Tongue Displacement Device in Decreasing the Radiation Dose to Tongue and Preventing Proton Beam Overshoot in Proton Therapy for Unilateral Head and Neck Cancer

The aim of this study was to evaluate the dosimetric characteristics of a semi-customized tongue displacement device (SCTDD) fabricated using a 3D printer for patients receiving unilateral head and neck irradiation with intensity-modulated proton therapy (IMPT) and assess its feasibility as a proton beam stopper compared to a standard mouthpiece (SMP). Seven consecutive patients, three with tonsil cancer, and four with oral cavity cancer were included in this retrospective study. Planning computed tomography (CT) images of each patient were acquired for each device. Both the SCTDD and SMP plans were generated using a single-field optimized IMPT. The clinically relevant dose-volume parameters for the organs at risk (OARs), especially the tongue, were compared between the SCTDD and SMP plans. Additionally, to assess the feasibility of SCTDD as a proton beam stopper, the dose to the contralateral oral mucosa (COM) was compared with that from sMP use. The use of scTDD resulted in a statistically significant decrease in the radiation dose to the tongue and COM compared to sMP. The median mean dose to the tongue was significantly reduced with SCTDD (18.3 Gy(RBE)) compared to the SMP (22.9 Gy(RBE)) (p = 0.016). The percentages of tongue volume receiving doses between 15 and 60 Gy(RBE) were significantly lower with SCTDD. In the COM, SCTDD resulted in a significantly lower median mean (2.9 Gy(RBE) vs. 7.9 Gy(RBE), p = 0.018) and maximum dose (39.1 Gy(RBE) vs. 41.6 Gy(RBE), p = 0.018) doses compared to SMP. The SCTDD effectively decreased the radiation dose to the tongue compared to SMP in patients undergoing unilateral head and neck irradiation with IMPT and acted as a proton beam stopper to protect normal tissues located behind the target volume, such as the COM.

Elective neck irradiation in the management of esthesioneuroblastoma: a systematic review and meta-analysis

Background: There is no consensus about the optimal management of the neck in clinically node negative esthesioneuroblastoma (ENB). The aim of this study is to assess the impact of elective neck irradiation (ENI) in terms of regional disease control and survival. Methods: The study was performed according to the PRISMA guidelines searching on Scopus, PubMed/MEDLINE, and Google Scholar databases. The primary outcome was the regional recurrence rate (RRR), that was reported as odds ratio (OR) and 95% confidence interval (CI). Secondary outcomes were the overall survival (OS), and the distant-metastases free survival (DMFS), that were reported as logarithm of the hazard ratios (logHRs) and 95% confidence intervals (CIs). Results: A total of 489 clinically node negative patients were included from 9 retrospective studies. ENI significantly reduced the risk of regional recurrence compared to no treatment. No difference was measured between ENI and observation, according to both OS and DMFS. No stratified analysis could be performed based on Kadish stage and Hyams grade. Conclusions: ENI should be recommended to improve the regional disease control. No advantage was measured in terms of survival or distant metastases with a low quality of evidence. Further prospective studies should be designed to understand if ENI could be avoided in early stage and low-grade tumors.

Tissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor Signaling

Oral mucositis (OM) is a treatment-limiting adverse side effect of radiation and chemotherapy. Approximately 80% of patients undergoing radiotherapy (RT) for head and neck cancers (HNC) develop OM, representing a major unmet medical condition. Our understanding of the immunopathogenesis of OM is limited, due in part to the surprising paucity of information regarding healing mechanisms in the oral mucosa. RNAseq of oral tissue in a murine model that closely mimics human OM, showed elevated expression of IL-17 and related immune pathways in response to head and neck irradiation (HNI). Strikingly, mice lacking the IL-17 receptor (IL-17RA) exhibited markedly more severe OM. Restoration of the oral mucosa was compromised in Il17ra−/− mice and components associated with healing, including matrix metalloproteinase 3, 10 and IL-24 were diminished. IL-17 is typically associated with recruitment of neutrophils to mucosal sites following oral infections. Unexpectedly, in OM the absence of IL-17RA resulted in excessive neutrophil recruitment and immunopathology. Instead, neutrophil activation was IL-1R-driven in Il17ra−/− mice. Blockade of IL-1R and depletion of neutrophils lessened the severity of damage in these mice. Overall, we show IL-17 is protective in OM through multiple mechanisms including restoration of the damaged epithelia and control of the neutrophil response. We also present a clinically relevant murine model of human OM to improve mechanistic understanding and develop rational translational therapeutics.

603 CHALLENGES IN THE MANAGEMENT OF SEVERE ORTHOSTATIC HYPOTENSION ASSOCIATED WITH SUPINE HYPERTENSION IN A PATIENT WITH AUTONOMIC DYSFUNCTION ON BACKGROUND OF NASOPHARYNGEAL CARCINOMA AND TYPE II DIABETES MELLITUS

Introduction Combined chemotherapy and radiotherapy increases long term survival in patients with nasopharyngeal carcinoma. However, radiotherapy of the carotid sinus or brain stem can evolve labile hypertension and orthostatic intolerance from chronic baroreflex failure. Diabetes would also cause this neuropathy. Management of patients with Supine hypertension-Orthostatic hypotension can be very challenging. Methods A case report was done on a 71-year-old man with metastatic nasopharyngeal carcinoma status post radiation therapy who was admitted with severe supine hypertension-orthostatic hypotension. Patient was managed with both non-pharmacological and pharmacological methods, and monitored for postural symptoms, complications of severe supine hypertension—which has been linked to left ventricular hypertrophy and kidney dysfunction, and placed on 24 hour ambulatory blood pressure monitoring to aid in management so as to prevent hypertension induced organ damage. Results This review outlines the pathophysiology of Supine hypertension-Orthostatic hypotension, treatment complications and potential management strategies recommendations for this group of patients. It revealed the benefit of having a 24 hour ambulatory blood pressure monitoring, which provides insight on the timing and magnitude of an individual’s blood pressure fluctuations throughout the day so as to further guide management. Conclusion Chronic baroreflex failure is a late sequela of neck irradiation for naso-pharyngeal carcinoma due to accelerated atherosclerosis in the region of the carotid sinus baroreceptor. Treatment goal is achieved with adequate control of pre-syncopal symptoms and prevention of long term complications. Non-pharmacological interventions remain the first line of therapy, followed by pharmacological interventions as necessary. Nonetheless, management of blood pressure in these elderly patients with baroreflex dysfunction remains challenging and should be individualized. Moving forward, a prospective study on the incidence of late onset, iatrogenic baroreflex failure as a late complication of neck irradiation and its particular relationship to carotid arterial rigidity should be conducted to increase awareness, timely diagnosis and management of the condition among physicians.

Navigating the Debate on Large (4+cm) Thyroid Nodules: Local Insight on a Persisting Problem

Background: Thyroid nodules are a common clinical finding, however discordant practice guidelines for managing large nodules may result in unnecessary surgeries and excess costs. Recent data suggest similar false negative rates in fine needle aspiration (FNA) biopsies between small (<4cm) and large (4+ cm) nodules, indicating that monitoring rather than surgery may be appropriate for large nodules. Evaluating current management strategies may reveal insights regarding excess surgeries, costs and opportunities for improvement. Objectives: The goal of this project was to describe the patients at our institution with large thyroid nodules and determine the proportion of potentially unnecessary surgeries and the associated predictors. Methods: This was a retrospective cohort study that included patients who received a FNA of nodule (s) ≥4cm between 11/1/2014 and 10/31/2019 at our tertiary care institution. Patient demographics, sonographic nodule size, fine needle aspiration cytology, molecular testing results, final surgical pathology, history of neck irradiation, family history of thyroid cancer, presence of compressive symptoms or presence of a toxic nodule or toxic multinodular goiter, were compared between patients who had surgery and those who did not. A surgery was considered inappropriate if the FNA result was benign in the absence of any of the following: a suspicious result on molecular testing, compressive symptoms, family history of thyroid cancer in a first degree relative, history of neck irradiation, toxic nodule or toxic multinodular goiter or substernal extension. Continuous variables were evaluated using Wilcoxon rank-sum test while categorical variables were tested using chi-square or Fisher’s exact test. Results: A total of 177 patients had a 4+ cm nodule during the timeframe. Half of patients (54.2%)with 4+ cm nodules had surgery. Patients who underwent surgery were significantly younger (51.5 years vs 62 years; P<0.001), more likely to report obstructive symptoms (34.4% vs 12.1%; P=0.001) and have a larger nodule size (5.0 cm vs 4.7 cm; P=0.26) than patients who did not have surgery. Forty-one patients with benign (Bethesda II) FNA results went on to have surgery. All 41 patients were found to be negative at surgery, yielding a false negative rate of 0.0% in our cohort. Twenty-three surgeries (24.0%) were considered inappropriate and overall 13% (23/177) of patients with 4+cm nodules had unnecessary surgery. The median charge for these surgeries was $13,183. Conclusion: Approximately half of our patients with 4+ cm nodules had surgery, especially patients who are younger, report obstructive symptoms, and have larger nodule sizes. Overall 13% of our patients with 4+cm nodules had unnecessary surgery revealing opportunities for improving care and costs.