Comparison of Doses to Parotid, Temporomandibular Joint, and Pharyngeal Constrictor Muscles Using Different Techniques in Radiotherapy for Oropharyngeal Cancer.

OBJECTIVE: The purpose of this research was to compare two treatment techniques for oropharyngeal cancers: conventional linac-based static intensity-modulated radiotherapy (sIMRT) and helical tomotherapy (HT). The study examined several parameters, including target coverage, organs at risk, integral dose, and beam on time. Additionally, the study evaluated the doses to the parotid, temporomandibular joint, and pharyngeal constrictor muscles, which are important for swallowing. METHOD: The present study retrospectively analyzed the data of 13 patients with oropharyngeal cancer who underwent radiotherapy between 2019 and 2021. The treatment plans for each patient were regenerated using both sIMRT and HT treatment planning systems with the sequential boost method. The techniques were evaluated and compared based on dose-volume histogram, homogeneity index, and conformity index parameters. The target coverage and organs at risk were statistically compared for two techniques. Additionally, the doses received by the healthy tissue volume were obtained for integral dose evaluation. The beam on time for each technique was assessed. RESULTS: When considering planning target volume evaluation, there was no difference in Dmeans between the two techniques and sIMRT demonstrated higher D2% values compared to the HT. The HT technique had better results for all organs at risk, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle. As for integral dose, it has been shown that the sIMRT technique provides better protection compared to HT. In addition, the beam on time was also longer with the HT technique. CONCLUSION: Both techniques may provide optimal target coverage for patients with oropharyngeal cancer. HT conferred notable advantages, especially with regard to critical structures implicated in swallowing, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle, in comparison to sIMRT.

Preliminary Simulation Study of Carotid Artery and Pharyngeal Constrictor Muscle Sparing-Radiotherapy in Glottic Carcinoma.

BACKGROUND: This preliminary simulation study aimed to compare the dosimetric outcomes of carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) in patients with T1N0M0 glottic carcinoma undergoing helical tomotherapy-intensity modulated radiotherapy (HT-IMRT) and 3-dimensional conformal radiotherapy (3D-CRT) plans. METHODS: In addition to the clinical target volume (CTV) which was defined as the entire larynx, the CAs and PCM of 11 glottic carcinoma patients were delineated. The CTV was uniformly expanded 5 mm to create a planning target volume (PTV) relative to the PCM and at a distance of 2 mm from the CA. The dosimetric characteristics in HT-IMRT and lateral opposed fields-based 3D-CRT plans were analyzed. RESULTS: Median D95%and V100% of PTV were significantly higher in HT-IMRT (p < 0.001) compared to 3D-CRT. The right/left CA dosimetric outcomes, including the mean doses (20.7/21.5 Gy versus 48.7/50.5 Gy), Dmax (53.6/52.0 Gy versus 67.4/67.7 Gy), V30 (25.0/27.1% versus 77.6/80.3%), V40 (8.0/7.9% versus 74.6/71.9%), and V50 (2.0/1.2% versus 70.0/71.6%) were also significantly lower in HT-IMRT (p < 0.05), similar to the mean PCM doses (49.6 Gy versus 62.6 Gy for 3D-CRT;p < 0.001), respectively. CONCLUSIONS: Our present results demonstrated the feasibility of simultaneous sparing of the CAs and PCM in HT-IMRT- compared to 3D-CRT plans in glottic carcinoma patients undergoing definitive radiotherapy.

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.

The Changes in Pharyngeal Constrictor Muscles Related to Head and Neck Radiotherapy: A Systematic Review.

It is well known that radiation damage of the pharyngeal constrictor muscles, the glottic larynx, and the supraglottic larynx may lead to dysphagia, an unwanted effect of head and neck radiotherapy. The reduction of radiotherapy-induced dysphagia might be achieved by adaptive radiotherapy. Although the number of studies concerning adaptive radiotherapy of head and neck cancer is continuously increasing, there are only a few studies concerning changes in dysphagia-related structures during radiotherapy.The goal of this review is to summarize the current knowledge about volumetric, dosimetric, and other changes of the pharyngeal constrictor muscles associated with head and neck radiotherapy. A literature search was performed in the MEDLINE database according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The conclusions of 8 studies that passed the criteria indicate a significant increase in the volume and the thickness of the pharyngeal constrictor muscles during radiotherapy. Moreover, the changes in magnetic resonance imaging signal intensity of the pharyngeal constrictor muscles correlate with the absorbed dose (typically higher than 50 Gy) and also with the grade of dysphagia. This systematic review presents 2 variables, which are suitable for estimation of radiotherapy-related pharyngeal constrictor muscles changes-magnetic resonance imaging signal intensity and the thickness. In the case of the thickness, there is no consensus in the level of the measurement-C2 vertebra, C3 vertebra, and the middle of the craniocaudal axis are used. It seems that reference to a position associated with a vertebral body could be more reproducible and beneficial for future research. Although late pharyngeal toxicity remains a challenge in head and neck cancer treatment, better knowledge of radiotherapy-related changes in the pharyngeal constrictor muscles contributes to adaptive radiotherapy development and thus improves the treatment results.

Influence of radiation dose to pharyngeal constrictor muscles on late dysphagia and quality of life in patients with locally advanced oropharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: Patients with oropharyngeal carcinoma (OPC) often have difficulty swallowing, which may affect quality of life (QoL). Radiation dose to constrictor muscles plays an important role. METHODS: 54 patients with locally advanced OPC were evaluated after intensity-modulated radiotherapy. Data were collected at standardized intervals using the EORTC questionnaires QLQ-C30 and QLQ-HN35 within two years. The pharyngeal constrictors (superior, middle, and inferior) were each contoured as an organ at risk. Influence of dose to the constrictors (≥55 Gy vs. <55 Gy) on late dysphagia and QoL was analyzed using the t­test. RESULTS: Late radiation-induced dysphagia depends significantly on the dose to the lower pharyngeal constrictor. At a dose of ≥55 Gy, 14 (64%) patients developed dysphagia grade ≤2 and 8 (36%) patients grade ≥3. At a dose of <55 Gy, the distribution at the end of radiotherapy (RT) was similar: 22 (69%) patients with dysphagia grade ≤2, 10 (31%) with grade ≥3. There was no dose-dependent difference in the severity of dysphagia in the acute phase (p = 0.989). There were differences 18 months after the end of RT: ≥55 Gy: 19 (86%) patients showed dysphagia grade ≤2; 3 (14%) grade ≥3. At <55 Gy, 31 (97%) patients developed grade ≤2, 1 (3%) grade ≥3 (18 months: p = 0.001; 24 months: p = 0.000). Late dysphagia is also dependent on the dose level of the middle constrictor muscle (6 months: p = 0.000; 12 months: p = 0.005, 18 months: p = 0.034). After 24 months, there was no significant difference (p = 0.374). CONCLUSION: Radiation dose to the upper constrictor muscle appears to be of little relevance. The middle and lower constrictor should be given special consideration to avoid late dysphagia. Long-term QoL is independent on radiation dose.

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.

A prospective longitudinal assessment of MRI signal intensity kinetics of non-target muscles in patients with advanced stage oropharyngeal cancer in relationship to radiotherapy dose and post-treatment radiation-associated dysphagia: Preliminary findings from a randomized trial.

PURPOSE: To assess quantitative signal intensity (SI) kinetics obtained from serial MRI of swallowing muscles as a potential imaging biomarker of radiation-induced dysphagia in oropharyngeal cancer (OPC) patients receiving radiotherapy (RT). METHODS: Patients were enrolled under an IRB approved Phase II/III randomized trial. Patients underwent serial MRIs at pre-, mid-, and post-RT. Normalized T1, T1+ contrast (T1 + C), and T2 SI for swallowing muscle volumes-of-interest (VOIs) were collected and delta SI changes (Δ) were calculated. Mid- and post-RT SI relative to baseline were assessed and correlations between radiation dose and percent change in SI were calculated. Independent samples' t-tests were used to compare the percent change of SI between patients divided into two groups based on dysphagia status post-RT. RESULTS: Forty-six patients with stage III/IV HPV+ OPC were included in this study. Relative to baseline, mean T2 and T1 + C SIs for middle pharyngeal constrictor were both significantly higher at mid- and post-RT (p < 0.004 for all). Superior pharyngeal constrictor also showed a significant increase in T1 + C SI at mid-RT (p = 0.0004). Additional muscle VOIs showed significant changes post-RT, but not earlier at mid-RT. Both mid- and post-RT doses were significantly correlated with the percent change of normalized T2 and T1 + C SI for examined muscle VOIs (p < 0.002). Mean percent changes of normalized T2 SI at mid-RT relative to baseline for all muscle VOIs were significantly higher in patients who developed grade ≥2 dysphagia relative to patients with no/mild dysphasia (mean Δ%: 8.2% vs 1.9%; respectively, p = 0.002). However, at post-RT, these changes were only significant in T1 SI (11.2% vs -1.3%; p < 0.0001). CONCLUSION: Signal intensity kinetics of radiation injury can be broadly correlated with the functional muscular defect. Serial MRI during the course of RT may provide an opportunity to quantitatively track muscular pathology for subclinical detection of patients at high risk to develop dysphagia.

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.

Radiotherapy dose-volume parameters predict videofluoroscopy-detected dysphagia per DIGEST after IMRT for oropharyngeal cancer: Results of a prospective registry.

PURPOSE: Our primary aim was to prospectively validate retrospective dose-response models of chronic radiation-associated dysphagia (RAD) after intensity modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate a grade ≥2 cut-point of the published videofluoroscopic dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as radiation dose-dependent. MATERIAL AND METHODS: Ninety-seven patients enrolled on an IRB-approved prospective registry protocol with stage I-IV OPC underwent pre- and 3-6 month post-RT videofluoroscopy. Dose-volume histograms (DVH) for swallowing regions of interest (ROI) were calculated. Dysphagia severity was graded per DIGEST criteria (dichotomized with grade ≥2 as moderate/severe RAD). Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose-volume effects associated with moderate/severe RAD. RESULTS: 31% developed moderate/severe RAD (i.e. DIGEST grade ≥2) at 3-6 months after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid (GHM), superior pharyngeal constrictor (SPC), and supraglottic region were associated with DIGEST grade ≥2 RAD. V61 ≥ 18.57% of GHM demonstrated optimal model performance for prediction of DIGEST grade ≥2. CONCLUSION: The findings from this prospective longitudinal registry validate prior observations that dose to submental musculature predicts for increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use as an endpoint in trials or predictive dose-response analysis of videofluoroscopy results.

Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.

PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.

Dosimetric Predictors of Patient-Reported Xerostomia and Dysphagia With Deintensified Chemoradiation Therapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

PURPOSE/OBJECTIVE(S): To estimate the association between different dose-volume metrics of the salivary glands and pharyngeal constrictors with patient reported severity of xerostomia/dysphagia in the setting of deintensified chemoradiation therapy (CRT). METHODS AND MATERIALS: Forty-five patients were treated on a phase 2 study assessing the efficacy of deintensified CRT for favorable-risk, HPV-associated oropharyngeal squamous cell carcinoma. Patients received 60 Gy intensity modulated radiation therapy with concurrent weekly cisplatin (30 mg/m2), and reported the severity of their xerostomia/dysphagia (before and after treatment) using the patient-reported outcome version of the Common Terminology Criteria for Adverse Events (CTCAE) (PRO-CTCAE). Individual patient dosimetric data of the contralateral parotid and submandibular glands and pharyngeal constrictors were correlated with changes in PRO-CTCAE severity. A change in severity (from baseline) of ≥2 was considered clinically meaningful. Associations between dose-volume metrics and patient outcomes were assessed with receiver operating characteristic (ROC) curve and logistic regression model. RESULTS: Six months after CRT, patients reporting <2 change in xerostomia severity (n=14) had an average Dmean = 22 ± 9 Gy to the sum of the contralateral glands (parotid + submandibular) compared with the patients reporting ≥2 change (n=21), who had an average Dmean = 34 ± 8 Gy. V15 to V55 for the combined contralateral glands showed the strongest association with xerostomia (area under the curve [AUC] = 0.83-0.86). Based on the regression analysis, a 20% risk of toxicity was associated with V15 = 48%, V25 = 30%, and Dmean=21 Gy. Six months after CRT, patients reporting <2 change in dysphagia severity (n=26) had an average V55 = 76 ± 13 (%) to the superior pharyngeal constrictor compared with the patients reporting ≥2 change in severity (n=9), who had average V55 = 89 ± 13 (%). V55to V60 had the strongest association with dysphagia (AUC = 0.70-0.75). Based on the regression analysis, a 20% risk of toxicity was associated with V55 = 78%, V60 = 40%. The findings at 12 months were similar. CONCLUSIONS: After deintensified CRT, the rate of patient-reported xerostomia/dysphagia appears to be associated with the V15 of the combined contralateral salivary glands and V55 to V60 of the superior pharyngeal constrictors.

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.

Laryngeal tumours and radiotherapy dose to the cricopharyngeus are predictive of death from aspiration pneumonia.

OBJECTIVES: Aspiration pneumonia is an under-reported treatment sequelae following radiotherapy for head and neck cancer (HNC) patients. This study aims to investigate its incidence and risk factors in this population. MATERIALS AND METHODS: A retrospective review of all HNC patients that had received radiotherapy or chemo radiotherapy with radical intent at a single institution was undertaken (n=206). Dose delivered to the pharyngeal constrictors, base of tongue and cricopharyngeus was calculated and compared between those patients who had died from aspiration pneumonia and those who are alive or had died from other causes. RESULTS: In a cohort of 206 patients, the median time of follow up was 3.5years (IQR 1.8-4.9years). The cause of death was known in 80 and one of the leading causes of non-cancer related mortality was aspiration pneumonia (n=12) equating to an annual incidence of 0.016. Patients with a tumour located in the larynx had a higher risk of death compared to other sites (p=0.005). The mean cricopharyngeal dose was significantly higher in those patients who died of aspiration pneumonia (p=0.023) compared to those who were still alive or had died from other causes. In a multivariate regression analysis, maximum cricopharyngeal dose is a significant predictor of death from aspiration pneumonia. CONCLUSION: Dose to the cricopharyngeus and tumours located within the larynx is associated with an increased mortality due to aspiration pneumonia. Clinical awareness of high risk groups and more studies into causative nature are needed.

Dysphagia - Results from multivariable predictive modelling on aspiration from a subset of the ARTSCAN trial.

PURPOSE: To establish predictive models for late objective aspiration and late patient-reported choking based on dose-volume parameters and baseline patient and treatment characteristics, for patients with head and neck cancer undergoing definitive radiotherapy (RT). The impact of electively treated volume on late aspiration was also investigated. METHODS AND MATERIAL: This prospective cohort is a subsample of 124 survivors from the ARTSCAN study. Late aspiration was identified with videofluoroscopy, at a minimum of 25months after the start of RT. Patient-reported choking was analysed at 12 and 60months post RT using the EORTC Quality of Life Module for Head and Neck Cancer 35. Univariable and multivariable analyses were performed to describe the association between clinical factors and dose-volume descriptors for organs at risk (OARs) and late dysphagia. RESULTS: Aspiration was found in 47% of the eligible patients. Mean dose to the middle pharyngeal constrictor (MPC), neck dissection post RT and age at randomisation in ARTSCAN were associated to late aspiration. Mean dose to the superior pharyngeal constrictor (SPC) and swallowing complaints at baseline were associated to patient reported choking at both time-points. CONCLUSIONS: Three separate risk groups for late aspiration, and two risk groups for late patient-reported choking were identified based on number of risk factors. The size of the electively treated volume could be used as a surrogate for individual OARs predicting late aspiration.

[Head and neck intensity-modulated radiation therapy: Normal tissues dose constraints. Pharyngeal constrictor muscles and larynx]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures : dose de tolérance des tissus sains. Muscles constricteurs du pharynx et larynx.

Radio-induced pharyngolaryngeal chronic disorders may challenge the quality of life of head and neck cancer long survivors. Many anatomic structures have been identified as potentially impaired by irradiation and responsible for laryngeal edema, dysphonia and dysphagia. Some dose constraints might be plausible such as keeping the mean dose to the pharyngeal constrictor muscles under 50 to 55Gy, the mean dose to the supra-glottic larynx under 40 to 45Gy and, if feasible, the mean dose to the glottic larynx under 20Gy. A reduction of the dose delivered to the muscles of the floor of the mouth and the cervical esophagus would be beneficial as well. Nevertheless, the publications available do not provide an extensive enough level of proof. One should consider limiting as low as possible the dose delivered to these structures without compromising the quality of irradiation of the target tumor volumes.

Magnetic resonance imaging of swallowing-related structures in nasopharyngeal carcinoma patients receiving IMRT: Longitudinal dose-response characterization of quantitative signal kinetics.

BACKGROUND: We aim to characterize serial (i.e., acute and late) MRI signal intensity (SI) changes in dysphagia-associated structures as a function of radiotherapy (RT) in nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS: We retrospectively extracted data on 72 patients with stage III-IV NPC treated with intensity-modulated RT (IMRT). The mean T1- and T2-weighted MRI SIs were recorded for the superior pharyngeal constrictor (SPC) and soft palate (SP) at baseline, early-after IMRT, and last follow up, with normalization to structures receiving <5 Gy. RESULTS: All structures had a significant increase in T2 SIs early after treatment, irrespective of the mean dose given. At last follow-up, the increase in T2 SI subsided completely for SPC and partially for SP. The T1 SI did not change significantly in early follow-up images of both structures; on late follow-up, patients with mean doses >62.25 Gy had a significant decrease in the corresponding T1 SI for SPC (1.6 ± 0.4 vs. 1.3 ± 0.4, P=0.007) but decreased non-significantly for SP. CONCLUSIONS: Serial MRI acquisitions enable the identification of both early and late radiation-induced changes in swallowing structures after definitive IMRT for NPC. Dose dependent decrease in late T1 SI is associated with higher RT doses to the superior pharyngeal constrictor muscle; while dose independent increase in SI for both structures in early post-RT T2 images is observed and subsides after therapy. Further efforts will seek to elucidate the relationship between dose-dependent muscle SI changes and functional alteration of swallowing muscles.

Radiation dose to the tongue and velopharynx predicts acoustic-articulatory changes after chemo-IMRT treatment for advanced head and neck cancer.

The aim of this study was to investigate to what extent changes in speech after C-IMRT treatment are related to mean doses to the tongue and velopharynx (VP). In 34 patients with advanced hypopharyngeal, nasopharyngeal, or oropharyngeal cancer, changes in speech from pretreatment to 10 weeks and 1 year posttreatment were correlated with mean doses to the base of tongue (BOT), oral cavity (OC) and tonsillar fossa/soft palate (VP). Differences in anteroposterior tongue position, dorsoventral degree of tongue to palate or pharynx constriction, grooving, strength, nasality, and laryngeal rise, were assessed by acoustic changes in three speech sounds that depend on a (post-) alveolar closure or narrowing (/t/, /s/, /z/), three with a tongue to palate/pharyngeal narrowing (/l/, /r/, /u/), and in vowel /a/ at comfortable and highest pitch. Acoustically assessed changes in tongue positioning, shape, velopharyngeal constriction, and laryngeal elevation were significantly related to mean doses to the tongue and velopharynx. The mean dose to BOT predicted changes in anteroposterior tongue positioning from pre- to 10-weeks posttreatment. From pretreatment to 1-year, mean doses to BOT, OC, and VP were related to changes in grooving, strength, laryngeal height, nasality, palatalization, and degree of pharyngeal constriction. Changes in speech are related to mean doses to the base of tongue and velopharynx. The outcome indicates that strength, motility, and the balance between agonist and antagonist muscle forces change significantly after radiotherapy.

Long-term quality of life after swallowing and salivary-sparing chemo-intensity modulated radiation therapy in survivors of human papillomavirus-related oropharyngeal cancer.

PURPOSE: To evaluate long-term health-related quality of life (HRQOL) in 2 prospective studies of chemo-intensity modulated radiation therapy (chemo-IMRT) for oropharyngeal cancer (OPC). METHODS AND MATERIALS: Of 93 patients with stage III/IV OPC treated on prospective studies of swallowing and salivary organ-sparing chemo-IMRT, 69 were eligible for long-term HRQOL assessment. Three validated patient-reported instruments, the Head and Neck QOL (HNQOL) questionnaire, the University of Washington quality of life (UWQOL) questionnaire, and the Xerostomia Questionnaire (XQ), previously administered from baseline through 2 years in the parent studies, were readministered at long-term follow-up, along with the Short-Form 36. Long-term changes in HRQOL from before treatment and 2 years were evaluated. RESULTS: Forty patients (58%) with a median follow-up of 6.5 years participated, 39 of whom (97.5%) had confirmed human papillomavirus-positive OPC. Long term, no clinically significant worsening was detected in mean HRQOL scores compared with 2 years, with stable or improved HRQOL from before treatment in nearly all domains. "Moderate" or greater severity problems were uncommon, reported by 5% of patients for eating, 5% for swallowing, and 2.5% and 5% by HNQOL and UWQOL summary scores, respectively. Freedom from percutaneous endoscopic gastrostomy tube dependence and stricture dilation beyond 2 years was 97.5% and 95%, respectively. Eleven percent and 14% of patients reported "moderate" or "severe" long-term worsening in HNQOL Pain and Overall Bother domains, respectively, which were associated with mean dose to the cervical esophagus, larynx, and pharyngeal constrictors. CONCLUSIONS: At more than 6 years' median follow-up, OPC patients treated with swallowing and salivary organ-sparing chemo-IMRT reported stable or improved HRQOL in nearly all domains compared with both before treatment and 2-year follow-up. New late toxicity after 2 years was uncommon. Further emphasis on sparing the swallowing organs may yield additional HRQOL gains for long-term OPC survivors.

Rehabilitación de músculos orofaríngeos con ejercicios y electroterapia para el síndrome de apnea-hipoapnea obstructiva del sueño / Rehabilitation of oropharyngeal muscles with muscle reeducation and electrostimulation in obstructive sleep apnea syndrome

Introducción. El síndrome de apnea obstructiva del sueño (SAOS) tiene repercusiones importantes en la morbimortalidad de los pacientes. Los tratamientos alternos a la presión positiva continua en la vía aérea (CPAP) han resultado poco eficaces, poco seguros o de alta complejidad. Objetivo. Describir los efectos de un programa ambulatorio de reeducación de la musculatura orofacial y extralaríngea y aplicación de electroestimulación (TENS) aplicado a pacientes con SAOS en un hospital universitario de nivel III. Diseño. Estudio de serie de casos incidentes, prospectivo, con pacientes seleccionados consecutivamente. Material y métodos. Diecisiete pacientes con SAOS leve, moderado o severo que asistieron a 24 sesiones (3 semanales) de 30 minutos, de ejercicios orofaríngeos y electroestimulación. Los pacientes fueron evaluados al inicio y al final de la intervención mediante antropometría, polisomnografía, escala de somnolencia de Epworth, SAQLI y tolerancia al CPAP. La tolerancia al CPAP fue evaluada por una escala visual calificada de 1 a 10 (10 correspondía a tolerancia máxima). Las variables cualitativas se describieron en frecuencias y las variables cuantitativas en promedios o medianas dependiendo del tipo de distribución. Resultados. El índice de apnea-hipoapnea mejoró de 22 a 13 por hora, el SAQLI mejoró de 4,65 a 5,33 y Epworth pasó de 7 a 5 después de la intervención. La tolerancia al CPAP mejoró de 3 a 9. Las sesiones fueron bien toleradas, no se presentaron eventos adversos importantes. Cuatro pacientes presentaron dolor muscular facial. Conclusiones. Los ejercicios de reeducación con electroterapia son fáciles, reproducibles, seguros y potencialmente beneficiosos para el SAOS, con mínimos efectos secundarios (AU)

Introduction. Obstructive sleep apnea syndrome (OSA) is associated with increased morbidity and mortality. Alternative interventions to continuous positive airway pressure (CPAP) lack efficacy and safety or are highly complex. Objective. To describe the effects of an outpatient program of orofacial and extralaryngeal muscle re-education combined with electro-stimulation (TENS) of the same muscle groups in patients with OSA attending a tertiary level university hospital. Design. Prospective, incident case series, with consecutively selected patients. Methods. Participants consisted of 17 patients with mild, moderate or severe OSA who attended 24 thirty-minute sessions (three per week) of oropharyngeal exercises and electro-stimulation. The patients were evaluated at the beginning and end of the intervention by anthropometry, polysomnography, the Epworth sleepiness scale, and the Calgary Sleep Apnea Quality of Life (SAQLI) index. CPAP tolerance was evaluated by a visual scale rated from 1 to 10 (10 indicating maximum tolerance). Qualitative variables were described by frequencies, and quantitative variables by means and medians, depending on the type of distribution. Results. After the intervention, the apnea - hypopnea index improved from 22 to 13 per hour, the SAQLI index improved from 4.65 to 5.33, and the Epworth scale from 7 to 5. CPAP tolerance increased from 3 to 9. The sessions were well tolerated with no adverse events of importance. Four patients reported facial muscular pain. Conclusions. Electrotherapy plus active exercises of the oropharyngeal muscles are easy, feasible, safe, and potentially beneficial for OSA, with minimal side effects (AU)