Late Dysphagia Research Articles

Dysphagia and Dysphonia After Head and Neck Cancer.

The purpose of this work is to synthesize the latest developments in diagnosis and management of acute and late dysphagia and dysphonia in oral cavity cancer. A literature search was conducted using PubMed, Web of Science, Embase and Google Scholar in May 2024 of articles published between 2021 and 2024. Keywords in the search terms included oral cavity cancer, dysphagia, dysphonia, deglutition, swallowing, voice, oral cavity cancer treatment, oral cavity radiation, chemotherapy, dysgeusia, xerostomia, swallow preservation. Twenty-seven pertinent studies fit the inclusion criteria. The most common dysphagic complaints following head and neck cancer are trismus, xerostomia, mucositis and dysphagia. Dysphonia, change in voice is reported by half of head and neck cancer survivors. Fibrosis and neuropathy following radiation therapy to the oral cavity, tongue, oropharynx and its surrounding structures is the most common etiology of post-treatment dysphonia. Oral cavity cancers cause speech and swallowing dysfunction due to both anatomic and post-treatment changes. These sequalae can be detrimental to the quality of life of the head and neck cancer survivor. For both dysphagia and dysphonia after head and neck cancer early speech and swallow therapy with a Speech Language Pathologist are essential to restoring and maintaining function.

How enteral nutrition modes influence nasopharyngeal carcinoma survivors with late dysphagia after radiotherapy: a randomized controlled study.

Palliation to late dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC) continues to be a challenge. Intermittent oro-esophageal tube feeding (IOE) is an emerging enteral nutrition mode that can address nutrition and quality of life issues related to nasogastric tube feeding (NGT). This study aims to investigate the effect of IOE versus NGT in late dysphagia after radiotherapy for NPC. This randomized controlled study included 82 NPC survivors with late dysphagia after radiotherapy. The subjects were randomized divided into the IOE and NGT groups (n1 = n2 = 41). Both groups received standard-of-care rehabilitation. Enteral nutrition supports were administered through IOE or NGT accordingly. This study lasted 2weeks for each participant. The primary outcome was nutritional status including albumin, hemoglobin, total serum protein, and body mass index. The secondary outcomes were (i) the functional oral intake scale (FOIS), (ii) the penetration-aspiration scale (PAS), (iii) oral transit time (OTT), (iv) hyoid pause time (HPT), (v) pharyngeal transport time (PTT), and (vi) swallowing-quality of life (SWAL-QoL). Three cases quitted the study halfway and there were no significant baseline differences between the IOE (n = 40) and NGT (n = 39) groups. Both time and group effects were significant in all nutritional indicators. The time effect was significant in the FOIS levels, OTT and PTT, while the group effect was not. Either time or group effect were insignificant in the PAS levels and HPT. Both group and time effects were significant in the SWAL-QoL total scores (zGroup = 5.080, P < 0.001; zTime = 18.005, P < 0.001). The significance of time and group effects varied across different dimensions of the SWAL-QoL. Rehabilitation interventions can improve swallowing function among NPC survivors with late dysphagia after radiotherapy. In this population who received standard-of-care rehabilitation, IOE is more conducive to the improvement of nutritional status, and swallowing-related quality of life. ClinicalTrials.gov Identifier: NCT06301763.

Beyond complete remission: A comparative analysis of long-term laryngeal function in patients with hypopharyngeal and laryngeal cancer following radiotherapy and concurrent chemoradiation.

This study evaluates functional larynx preservation in patients with hypopharyngeal cancer (HPC) and laryngeal cancer (LC) who achieved complete remission following radiotherapy (RT) or concurrent chemoradiation (CCRT). HPC and LC patients treated with RT/CCRT from 1999 to 2017 were retrospectively analyzed. Severe late dysphagia and tracheostomy cases were assessed to determine laryngeal function. Long-term preservation rate of functional larynx and associated factors were evaluated. Of 152 patients (55 HPC, 97 LC), nine developed severe dysphagia, occurring on average 58.2 months post-treatment. HPC and cervical node metastasis significantly increased the risk of laryngeal function impairment (p < 0.001 and p = 0.014, respectively), presenting a continued decline in functional larynx preservation rate beyond 10 years. Patients with HPC and cervical node metastasis demonstrate an increased risk for long-term laryngeal function impairment despite successful oncologic outcomes. This risk extends beyond 10 years, underscoring the need for prolonged monitoring and comprehensive support.

Impact of Toupet fundoplication with bougie on post-operative dysphagia and quality of life.

Numerous studies comment on quality of life outcomes comparing complete and partial fundoplication with or without a bougie. Society guidelines are moving toward recommending partial fundoplication over complete fundoplication due to improved side effect profile with similar outcomes. Retrospective studies and randomized trials have elucidated that use of a bougie during Nissen fundoplication does impact long-term dysphagia. To date there are no retrospective or prospective data that guide practice for partial fundoplications. The purpose of this project is to investigate the clinical implications of using a bougie for Toupet fundoplication with regard to short-term and long-term dysphagia and need for further therapeutic interventions. A retrospective review of a prospectively maintained gastroesophageal database was performed. Demographic, pre-operative quality of life outcomes data, perioperative, and post-operative quality of life outcomes data of 373 patients from 2011 to 2022 undergoing Toupet fundoplication without bougie or with a traditional Savary 56Fr or 58Fr bougie were reviewed. The two groups were compared using student's t-test to identify statically significant differences between the groups. Between 2011 and 2022, 373 patients underwent Toupet fundoplication (276 with traditional bougie, 97 without). Median follow-up in the bougie group was 19months, versus 9months in the non bougie group. There was no difference between early (3weeks) and late dysphagia scores (6months). In the bougie group there were two mucosal perforations due to the bougie. There were no statistically significant differences in GERD-HRQL, gas bloat, and dysphagia scores between groups at one year. There is no difference observed in early or late dysphagia scores, GERD-HRQL, gas bloat or need for dilation in patients undergoing Toupet fundoplication with or without a traditional bougie. It is reasonable to discontinue the use of a traditional bougie during Toupet fundoplication, especially due to risk of esophageal perforation.

Pharyngeal Constrictor Dose–Volume Histogram Metrics and Patient-Reported Dysphagia in Head and Neck Radiotherapy

AimsHead and neck radiotherapy long-term survival continues to improve and the management of long-term side-effects is moving to the forefront of patient care. Dysphagia is associated with dose to the pharyngeal constrictors and can be measured using patient-reported outcomes to evaluate its effect on quality of life. The aim of the present study was to relate pharyngeal constrictor dose–volume parameters with patient-reported outcomes to identify prognostic dose constraints. Materials and methodsA 64-patient training cohort and a 24-patient testing cohort of oropharynx and nasopharynx cancer patients treated with curative-intent chemoradiotherapy were retrospectively examined. These patients completed the MD Anderson Dysphagia Inventory outcome survey at 12 months post-radiotherapy to evaluate late dysphagia: a composite score lower than 60 indicated dysphagia. The pharyngeal constrictor muscles were subdivided into four substructures: superior, middle, inferior and cricopharyngeal. Dose–volume histogram (DVH) metrics for each of the structure combinations were extracted. A decision tree classifier was run for each DVH metric to identify dose constraints optimising the accuracy and sensitivity of the cohort. A 60% accuracy threshold and feature selection method were used to ensure statistically significant DVH metrics were identified. These dose constraints were then validated on the 24-patient testing cohort. ResultsExisting literature dose constraints only had two dose constraints performing above 60% accuracy and sensitivity when evaluated on our training cohort. We identified two well-performing dose constraints: the pharyngeal constrictor muscle D63% < 55 Gy and the superior–middle pharyngeal constrictor combination structure V31Gy < 100%. Both dose constraints resulted in ≥73% mean accuracy and ≥80% mean sensitivity on the training and testing patient cohorts. In addition, a pharyngeal constrictor muscle mean dose <57 Gy resulted in a mean accuracy ≥74% and mean sensitivity ≥60%. ConclusionMid-dose pharyngeal constrictor muscle and substructure combination dose constraints should be used in the treatment planning process to reduce late patient-reported dysphagia.

De-intensification of postoperative radiotherapy in head and neck cancer irrespective of human papillomavirus status-results of a prospective multicenter phase II trial (DIREKHT Trial).

Current standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated. Patients with newly diagnosed HNSCC after surgery (with resection margins ≥1 mm and cM0) with the following tumor stages (TNM 7th Edition) were eligible for the study: oral cavity, oropharynx, or larynx: pT1-3, pN0-pN2b; hypopharynx: pT1-2, pN1. The patients should have either a low risk of local recurrence [≤pT2, resection margin ≥5 mm, no peritumoral lymphangiosis (L0), and no perineural invasion] or contralateral lymph node metastasis (≤3 ipsilateral lymph node metastases, in case of well-lateralized oropharyngeal or oral cavity cancer contralateral cN0, otherwise pN0). Patients were assigned to three different treatment regimes with reduction of the treated volume, radiation dose, or both, according to tumor stage and results of surgery performed. The primary objective was to show an LRR of <10% after 2 years. A total of 150 patients were enrolled. Tumor localizations were as follows: n = 53 (35.3%), oral cavity; n = 94 (62.7%), oropharynx (82% HPV-positive); n = 2 (1.3%), hypopharynx; and n = 1 (0.7%), larynx. A total of 61 patients (41.0%) were stage IVA, 81 (54.0%) were stage III, and 8 (5.3%) were stage II. Median follow-up was 36 months. Cumulative incidence of 2y-LRR was 5.6% (95% CI: 1.7%-9.2%) in the whole study population and 14.1% (95% CI: 3.8%-23.2%) in patients with oral cavity cancer. Cumulative incidence of 2y-LRR in non-irradiated or dose-reduced regions was 3.5% (95% CI: 0.4%-6.5%). After 2 years, disease-free survival was 92% (95% CI: 87%-96%) and overall survival was 94% (95% CI: 90%-98%) for the complete study cohort. Acute III° toxicity was as follows: dysphagia, 30%; xerostomia, 7%; mucositis, 19%; and dermatitis, 4%. Dysphagia and xerostomia decrease over time. After 27 months, late dysphagia III° and xerostomia II° were 1% and 9%, respectively. The study met its primary objective. De-intensification of postoperative radiotherapy irrespective of HPV status in a predefined patient population is associated with a favorable toxicity profile without compromising LRR. In an unplanned subgroup analysis, a significantly increased risk of LRR was observed in patients with oral cavity cancer. In these patients, de-intensified radiotherapy should be applied with caution.

Predictive Factors for Chemoradiation-Induced Oral Mucositis and Dysphagia in Head and Neck Cancer: A Scoping Review

Despite advances in head and neck cancer treatment, virtually all patients experience chemoradiation-induced toxicities. Oral mucositis (OM) and dysphagia are among the most prevalent and have a systemic impact on patients, hampering treatment outcome and harming quality of life. Accurate prediction of severe cases is crucial for improving management strategies and, ultimately, patient outcomes. This scoping review comprehensively maps the reported predictors and critically evaluates the performance, methodology, and reporting of predictive models for these conditions. A total of 174 studies were identified from database searches, with 73 reporting OM predictors, 97 reporting dysphagia predictors, and 4 reporting both OM and dysphagia predictors. These predictors included patient demographics, tumor classification, chemoradiotherapy regimen, radiation dose to organs-at-risk, genetic factors, and results of clinical laboratory tests. Notably, many studies only conducted univariate analysis or focused exclusively on certain predictor types. Among the included studies, numerous predictive models were reported: eight for acute OM, five for acute dysphagia, and nine for late dysphagia. The area under the receiver operating characteristic curve (AUC) ranged between 0.65 and 0.81, 0.60 and 0.82, and 0.70 and 0.85 for acute oral mucositis, acute dysphagia, and late dysphagia predictive models, respectively. Several areas for improvement were identified, including the need for external validation with sufficiently large sample sizes, further standardization of predictor and outcome definitions, and more comprehensive reporting to facilitate reproducibility.

Quality of life and swallowing outcomes after early proactive swallowing rehabilitation by either transcutaneous neuromuscular electrical stimulation or exercise-based swallowing training in patients with nasopharyngeal carcinoma after radiotherapy.

Exercise-based swallowing training (EBST) and transcutaneous neuromuscular electrical stimulation (TNMES) are common modalities used to treat late dysphagia after radiotherapy for nasopharyngeal carcinoma (NPC). We aimed to investigate and compare the efficacies of EBST and TNMES as proactive treatments administered early after radiotherapy. Patients with early post-radiotherapy NPC (n = 120) underwent either TNMES or EBST. Flexible endoscopic evaluation of swallowing (FEES), quality of life (QOL), and swallowing function questionnaires were completed before the intervention as well as immediately, 6, and 12 months after the intervention. Outcome measures included the scores for the swallowing function score (SFS), penetration and aspiration scale (PAS), dynamic imaging grade of swallowing toxicity (DIGEST), functional oral intake scale (FOIS), swallowing performance status scale (SPSS), pharyngeal motor impairment (PMI), pharyngeal function impairment (PFI), and functional assessment after cancer therapy-nasopharyngeal (FACT-NP) questionnaire. Three months after radiotherapy, 31 and 34 patients underwent TNMES and EBST, respectively, and completed swallowing assessments at all four assessment timepoints. All patients showed post-radiotherapy impairments in the SFS, PAS, DIGEST, PMI, and PFI. Compared with the EBST group, the TNMES group showed significant improvements in the PFI and PMI scores, with small-to-medium effect sizes. Additionally, compared with the EBST group, the TNMES group demonstrated a trend toward slightly better improvements in the PAS, DIGEST, FOIS, and SPSS scores immediately and 6 months after the intervention. The SFS scores improved from baseline in both groups; however, the TNMES group showed an earlier improvement. Finally, the TNMES group showed better QOL according to the FACT-NP than the EBST group. Proactive TMNES and EBST are safe and feasible modalities for improving swallowing in patients with NPC when administered early after radiotherapy. Although TNMES showed better results than EBST, these results should be interpreted with caution given the study limitations. 1B.

Toxicities and clinical outcome of adjuvant dysphagia optimized versus standard intensity-modulated radiotherapy for post-operative oral cavity cancers: A prospective comparative study.

We prospectively assessed acute and late toxicity in post-operative oral cavity squamous cell carcinoma (PO-OCSCC) treated with adjuvant dysphagia optimized intensity-modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT). Fifty-six patients of PO-SCC without indications of concurrent chemotherapy were alternatively allocated to adjuvant Do-IMRT (n = 28) versus S-IMRT (n = 28) arms. High- and low-risk planning target volume received 60 and 54 Gy, respectively, in 30 fractions over 6 weeks. Dysphagia aspiration-related structures (DARS) were contoured in both arms. While dosimetric constraints were given in Do-IMRT arm, doses to DARS were only observed without dose constraints in S-IMRT arm. Acute and late toxicity were assessed by common terminology criteria for adverse events (CTCAE) v5.0 and RTOG criteria, respectively. The primary site of disease was buccal mucosa (64% vs. 53%) and oral tongue (21% vs. 32%), in Do-IMRT and S-IMRT, respectively. The mean doses to DARS was significantly less with Do-IMRT (all p < 0.001) as compared to S-IMRT. Median follow-up was 24.2 months. Grade ≥2 oral pain was less in the Do-IMRT arm (50% vs. 78.6%, p = 0.05). Grade ≥2 late dysphagia at 2 years were significantly less in Do-IMRT arm (0% vs. 17.9%, p = 0.016). Two-year locoregional control was 89.2% in Do-IMRT and 78.5% in S-IMRT (p = 0.261). DARS can be spared in PO-OCSCC patients treated with Do-IMRT without compromising coverage of the target volumes. Limiting doses to DARS leads to lesser acute and late toxicity without compromising locoregional control.

The Outcomes of Intensity Modulated Radiotherapy versus Conventional 2D Radiotherapy in Patients with Oropharyngeal or Hypopharyngeal Squamous Cell Carcinoma. A Case-Control Study

"Introduction: Head and neck cancers’ radiotherapy (RT) is challenging due to the irregular target volumes and the proximity of multiple organs at risk. The purpose of this study is to compare the toxicity, loco-regional control and the pattern of tumour recurrence after intensity modulated radiotherapy (IMRT) or conventional 2D radiotherapy (2D CRT) in patients with squamous cell carcinoma (SCC) oropharyngeal or hypopharyngeal cancers. Material and method: We retrospectively compared the outcomes of SCC oropharyngeal or hypopharyngeal cases treated by IMRT or 2D CRT from 1998 to 2010 in a Canadian Academic Hospital. We matched the patients in the two groups according to primary tumour location and clinical stage. The information on treatment, toxicity and outcomes was retrieved from patients’ medical records. For the patients having a recurrence after IMRT, the CT scan at relapse was fused with the planning CT. For the patients recurring after 2D CRT, we matched the CT images with the relative position of the radiotherapy fields. Statistical analysis was made using GraphPad Prism software. Results: We included a total of 50 patients in the IMRT group and 50 in the 2D CRT group. The median age was 62 and 58 years, respectively, and the median follow-up was 18 and 22.6 months, respectively. Some of the side effects were less frequent on the IMRT group compared to the 2D CRT: xerostomia (16% vs 64%, P=0.0036), mucositis (70% vs 74% P=0.5451), weight loss (18% vs 46% P= 0.0027), radionecrosis/mandibular fracture (0 % vs 2%), fibrosis (0% vs 10%), and telangiectasia (0% vs 4%). However, acute dermatitis and late dysphagia were more frequent in the IMRT group (44% vs 28% P=0.0042; and 14% vs 2% P=0.028; respectively). The overall survival at 2 years was for 74.03% for IMRT and 60% for 2D CRT (P&lt; 0.001) and the 5 years actuarial locoregional control was 89.54 % for IMRT group, and 62.48% for the 2DCRT group (P&lt; 0.001). Three patients from the IMRT group had a local recurrence (2 in-field and 1 marginal), while in the 2D-CRT group, there were 10 patients with a local recurrence (6 in-field and 4 marginal). Conclusion: SCC oropharyngeal and hypopharyngeal patients treated with IMRT and concurrent cisplatin had better outcomes and fewer side effects, when compared to similar cases treated with 2D CRT. The local recurrence had a similar pattern for both techniques."

Radiation therapy for cT1-2 carcinoma of the palatine tonsil diagnosed via a simple tonsillectomy: Dosimetry and patterns of care in the IMRT era

ObjectiveSmall carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated. Patients and methodsA retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018. Patients who received curative-intent intensity modulated radiotherapy (IMRT) without additional surgery were included. Target volumes were reviewed, and cumulative incidences of local failure and severe late dysphagia were calculated. ResultsFrom 638 oropharyngeal patients, 91 were diagnosed via simple tonsillectomy. Definitive IMRT with no additional surgery to the primary site was utilized in 57, and three with gross residual disease were excluded, leaving 54 for analysis. Margins were negative in 13%, close (<5 mm) in 13%, microscopically positive in 61%, and not reported in 13%. Doses typically delivered to gross disease (68–70.2 Gy in 33–35 fx or 66 Gy/30 fx) were prescribed to the tonsil bed in 37 (69%). Sixteen patients (29%) received doses from 60 to 66 Gy (≤2 Gy/fx) and one received 50 Gy (2 Gy/fx). No local failures were observed. One late oropharyngeal soft tissue ulcer occurred, treated conservatively (grade 2). At five years, the cumulative incidence of severe late dysphagia was 17.4% (95% CI 6.1–28.8%). ConclusionSmall tonsil carcinomas diagnosed by simple tonsillectomy represent a niche subset with favorable oncologic outcomes. Regardless, radiation oncologists tend to deliver full-dose to the tonsil bed. The necessity of this routine could be questioned in the modern era.

Management Strategies for Dysphagia Complicating Laparoscopic Nissen Fundoplication, Systematic Review

Abstract Background Gastroesophageal reflux disease (GERD) is a common global disorder. Manifestations of the disease range from occasional episodes of heartburn and regurgitation to the more serious complications of stricture and Barrett’s esophagus. Most patients manage their symptoms with a combination of dietary and lifestyle modifications and overthe-counter or prescription medications. Aim of the Work This study aims to assess the incidence, etiology, diagnosis and management strategies for dysphagia following laparoscopic Nissen fundoplication. Patients and Methods Published studies discussing dysphagia as a complication of laparoscopic Nissen fundoplication. Patients developed dysphagia after laparoscopic Nissen fundoplication as primary anti-reflux surgery, the type of intervention was laparoscopic Nissen fundoplication. Types of outcome measures: Incidence, etiology, diagnosis and management strategies for dysphagia following laparoscopic Nissen fundoplication. The published English-language literature will be searched in the databases PUBMED, EMBASE, Google Scholar, Science direct and Cochrane Register of Controlled Trails (The Cochrane Library). The search terms will be employed: “Nissen fundoplication” “early dysphagia” “ late dysphagia”. Results In our present systematic review, we observed that the incidence of post-operative dysphagia after laparoscopic Nissen fundoplication among the included studies ranged from 8.2% to 42.8% with average percent of 33.2%. Transient postoperative dysphagia was more prominent in most of the included studies with average 52.8%, while persistent dysphagia was in reported in 47.2% of cases. In the present systematic review and meta-analysis, 707 of patients who developed postoperative dysphagia responded to conservative management with percent of 92.4%, while the remaining 58 patients required more invasive modalities. Endoscopic dilatation was performed in 54 (7.1%) of patients, while the remaining 4 patients (0.5%) were indicated for surgical reintervention. Conclusion Post laparoscopic Nissen fundoplication dysphagia is one of the most common complications, most cases present with a transient course that require no more than conservative management. In few conditions, more invasive procedures maybe required to control that condition.

Routine Prophylactic Percutaneous Endoscopic Gastrostomy in Head and Neck Cancers with Bilateral Neck Irradiation: A Regional Cancer Experience in New Zealand.

Patients with head and neck cancer (HNC) are particularly susceptible to dysphagia and malnutrition. Prophylactic percutaneous endoscopic gastrostomy (PEG) placement is a method used to manage these issues, but practices vary among institutions. At Midcentral District Health Board, patients receiving radiotherapy to the primary and bilateral neck regions routinely undergo prophylactic PEG placement. This study aimed to review the nutritional and PEG-related outcomes of these patients. Records of 49 patients were retrospectively reviewed. Their demographics, tumour and treatment characteristics were recorded. We evaluated patient weight loss, non-elective hospitalisation, treatment interruption rates, PEG-related complications, usage, dependency rates and late dysphagia rates. Oropharyngeal cancers were the most common primary site (61.2%), and 83.7% of patients received primary chemoradiotherapy. Mean weight loss at treatment completion was 5.6% ± 4.3 (4.6 kg ± 3.9). The rate of non-elective hospitalisations was 26.5%, and only 2% of patients had treatment interruptions. Peristomal infection was the most frequent PEG complication (20.4%). No PEG-related mortality was reported. Median duration of PEG dependency was 97 days (14-388 days). Two patients remained permanently dependent at 3 years due to grade 3 dysphagia, and six patients experienced grade ≥2 late dysphagia. Our study showed that prophylactic PEG tube placement was relatively safe, with a high utilisation rate and low long-term dependence on PEG tubes after treatment completion. However, complications related to their use should be addressed through a multidisciplinary approach, with careful assessment by clinicians. The weight loss and hospitalisation rates observed were consistent with earlier studies that utilised prophylactic PEG tubes.

OC-0088 Deep learning NTCP model for late dysphagia based on 3D dose, CT and segmentations

OC-0088 Deep learning NTCP model for late dysphagia based on 3D dose, CT and segmentations

Dose Escalation of Oropharyngeal Cancer: Long-Time Follow-Up and Side Effects.

Previous studies on dose-escalated radiotherapy in head and neck cancer have shown mixed results, and it is not established which patients would benefit from dose escalation. Further, while dose escalation does not appear to increase late toxicity, this needs to be confirmed with longer follow-up. In this study, we analysed treatment outcome and toxicity in 215 patients with oropharyngeal cancer treated with dose-escalated radiotherapy (>72 Gy, EQD2, α/β = 10 Gy, boost by brachytherapy or simultaneous integrated boost) and a matched cohort of 215 patients treated with standard dose external-beam radiotherapy (68 Gy) between 2011 and 2018 at our institution. The 5-year overall survival (OS) was 77.8% (72.4-83.6) and 73.7% (67.8-80.1) in the dose-escalated and standard dose group, respectively (p = 0.24). Median follow-up was 78.1 (49.2-98.4) and 60.2 (38.9-89.4) months in the dose-escalated and standard dose groups, respectively. Grade ≥3 osteoradionecrosis (ORN) and late dysphagia were more common in the dose-escalated group compared to the standard dose group, with 19 (8.8%) vs. 4 (1.9%) patients developing grade ≥3 ORN (p = 0.001), and 39 (18.1%) vs. 21 (9.8%) patients developing grade ≥3 dysphagia (p = 0.01). No predictive factors to help select patients for dose-escalated radiotherapy were found. However, the remarkably good OS in the dose-escalated cohort, despite a predominance of advanced tumour stages, encourages further attempts to identify such factors.

Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial

ObjectivesTo address whether sparing the medial retropharyngeal lymph node (MRLN) region from elective irradiation volume provides non-inferior local relapse-free survival versus standard radiotherapy in patients with nasopharyngeal carcinoma.DesignOpen-label, non-inferiority, multicentre,...

Chemoradiotherapy with 3-weekly CDDP 80 mg/m2 for head and neck squamous cell carcinoma: 5-year survival data from a phase 2 study.

The global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2. A phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated. The median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia. The survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia.

Chronic Dysphagia in Patients Treated with Head and Neck Intensity-Modulated Radiotherapy: Incidence, Risk Factors and Implications

<h3>Purpose/Objective(s)</h3> Late dysphagia after head and neck radiotherapy is an important driver of poor quality-of-life. We aimed to identify risk factors associated with long-term gastrostomy tube (g-tube) dependence in patients with head and neck squamous cell carcinoma treated with definitive or postoperative radiotherapy. <h3>Materials/Methods</h3> A retrospective cohort analysis of patients with head and neck squamous cell carcinoma treated with definitive or adjuvant intensity-modulated radiotherapy was performed. Patients with locoregional or distance recurrence were excluded from the analysis. G-tube dependence was used as a surrogate marker for late dysphagia, and its placement and removal from initial presentation to last follow-up was tracked. The risk of g-tube dependence from years one through five was calculated, and factors associated with 1- and 2-year g-tube use were analyzed with multivariable logistic regression. <h3>Results</h3> Our analytic cohort consisted of 421 survivors with head and neck squamous cell cancer treated from 2001 to 2018. A total of 210 patients required a g-tube with 80, 124, and 13 g-tubes placed before, during, and after radiotherapy, respectively. The median follow-up of the entire cohort was 4 years (IQR 3-5), with 314, 222, and 124 patients at-risk in years 3, 4 and 5. The Kaplan-Meier g-tube dependence rate at 1 and 2 years after radiotherapy were 11% and 6%, respectively, and 5%, 3% and 2% at three, four and five years, respectively. On multivariable regression analysis on 1-year g-tube dependence, history of depression or anxiety (odds ratio, OR, 95% confidence interval, CI, 3.86 [1.47, 10.3]), clinical T3/T4 stage (3.75 [1.60, 9.30]), clinical N2 or N3 stage (3.66 [1.03, 14.4]), baseline swallowing impairment to both solids and liquids (11.1 [3.22, 41.8]), and intra-treatment weight loss greater than 10% (3.75 [1.51, 9.81]) were significant predictors. A total of 390 patients had adequate follow-up data for the 2-year analysis. On multivariable analysis, age (1.06 [1.00, 1.14]), clinical N2/N3 stage (15.2 [1.72, 393]), and baseline swallowing impairment to both solids and liquids (95% confidence interval: 41.5 [5.59, 551]) were significantly associated with increased odds of 2-year g-tube dependence. Definitive vs. adjuvant treatment was not significantly associated with 1 or 2-year g-tube dependence. Out of 22 patients with g-tube dependence at two years after radiotherapy, only six (27%) patients had a known tube removal in the years to follow. <h3>Conclusion</h3> The overall incidence of prolonged g-tube dependence is low but not trivial, and the vast majority of patients with dependence at two years remained dependent permanently. We have identified a cohort at highest risk for long-term use, for whom early interventions should be targeted since late removal becomes progressively more unlikely.

Abnormal response after multiple rapid swallow provocation is not predictive of post-operative dysphagia following a tailored fundoplication approach.

The aim was to evaluate the clinical significance of multiple rapid swallows (MRS) during high-resolution manometry (HRM) prior to fundoplication. Despite pre-operative HRM, up to 38% of patients report post-fundoplication dysphagia. Suggestion that MRS improves prediction of dysphagia after fundoplication has not been investigated when using a tailored approach. We hypothesize response to MRS is predictive of dysphagia after tailored fundoplication. A retrospective cohort study was performed on patients undergoing HRM with MRS provocation 5/2019-7/2021 at a single institution. Patients who underwent subsequent index laparoscopic fundoplication, without peptic stricture or achalasia, were included. After performing standard 10-swallow HRM, MRS provocation was performed. Patient-reported dysphagia frequency scores were collected at initial consultation and post-operative follow-up. At least weekly symptoms were considered clinically significant. Normal MRS response was defined as adequate deglutitive inhibition and MRS contractile response. Fundoplications were tailored based on standard HRM values. HRM was performed in 1201 patients, 220 met inclusion criteria. Clinically significant pre-operative dysphagia was reported by 85 (38.6%). Patients undergoing partial fundoplication (n = 123, 55.9%) had lower mean distal contractile integer, distal esophageal contraction amplitude, and percent peristalsis (p < 0.005). Post-operatively, 120 (54.5%) were without dysphagia, 59 (26.8%) had improved dysphagia, 26 (11.8%) had unchanged dysphagia, and 15 (6.8%) reported new dysphagia. There was no statistical difference in early or late dysphagia outcome between tailored fundoplication groups (p = 0.69). On univariate and multivariate analysis, neither MRS response, nor standard HRM metrics were significantly associated with post-operative dysphagia. Younger age (OR 0.96, 95% CI 0.94-0.986, p = 0.042) and the presence of pre-operative dysphagia (OR 2.54, 95% CI 1.17-5.65, p = 0.015) were significant predictors of post-operative dysphagia. The risk of clinically significant dysphagia post-fundoplication is low when using a tailored approach based on standard HRM metrics. Additional data provided by MRS does not add to surgical decision-making using the investigated approach.

Comparison of Dosimetric Parameters in Dysphagia Aspiration-Related Structures and Clinical Correlation in Head and Neck Cancer Patients Treated With Radiotherapy.

IntroductionChemoradiotherapy plays a major role in the treatment of head and neck cancer (HNC). Persistent dysphagia following primary chemoradiotherapy for head and neck cancers can have a devastating effect on a patient’s quality of life. Many studies have shown that the dosimetric sparing of critical structures which were included in swallowing such as the pharyngeal constrictor muscle and larynx can provide improved functional outcomes and better quality of life. However, there are no current randomized studies confirming the benefits of such swallowing-sparing strategies. The aim is to evaluate late dysphagia after chemoradiotherapy for head and neck cancer and to examine its correlation with clinical and dosimetric parameters.Materials and methodsThe period of this prospective study was from November 2018 to March 2020. Patients were divided randomly in 1:1 ratio into two groups, group 1 and group 2, each with 25 patients. Group 1 was planned by three-dimensional conformal radiotherapy (3D-CRT) technique and group 2 was planned by intensity-modulated radiotherapy technique (IMRT) technique. Treatment was delivered after approval of radiotherapy plan. To evaluate the dose to dysphagia aspiration-related structures (DARS), these structures were contoured and dose-volume histograms were generated. Various dosimetric parameters of DARS were evaluated. Swallowing status was clinically evaluated based on the Radiation Therapy Oncology Group and the Common Terminology Criteria for Adverse Events, version 5.ResultsA significant advantage was seen with intensity-modulated radiotherapy technique (IMRT) in comparison to three-dimensional conformal radiotherapy (3D-CRT) in terms of mean dose delivered to the pharyngeal constrictor muscles (66.03 Gy vs 68.77 Gy, p=0.003). The mean dose delivered to the combined dysphagia/aspiration-related structures (DARS) was statistically significantly lower in IMRT compared to 3D-CRT (66.15 Gy vs. 70.09 Gy, p<0.001). Other dose-volumes were also reduced in IMRT group (V30: {98.64% vs. 99.88%, p=0.05}; V50: {90.49% vs. 99.02%, p=0.0002}; V60: {83.92% vs. 95.04, p=0.0002}; D50: {70 Gy vs. 71.16 Gy, p=0.001); and D80: {61.18 Gy vs. 67.39 Gy, p=0.01}. Futhermore, the clinical worsening of dysphagia was less common in IMRT group (48% vs. 80%, p=0.039).ConclusionIMRT can reduce the high-dose volumes received by the DARS receiving high doses by sparing these structures through optimization. This may provide a significant additional benefit that could improve dysphagia and hence the quality of life of patients with head and neck cancer.