective and safe tool in many surgeries, but the studies of its effect on oral soft tissue ablation are insufficient. This study aimed to investigate the effect of soft tissue ablation with a 1030-nm femtosecond laser on temperature and depth. Twenty Sprague-Dawley rat tongue specimens were obtained and flat-mounted. The 1030-nm femtosecond laser was controlled by a computer system, with a set distance of 4.7 mm between the laser aperture and soft tissue surfaces. Ten specimens were ablated for > 1 min with or without air-cooling for temperature measurement, while the other 10 specimens were ablated for depth measurements, using the following parameters: (i) 3 W, 2000 mm/s; (ii) 3 W, 4000 mm/s; (iii) 5 W, 2000 mm/s; (iv) 5 W, 4000 mm/s; (v) 8 W, 2000 mm/s; (vi) 8 W, 4000 mm/s. Temperature changes were measured using a type-K thermocouple. The depth attained using different power and scanning speed settings was measured by a three-dimensional morphology measurement laser microscope. Laser power, scanning speed, and air-cooling effects were determined. Higher energy and lower speed induced higher temperatures (p < 0.05), which were significantly decreased by air-cooling (p < 0.05). The lowest ablation depth was obtained at 3 W and 4000 mm/s (72.63 ± 6.47 µm) (p < 0.05). The greatest incision depth was achieved at 8 W and 2000 mm/s (696.19 ± 35.37 µm), or 4000 mm/s (681.16 ± 55.65 µm) (p < 0.05). The 1030-nm femtosecond laser application demonstrates clinically acceptable ablation efficiency, without marked temperature damage, in a controlled manner.

Comparison of the IPSA and HIPO algorithms for interstitial tongue high-dose-rate brachytherapy.

PURPOSE: This study aimed to compare the inverse planning simulated annealing (IPSA) stochastic algorithm with the hybrid inverse planning and optimization (HIPO) algorithm for interstitial tongue high-dose-rate (HDR) brachytherapy. METHODS: Twenty patients who received radiotherapy for tongue cancer using interstitial HDR brachytherapy were retrospectively selected for this study. Oncentra Brachy v. 4.3 was used for IPSA and HIPO planning. Four to eight fixed catheter configurations were determined according to the target shape. During the optimization process, predetermined constrain values were used for each IPSA and HIPO plan. The dosimetric parameters and dwell time were analyzed to evaluate the performances of the plans. RESULTS: The total dwell time using IPSA was 4 seconds longer than that of HIPO. The number of active positions per catheter for the IPSA plans were approximately 2.5 fewer than those of the HIPO plans. The dose-volumetric parameters related to the clinical target volume with IPSA were lower than those with HIPO. In terms of the dose-volumetric parameters related to normal tissue, HIPO tended to associate with slightly higher values than IPSA, without statistical significance. After GrO, the target coverages were satisfied to clinical goal for all patients. The total dwell times was approximately increased by 10%. CONCLUSIONS: The IPSA and HIPO dose optimization algorithms generate similar dosimetric results. In terms of the dwell time, HIPO appears to be more beneficial.

Effects of ionizing radiation and HPSE1 inhibition on the invasion of oral tongue carcinoma cells on human extracellular matrices in vitro.

Chemoradiation is an established approach in the treatment of advanced oral tongue squamous cell carcinoma (OTSCC), but therapy may cause severe side-effects due to signal interchanges between carcinoma and the tumour microenvironment (TME). In this study, we examined the potential use of our human 3D myoma disc and Myogel models in in vitro chemoradiation studies by analysing the effects of ionizing radiation (IR) and the combined effect of heparanase I (HPSE1) inhibitors and IR on OTSCC cell proliferation, invasion and MMP-2 and - 9 production. Finally, we analysed the long-term effects of IR by studying clones of previously irradiated and invaded HSC-3 cells. We found that in both human uterine leiomyoma-based extracellular matrix models IR inhibited the invasion of HSC-3 cells, but blocking HPSE1 activity combined with IR induced their invasion. Low doses of IR increased MMP expression and initiated epithelial-mesenchymal transition in cells cultured on myoma discs. We conclude that myoma models offer consistent methods for testing human carcinoma cell invasion and phenotypic changes during chemoradiation treatment. In addition, we showed that IR had long-term effects on MMP-2 and - 9, which might elicit different HSC-3 invasion responses when cells were under the challenge of HPSE1 inhibitors and IR.

Protective effects of systemic dermatan sulfate treatment in a preclinical model of radiation-induced oral mucositis.

PURPOSE: Oral mucositis is a frequent, dose-limiting side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is based on multiple tissue changes, which could offer targets for a biologically tailored treatment. The potential of dermatan sulfate (DS) to modulate radiation-induced oral mucositis was tested in an established preclinical mucositis model. METHODS: Irradiation was either applied alone or in combination with daily DS treatment (4 mg/kg, subcutaneously) over varying time intervals. Irradiation comprised single dose irradiation with graded doses to the lower tongue surface or daily fractionated irradiation of the whole tongue. Fractionation protocols (5â€¯× 3 Gy/week) over one (days 0-4) or two weeks (days 0-4, 7-11) were terminated by an additional local single dose irradiation to a defined treatment field on the lower tongue surface to induce the mucosal radiation response. The additional single dose irradiation (top-up) on day 7 (after one week of fractionation) or day 14 (after 2 weeks of fractionation) comprised graded doses in order to generate full dose-effect curves. Ulceration of the epithelium of the lower tongue, corresponding to confluent mucositis, was analysed as clinically relevant endpoint. Additionally, the time course parameters, latent time and ulcer duration were analysed. RESULTS: DS treatment significantly reduced the incidence of ulcerations. DS application over longer time intervals resulted in a more pronounced reduction of ulcer frequency, increased latent times and reduced ulcer duration. CONCLUSION: DS has a significant mucositis-ameliorating activity with pronounced effects on mucositis frequency as well as on time course parameters.

Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis.

Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR2-overexpressing MSCs (MSCsCXCR2) for mucositis treatment. Indeed, MSCsCXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSCCXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

Outpatient erbium:YAG (2940 nm) laser treatment for snoring: a prospective study on 40 patients.

Snoring is a sleep phenomenon due to the partial upper airway obstruction during sleep which causes vibration of the tissues of the rhino-oro-hypopharynx and less frequently the larynx. This study evaluated the use and effectiveness of the erbium:YAG 2940-nm laser as an adjunctive in providing treatment for patients suffering from chronic snoring-related sleep disorders. A prospective study of 40 consecutive patients with snoring and sleep disorders was performed, assessing data before and after three Er:YAG laser treatment sessions. During laser treatment, the pain was almost absent. There were no side effects, except a very mild sore throat in 1 out of 40 patients. The patient's evaluation of satisfaction of the results obtained after the treatments showed that 85% of cases were very satisfied, 5 patients (12.5%) reported being fairly satisfied with the treatment and only 1 subject (2.5%) was not satisfied. Mallampati, Friedman Tongue Position, and degree of O (oropharynx) at nose oropharynx hypopharynx and larynx classification were significantly decreased after the laser sessions. The decrease of Epworth Sleepiness Scale and Visual Analogue Scale for loudness of snoring, waking up during sleep because of snoring, dry mouth on waking, and choking was all statistically significant. The incidence of dreaming during the night also raised significantly; 30/40 (75%) of cases perceived less tightness in their throat and better breathing after treatment. These results were stable at 20 months follow-up (14-24 q) in 72% of cases. Nonsurgical and non-invasive Er:YAG laser treatment demonstrated to be a valid procedure in reducing the loudness of snoring.

940-nm Diode Laser-Assisted Management of Tongue Abscess.

The tongue is a muscular organ with a rich blood supply and acts as an immune defence mechanism. The occurrence of a tongue abscess without immune deficiency is rare. The purpose of this report is to present the case of an eight-year-old boy with a spherical, pinkish-yellow, fluctuant, nontender swelling measuring two cm in diameter on the right anterolateral border of the tongue, causing difficulty in swallowing and speaking. Ultrasonography was performed, followed by a 940-nm diode laser-assisted incision and drainage under local anesthesia. Healing was uneventful, with no recurrence for two years now. A tongue abscess can be life-threatening due to its ability to cause respiratory obstruction. The diode laser can be a safe and effective tool for its management.

The effects of concurrent chemoradiation therapy to the base of tongue in a preclinical model.

OBJECTIVES/HYPOTHESIS: To develop a clinically relevant model of oropharyngeal concurrent chemoradiation therapy (CCRT) in order to quantify the effects of CCRT on tongue function and structure. CCRT for advanced oropharyngeal cancer commonly leads to tongue base dysfunction and dysphagia. However, no preclinical models currently exist to study the pathophysiology of CCRT-related morbidity, thereby inhibiting the development of targeted therapeutics. STUDY DESIGN: Animal model. METHODS: Twenty-one male Sprague-Dawley rats were randomized into three groups: 2 week (2W), 5 month (5M), and control (C). The 2W and 5M animals received cisplatin, 5-fluorouracil, and five fractions of 7 Gy to the tongue base; the C animals received no intervention. In vivo tongue strength and displacement, as well as hyoglossus muscle collagen content, were assessed. Analyses were conducted 2 weeks or 5 months following completion of CCRT in the 2W and 5M groups, respectively. RESULTS: Peak tetanic and twitch tongue forces were significantly reduced in both 2W and 5M animals compared to controls (tetanic: P = .0041, P = .0089, respectively; twitch: P = .0201, P = .0020, respectively). Twitch half-decay time was prolonged in 2W animals compared to controls (P = .0247). Tongue displacement was significantly reduced across all testing parameters in 5M animals compared to both the C and 2W groups. No differences in collagen content were observed between experimental groups. CONCLUSIONS: The current study is the first to describe a preclinical model of CCRT to the head and neck with an emphasis on clinical relevance. Tongue strength decreased at 2 weeks and 5 months post-CCRT. Tongue displacement increased only at 5 months post-CCRT. Fibrosis was not detected, implicating alternative causative factors for these findings. LEVEL OF EVIDENCE: NA Laryngoscope, 1783-1790, 2018.

Tongue-out versus tongue-in position during intensity-modulated radiotherapy for base of tongue cancer: Clinical implications for minimizing post-radiotherapy swallowing dysfunction.

BACKGROUND: The purpose of this study was to assess whether different tongue positions change the radiation doses to swallowing organs at risks: the pharyngeal constrictor, oral cavity, and larynx during intensity-modulated radiotherapy (IMRT) for base of tongue (BOT) cancer. METHODS: IMRT plans with Tongue-out (IMRT-TO) and tongue-in position (IMRT-TI) was compared in 3 cases. RESULTS: Distance from BOT to pharyngeal constrictor was increased to 1.8 ± 0.8 cm with IMRT-TO from 0.9 ± 0.6 cm with IMRT-TI (P < .01). Compared to IMRT-TI, IMRT-TO significantly decreased the radiation dose to the anterior oral cavity, oral tongue, superior pharyngeal constrictor, middle pharyngeal constrictor, and supraglottic larynx (all P ≤ .04). IMRT-TO also had a smaller volume irradiated than IMRT-TI to the anterior oral cavity and the oral tongue receiving ≥30 Gy (V30) and V35, and superior pharyngeal constrictor and middle pharyngeal constrictor for V55 and V65 (all P ≤ .04). CONCLUSION: Dosimetric advantage with IMRT-TO over IMRT-TI may potentially reduce post-IMRT swallowing dysfunction in selected patients with BOT cancer.

Melatonin protects rats from radiotherapy-induced small intestine toxicity.

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.

Early inflammatory changes in radiation-induced oral mucositis : Effect of pentoxifylline in a mouse model.

PURPOSE: Early inflammation is a major factor of mucosal reactions to radiotherapy. Pentoxifylline administration resulted in a significant amelioration of radiation-induced oral mucositis in the mouse tongue model. The underlying mechanisms may be related to the immunomodulatory properties of the drug. The present study hence focuses on the manifestation of early inflammatory changes in mouse tongue during daily fractionated irradiation and their potential modulation by pentoxifylline. MATERIALS AND METHODS: Daily fractionated irradiation with 5 fractions of 3 Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were euthanized every second day between day 0 and 14. Pentoxifylline (15 mg/kg, s. c.) was administered daily from day 5 to the day before sacrifice. The expression of the inflammatory proteins TNFα, NF-κB, and IL-1ß were analysed. RESULTS: Fractionated irradiation increased the expression of all inflammatory markers. Pentoxifylline significantly reduced the expression of TNFα and IL-1ß, but not NF-κB. CONCLUSION: Early inflammation, as indicated by the expression of the inflammatory markers TNFα, NF-κB, and IL-1ß, is an essential component of early radiogenic oral mucositis. Pentoxifylline differentially modulated the expression of different inflammatory markers. The mucoprotective effect of pentoxifylline does not appear to be based on modulation of NF-κB-associated inflammation.