Targeted antiviral treatment using non-ionizing radiation therapy for SARS-CoV-2 and viral pandemics preparedness: Technique, methods and practical notes for clinical application.

OBJECTIVE: Pandemic outbreaks necessitate effective responses to rapidly mitigate and control the spread of disease and eliminate the causative organism(s). While conventional chemical and biological solutions to these challenges are characteristically slow to develop and reach public availability; recent advances in device components operating at Super High Frequency (SHF) bands (3-30 GHz) of the electromagnetic spectrum enable novel approaches to such problems. METHODS: Based on experimentally documented evidence, a clinically relevant in situ radiation procedure to reduce viral loads in patients is devised and presented. Adapted to the currently available medical device technology to cause viral membrane fracture, this procedure selectively inactivates virus particles by forced oscillations arising from Structure Resonant Energy Transfer (SRET) thereby reducing infectivity and disease progression. RESULTS: Effective resonant frequencies for pleiomorphic Coronavirus SARS-CoV-2 is calculated to be in the 10-17 GHz range. Using the relation y = -3.308x + 42.9 with x and y representing log10 number of virus particles and the clinical throat swab Ct value respectively; in situ patient-specific exposure duration of ~15x minutes can be utilized to inactivate up to 100% of virus particles in the throat-lung lining, using an irradiation dose of 14.5 ± 1 W/m2; which is within the 200 W/m2 safety standard stipulated by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). CONCLUSIONS: The treatment is designed to make patients less contagious enhancing faster recoveries and enabling timely control of a spreading pandemic. ADVANCES IN KNOWLEDGE: The article provides practically applicable parameters for effective clinical adaptation of this technique to the current pandemic at different levels of healthcare infrastructure and disease prevention besides enabling rapid future viral pandemics response.

The relationship between posterior pharyngeal wall thickness and swallowing function after radiation therapy.

Background: Dysphagia is a complication following radiation therapy (RT) for head and neck cancers (HNC). Radiologic findings of posterior pharyngeal wall thickening (PPWT) after RT has not been quantified and correlated to swallowing outcomes.Aims/objective: To evaluate PPWT and its impact on swallowing function following RT.Material and methods: Retrospective analysis of pre- and three-month post-RT PPWT, demographics, oncologic history, and swallowing parameters of patients undergoing RT for HNC. Multivariate analysis of variance was performed to evaluate the effect of PPWT on swallowing outcomes.Results: The mean age of the cohort (n = 207) was 61.8 (± 11.29) years. The mean PPWT increased by 0.28 (± 0.19) cm (p = .00) three-months after RT. A significant difference in PPWT score between tumor subsites, χ2(2) = 45.883, p = .00, with the highest mean rank score of 135.97 for nasopharynx and 103.46 for oropharynx. PPWT was significantly associated with increased pyriform sinus retention, higher Penetration-Aspiration Scale (PAS) scores and post-deglutitive aspiration (p < .05).Conclusions and significance: PPWT increase significantly after RT for HNC. Increased PPWT was associated with mean radiation dose to the nasopharynx and oropharynx and was an independent risk factor for increased pharyngeal residue, higher PAS scores, and timing of aspiration (p < .05).

Pharyngeal-sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work-up.

OBJECTIVE: In patients with head and neck carcinoma of unknown primary (HNCUP;pT0) following TORS-assisted workup, we have adopted a pharyngeal-sparing radiation therapy (PSRT) approach targeting only the at-risk neck and omitting treatment of the pharynx. We report outcomes following PSRT, and compare to institutional historical control subjects who received pharyngeal-targeted RT (PRT). METHODS: Between 2009 and 2018, 172 patients underwent TORS-assisted endoscopy as part of their workup for HNCUP. Following TORS, 54 patients had pT0 disease, of which 45 received RT. Forty-nine percent received PSRT and 51% received PRT. RESULTS: No statistically significant differences existed between the PSRT and PRT groups with respect to overall nodal distribution, p16 positivity (55% vs. 43%, P = .12), neck dissection rates (77% vs. 65%, P = .51), and administration of chemotherapy (55% vs. 65%, P = .55). Median follow-up for PSRT and PRT groups were 24 and 28 months, respectively (P = .04). Two-year RFS was 86% and 74% for PSRT and PRT patients, respectively (log-rank P = .30). Three and six patients recurred after PSRT and PRT, respectively. Two-year OS for PSRT and PRT patients was 91% and 74%, respectively (log-rank P = .31). Compared to PRT, PSRT was associated with statistically significantly less: grade 2+ mucositis (18% vs. 91%, P < .01), new opioid requirement (27% vs. 91%, P < .01), mean weight loss during RT (6.2 lbs vs. 17.4 lbs, P < .01), feeding tube placement during RT (5% vs. 43%, P < .01), and treatment-related unplanned hospitalizations (9% vs. 39%, P = .04). CONCLUSION: Following TORS-assisted management of patients with pT0 HNCUP, we observed reduced toxicity following PSRT compared to PRT without apparent compromise of disease cure. LEVEL OF EVIDENCE: Level 3 evidence, retrospective review comparing cases and controls Laryngoscope, 130:691-697, 2020.

The prognostic value of CT-based image-biomarkers for head and neck cancer patients treated with definitive (chemo-)radiation.

OBJECTIVES: The aim of this study was to investigate whether quantitative CT image-biomarkers (IBMs) can improve the prediction models with only classical prognostic factors for local-control (LC), regional-control (RC), distant metastasis-free survival (DMFS) and disease-free survival (DFS) for head and neck cancer (HNC) patients. MATERIALS AND METHODS: The cohort included 240 and 204 HNC patients in the training and validation analysis, respectively. Clinical variables were scored prospectively and IBMs of the primary tumor and lymph nodes were extracted from planning CT-images. Clinical, IBM and combined models were created from multivariable Cox proportional-hazard analyses based on clinical features, IBMs, and both for LC, RC, DMFS and DFS. RESULTS: Clinical variables identified in the multivariable analysis included tumor-site, WHO performance-score, tumor-stage and age. Bounding-box-volume describing the tumor volume and irregular shape, IBM correlation representing radiological heterogeneity, and LN_major-axis-length showing the distance between lymph nodes were included in the IBM models. The performance of IBM LC, RC, DMFS and DFS models (c-index(validated):0.62, 0.80, 0.68 and 0.65) were comparable to that of the clinical models (0.62, 0.76, 0.70 and 0.66). The combined DFS model (0.70) including clinical features and IBMs performed significantly better than the clinical model. Patients stratified with the combined models revealed larger differences between risk groups in the validation cohort than with clinical models for LC, RC and DFS. For DMFS, the differences were similar to the clinical model. CONCLUSION: For prediction of HNC treatment outcomes, image-biomarkers performed as good as or slightly better than clinical variables.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma without hypopharyngeal invasion: dose distribution and clinical outcome.

Hypopharyngeal invasion would be a key finding in determining the extent of the irradiation fields in patients with cervical esophageal squamous cell carcinoma (CESCC). This study aimed to investigate the clinical outcomes of chemoradiotherapy using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) omitting upper cervical lymph nodal irradiation in CESCC without hypopharyngeal invasion, and the dosimetric superiority of SIB-IMRT to 3D conformal radiotherapy (3DCRT). We retrospectively identified 21 CESCC patients without hypopharyngeal invasion [clinical Stage I/II/III/IV (M1LYM); 3/6/5/7] (UICC-TNM 7th edition) who underwent chemoradiotherapy using SIB-IMRT between 2009 and 2015. SIB-IMRT delivered 60 Gy to each primary tumor and the metastatic lymph nodes, and 48 Gy to elective lymph nodal regions, including Levels III and IV of the neck, supraclavicular, and upper mediastinal lymphatic regions, in 30 fractions. The overall survival rate, locoregional control rate, and initial recurrence site were evaluated. 3DCRT plans were created to perform dosimetric comparisons with SIB-IMRT. At a median follow-up of 64.5 months, the 5-year locoregional control and overall survival rates were 66.7% and 53.4%, respectively. Disease progressed in eight patients: all were locoregional progressions and no patients developed distant progression including upper cervical lymph nodal regions as initial recurrence sites. The planning study showed SIB-IMRT improved target coverage without compromising the dose to the organs at risk, compared with 3DCRT. In conclusion, omitting the elective nodal irradiation of the upper cervical lymph nodes was probably reasonable for CESCC patients without hypopharyngeal invasion. Locoregional progression remained the major progression site in this population.

Perspectives on optimizing radiotherapy dose to the dysphagia/aspiration-related structures for patients with head and neck cancer.

PURPOSE OF REVIEW: The purpose of this study is to provide an overview on the methodologies, outcomes and clinical implications of studies that have investigated swallowing outcomes after head and neck cancer (HNC) treatment when reducing radiotherapy dose to specific dysphagia/aspiration-related structures (DARS). RECENT FINDINGS: Overall, there is limited recent evidence, with a lack of high-quality studies, which examine the outcomes of DARS-optimized radiotherapy treatment. Large variations exist in the methodology of these studies in regards to which DARS are delineated and how swallowing outcomes are measured. Consequently, there is a wide range of dose limits recommended to a variety of DARS structures. Despite these limitations, there appears to be a general consensus that optimizing dose to the DARS will result in some reduction of dysphagia after radiotherapy without compromising on treatment to the tumour. SUMMARY: More rigorous study must be completed to determine the true extent of clinical benefit from this practice. Institutions must take into consideration the limitations of the evidence as well as logistical costs of implementing this technique into practice. However, optimizing dose to the DARS appears to be a well-tolerated practice that may have substantial positive benefits for patients' swallowing function and quality of life after HNC treatment.

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

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

Clinical outcome of sodium alginate therapy in radiation-induced pharyngeal mucositis: experience of a single Japanese institution

Purpose: We investigated the clinical outcome of sodium alginate treatment in radiation-induced pharyngeal mucositis (RIPM) after neck irradiation. Materials and methods: The study population included 32 patients (11 lung cancer, 10 breast cancer, 7 head and neck cancer, and 4 other primary lesions) who underwent neck external beam radiotherapy at the authors' institution between June 2006 and 2016. The patients received 5% sodium alginate solution orally for RIPM. Those who were followed up for less than 2 months or did not receive 5% sodium alginate were excluded from this retrospective study. RIPM was graded weekly as an acute toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4. The administration of 10-15 ml of sodium alginate before each meal was continued until the radiotherapy was completed and after resolution of odynophagia. The efficacy of sodium alginate was assessed by two radiation oncologists as follows: Grade I, ineffective; grade II, moderately effective; grade III, very effective. When sodium alginate was ineffective, other analgesics, such as nonsteroidal antiinflammatory drugs (NSAIDS) or opioids, were added. Relationships between the presence/absence of additional analgesics and the radiation dose were investigated. Results: The median duration from the start of irradiation to sodium alginate administration was 15 days (range, 5­36 days). RIPM improved in 29/32 patients (grade: II, n = 22; III, n = 7). Three patients showed no improvement. No sodium alginate-related toxicities occurred. Additional analgesics were required in 5/32 patients. The radiation dose in these 5 patients was significantly higher than that in the sodium alginate-alone group (63.6 ± 7.8 Gy vs 48.3 ± 14.8Gy, P = 0.02). Patients who received > 50 Gy tended to require additional analgesics more frequently than those who received ≤50Gy (P = 0.10). Conclusions: The concurrent administration of sodium alginate and neck irradiation was feasible and tolerable without obvious toxicities. Under certain conditions sodium alginate could be a promising alternative to NSAIDs and opioids in RIPM. The results justify further prospective evaluations with detailed treatment protocols to clarify whether sodium alginate can improve RIPM (AU)

[The treatment effect of eustachian tube atresia with laser and connical plastic tube after radiotherapy for nasopharyngeal carcinoma].

Objective: To investigate the method in treatment of Eustschian tube atresia caused by radiotherapy. Methods: Two cases diagnosed of Eustschian tube atresia following radiotherapy were retrospectively analyzed in Department of Otorhinolaryngology, Divided Hospital of Shanghai University Communication Affiliated First People Hospital in Apr. 2014 and Oct. 2015. Both cases were female, 65 and 64 years old, and accepted radiotherapy six and 20 years ago respectively. The pharyngeal orifices of Eustschian tube were found to be totally closed under endoscope. The closed Eustschian tubes were re-opened by laser and re-shaped by a slim and conical plastic tube for more than six months. They were followed up and evaluated over 12 months. Results: At six and 12 months after treatment, round mouths were formed in the pharyngeal orifice of Eustachian tube, and the patients had no resistance in Valsalva's test. No shrink or abnormal opening of orifice was found at follow-up of 20 and 12 months. Conclusion: The method of re-opening by laser and re-shaping by a slim and conical plastic tube is recommended to treat Eustschian tube occlusion caused by radiotherapy.

A longitudinal evaluation of early anatomical changes of parotid gland in intensity modulated radiotherapy of nasopharyngeal carcinoma patients with parapharyngeal space involvement.

INTRODUCTION: Radiotherapy of nasopharyngeal carcinoma patients with parapharyngeal space (PPS) involvement may deliver high dose to the parotid gland. This study evaluated parotid gland changes during and up to 3 months after radiotherapy. METHODS: Kilovoltage computed tomography (CT) scans of head and neck region of 39 nasopharyngeal carcinoma patients with PPS involvement were performed at pre-radiotherapy, 10th, 20th and 30th fractions and 3 months after treatment. The parotid glands were contoured in pre-radiotherapy planning CT scan and in subsequent scans. Dice similarity coefficient (DSC), percentage volume change and centroid movement between the planning CT and the subsequent CTs were obtained from the contouring software. In addition, the distance between medial and lateral borders of parotid glands from the mid-line at various time intervals were also measured. RESULTS: The ipsilateral parotid gland received a mean dose of about 5 Gy higher than the contralateral side. The mean DSC and parotid volume decreased by more than 30% at 20th fraction and reached the minimum at 30th fraction. Partial recovery was observed at 3 months after treatment. The centroid displacement followed a similar pattern, which moved medially and superiorly by an average of 0.30 cm and 0.18 cm, respectively, at 30th fraction. The changes in ipsilateral gland were slightly greater than the contralateral side. CONCLUSIONS: Substantial volume change and medial movement of parotid gland were observed with slightly greater magnitude in the ipsilateral side. Adaptive radiotherapy was suggested at around 15th to 20th fraction so as to optimise the original dose distribution of the plan.

Videofluoroscopic Swallow Examination Does Not Accurately Detect Cricopharyngeal Radiation Strictures.

Videofluoroscopy is the standard technique to evaluate dysphagia following radiotherapy for head and neck cancer (HNC). The accuracy of radiography in detecting strictures at the pharyngoesophageal junction is unknown. Our aim was to determine the diagnostic accuracy of videofluoroscopy in detecting strictures at the pharyngoesophageal junction prior to endoscopic dilatation in a consecutive series of HNC survivors with dysphagia. Presence of a stricture on videofluoroscopy was determined by 3 experienced blinded investigators and compared against a gold standard, defined as presence of a mucosal tear during endoscopic dilatation. In 10 of 33 patients, there was complete agreement among observers with respect to the presence or absence of a stricture. Overall, the concordance among observers in identification of strictures was very poor, with a kappa of 0.05 (P = .30). The diagnostic sensitivity and specificity of videofluoroscopy in detecting strictures was 0.76 and 0.58, respectively. Videofluoroscopy alone is inadequate to detect strictures in HNC survivors with dysphagia.

Beyond mean pharyngeal constrictor dose for beam path toxicity in non-target swallowing muscles: Dose-volume correlates of chronic radiation-associated dysphagia (RAD) after oropharyngeal intensity modulated radiotherapy.

PURPOSE/OBJECTIVE(S): We sought to identify swallowing muscle dose-response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer. MATERIALS/METHODS: T1-4 N0-3 M0 oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following ⩾12months post-IMRT: videofluoroscopy/endoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), masseter (MM), buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose-volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic-RAD, for use in a multivariate (MV) model. RESULTS: Of 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving⩾69Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal among tested MV models (AUC 0.835). CONCLUSION: In addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible.

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

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

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

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

Patterns of long-term swallowing dysfunction after definitive radiotherapy or chemoradiation.

OBJECTIVES: To identify patterns of long-term, radiation-induced swallowing dysfunction after definitive radiotherapy with or without chemotherapy (RT or CHRT) and to determine which factors may explain these patterns over time. MATERIAL AND METHODS: The study population consisted of 238 consecutive head and neck cancer patients treated with RT or CHRT. The primary endpoint was ⩾grade 2 swallowing dysfunction at 6, 12, 18 and 24months after treatment. Cluster analysis was used to identify different patterns over time. The differences between the mean dose to the swallowing organs at risk for each pattern were determined by using dose maps. RESULTS: The cluster analysis revealed five patterns of swallowing dysfunction: low persistent, intermediate persistent, severe persistent, transient and progressive. Patients with high dose to the upper pharyngeal, laryngeal and lower pharyngeal region had the highest risk of severe persistent swallowing dysfunction. Transient problems mainly occurred after high dose to the laryngeal and lower pharyngeal regions, combined with moderate dose to the upper pharyngeal region. The progressive pattern was mainly seen after moderate dose to the upper pharyngeal region. CONCLUSIONS: Various patterns of swallowing dysfunction after definitive RT or CHRT can be identified over time. This could reflect different underlying biological processes.

Definitive chemo-radiotherapy for squamous cell carcinoma of the pharynx: impact of baseline low hemoglobin level (<12 g/dL) and post-radiation therapy F-18 FDG-PET/CT.

OBJECTIVE: To identify reliable predictors of overall survival (OS), locoregional control (LC), and metastasis-free survival (MFS) after definitive concurrent chemo-radiotherapy (CCRT) for squamous cell carcinoma (SCC) of the pharynx (nasopharynx, oropharynx and hypopharynx), we examined 16 potential prognostic factors, including pre-treatment hemoglobin level and pre- and post-treatment [(18)F]fluorodeoxyglucose positron emission tomography CT (F-18 FDG-PET/CT) maximum standardized up-take values (SUVmax) of primary sites and lymph node (LN) regions. METHODS: We retrospectively reviewed records of 70 patients treated with definitive CCRT for pharyngeal cancer in our institution during July 2006-April 2012, with particular regard to 16 prognostic factors: age, sex, T stage, N stage, retropharyngeal LN (RPLN) involvement, existence of multiple primary cancer, treatment interruptions, overall treatment time, chemotherapy type, pre-treatment hemoglobin level, pre-treatment body mass index, enteral feeding period, and pre- and post-treatment F-18 FDG-PET/CT SUVmax of primary site and LN region. All patients in our cohort underwent pre- and post-treatment F-18 FDG-PET/CT. RESULTS: Multivariate analysis associated improved OS with pre-treatment hemoglobin level (≥12 g/dL; hazard ratio [HR] 3.902; 95 % confidence interval [CI] 1.244-12.236; P = 0.020) and post-treatment SUVmax (primary site) (SUVmax <5.00; HR 4.237; 95 % CI 1.072-16.747; P = 0.039). Improved LC was associated with pre-treatment hemoglobin level (≥12 g/dL; HR 2.983; 95 % CI 1.123-7.920; P = 0.028), and post treatment SUVmax (primary site) (SUVmax <5.00; HR 5.233; 95 % CI 1.582-17.309; P = 0.007). No variable was found to be significant for improved MFS. CONCLUSIONS: Significant predictors for outcome in pharyngeal SCC treated with definitive CCRT were pre-treatment baseline hemoglobin level and post-treatment F-18 FDG-PET/CT SUVmax for primary site. Patients who have hemoglobin level lower than 12 g/dL may tend to have dismal prognosis. Additional treatment should be considered in those who have higher SUVmax at primary site in post-treatment F-18 FDG-PET/CT finding.

Functional swallowing outcomes in nasopharyngeal cancer treated with IMRT at 6 to 42 months post-radiotherapy.

We sought to evaluate the swallowing function of 18 patients surviving nasopharyngeal cancer, who had been treated using an intensity-modulated radiotherapy (IMRT) protocol designed to minimise functional impairment. We compared the outcomes of a patient-reported oral function score with fiberoptic endoscopic examination of swallow (FEES), Australian Therapy Outcome Measures (AusTOMs) and a measure of trismus. While all patients returned to a fully oral diet, there was ongoing swallow dysfunction characterised by bolus residue and delay, but no aspiration. Dysphagia was of mild or moderate severity on all measures, generally because of the need for texture modification, impaired bolus transit or dysgeusia. There was xerostomia on self-reported measurement combined with reports of behaviours adaptive to xerostomia on AusTOMs; however, salivary functioning was less impaired on FEES. There was no trismus in this cohort. Our cohort lacked the morbidity experienced by cohorts reported in earlier studies, potentially due to the use of IMRT.

Dose to the inferior pharyngeal constrictor predicts prolonged gastrostomy tube dependence with concurrent intensity-modulated radiation therapy and chemotherapy for locally-advanced head and neck cancer.

BACKGROUND AND PURPOSE: To determine if dose and/or dose-volume parameters to anatomic swallowing structures are predictive of gastrostomy tube (PEG) dependence from chemotherapy-intensity modulated radiotherapy (IMRT) in locally advanced head and neck cancer (LAHNC). METHODS AND MATERIALS: A retrospective study was performed on 141 consecutive patients with LAHNC (squamous cell) treated with definitive chemoIMRT with weekly concurrent carboplatin and paclitaxel. Late dysphagia was assessed by length of PEG requirement. Analysis of IMRT dose was retrospectively performed for critical swallowing structures. RESULTS: Approximately 62% of patients required PEG, the majority placed during treatment. Mean and median time for PEG was 7.7 and 4.4 months respectively (range 1.4-43.8). Only IMRT dose to the inferior constrictor was significantly associated with length of PEG. Mean dose (of individual mean doses) was 47 Gy for prolonged PEG use versus 41 Gy for PEG ⩽ 12 months. V40 to the inferior constrictor also correlated with PEG >12 months (p = 0.02) with a mean V40 of 48% versus 41% for PEG ⩽ 12 months. CONCLUSIONS: IMRT dose to the inferior constrictor correlated with persistent dysphagia requiring prolonged PEG use. Maintaining mean inferior constrictor dose to ⩽ 41 Gy and V40 to ⩽ 41% may help minimize gastrostomy tube dependence.

Laryngeal sensation and pharyngeal delay time after (chemo)radiotherapy.

The objective of the study was to evaluate the association between changes in laryngeal sensation and initiation of swallowing reflex or swallowing function before and after (chemo)radiotherapy. A prospective study was conducted in a tertiary referral university hospital. Thirteen patients who received (chemo)radiotherapy for treatment of laryngeal or hypopharyngeal cancer were included. Laryngeal sensation was evaluated at the tip of the epiglottis before and 1, 3 months, and 1 year after (chemo)radiotherapy. Videofluoroscopy was performed at the same time. Quantitative determinations included changes in laryngeal sensation, computed analysis of pharyngeal delay time, the distance and velocity of hyoid bone movement during the phase of hyoid excursion, and pharyngeal residue rate (the proportion of the bolus that was left as residue in the pharynx at the first swallow). Laryngeal sensation significantly deteriorated 1 month after (chemo)radiotherapy, but there was a tendency to return to pretreatment levels 1 year after treatment. Neither pharyngeal delay time nor displacement of the hyoid bone changed significantly before and after (chemo)radiotherapy. In addition, there was no significant difference in the mean velocity of hyoid bone movement and the amount of stasis in the pharynx at the first swallow before and after (chemo)radiotherapy. After (chemo)radiotherapy, laryngeal sensation deteriorated. But, in this study, videofluoroscopy showed that swallowing reflex and function were maintained.