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Objective: Osteoradionecrosis (ORN) is a severe late complication after radiotherapy but current knowledge on ORN risks in the setting of postoperative radiotherapy (PORT) is limited. We studied the incidence and risk factors of ORN in patients with oral cavity cancers (OCC, treated with PORT., Patients and Methods: A retrospective cohort study was conducted including OCC patients (mainly squamous cell) treated with postoperative intensity modulated radiotherapy between 2010 and 2018 with > 1 year disease-free survival. Cumulative incidences of ORN were computed using the Kaplan Meier method. Clinical and dosimetric risk factors for mandibular ORN were evaluated using Cox regression models., Results: Within our cohort (N = 227, median follow-up 49 months) we observed 46 cases of ORN, mainly in the mandible (n = 41). The cumulative incidence of mandibular ORN was 15.9 % (SE 2.5 %) at three years and 19.8 % (SE 3.0 %) at five years. At univariable analysis, smoking, mandibular mandibulotomy or segment resection, mean dose to the mandible, and mandible volume (%) ≥ 60 Gy (V60) were significantly associated with increased ORN risks. At multivariable analysis, smoking (HR 2.13, 95 %CI 1.12-4.06) and V60 (HR 1.02 per 1 % increase, 95 %CI 1.01-1.04) remained predictive factors. For active smokers with a high V60 ≥ 40 % we observed rapid ORN development with a 1-year incidence of 29 % vs 6 % for others (p < 0.01)., Conclusion: OCC Patients treated with PORT are at high risk for mandibular ORN. We identified the mandibular volume receiving ≥ 60 Gy as the dominant risk factor, especially in active smokers. Limiting high-dose volumes at treatment planning may decrease ORN risks., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The locoregional failure (LRF) rate in human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) remains disappointingly high and toxicity is substantial. Response prediction prior to or early during treatment would provide opportunities for personalised treatment. Currently, there are no accurate predictive models available for correct OPSCC patient selection. Apparently, the pivotal driving forces that determine how a OPSCC responds to treatment, have yet to be elucidated. Therefore, the holistiC early respOnse assessMent for oroPharyngeaL cancer paTiEnts study focuses on a holistic approach to gain insight in novel potential prognostic biomarkers, acquired before and early during treatment, to predict response to treatment in HPV-negative patients with OPSCC., Methods and Analysis: This single-centre prospective observational study investigates 60 HPV-negative patients with OPSCC scheduled for primary radiotherapy (RT) with cisplatin or cetuximab, according to current clinical practice. A holistic approach will be used that aims to map the macroscopic (with Intra Voxel Incoherent Motion Diffusion Kurtosis Imaging (IVIM-DKI); before, during, and 3 months after RT), microscopic (with biopsies of the primary tumour acquired before treatment and irradiated ex vivo to assess radiosensitivity), and molecular landscape (with circulating tumour DNA (ctDNA) analysed before, during and 3 months after treatment). The main end point is locoregional control (LRC) 2 years after treatment. The primary objective is to determine whether a relative change in the mean of the diffusion coefficient D (an IVIM-DKI parameter) in the primary tumour early during treatment, improves the performance of a predictive model consisting of tumour volume only, for 2 years LRC after treatment. The secondary objectives investigate the potential of other IVIM-DKI parameters, ex vivo sensitivity characteristics, ctDNA, and combinations thereof as potential novel prognostic markers., Ethics and Dissemination: The study was approved by the Medical Ethical Committee of Erasmus Medical Center. The main results of the trial will be presented in international meetings and medical journals., Trial Registration Number: NL8458., Competing Interests: Competing interests: The department of radiotherapy has research collaborations with Elekta AB, Stockholm, Sweden and with Accuray, Sunnyvale, California, USA and Varian, Palo Alto, California, USA., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We studied the relationship between trismus (maximum interincisor opening [MIO] ≤35 mm) and the dose to the ipsilateral masseter muscle (iMM) and ipsilateral medial pterygoid muscle (iMPM)., Methods: Pretreatment and post-treatment measurement of MIO at 13 weeks revealed 17% of trismus cases in 83 patients treated with chemoradiation and intensity-modulated radiation therapy. Logistic regression models were fitted with dose parameters of the iMM and iMPM and baseline MIO (bMIO). A risk classification tree was generated to obtain optimal cut-off values and risk groups., Results: Dose levels of iMM and iMPM were highly correlated due to proximity. Both iMPM and iMM dose parameters were predictive for trismus, especially mean dose and intermediate dose volume parameters. Adding bMIO, significantly improved Normal Tissue Complication Probability (NTCP) models. Optimal cutoffs were 58 Gy (mean dose iMPM), 22 Gy (mean dose iMM) and 46 mm (bMIO)., Conclusions: Both iMPM and iMM doses, as well as bMIO, are clinically relevant parameters for trismus prediction., (© 2019 Wiley Periodicals, Inc.)

Reduced hyoid displacement is thought to contribute to aspiration and pharyngeal residues in head and neck cancer (HNC) patients with dysphagia. To further study hyoid elevation and anterior excursion in HNC patients, this study reports on temporal/kinematic measures of hyoid displacement, with the additional goal to investigate correlations with clinical swallowing impairment. A single-blind analysis of data collected as part of a larger prospective study was performed at three time points before and after chemoradiotherapy. Twenty-five patients had undergone clinical swallowing assessments at baseline, 10-weeks, and 1-year post-treatment. Analysis of videofluoroscopic studies was done on different swallowing consistencies of varying amounts. The studies were independently reviewed frame-by-frame by two clinicians to assess temporal (onset and duration) and kinematic (anterior/superior movement) measures of hyoid displacement (ImageJ), laryngeal penetration/aspiration, and presence of vallecula/pyriform sinus residues. Patient-reported oral intake and swallowing function were also evaluated. Mean maximum hyoid displacement ranged from 9.4 mm (23 % of C2-4 distance) to 12.6 mm (27 %) anteriorly, and from 18.9 mm (41 %) to 24.9 mm (54 %) superiorly, depending on bolus volume and consistency. Patients with reduced superior hyoid displacement perceived significantly more swallowing impairment. No correlation between delayed or reduced hyoid excursion and aspiration or residue scores could be demonstrated. Hyoid displacement is subject to variability from a number of sources. Based on the results, this parameter seems not very valuable for clinical use in HNC patients with dysphagia.

Objectives/hypothesis: Evaluation of treatment results of orthovoltage X-rays for a selection of previously untreated favorable basal cell carcinomas (BCC) in the head and neck area concerning local control, cosmetic and functional outcome, and toxicity profile., Methods: A consecutive series of patients with primarily treated BCCs who were irradiated by means of orthovoltage X-rays in the Netherlands Cancer Institute in Amsterdam between January 2000 and February 2015 were retrospectively evaluated., Results: Two hundred fifty-three BCCs in 232 patients were primarily treated with orthovoltage X-rays. The local control rates at 1, 3, and 5 years for this selection of basal cell carcinomas were 98.9%, 97.5%, and 96.3%, respectively. Tumor size was the only significant predictor for local control because BCCs < 20 mm had a significantly higher 5-year local control rate than lesions ≥ 20 mm (96.8% vs. 89.4%, P = 0.041). Acute toxicity healed spontaneously without medical intervention, and late toxicity rates were low. Functional impairments were negligible, and the cosmetic outcome was excellent., Conclusion: Orthovoltage therapy for well-selected favorable BCCs in the head and neck area resulted in excellent local control rates, a low toxicity profile, and apparently satisfactory functional and cosmetic outcomes. Orthovoltage irradiation is a good alternative for surgery for BCCs with favorable histologic prognosis at locations that are at risk for postoperative functional or cosmetic changes, such as the nose or canthus., Level of Evidence: 4. Laryngoscope, 126:1796-1802, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

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.

Background: Plan adaptation during the course of (chemo)radiotherapy of H&N cancer requires repeat CT scanning to capture anatomy changes such as parotid gland shrinkage. Hydration, applied to prevent nephrotoxicity from cisplatin, could temporarily alter the hydrogen balance and hence the captured anatomy. The aim of this study was to determine geometric changes of parotid glands as function of hydration during chemoradiotherapy compared to a control group treated with radiotherapy only., Methods: This study included an experimental group (n = 19) receiving chemoradiotherapy, and a control group (n = 19) receiving radiotherapy only. Chemoradiotherapy patients received cisplatin with 9 l of saline solution during hydration in the first, fourth and seventh week. The delineations of the parotid glands on the planning CT scan were automatically propagated to Cone Beam CT scans using deformable image registration. Relative volume and position of the parotid glands were determined at the second chemotherapy cycle (week four) and at fraction 35., Results: When saline solution was administrated, the volume temporarily increased on the first day (7.2 %, p < 0.001), second day (10.8 %, p < 0.001) and third day (7.0 %, p = 0.016). The gland positions shifted lateral, the distance between glands increased on the first day with 1.5 mm (p < 0.001), on the second day 2.2 mm (p < 0.001). At fraction 35, with both groups the mean shrinkage was 24 % ± 11 % (1SD) and the mean medial distance between the parotid glands decreased by 0.47 cm ± 0.27 cm., Conclusions: Hydration significantly modulates parotid gland geometry. Unless, in the context of adaptive RT, a repeat CT scan is timed during a chemotherapy cycle, these effects are of minor clinical relevance.

Background and Purpose: To assess the impact of intensity modulated radiotherapy (IMRT) versus conventional radiation on late xerostomia and Quality of Life aspects in head and neck cancer patients. PATIENTS AND NETHODS: Questionnaires on xerostomia in rest and during meals were sent to all patients treated between January 1999 and December 2003 with a T1-4, N0-2 M0 head and neck cancer, with parotid gland sparing IMRT or conventional bilateral neck irradiation to a dose of at least 60 Gy, who were progression free and had no disseminated disease (n = 192). Overall response was 85% (n = 163); 97% in the IMRT group (n = 75) and 77% in the control group (n = 88) the median follow-up was 2.6 years. The prevalence of complaints was compared between the two groups, correcting for all relevant factors at multivariate ordinal regression analysis., Results: Patients treated with IMRT reported significantly less difficulty transporting and swallowing their food and needed less water for a dry mouth during day, night and meals. They also experienced fewer problems with speech and eating in public. Laryngeal cancer patients in general had fewer complaints than oropharynx cancer patients but both groups benefited from IMRT. Within the IMRT group the xerostomia scores were better for those patients with a mean parotid dose to the "spared" parotid below 26 Gy., Conclusion: Parotid gland sparing IMRT for head and neck cancer patients improves xerostomia related quality of life compared to conventional radiation both in rest and during meals. Laryngeal cancer patients had fewer complaints but benefited equally compared to oropharyngeal cancer patients from IMRT.