Middle Constrictor Research Articles

Designing a New Planning Target Volume Based on Rotation in Patients With Oropharyngeal Cancer

Studies show that rotation is a significant source of target displacement. The standard isotropic expansion of Clinical Target Volume (CTV) to Planning Target Volume (PTV) neglects rotation. While imaging and 6D couch corrections perform a single shift through isocenter, they poorly track off-axis rotations through the spine or spine shifts that produce twists or arching. This study aims to determine dosimetric differences in head and neck patients when a standard expansion PTV is replaced by one that tracks the space occupied by target due to uncorrected rotational error. To perform off-axis rotation, a hypothetical point was placed in the center of the cervical spinal canal on Computed Tomography (CT) scan and the image was rotated around the longitudinal axis ±5°. Comparison plans were generated using a standard 3mm isotropic CTV expansion against the new PTV formed of the rotated CTV to evaluate mean dose reduction to superior Pharyngeal Constrictor Muscle (PCM). A published Normal Tissue Complication Model (NTCP) was used to predict dysphagia probability, based on the dose to superior PCM and supraglottis. The average percent change for PTV volume and overlap with superior, middle and inferior PCMs in a pool of 20 patients was -19%, -37%, -59% and -45.2%. The new rotational PTV causes more reduction in the superior PCM overlap in base of tongue lesions compared to tonsillar lesions (57.8% versus 25.8%, p = 0.01 as well as middle PCM overlap (73% versus 49%). The smallest isotropic expansion that covers the target when the spine rotates ±5° was 5 mm. 35% of patients required an expansion more than 3 mm to account for off-axis rotation. In 10 patients randomly selected for VMAT planning, the average change to the volume overlap of PTV70 with superior PCM using the standard and new PTV was 45% (8-100%), with an average mean dose reduction of 2.7 Gy. Based on the NTCP model, 50% of cases had a 30% or more probability of swallowing complications. Using the new technique, the NTCP decreased to less than 30% in 80% of these patients. Considering other Organs at Risk (OARs) constraints, there was not a difference between the new plan versus the standard plan. Designing a new PTV based on spinal rotation result in less volume overlap between PTV and PCM and can ultimately lead to less mean superior PCM dose and risk of dysphagia. A standard 3mm isotropic expansion is insufficient to cover the target volume due to spine rotation, and a 5mm margin is needed.

The effect of designing a rotational planning target volume on sparing pharyngeal constrictor muscles in patients with oropharyngeal cancer.

BackgroundPlanning target volume (PTV) has been used to account for variations in tissue, patient and beam position. In oropharyngeal cancers, an isotropic expanded PTV has been used.AimThe aim of this study was to design a new margin formula that would cover the space occupied by an oropharyngeal clinical target volume (CTV) with ±5‐degree rotation around the spine in order to reduce the pharyngeal constrictors overlap with PTV compared to an isotropic expanded PTV.MethodsWe retrospectively evaluated 20 volumetric‐modulated arc therapy (VMAT) plans. In order to perform an off‐axis rotation, a hypothetical point was placed through the center of the cervical spinal canal and the image was then rotated around the longitudinal axis ±5 degrees. This created a new set of CTVs that were combined to form the new rotational PTV. The overlap between the pharyngeal constrictor muscles (PCMs) and both PTVs was then evaluated.ResultsThe new rotational PTV causes reduction in the superior PCM overlap in the base of tongue (BOT) lesions compared to tonsillar lesion, 57.8% vs 25.8%, P = 0.01, as well as middle PCM overlap, 73% vs 49%, P = 0.04. Average percent change for PTV volume and overlap with the superior, middle, and inferior PCMs are as followed: −19%, −37%, −59.4%, and −45.2. The smallest isotropic expansion that covers the new rotational PTV was between 3 and 5mm with the average tumor center shift of 0.49 cm.ConclusionThis new rotational PTV causes significant reduction of the overlap volume between PCMs and PTVs in order to spare the PCMs compared to isotropic expanded PTV.

Training and validation of a commercial deep learning contouring platform

We present our experience with training and validation of a commercially available deep learning algorithm for organs at risk(OAR) auto-contouring. Computed tomography(CTs) with OARs from a cohort of 213 head and neck(H&N) patients were used for training the deep learning model. A separate cohort of 85 CTs and structure sets was used for validation. All OARs (13) were contoured by a single physician. Metrics such as the DICE similarity coefficient (DSC), Jaccard similarity coefficient (JSC), and volumetric difference (VD) were used to analyze contouring variation. Mean DSC and JSC values ranged 0.48-0.89 and 0.32-0.8, respectively, depending on OAR. A DSC value ≥0.7 indicated low inter-observer variability. In our study, all but one of the contours were above this threshold. DSC for the middle pharyngeal constrictor had the lowest value of all the contours. This may be due to the small volume of this structure. Qualitative assessment of auto-segmented structure samples confirmed the reliability of DSC by demonstrating the compatibility between the expert’s evaluation and DSC values. Overall, we found that deep learning auto contouring is a useful tool to speed up the process of contouring in radiotherapy treatment planning.

Nerve fiber analysis of the lingual branch of the glossopharyngeal nerve in human adult subjects.

Fibers of the glossopharyngeal part of the superior constrictor muscle are connected with fibers of the transverse lingual muscle, forming a ring of muscle at the base of the tongue. This group of muscles constrict the midpharyngeal cavity during retrusive movement of the tongue. The purpose of this study is to identify the contribution of the lingual branch of the glossopharyngeal nerve to the neuro-motor control of three muscles: the glossopharyngeal part of the superior pharyngeal constrictor muscle, the palatopharyngeal and the palatoglossus muscles. Six en bloc samples (9 sides), including the tissue from the skull base to the hyoid bone were obtained from adult human cadavers. Nerve fiber of the lingual branch of the glossopharyngeal nerve (main root of the glossopharyngeal nerve) was examined by the use of a binocular stereomicroscope. We observed that, after branching to the stylopharyngeal muscle, the lingual branch of the glossopharyngeal nerve branched to the glossopharyngeal part of the superior pharyngeal constrictor muscle, the palatopharyngeal and the palatoglossus muscles before inserting into the space between the muscle layers of the superior and middle pharyngeal constrictors. These neuromuscular arrangements may suggest the presence of specialized constrictive movements of the midpharygeal cavity at the level of the base of the tongue with the retrusive movement of the tongue. The simultaneous contraction of the palatopharyngeal and palatoglossus muscles on the pharyngeal stage of deglutition may aid in the passage of bolus from the oral cavity to the midpharyngeal cavity by increasing pharyngeal pressure.

An in silico comparative planning study investigating the predicted benefit of dysphagia-optimised volumetric arc therapy (Do-VMAT), relative to standard VMAT (S-VMAT), to reduce radiotherapy-associated dysphagia (RAD) in oropharyngeal cancers (OPC).

e18540 Background: RAD is a significant treatment-related functional morbidity in OPC and is associated with irradiation of the pharyngeal constrictor muscle (PCM). This study investigated whether a novel PCM-sparing Do-VMAT technique reduced the risk of RAD, compared to S-VMAT. Methods: Twenty OPC patients who previously underwent radiotherapy (RT) to bilateral neck were selected for this retrospective study. For each patient, S-VMAT and Do-VMAT plans were created. In both arms, the mucosal and nodal tumour received 65 Gy while the remaining oropharynx and at-risk nodal levels received 54 Gy; delivered in 30 fractions over 6 weeks. For Do-VMAT, a mandatory mean dose constraint of < 50 Gy to the volume of the combined superior (SPCM) and middle PCM (MPCM) together with an optimal dose constraint of < 20 Gy to the volume of inferior PCM (IPCM), lying outside the high-dose clinical target volume, were additionally defined and optimised to minimise PCM dose. Normal tissue complication probabilities for physician-scored RAD at 6 months (RAD6M) were determined as per the model by Christianen et al in which the 2 variables were mean dose to SPCM and supraglottic larynx (SGL). Statistical analysis was performed using paired t tests. Results: All plans had adequate target volume coverage, and dose to critical organs were within acceptable parameters. Dose to the parotid and submandibular glands were similar between the 2 RT techniques. The mean integral dose was 110.8 Gy-litre (standard deviation 17.1) with S-VMAT and 103.4 Gy-litre (15.4) with Do-VMAT, p < 0.001. With Do-VMAT, the average of the mean dose to PCM, SPCM, MPCM, IPCM, and SGL were 9.3 Gy (1.4), 4.7 Gy (1.7), 7.4 Gy (3.6), 22.7 Gy (4.1), and 2.6 Gy (2.3) respectively lower than S-VMAT (p < 0.001 for all). The mean predicted risk for RAD6M was 31.0 % (4.4) with S-VMAT, and 23.9 % (3.8) with Do-VMAT, p < 0.001. The absolute reduction in estimated toxicity risk with Do-VMAT was > 5 %, the minimally clinically important difference, in every patient. Conclusions: Do-VMAT demonstrated clinically relevant reductions in the predicted risk of RAD, compared to S-VMAT, by reducing dose to the PCM in OPC. The clinical benefits of Do-VMAT is being prospectively evaluated in DARS (CRUK/14/014), a randomised phase III study.

Results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer.

6508 Background: Most newly diagnosed oro- & hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. CRUK/14/014 investigated if using Do-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Methods: Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary & nodal tumour; 54Gy/30f to remaining pharyngeal subsite & nodal areas at risk of microscopic disease) or Do-IMRT. The volume of the superior & middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in Do-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site & AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints included local control. Results: 112 patients (56 S-IMRT, 56 Do-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&4 disease; 86% had concomitant chemotherapy only, 4% induction & concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was S-IMRT 49.8Gy (IQR 47.1-52.4) vs. Do-IMRT 28.4Gy (21.3–37.4), p < 0.0001; superior & middle PCM dose was S-IMRT 57.2Gy (56.3–58.3) vs. Do-IMRT 49.7Gy (49.4–49.9), p < 0.0001. Do-IMRT had significantly higher MDADI scores: S-IMRT 70.3 (SD 17.3) vs. Do-IMRT 77.7 (16.1), p = 0.016. 3 local recurrences (1 S-IMRT, 2 Do-IMRT) have been reported. Conclusions: Do-IMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC. Clinical trial information: 25458988 .

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

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. 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 (≥55Gy vs. <55Gy) on late dysphagia and QoL was analyzed using the t‑test. 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). 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.

Dosimetric factors associated with long-term patient-reported outcomes after definitive radiotherapy of patients with head and neck cancer

BackgroundThe aim of this study was to explore the relationships between dosimetric parameters of organs at risk and patient-reported outcomes (PRO) after radiotherapy of patients with head and neck cancer.MethodsPRO data of 53 patients with head and neck cancer treated with radiotherapy were prospectively collected. These data concerned health-related quality of life (HRQOL) and were collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and head and neck cancer module (QLQ-H&N35). Patients were divided into “severe-deterioration” and “mild-deterioration” groups on the basis of degree of deterioration HRQOL > 6 months after completing treatment. The relationships between HRQOL deteriorations and patient-related or dosimetry-related factors were evaluated. P < 0.0013 according to Bonferroni correction was considered to denote statistical significance.ResultsRegarding “trouble with social eating (HNSO)” and “coughing (HNCO),” there were significant differences between the severe-deterioration and mild-deterioration groups in mean dosages to the superior pharyngeal constrictor muscle (SPC) (HNSO: 62.5 Gy vs 54.2 Gy; p = 0.00029, and HNCO: 61.5 Gy vs 54.1 Gy; p = 0.0012) and parotid gland (HNSO: 24.1 Gy vs 20.5 Gy; p = 0.000056, and HNCO: 24.2 Gy vs 20.3 Gy; p = 0.00043). Regarding “nausea and vomiting,” there was a significant difference between the two groups in the mean dosage to the middle pharyngeal constrictor muscle (MPC: 61.9 Gy vs. 58.4Gy; P = 0.00059).ConclusionsWe found that dosages to the SPC and parotid gland were associated with severe deterioration in HRQOL attributable to difficulty in HNSO and HNCO, whereas dosage to the MPC was associated with severe deterioration attributable to nausea and vomiting.

Relationship of CT Radiomics and Dose Texture to Radiation-Induced Swallow Dysfunction in Head and Neck Cancer

Recent studies have shown that radiotherapy (RT) dosimetry is associated with an increased incidence of dysphagia in head and neck cancer (HNC) patients. The purpose of this work was to develop a dysphagia model using a comprehensive atlas of swallow-related structures to determine the predictive value of imaging and dose features of HNC patients who were evaluated for dysphagia after RT. We hypothesized that imaging and dosimetry features would be significantly correlated to patient reported scores of dysphagia. CT images and dysphagia scores were prospectively collected in HNC patients. We used the 3 month post-RT patient reported Sydney Swallow Questionnaire (SSQ) that has been validated to measure pharyngeal swallow as the primary endpoint. CT images were acquired prior to RT at the time of simulation. Swallow-related structures identified as important to swallow function (e.g. ipsi/contralateral parotid and submandibular glands [iPG, cPG, iSG, cSG], middle constrictors [MPC], anterior and posterior digastrics [ADM, PDM], mylohyoid [MHM], genioglossus [GGM], hyoglossus [HM], and cricopharyngeus [CP]) were segmented. For each segmented salivary gland, high-dimensional image features were extracted from CT images using a python software package. For each swallow-related structure, high-dimensional features were extracted from the structure’s dose distribution. Major categories of extracted features included shape, first order statistics, gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), and gray level size zone matrix (GLSZM). Multivariate regression was performed using the Enter method to identify the predictors of SSQ. The variables considered for modeling were chosen based on statistically significant univariate relationships with SSQ (p<0.005). All statistical analysis was performed in statistical software. In 136 patients, total SSQ at 3 months post-RT was correlated with the MHM D10, GLCM informational measure of correlation of dose, and GLSZM gray level non-uniformity of dose; cSG minimum dose and D10, HM minimum dose; and MPC GLCM inverse difference of dose (r>0.30, p<0.005). In terms of CT image features, SSQ was related to cPG GLCM cluster shade and prominence, iSG GLCM difference variance, and iPG GLCM correlation (r>0.30, p<0.005). In a multivariate analysis (R=0.65, p<0.001), CT iPG GLCM correlation, iSG GLCM difference variance, MPC inverse difference of dose and MHM D10 contributed significantly to the model (p<0.05). Salivary gland image features of CT intensity heterogeneity such as the iSG difference variance as well as the dose to 10% of the MHM and homogeneity of the dose to the MPC (identified by the inverse difference of dose) were significant predictors of dysphagia post-RT. These results suggest that both salivary structure and dose to swallow muscles are important dysphagia predictors and the promise of this approach for a comprehensive RT-dysphagia model.

178. Trial prospettico per predire la correlazione dose risposta nei muscoli costrittori faringei in pazienti con tumore testa-collo Prospective trial to predict the pharyngeal constrictor muscle dose-response correlation in head and neck cancer patients

PurposeRadiotherapy, alone or combined with chemotherapy, is a treatment modality used frequently in head and neck cancer. It is important to delineate organs in the head and neck at risk for radiation-induced swallowing dysfunction (RISD). Irradiation of the Pharyngeal Constrictor Muscle (PSCM) seems to play a crucial role in swallowing dysfunctions and in particular in the voice and speech quality changes. Purpose of our retrospective study was to identify which dose volume histogram parameters are most important to predict patient radiation-induced swallowing dysfunction, voice and speech quality. MethodsPatients with head and neck cancer who previously underwent Tomotherapy treatment are selected. The prescribed radiotherapy is based on SIB technique for all PTVs irradiated simultaneously over 30 daily. Doses of 67.5, 60 and 54–57 Gy were prescribed to primary tumour, high-risk nodal regions and low-risk nodal regions, respectively. Upper PSCM, middle PSCM and lower PSCM were outlined separately and DVHs are stored for each patient using basal planning CT and weekly MVCT. Univariate and multivariate analysis will be used to identify novel dosimetric predictors of toxicity and predictors of quality of life assessed using appropriate questionnaires taking into consideration the actual delivered dose. ResultsThe study started in July 2017 and the up to now 8 patients have been included in the study. Preliminary results suggest the importance of taking into consideration the dosimetric information based on basal planning CT and MVCT in order to improve the evaluation of toxicity rate and occurrence, which are still ongoing. ConclusionsDosimetric factors based on planning CT and MVCT seem to improve the identification of appropriate predictors of toxicity. More patients are to be included in the study to fully confirm these preliminary results.

A prospective radiobiological study of acute esophagitis and swallowing dysfunction in head-and-neck radiotherapy

Introduction: Esophagitis is one of the main causes of swallowing dysfunction after radiation therapy (RT) for head and neck cancer (HNC).It significantly affects patients’ quality of life as well as having a potentially negative impact on their long term survival. However, little has been investigated on the dose-response and normal tissue complication probability (NTCP) of esophagitis in the cervical esophagus (CE), although it is often at risk in neck irradiation. The aim of this study was to investigate the incidence and dose-response relation for acute esophagitis in HNC patients undergoing 3D conformal RT. Materials and Methods: This prospective study consisted of 50 HNC patients. The main studied endpoint was grade 2 or higher acute esophagitis according to the Common Terminology Criteria for Adverse Events v.4 scoring criteria within 9 weeks after the start of RT, assessed using the EORTC QLQ-H&N-35 questionnaire. The mean dose and dose-volume parameters were analyzed for CE and eight other swallowing-related structures including: superior, middle and inferior pharyngeal constrictor muscles (SPCM, MPCM and IPCM, respectively), esophagus inlet muscle (EIM), supraglottic larynx (SGL), base of tongue (BT), glottic larynx and cricopharyngeal muscle. Then, due to the lack of model parameters for acute esophagitis in the CE, the ability of four sets of LKB model parameters available for predicting the NTCP of this endpoint for middle and lower esophagus was evaluated based on the mean CE dose in these patients. Results: Forty three patients (86%) experienced grade ≥ 2 acute esophagitis in the follow-up period (no grades 4 or 5). The V30 of the SPCM, V30-V40 of the MPCM, V50 of the EIM, V40-V55 of the CE, V60 of the BT, and V20-V40 of the SGL, and the mean doses of these six structures, correlated with swallowing dysfunction. The mean dose to the CE was the most significant parameter. The LKB model parameters TD50= 47 Gy, m= 0.36, n= 0.069 showed the current best fit to the observed NTCP. Conclusion: The mean dose and V40-V55 to the CE were significantly associated with swallowing dysfunction. The high number of patients who experienced swallowing complications in this study adds evidence to the necessity of advanced treatment planning and delivery techniques that offer dose optimization to reduce esophagitis in HNC RT. Better LKB model parameters for predicting swallowing dysfunction due to CE dose are also required.

Radiation-Associated Chronic Dysphagia Assessment by Flexible Endoscopic Evaluation of Swallowing (FEES) in Head and Neck Cancer Patients: Swallowing-Related Structures and Radiation Dose-Volume Effect.

We aimed to restore dose-volume parameters of swallowing-related structures (SRSs) by evaluating long-term swallowing dysfunctions after radiotherapy (RT) in head and neck cancer patients (HNCPs). Head and neck cancer patients whose pharyngeal region was involved in RT portal and treated with definitive RT/chemoradiotherapy (CRT) were included in the analyses. Patients underwent objective swallowing assessment by flexible endoscopic evaluation of swallowing (FEES). Volumes of SRSs that received 55 Gy (V55) (mean dose [Dmean]) were evaluated according to the dose-volume histograms of each patient. For every SRS, optimal dose-volume cut-off values were determined by receiver operating characteristic curve analysis. Fifty-five patients at a median 20 months (range, 12-26 months) after their treatments were evaluated. There was a strong negative correlation between FEES scores and dose-volume parameters of SRS ( r ⩽ -0.5, P < .0001). According to our results, middle pharyngeal constrictor (MPC) and inferior pharyngeal constrictor (IPC) had a Dmean > 57 Gy, base of tongue (BOT) Dmean > 50 Gy, supraglottic larynx (SGL) and glottic larynx (GL) Dmean > 55 Gy, and cervical esophagus (CE) Dmean > 45 Gy. MPC V55 > 70%, IPC V55 > 50%, BOT V55 > 65%, CE V55 > 40%, and SGL and GL V55 > 50% were significant predictors for dysphagia. It was found that dysphagia correlates strongly with dose-volume parameters of SRSs. IPC, SGL, and CE were found to be structures significantly associated with dysphagia.

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

PurposeTo 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). MethodsPatients 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. ResultsForty-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). ConclusionSignal 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.

Investigating Laryngeal “Tilt” on Same-pitch Phonation—Preliminary Findings of Vocal Mode Metal and Density Parameters as Alternatives to Cricothyroid-Thyroarytenoid “Mix”

The objective of this work was to study the parameters "metal" and "density" and their combinatory conditions in relation to the vocal modes Overdrive, Edge, and Curbing from the pedagogical method Complete Vocal Technique by means of laryngostroboscopic imaging, high-speed videoendoscopy, electroglottography (EGG), long-time-average spectrum (LTAS), and acoustics. This is a three-subject exploratory study. Three singers were recorded performing various metal and density conditions of Overdrive, Edge, and Curbing from the Complete Vocal Technique method by means of laryngostroboscopic imaging using a videonasoendoscopic camera system and the Laryngostrobe program, high-speed videoendoscopy, EGG, LTAS, and acoustic signals using SpeechStudio. A laryngeal tilt was discovered as related to the condition of "reduced density" on same-pitch phonation, with observations of the thyroid cartilage tilting forward, stretching of the mucosa covering the cricoid-arytenoid complex and the posterior cricoid, and an upward posterior, slightly superior, contraction of the middle constrictor muscle in the pharyngeal wall. A resulting associated reduced contact quotient was observed on EGG, as well as a lowered mean sound pressure level. On LTAS, the laryngeal tilt was associated with a decrease of spectral energy in areas between the 7th and the 20th harmonic. The subjects of the study were able to perform the tilt without changing pitch or volume. Singers can perform laryngeal tilt during same-pitch phonation in the vocal modes Overdrive, Edge, and Curbing. The parameters of density and metal establish a more precise and anatomically grounded terminology than "mix register."

Ultrasound-Guided Glossopharyngeal Nerve Block: A Cadaver and a Volunteer Sonoanatomy Study.

Glossopharyngeal nerve (GPN) blocks are usually performed by topical, intraoral, or peristyloid approaches, which carry significant complication risks due to the proximity of important neurovascular structures. This study presents a proof of concept for a new ultrasound (US)-guided technique, which would block the GPN distally, in the parapharyngeal space, away from the immediate vicinity of high-risk collateral structures. Five cadaver heads were dissected, and the location of the GPN was explored bilaterally. In 40 healthy volunteers (20 men and 20 women; median age, 35.5 years [range, 24-69 years]) parapharyngeal sonograms were obtained, saved, and analyzed. To assess the technical feasibility of a distal GPN block in the parapharyngeal space, unilateral US-guided dye injections were performed in 3 fresh cadavers, followed by dissections. The GPN was consistently identified between the stylopharyngeal and middle pharyngeal constrictor muscles in all cadaver specimens. The median distance between the GPN and the ipsilateral greater horn of the hyoid bone was 2.4 cm (range, 2.3-2.7 cm) on the right and 2.6 cm (range, 2.3-2.9 cm) on the left. The mean skin-to pharyngeal wall distances in the volunteers were 2.03 (SD, 0.41) cm on the right and 2.02 (SD, 0.45) cm on the left. The mean hyoid bone-to-pharyngeal wall distances were 2.04 (SD, 0.35) cm (right) and 2.07 (SD, 0.35) cm (left). The fresh cadaver dissections demonstrated dye deposition adjacent to the GPN in the parapharyngeal space in all specimens. Based on our anatomical results in cadavers and healthy volunteers, we submit that successful and safe blockade of the distal GPN at the pharyngeal wall level is technically feasible under US guidance.

Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy PEG dependence in oropharynx cancer patients treated with split-neck IMRT technique

BackgroundRadiation therapy-related dysphagia is worsened by xerostomia. The submandibular glands (SMG) produce saliva rich in lubricating mucins, and sparing the SMG has been shown to reduce xerostomia. The goal of this study was to determine whether SMG sparing IMRT is associated with reduced post-treatment PEG dependence in locally advanced oropharynx cancer patients.MethodsPatients treated with definitive radiation therapy for oropharynx cancer were included in this retrospective study. Those with disease recurrence were excluded. Salivary glands and swallowing-related organs at risk, including pharyngeal constrictors, were contoured. Primary endpoint was time from end of radiation treatment to freedom from gastrostomy (PEG) tube dependence. Cox proportional hazards regression and logistic regression were used to assess influence of normal tissue doses on swallowing related endpoints.ResultsSixty-nine patients were included. All had stage III/IV disease and 97% received concurrent systemic therapy. Fifty-seven percent had contralateral SMG (cSMG) mean dose <50 Gy, a level shown to predict for xerostomia. Eighty four percent of patients had a PEG tube placed electively. On univariate analysis, the strongest predictor of time to freedom from PEG tube dependence was cSMG dose (HR 0.97 per Gy (95% CI 0.95–0.98), p < 0.0001). This relationship persisted on multivariate analysis (p = 0.052). The dose to superior and middle pharyngeal constrictor muscles, and larynx were also significant on univariate analysis. Patients with cSMG dose less than median (42 Gy, n = 34) had a significantly shorter time to freedom from PEG dependence: median 1.9 vs. 3.5 months, p < 0.0001. At 6 months, 3% of patients with cSMG dose < 42 Gy were PEG dependent compared to 31% with cSMG dose > 42 Gy (p = 0.002).ConclusionsPatients treated with cSMG sparing radiotherapy had significantly shorter time to PEG tube removal after treatment, suggesting a clinically meaningful reduction in subacute dysphagia compared to non-cSMG sparing treatment.

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

PurposeTo 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 materialThis 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. ResultsAspiration 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. ConclusionsThree 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.

A Novel Imaging Analysis Method for Capturing Pharyngeal Constriction During Swallowing

Videofluoroscopic imaging of swallowing known as the Modified Barium Study (MBS) is the standard of care for assessing swallowing difficulty. While the clinical purpose of this radiographic imaging is to primarily assess aspiration risk, valuable biomechanical data is embedded in these studies. Computational analysis of swallowing mechanics (CASM) is an established research methodology for assessing multiple interactions of swallowing mechanics based on coordinates mapping muscle function including hyolaryngeal movement, pharyngeal shortening, tongue base retraction, and extension of the head and neck, however coordinates characterizing pharyngeal constriction is undeveloped. The aim of this study was to establish a method for locating the superior and middle pharyngeal constrictors using hard landmarks as guides on MBS videofluoroscopic imaging, and to test the reliability of this new method. Twenty de-identified, normal, MBS videos were randomly selected from a database. Two raters annotated landmarks for the superior and middle pharyngeal constrictors frame-by-frame using a semi-automated MATLAB tracker tool at two time points. Intraclass correlation coefficients were used to assess test-retest reliability between two raters with an ICC = 0.99 or greater for all coordinates for the retest measurement. MorphoJ integrated software was used to perform a discriminate function analysis to visualize how all 12 coordinates interact with each other in normal swallowing. The addition of the superior and middle pharyngeal constrictor coordinates to CASM allows for a robust analysis of the multiple components of swallowing mechanics interacting with a wide range of variables in both patient specific and cohort studies derived from common use imaging data..

Surgical anatomy and physiology of swallowing

Deglutition, the act of swallowing, is an extremely complex process involving approximately 50 pairs of muscles and nerves that are responsible for preparing and transferring food and liquids from the mouth to the stomach. A problem with any of these structures can lead to dysphagia and a decrease in the quality of life in patients suffering from it. To successfully diagnose and treat dysphagia, a thorough understanding of deglutition is essential. The anatomy and physiology of the swallowing process is reviewed as it pertains to operative approach and technique.

Volumetric modulated arc therapy (VMAT) and simultaneous integrated boost in head-and-neck cancer: is there a place for critical swallowing structures dose sparing?

To explore the potential of volumetric-modulated arc therapy (VMAT) to reduce the risk of swallowing problems after curative chemoradiotherapy. 20 patients with head and neck cancer who previously underwent radiotherapy were selected. Radiotherapy was prescribed according to simultaneous integrated boost technique with all targets irradiated simultaneously over 30 daily fractions. Doses of 70.5 (67.5), 60.0 and 55.5 Gy were prescribed to primary tumour, high-risk nodal regions and low-risk nodal regions, respectively. Pharyngeal constrictor muscles (PCM) and glottic and supraglottic larynx (SGL) were considered organs at risk related to swallowing dysfunction (SW-OARs). Upper pharyngeal constrictor muscles (uPCM), middle pharyngeal constrictor muscles (mPCM) and lower pharyngeal constrictor muscles (lPCM) part of PCM were also outlined separately. Clinical standard plans (standard-VMAT) and plans aiming to spare SW-OARs (swallowing dysfunction-VMAT) were also created. Normal tissue complication probabilities (NTCP) for physician-rated swallowing dysfunction were calculated using a recently predictive model developed by Christianen et al. Planning with two strategies demonstrated comparable planning target volume coverage and no differences in sparing of parotid glands and other non-swallowing organs at risk. SW-VMAT plans provided mean dose reduction for uPCM and SGL by 3.9 and 4.5 Gy, respectively. NTCP values for Radiation Therapy Oncology Group grade 2-4 swallowing dysfunction was decreased by 9.2%. Dose reductions with SW-VMAT depended on tumour location and overlap with SW-OARs. VMAT plans aiming at sparing swallowing structures are feasible, providing a significant reduction in NTCP swallowing dysfunction with respect to conventional VMAT. Dysphagia is today considered one of the dose-limiting toxicities of chemoradiotherapy. The dose sparing of swallowing structures represents a major challenge in radiotherapy. VMAT is a complex new technology having the potential to significantly reduce the risk of dysphagia after curative chemoradiotherapy.