Base Of Tongue Research Articles

Concordance between head and neck MRI and histopathology in detecting laryngeal subsite invasion among patients with laryngeal cancer

BackgroundAccuracy of head and neck MRI (HN-MRI) in predicting tumor invasion of laryngeal site/subsites in patients with laryngeal cancer prior to laryngectomy is poorly evaluated in the literature. Therefore, we aim to evaluate the diagnostic value of HN-MRI in accurate pre-operative estimation of tumor invasion to laryngeal subsites in patients with laryngeal cancer.MethodsPatients with laryngeal cancer who underwent HN-MRI for cancer staging and underwent total laryngectomy between 2008 and 2021 were included. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of HN-MRI in predicting tumor invasion of laryngeal subsites were calculated based on concordance between the HN-MRI and histopathological results.ResultsOne hundred and thirty-seven patients underwent total laryngectomy [primary: 82/137(60%), salvage 55/137(40%)]. The utilization of HN-MRI resulted in the downstaging of 16/137 (11.6%) patients and the upstaging of 8/137 (5.8%) patients. For the whole cohort, there was a significant discordance between HN-MRI and histopathology for T-category; out of 116 cT4a disease, 102(87.9%) were confirmed to have pT4a disease, and out of 17 cT3 disease, 9(52.9%) were confirmed to have pT3 disease, p < 0.001. The MRI overall diagnostic accuracy of predicting tumor invasion was 91%, 92%, 82%, 87%, 72%, 76%, 65% and 68% for base of tongue, arytenoid, vocal cord, posterior commissure, pre-epiglottic space, cricoid cartilage, inner thyroid cortex, and subglottis, respectively.ConclusionsIn patients with laryngeal cancer undergoing total laryngectomy, HN-MRI demonstrates promising accuracy in predicting tumor invasion of specific laryngeal subsites (e.g., base of tongue). Our findings showed the potential of HN-MRI as a valuable tool for pre-operative planning and treatment decision-making in this patient population.

Obstructive Sleep-Disordered Breathing in Infants with Normal Awake Clinical Examination: Contribution of Drug-Induced Sleep Endoscopy.

To determine the cause of obstructive sleep-disordered breathing using drug-induced sleep endoscopy (DISE) in infants without co-morbidities and with normal clinical examination. This prospective study was conducted between December 2019 and June 2022 (31 mo). All infants referred for obstructive sleep-disordered breathing with normal clinical examination and flexible laryngoscopy were included and underwent DISE. The location of the obstructive sites was scored similarly according to the NAVOTEL scoring system, previously established and validated by authors' team. Thirty-two infants were included. DISE identified an obstructive site in 94% of cases. The mean age was 16.4 mo, and the median was 16.7 mo. The obstructive sites found were isolated sleep laryngomalacia (37.4%), adenotonsillar hypertrophy (21.8%), isolated adenoidal hypertrophy (6.3%), adenotonsillar hypertrophy associated with sleep laryngomalacia (6.3%), circumferential upper airway narrowing (6.3%), glossoptosis (6.3%), isolated inferior turbinate hypertrophy (3.1%), adenoidal and tongue base hypertrophy (3.1%), and adenoidal hypertrophy with sleep laryngomalacia (3.1%). No obstructive causes could be found in 2 cases (6.3%). DISE identified an obstructive site in 30/32 patients (93.8%) and guided the surgical management in 26/32 cases (81.3%) during the same general anesthesia. The infants without surgical obstacles were referred for medical treatment. DISE is an excellent diagnostic and pre-therapeutic tool in infants with no apparent cause at the awake examination to identify the obstructive sites and guide the treatment.

Fluoroscopic-Assisted Tongue Suspension: Advancement and Innovation in the Management of Complex Pediatric Obstructive Sleep Apnea.

The primary aim of this study is to describe a novel surgical technique developed for tongue base suspension (TBS). The second aim of this study is to assess the efficacy of the developed procedure by quantifying preoperative and postoperative polysomnographic outcomes for pediatric patients undergoing fluoroscopic-assisted tongue suspension (FATS) with the Encore System. Our hypothesis is that our FATS technique will provide at least a 50% reduction in the Apnea/Hypopnea Index (AHI), including in the medically complex pediatric population. Retrospective case series. An electronic medical record review was conducted of patients who underwent FATS by a single surgeon at a tertiary care medical center between December 2019 and June 2022. Inclusion criteria included all patients <18 years old with evidence of OSA or sleep-disordered breathing and who had glossoptosis on sleep endoscopy. Data extracted from the medical record included age, gender, medical comorbidity history, reason for referral, history of airway surgeries, length of hospital stay, surgical complications data, and preoperative and postoperative polysomnographic data. Surgical success was defined by at least a 50% reduction in AHI. Thirty patients (53.3% male) with a mean age of 6.3 (±5.3, 0.16-17) years underwent FATS over the study period. Most patients (93%) had an underlying comorbidity: cerebral palsy (37%), chromosomal abnormalities (23%), Down syndrome (13%), Pierre-Robin sequence (10%), and obesity (10%). The majority of patients (77%) were explicitly referred for tracheostomy placement secondary to failed management of OSA. 21 patients completed both preoperative and postoperative polysomnograms. The mean preoperative AHI, obstructive AHI (oAHI), and respiratory disturbance index (RDI) were 28.8 (±19.8), 30.8 (±19.6), and 30.5 (±19.3), respectively. The mean postoperative AHI, oAHI, and RDI were 7.3 (±9.2), 7.5 (±9.1), and 7.9 (±9.3), respectively. The mean change in AHI was -21.5 (±21.4) events/h (p < 0.01, 95% CI -29.0 to -11.4 events/h). The mean percentage decrease in AHI was 74.7%. The mean change in oAHI and RDI were -23.3 (±21.9) events/h (p < 0.01 95% CI- 39.9 to -21.4 events/h) and -22.5 (±21.5) events/h (p < 0.01, 95% CI- 31.5 to -12.4 events/h), respectively. The mean percentage decrease in oAHI and RDI was 75.6% and 73.8%, respectively. Surgical success occurred in 16 of the 21 (76%) patients. Of the 23 patients referred explicitly for tracheostomy placement, 21 (91%) were able to avoid tracheostomy placement secondary to improvements in OSA. Patients undergoing fluoroscopic-assisted TBS revealed statistically significant improvements in AHI, oAHI, and RDI, with an overall surgical success rate of 76%. Complication rates were minimal, despite the complex nature of the study population. FATS should be considered a viable surgical approach in pediatric patients with an identified base of tongue obstruction and OSA. 4 Laryngoscope, 134:S1-S9, 2024.

A case of acute submandibular sialadenitis caused by a fish bone that strayed into the submandibular gland duct

AbstractBackgroundFish bones commonly stray into the tongue base, palatine tonsils, and pharyngeal mucosa but rarely into the submandibular gland duct.Case presentationA 74‐year‐old man developed acute sialadenitis after a fish bone strayed into the submandibular gland duct. Laboratory data revealed elevated S‐amylase level; computed tomography (CT) revealed linear opacification along the submandibular gland duct. Electron microscopic analysis confirmed the object to be a fish bone; the bone discharged spontaneously prior to a scheduled excision.ConclusionIdentification of foreign bodies is difficult with CT or other imaging modalities alone. Additional detailed examination, such as electron microscopy analysis, is required.

Coiled tube of femoral anterolateral flap for repair of circumferential defect after operation of advanced hypopharyngeal carcinoma

Objective: To investigate the clinical application value of coiled tube of femoral anterolateral flap in the repair of circumferential defect after resection of advanced hypopharyngeal carcinoma. Methods: Clinical data of 42 patients with advanced hypopharyngeal cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to April 2022 were retrospectively analyzed, including 41 males and 1 female, aged from 33 to 82 years old. All patients received surgical treatment, including total laryngectomy plus total laryngopharyngectomy in 20 cases, total laryngectomy, total laryngopharyngectomy and resection of partial tongue base in 8 cases, total laryngectomy, total laryngopharyngectomy and resection of cervical esophagus in 9 cases, total laryngectomy, total laryngopharyngectomy, and resection of partial tongue base and cervical esophagus in 5 cases. The postoperative circumferential defects were repaired with the coil tube of anterolateral femoral skin flap in phase Ⅰ, and the healing status of the flap, wound healing and swallowing function were observed. All cases were followed up. Results: The lengths of the hypopharyngeal defects were 7-18 cm and the sizes of the harvested flaps were 6 cm×9.5 cm-10 cm×20 cm. Flaps survived in 41 cases, flap necrosis occurred in one case, and the survival rate of flaps was 97.6%. One artery and one vein were anastomosed in 40 cases, and one artery and two veins were anastomosed in 2 cases. Postoperative cervical wound infection occurred in 5 cases, and pharyngeal fistula occurred in 2 cases. Three months of follow-up after surgery, 31 cases had normal diet, 9 cases presented with semi-liquid diet and 2 cases with liquid diet. Following up for 6-65 months, recurrence and metastasis occurred in 14 patients (33.3%), including primary site recurrence in 4 cases (9.5%), cervical lymph node recurrence in 6 cases (14.3%), and distant metastasis in 4 cases (9.5%). The 1-year and 3-year overall survival rates were respectively 79.4% and 60.5%. Conclusion: Coiled tube of femoral anterolateral flap is an ideal skin flap for repair of circumferential defects after resection of advanced hypopharyngeal carcinoma.

The Expression of Amino Acid and Fatty Acid Receptors Show an Age-Dependent Pattern Involving Oral Cavity, Jejunum and Lower Gut Sensing in Broiler Chickens.

This work aimed to evaluate the gene expression of amino acids (AA) and fatty acids (FA) sensors in the gastrointestinal tract (GIT) of chickens at two different ages (7 and 26 days post-hatch). Sixteen broilers (Ross 308) were selected, and ten sections of the GIT, including upper (tongue base, upper palate, crop, proventriculus), middle (gizzard, duodenum, jejunum, ileum), and lower GIT section (cecum, colon) were collected for analysis. Relative gene expression of AA (T1R1, T1R3, mGluR1, mGluR4, CaSR, GPR139, GPRC6A, GPR92) and FA (FFAR2, FFAR3, FFAR4) sensors were assessed using qPCR. The statistical model included age, GIT section, and gene. In addition, the correlations between gene expressions were calculated. At day 7, a significantly (p = 0.004) higher expression of AA sensors in the oral cavity and FA sensors in the lower GIT section (i.e., cecum and colon) compared to the middle section was recorded. A higher expression of AA compared to FA sensors was detected at the upper GIT section in 7 (p < 0.001) and 26-day-old chickens (p = 0.026). Thus, at day 7, AA sensors were predominantly (p < 0.05) expressed in the upper GIT section (mainly oral cavity), while FA sensors were mainly expressed in the lower GIT section, at cecum (FFR2 and 4) or colon (FFAR3). These results may indicate that in early life, both ends of the GIT are fundamental for feed intake (oral cavity) and development of the microbiota (cecum and colon). In contrast, at 26 days of age, the results showed the emergence of both AA and FA sensors in the jejunum, presumably indicating the essential role of the jejunum in the digestion absorption of nutrients and the signaling to the brain (gut-brain axis) through the enteroendocrine system. Significant positive correlations were observed between T1R1 and T1R3 (r = 0.85, p < 0.001), CaSR and T1R1 (r = 0.78, p < 0.001), CaSR and T1R3 (r = 0.45, p < 0.050), and mGluR1 and FFAR3 (r = 0.46, p < 0.050). It is concluded that the gene expression is greater in the oral cavity for AA sensors and the lower gut for FA sensors. On day 26, the role of jejunum regarding nutrient sensing is highlighted.

The morphometrical evaluation after uvulopalatopharyngoplasty.

The aim of this study was to evaluate the efficacy of uvulopalatopharyngoplasty (UPPP) and the corresponding postoperative morphometrical changes. Patients diagnosed with obstructive sleep apnea syndrome who complained of snoring and apnea were enrolled in this study. Pre- and postoperative tests, including CTs, pharyngeal volume (PV), cross-sectional area (CSA), and six-category morphometrical studies, were performed. Of 11 patientsincluded, 10 showed improvement of symptoms. BMI correlated with the respiratory event index (REI). In terms of PV, there was a significantlywider postoperative area. The rate of change between preoperative REI and postoperative REI (ΔREI) correlated with the amount of change of PV between preoperative PV and postoperative PV (ΔPV). CSA increased postoperatively and correlated with REI. Uvula space (UV) and distance between the hyoid bone and the base of the tongue (HB) increased postoperatively, and posterior airway space (PAS) and epiglottic space (Epi) decreased postoperatively. UV and PAS were significant (p = 0.046, 0.014). UV was related to REI. Widening the PV, increasing CSA, and the posterior movement of the tongue base after UPPP surgery were found. The improvement of REI did not depend only on volume. These results suggest that it was important not only to widen the PV but also to improve the shape of the pharynx.

Anatomy-Specific Classification Model Using Label-Free FLIm to Aid Intraoperative Surgical Guidance of Head and Neck Cancer.

Intraoperative identification of head and neck cancer tissue is essential to achieve complete tumor resection and mitigate tumor recurrence. Mesoscopic fluorescence lifetime imaging (FLIm) of intrinsic tissue fluorophores emission has demonstrated the potential to demarcate the extent of the tumor in patients undergoing surgical procedures of the oral cavity and the oropharynx. Here, we report FLIm-based classification methods using standard machine learning models that account for the diverse anatomical and biochemical composition across the head and neck anatomy to improve tumor region identification. Three anatomy-specific binary classification models were developed (i.e., "base of tongue," "palatine tonsil," and "oral tongue"). FLIm data from patients (N = 85) undergoing upper aerodigestive oncologic surgery were used to train and validate the classification models using a leave-one-patient-out cross-validation method. These models were evaluated for two classification tasks: (1) to discriminate between healthy and cancer tissue, and (2) to apply the binary classification model trained on healthy and cancer to discriminate dysplasia through transfer learning. This approach achieved superior classification performance compared to models that are anatomy-agnostic; specifically, a ROC-AUC of 0.94 was for the first task and 0.92 for the second. Furthermore, the model demonstrated detection of dysplasia, highlighting the generalization of the FLIm-based classifier. Current findings demonstrate that a classifier that accounts for tumor location can improve the ability to accurately identify surgical margins and underscore FLIm's potential as a tool for surgical guidance in head and neck cancer patients, including those subjects of robotic surgery.

Subcutaneous Emphysema Following Nasal Positive Airway Pressure Therapy in a Patient With a History of Tongue Base Tumor Resection

Positive airway pressure (PAP) therapy is chosen as the primary modality for most patients with obstructive sleep apnea due to its efficacy and safety. However, PAP therapy can cause potential side effects, including barotrauma, which in most cases is benign and manageable. Nevertheless, rare but serious complications, such as subcutaneous emphysema, may also occur. Here, I present a case of a middle-aged man with a history of tongue base tumor resection who developed subcutaneous emphysema in the neck following nasal PAP therapy. This case highlights the potential risk associated with previous surgical interventions and PAP therapy.

Definitive Chemoradiation Treatment Response Evaluation Using NI-RADS and ctHPVDNA for HPV-Associated Oropharyngeal Squamous Cell Carcinoma

To compare the evaluation of treatment response among patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive (chemo)radiotherapy (CRT). Patients with locally advanced HPV-associated OPSCC treated with definitive radiotherapy (RT) or CRT from 2019 to 2022 at a single institution were reviewed. Patients underwent standard 3-month post-CRT positron emission tomography/computed tomography (PET/CT) scan with or without contrast enhanced CT (CECT) of the head and neck. Plasma circulating tumor HPV DNA (ctHPVDNA) was collected from 2-8 months post-CRT. Equivocal findings on post-CRT imaging prompted repeat evaluation. Imaging response was assessed via NI-RADS (Neck Imaging Reporting and Data System) risk classification and independently reviewed by two board certified radiologists, both blinded to outcomes and ctHPVDNA values. Our cohort of 52 patients included: 87% males; median age 61.5; 63% never smokers, 31% former smokers, 6% current smokers; 44% tonsil primary, 46% base of tongue; 4% T0, 25% T1, 40% T2, 12% T3, 17% T4; 6% N0, 15% N1, 2% N2a, 44% N2b, 25% N2c, 8% N3 (AJCC 7th edition). Concurrent systemic therapy was received in 90%. During this period 71 PET/CTs and 15 CECTs were reviewed for treatment response evaluation; 44% (23/52) patients required additional imaging for equivocal findings; 62 ctHPVDNA blood samples were co-analyzed for treatment evaluation. The highest risk classification score between mucosa, primary, and/or neck site was: 42% NI-RADS 1, 48% NI-RADS 2, and 10% NI-RADS 3. Only patients with locoregional disease recurrence/progression were included for evaluation comparison between imaging and circulating biomarkers. No cancer events occurred without imaging and/or ctHPVDNA detection. Patients with NI-RADS score ≥2 during first post-CRT imaging evaluation more frequently underwent additional imaging (70% vs 30%, p<0.001). NI-RADS risk classification suggested 5 locoregional events (2 true positives, 3 false positives) resulting in 100% sensitivity, 94% specificity, 40% positive predictive value (PPV), and 100% negative predictive value (NPV). Circulating tumor HPV-DNA identified 2 locoregional events (2 true positives, 0 false positives) resulting in 100% sensitivity, 100% specificity, 100% PPV, and 100% NPV. Salvage operations were performed in 2 of 3 patients with false positive disease by NI-RADS classification without any evidence of cancer on final pathology. While limited by the small number of recurrence events in this cohort, ctHPVDNA for HPV-associated OPSCC in conjunction with post-treatment imaging evaluation may limit the need for repeat imaging and unwarranted salvage operations that increase patient worry, morbidity, and financial toxicity. Additional prospective study is warranted.

Tailoring Radiation to the Contralateral Neck for Midline HPV-Mediated Oropharyngeal Squamous Cell Carcinoma (p16+ OPSCC)

De-intensification strategies for locally advanced p16+ OPSCC are under active investigation, including omission of contralateral neck radiation (RT) for well-lateralized T1-2N0-2a. This study evaluates the outcomes of omitting contralateral neck nodal levels for p16+ OPSCC that are not well-lateralized. A retrospective review was done of 134 consecutive patients with non-metastatic p16+ OPSCC that were not well-lateralized (< 1 cm from midline or ≥ 1 cm extension to soft palate or base of tongue) who were treated with definitive chemoradiation from 2013 to 2019. IMRT to an EQD2 6364-6735 cGy (200-220 cGy per fraction) was used to treat the primary tumor and ipsilateral or bilateral neck, with tailored nodal level coverage and dose, and with concurrent paclitaxel and carboplatin. Contralateral neck RT was tailored in 121 patients: omitted in 11, limited to level II in 9, and limited to level II and III in 101 (contralateral lower neck omitted); the remaining 13 had bilateral level II-IV neck RT. Local and regional recurrences were evaluated. Median follow up was 45.34 months. Local and/or regional recurrence was noted in 9/134 (6.7%). 3 (2%) recurred in the contralateral neck in unirradiated tissue (out-of-field). All three were salvaged. The remaining 6 recurrences (4%) were in-field; one was at the primary site and 5 were nodal (all ipsilateral). 4 of the 5 regional recurrences were in a location that was treated to EQD2 7000 cGy (all had PET avid nodal disease upfront that was included in the high dose level); the other region of recurrence was treated to an EQD2 6353 cGy (the only recurrence in a never smoker). 4 of the 5 neck recurrences underwent neck dissection; one further underwent adjuvant RT to 5940 cGy in 33 fractions and remains disease-free. 2 of those who underwent salvage neck dissection alone subsequently developed distant metastases. The majority of first recurrences were distant, 19.4% (26/134). 3-year progression free survival (PFS) was 74.41% (95% CI, 65.63-81.26). Taken together, regional recurrence rate in the contralateral, unirradiated neck was 2.5% (3/121) and ultimate locoregional control was 99% (132/134). Our tailored approach demonstrates a contralateral neck local control of 97.5% (118/121) regardless of tumor lateralization; those who recurred in unirradiated cervical lymph nodes were successfully salvaged. Limiting this analysis is moderate sample size and retrospective nature, but it raises important alternative de-escalation strategies (RT volume reduction) for p16+ OPSCC aside from dose reduction, which is under active investigation in phase II/III trials. Improved systemic therapies are needed to combat distant metastases. Prospective randomized clinical trials are needed for further evaluation of nodal omission for definitive chemoradiation of non-well-lateralized p16+ OPSCC.

Radiation Toxicity Profile Difference in p16+ vs. p16- Oropharyngeal Cancer Patients

p16+ oropharyngeal squamous cell carcinoma is radiosensitive and has better prognosis than p16-ve. However, the correlation between p16 reactivity and radiation toxicity profile in these patients has not been studied. Edmonton Symptom Assessment System (ESAS) is a generic patient reported symptom scale validated for patient reported outcome (PRO) assessments in head and neck cancer patients. We sought to review the ESAS and its psychometric properties in oropharyngeal cancer patients treated with concurrent chemoradiation (CCRT) stratified by their HPV status. To evaluate differences in magnitude and temporal trends in PRO before, during and after radiation treatments in both p16+ and p16-ve oropharyngeal cancer patients using ESAS scores. Prospectively collected ESAS scores for oropharyngeal cancer patients treated at a safety net hospital with CCRT were analyzed. Longitudinal variation in pain, depression, appetite and family distress scores before, during and up to 36 weeks after CCRT were evaluated at seven time points: prior to treatment, 1-3, 4-6, 7-10, 11-15, 16-20 and 20-36 weeks. Statistical analysis focused on data collected through repeated measurements for patients using ANOVA mixed regression analysis using p16 status as between subjects factor for each symptom. Three hundred fifty-five ESAS assessments were analyzed for each symptom for 64 oropharyngeal cancer patients treated with CCRT. Subsites identified were 21 (32.8%) tonsil, 15 (23.4%) base of tongue, 22 (34.4%) soft palate, and 6 (9.4%) oropharynx not specified. We identified 35 (54.7%) p16+ and 29 (45.3%) p16-ve patients. The median age of the cohort was 60 (range: min 39 - max 88); the median age was 59 for p16+ and 61 for p16-ve. Median total radiation dose was 6996 Gy. Pain scores peaked at 7-10 weeks for both groups but p16-ve had delayed peak 11-15 weeks as well. Depression scores stayed <4 for both populations but family distress, pain and appetite scores peaked for p16-ve between 11-15 weeks. Mean pain scores were similar for both populations and peak during CCRT for both however p16-ve patients have another peak after completion of CCRT. Family distress and decreased appetite also heighten during this post CCRT time for p16-ve patients which warrants a planned early intervention at 11-15 weeks for these patients to improve their quality of life.

A Phase II Trial Evaluating Rapid Mid-Treatment Nodal Shrinkage to Select for Adaptive Deescalation in p16+ Oropharyngeal Cancer Patients Undergoing Definitive Chemoradiation

The purpose of this study is to determine if rapid mid-treatment nodal shrinkage (RMNS) can identify patients with p16+ oropharyngeal cancer (OPC) who can be safely deescalated with reduced dose chemoradiation therapy (CRT). The primary endpoint was 2-year progression free survival (PFS). Inclusion criteria were as follows: T1-3, N1, M0 (AJCC 8th edition) p16+ OPC with <10 pack-year smoking history. All patients were initially planned for standard dose CRT (70 Gy) and weekly cisplatin. Patients were evaluated with a CT scan at week 4 for RMNS, defined as >40% nodal volumetric reduction from baseline. If RMNS was achieved, they proceeded to deescalated CRT (60 Gy). If not, they received standard CRT. Biomarker correlates were collected at baseline and week 4 of CRT including plasma TTMV (tumor tissue modified viral) HPV DNA and MRI diffusion weighted imaging (DWI). Univariate logistic regression analyses (UVA) were performed to evaluate predictors of RMNS. Odds ratios with 95% CI are reported, using a p<0.05 for statistical significance with a two-sided test. Wilcoxon rank sum tests were used to evaluate differences between the two groups using p < 0.05, 2-sided) for statistical significance. All statistical procedures were performed using R () with no adjustments for multiple testing. Thirty-six patients were enrolled: median age: 60 years; 81% male; primary site: 36% base of tongue, 53% tonsil, 11% both; T-stage: 39% T1, 50% T2, 11% T3; N-stage: 100% N1; any smoking history: 58% yes, 42% no; 67% (n = 24) had RMNS and received deescalated CRT while the remaining proceeded to standard CRT. At a median follow-up of 32.4 months, 2-year PFS between the standard and deescalated groups were 91.7% vs 90.9%, respectively (p = 0.97). All patients with recurrence underwent successful salvage treatment with 2-year OS 100% for all patients. On UVA, rapid TTMV HPV DNA clearance (baseline to week 4) (OR 12.0 [1.65-250], p = 0.034), lower MRI diffusivity (ADC) at baseline (OR 0.79 [0.61-0.97], p = 0.042) and week 4 (OR 0.76 [0.60-0.91], p = 0.009), and higher MRI diffusional kurtosis at baseline (OR 1.09 [1.01-1.21], p = 0.051) and week 4 (OR 1.24 [1.09-1.52], p = 0.009) were significantly associated with RMNS. When comparing the deescalated and standard cohorts, the mean baseline and week 4 MRI ADC were significantly lower and week 4 MRI diffusional kurtosis was significantly higher in the deescalated group. In this phase II study, rapid mid-treatment nodal shrinkage appeared to select favorable risk p16+ oropharynx cancer patients for treatment de-escalation. Rapid clearance of TTMV HPV DNA at week 4 as well as MRI DWI biomarkers of low ADC and high diffusional kurtosis values were correlated with RMNS. A larger study is planned to incorporate RMNS and biomarkers for further treatment de-escalation. Additional trial information is available at ClinicalTrials.gov (Identifier: NCT03215719).

Definitive Chemoradiotherapy for Salivary Gland Cancers

Surgical resection is the standard of care for salivary gland tumors of the head and neck. The role of radiotherapy is typically reserved for the adjuvant setting in those patients with high risk factors on surgical pathology. Surgical resection in some cases may lead to significant impairment in speech or swallowing due to location of the primary tumor. In other cases, patients may not be medically able to receive an oncologic resection. Our institution has developed a protocol for organ preservation for well-selected salivary gland malignancies. Here we report disease outcomes of salivary gland cancer patients treated with definitive chemoradiotherapy. We retrospectively reviewed all salivary gland cancer patients at our institution who received definitive chemoradiation from January 1990 to December 2019. Chemoradiation typically consisted of 4 to 6 alternating weekly cycles of paclitaxel (100 mg/m2 on d1), infusion 5-fluorouracil (600 mg/m2/d on d0-5), hydroxyurea (500 mg PO BID), and either 1.8 Gy or 2 Gy daily or 1.5 Gy twice-daily irradiation followed by a 9-day treatment break (TFHX). The Kaplan-Meier method was used to estimate rates of locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS). Nineteen patients met eligibility criteria and were included for analysis. 53% of patients had adenoid cystic histology. Salivary duct, mucoepidermoid, acinic cell, and myoepithelial histologies each were represented by 10.5% of patients. About 26% of tumors were located in the nasopharynx, 21% in the base of tongue and 26% in the parotid. 74% of the patients were node negative and 53% of patients had stage IVA disease. T3 disease occurred in 26.3% while T4a and T4b disease occurred in 31.6% each. Median follow-up was 45.8 (IQR: 29-66) months. 47% of patients were treated using a twice daily approach, while 53% were treated with daily fractionation with a median dose of 72 Gy (IQR: 70-75). Three-year locoregional control (LRC), distant-metastasis free survival (DMFS), and overall survival (OS) were 93%, 76%, and 81% respectively. Eight of nine distant failures had T4a/T4b disease. Accounting for competing risk of death, local failure was 5.6% at three years. The most common acute complications were grade 2-3 mucositis (74%) and skin toxicity (47%). One patient discontinued chemoradiation due to severe hand foot mouth syndrome. 42% of patients had late toxicity of xerostomia. Promising organ preservation is seen with concurrent chemoradiation for salivary gland cancer patients. Further prospective study of organ preservation in salivary gland cancers is warranted.

Intensity-Modulated Neutron Therapy (IMNT) for Head and Neck Cancer: Early Toxicity Outcomes

Locally advanced head & neck cancers (HNC) are challenging to treat due to abutment of critical, dose-limiting structures. Fast neutron radiotherapy (NT) is a high linear energy transfer (LET) modality that provides better local control than photons for radioresistant cancers such as salivary gland tumors, but there have been concerns of toxicity with 3D conformal neutron therapy in the past. Recent technological advances have enabled the planning and delivery of IMNT, which improves target conformality and may reduce toxicity compared to 3D conformal NT. We report the first clinical evaluation of early toxicity outcomes of IMNT for HNC. Study is a single-institution retrospective review of all HNC patients treated with curative-intent IMNT from 10/2022 to 2/2023, using a hospital-based cyclotron (50.5 MeV 1H+ beam incident on a Be target) equipped with an isocentric gantry and multileaf collimator (MLC). A commercial treatment planning system with custom neutron-specific scattering kernels was used for IMNT planning using 4-6 fields. Patient-specific quality assurance included ionization chamber measurements and a novel 12C(n,2n)11C positron emission portal imaging system. kV portal imaging was used to confirm patient setup prior to each treatment session. All patients were prescribed 18.4 Gy at 1.15 Gy/fraction, delivered 4 days/week, which is equivalent to an x-ray EQD2 of approximately 70 Gy (RBE ∼ 3.8). Clinical observations suggest the RBE for radioresistant HNC may be as large as 8. Patients underwent weekly toxicity assessment, and acute toxicities were graded (G) by CTCAE v5.0. Ten patients received IMNT, median age 61 (range 34-78). Primary tumor sites were base of tongue (n = 3), sinonasal (n = 3), parotid (n = 2), submandibular (n = 1), larynx (n = 1). Tumor histologies included adenoid cystic carcinoma (n = 7), other salivary gland carcinomas (n = 2) and mucosal melanoma (n = 1). Most had T4 disease (n = 8) and one had N3b disease. Six had surgical resection with high-risk features, and 6 had gross measurable disease prior to IMNT. None had concurrent systemic therapy. Uninvolved salivary glands were spared in most patients. All patients completed treatment. Median follow up was 22 days (0-48). Acute toxicities (n, G 1, 2, 3) included skin (8, 3, 0), dysgeusia (1, 6, 0), xerostomia (3, 5, 0), mucositis (2, 0, 5), nausea (3, 0, 1). One patient had >10% weight loss and brief admission for supportive care and PEG placement; one patient had prophylactic PEG; both regained oral independence during follow-up. There was no Grade 4+ toxicity. IMNT improves the therapeutic ratio compared to 3D conformal NT and expands indications for NT in patients with radiorefractory tumors. Acute toxicity compares favorably with photons. Longer clinical and toxicity follow-up is anticipated. A prospective trial is planned to evaluate quality of life measures.

Long-Term Results of Induction Chemotherapy Followed by 50 Gy Radiation Therapy Alone for Low-Risk HPV-Positive Oropharynx Cancer

The standard of care for non-operative management of human papillomavirus-related oropharynx cancer (HPV-OPC) consists of concurrent cisplatin chemotherapy with radiotherapy (RT) to a total dose of 70 Gy. While the oncologic outcomes of this treatment approach have been excellent, there are considerable acute and late toxicities. Here, we report the 5-year survival and toxicity outcomes of 2 prospective HPV-OPC response-adapted de-escalation trials, in which low-risk (LR) patients were treated with dose-reduced RT to 50 Gy, without concurrent chemotherapy. Patients with LR HPV-OPC and ≥50% response to induction by RECIST 1.1 treated per 2 prospective phase II trials as well as on a prospective cohort registry were included for analysis. Patients were considered LR if the following criteria were met: T1-T3, N0-N2b (AJCC 7th edition), and ≤20 pack-year smoking history. Patients were treated with induction chemo- or chemoimmunotherapy followed by RT alone to 50 Gy. In the early trial iteration, patients underwent a planned neck dissection following RT to confirm pathologic clearance of lymph nodes. Clinicodemographic characteristics were summarized using descriptive statistics. Overall survival (OS), progression-free survival (PFS), and local control (LC) were estimated using the Kaplan-Meier method. From January 2015 through March 2020, 73 patients met LR criteria, of which, 54 (74%) had ≥50% response by RECIST and were de-escalated to RT alone. The median follow-up was 58 (range 10-92) months. The median age was 58 (range 38-84) years, and 92.6% were male. 57.4% of patients never smoked, and 42.6% smoked no more than 20 pack-years. The primary site was tonsil for 53.7% and base of tongue for 46.3%. 24.1% were T1, 53.7% were T2, and 22.2% were T3. 1.9% were N0, 5.6% were N1, 11.1% were N2a, and 81.5% were N2b. The 5-year OS, PFS, and LC were 96.3% (95% CI 91.3%-100%), 96.2% (95% CI 91.2%-100%), and 98.1% (95% CI 94.6%-100%), respectively. 2 (3.7%) patients required a G-tube during RT and none at 1 year following completion of RT. Of the 30 patients with a planned neck dissection, 2 (6.7%) had residual pathologic nodal disease. With a median follow-up of 5 years, this analysis demonstrates excellent long-term local control, survival, and swallowing function among patients with low-risk HPV+ oropharynx cancer treated with induction systemic therapy followed by radiotherapy to 50 Gy without concurrent chemotherapy, including a large proportion of patients with N2b disease. Chemo-selection provides a means of identifying a favorable cohort of HPV+ oropharynx cancer patients who can safely receive RT dose de-escalation. Further work is needed to identify this population by other means, including radiographic and genomic factors.

Reducing the Risk of Post-RT Aspiration by Sparing Specific Aspiration Related Organs at Risk

Radiotherapy (RT)-induced aspiration is a serious and potentially life-threatening side effect. We identified functional swallowing units (FSUs), musculature involved in larynx elevation and tongue base retraction (R&O 2019; 130:62). FSUs were strongly related to aspiration. We developed a prediction model with baseline aspiration status and dose in FSUs as factors which performed well in predicting videofluoroscopy assessed RT-induced aspiration, at 6 months. FSUs are not yet recognized as Swallowing Organs at Risk (SWOARs) in daily practice and in treatment plan optimization. In the current study, we aimed to apply the aspiration prediction model in RT treatment plan optimization to actively spare the FSUs and establish the potential to reduce the risk of late RT-induced aspiration. The planning study included 30 HNC patients treated with definitive radiotherapy. We optimized VMAT plans directly on logistic regression models (R&O 2021; 162:85), including normal tissue complication probability (NTCP) models for xerostomia, dysphagia and aspiration, and logistic models for target volume coverage and overall plan quality. Automated plans were created with and without using the NTCP-model for aspiration, i.e., with and without specific sparing of the previously identified FSU, including musculature associated with aspiration. The FSU sparing plans were created with and without assuming baseline aspiration. All NTCP models were weighted equally during optimization. The NTCP of toxicities including salivary, swallowing and speech problems, pain and general symptoms were evaluated for each plan. All plans complied with all treatment planning quality criteria and were successful in limiting the risk of xerostomia and dysphagia. Plans optimized using the NTCP model for aspiration significantly reduced the risk of late aspiration (p < 0.001) and in all 30 patients. The optimizer of the planning system increased its efforts to spare the FSUs even more when baseline aspiration was assumed. Therefore, the aspiration risk reduction was greatest in these plans (average risk was reduced from 73.9 to 60.6%, versus from 37.8 to 29.5% in plans assuming no aspiration at baseline). Aspiration risk reduction by sparing FSUs did not reduce overall plan quality. A slight redistribution of dose was seen as a result of FSU sparing. The largest observed NTCP increase was 0.6% for moderate-to-severe xerostomia. FSU sparing unintentionally reduced the average NTCP of moderate-to-severe hoarseness and speech problems with 2.1% and 1.2%, respectively. Sparing all specific aspiration related organs at risk, including FSUs, during RT has the potential to significantly reduce the risk of RT-induced aspiration, especially in patients with pre-existing baseline aspiration. With automatic planning, FSUs sparing does not increase complexity of the treatment planning process and does not compromise treatment plan quality.

A Novel Method to Classify the Responses of Genioglossus to Negative Pressure in OSA Patients.

This study aims to develop a novel method to classify different genioglossus (GG) responses to upper airway (UA) negative pressure in obstructive sleep apnea (OSA) patients. A single-center, prospective, cohort study. Sleep Medical Center. Patients with OSA underwent drug-induced sleep endoscopy with synchronous genioglossus electromyography (ggEMG) and UA pressure monitoring. In spontaneous obstructive apnea events, the value of epiglottis negative pressure at the end of inspiration (Pepi ) and corresponding peak phasic ggEMG were recorded as pairing data for linear regression analysis to classify GG response modes: peak phasic ggEMG-Pepi linear mode (P < .05) were classified as group 1; others (P ≥ .05) were classified as group 2. Using nasopharyngeal tube (NPT) to reopen the palatopharyngeal cavity for comparing the improvement between the OSA patients with different GG response modes. Sixty subjects were analyzed for GG response modes: 22 patients were in group 1 (r2 = 0.233-0.867), and 38 patients were in group 2. The proportion of partial (63.16% vs 59.09%) or complete (36.84% vs 22.73%) collapse rate of the tongue base in group 2 was significantly higher (χ2 = 7.823, P = .020). The improvement of the apnea-hypopnea index after NPT placement in group 2 was significantly lower than in group 1 (59.09% vs 31.58%, χ2 = 4.339, P = .037). This novel method is advantageous for distinguishing OSA patients with different GG response abilities to UA negative pressure, whose GG responses conforming to peak phasic ggEMG-Pepi linear mode might be more suitable for palatopharyngeal surgery.

Abstract PO-044: Correlation between circulating tumor DNA and tumor volume in head and neck cancer

Abstract Purpose: NavDx is a DNA test that has been used widely in head and neck cancer to quantify fragments of circulating tumor tissue modified viral DNA (TTMV HPV DNA), an HPV-specific cancer biomarker that is shed into the blood. Circulating tumor DNA has shown promise in monitoring tumor progression and therapeutic efficacy and therefore has potential to assist in improved cancer diagnosis and treatment. Recent studies have demonstrated a correlation between circulating tumor DNA and tumor volume in metastatic pancreatic ductal adenocarcinoma and metastatic breast cancer. The purpose of the study is to determine whether there is a correlation between positive vs. negative circulating tumor DNA at baseline as well as the quantity of circulating fragments and tumor volume in head and neck cancer patients. Methods: In this retrospective cohort study, data was extracted from our NavDx database (Naveris Systems) for 39 patients with p16 positive head and neck cancer with subsites in the base of tongue and tonsil. Logistic regression analyses were performed to compare tumor volume and tumor site in all patients and then by the subsites of base of tongue and tonsil. To address multicollinearity, different models were created for primary tumor volume, nodal volume, and total tumor volumes. Contrast enhanced diagnostic or radiation treatment planning CT scans were imported into Varian Aria (Varian Medical Systems, Palo Alto, CA). The primary and nodal disease was delineated to determine the total and sub-volumes. The relationship was examined between the tumor volumes and positive vs. negative/indeterminate circulating tumor DNA. Linear regression analysis was also performed to assess the relationship between tumor volumes and circulating fragments of TTMV-HPV 16. Results: A total of 39 patients were included in the study, including 36 males and 3 females, ages ranging from 42 to 79, and patients staged from Stage I to Stage IVA. 13 patients underwent surgical intervention. Subsites included the tonsil for 21 patients and base of tongue for 19 patients that were included in the analysis. There was a positive correlation between nodal volume and circulating TTMV-HPV16 fragments (p= 0.024) in all patients. There was a difference in tumor volume with an odds ratio of 1.41 and nodal volume with an odds ratio of 1.04 compared with positive vs. negative circulating DNA in all patients (p = 0.374; p = 0.906). Conclusions: The data demonstrated a positive correlation between nodal volume and circulating TTMV-HPV 16 fragments (p = 0.024). There was a difference in tumor and nodal tumor volumes with positive vs. negative circulating tumor DNA in all patients, however this did not reach statistical significance. While there was an association with nodal volume, further investigation is needed to determine why patients with p16 positive head and neck cancer may have negative serum circulating tumor DNA. Additional studies with a larger sample size can also better elucidate the relationship between circulating tumor DNA and tumor burden in H&amp;N patients. Citation Format: Oghenefejiro Okifo, Vivian Wu, Samantha Tam, Sondos Al Khatib, Farzan Siddiqui. Correlation between circulating tumor DNA and tumor volume in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-044.

Comparative effectiveness of hypoglossal nerve stimulation and alternative treatments for obstructive sleep apnea: a systematic review and meta-analysis.

Continuous positive airway pressure (CPAP) is the primary therapeutic modality for obstructive sleep apnea (OSA) management. However, despite efforts to encourage patients to comply with CPAP usage, long-term adherence remains low. Consequently, surgical intervention for OSA is considered a secondary option for patients who exhibit non-compliance with CPAP. Therefore, we conducted systematic review and meta-analysis assessed the relative effectiveness of hypoglossal nerve stimulation (HNS) treatment and alternative surgical interventions for managing OSA. Five databases were searched. Studies were included if they measured polysomnography parameters and assessed sleep apnea-related quality of life (Epworth Sleepiness Scale [ESS]) both before and after HNS, and compared these outcomes with control, CPAP, or airway surgery (uvulopalatopharyngoplasty, expansion sphincter pharyngoplasty, or tongue base surgery) groups. A total of 10 studies (2209 patients) met the inclusion criteria. Compared to other airway surgeries, the rates of post-treatment apnea-hypopnea index (AHI) < 10 and < 15 events/h were significantly lower in the HNS group (odds ratio [OR] 5.33, 95% confidence interval [CI] 1.21-23.42; and 2.73, 95% CI 1.30-5.71, respectively). Additionally, postoperative AHI was significantly lower in the HNS group than in all other airway surgery groups (AHI: mean difference [MD] -8.00, 95% CI -12.03 to-3.97 events/h). However, there were no significant differences in the rate of post-treatment AHI < 5 events/h (OR 1.93, 95% CI 0.74-5.06) or postoperative ESS score (MD 0.40, 95% CI-1.52 to 2.32) between the two groups. HNS is an effective option for selected patients with moderate-to-severe OSA and CPAP intolerance.