Search

Background and Purpose: Patients with head and neck cancer (HNC) are particularly vulnerable to mental health concerns. Radiotherapy (RT) remains a key treatment modality for these malignancies, offering high chances of cure. However, the effects on mental health are not well defined. We aim to characterize longitudinally the prevalence and risk of depressive and anxiety symptoms over the course of RT in patients with HNC., Material and Methods: A literature search was performed from database inception until November 1st, 2024. PROSPERO/MOOSE-compliant and pre-registered (PROSPERO:CRD42023441432) systematic review identified studies longitudinally reporting in patients with HNC undergoing curative intent RT. Pooled prevalence and odds ratio of clinically significant anxiety and depressive symptoms between different treatment timepoints were estimated using random-effects meta-analysis., Results: 18 studies (total sample 1,920, mean age 59.9[SD = 3.17], 22.2 % female, 93.0 % white ethnicity) were included. Before RT, a pooled prevalence of depressive symptoms of 18.1 % (95 % confidence intervals [CI] = 13.1 %-24.4 %) was found. Short-term after completing RT (≤3 months), the prevalence of depressive symptoms peaked to 26.1 % (95 %CI = 18.9 %-35.0 %), decreasing in long-term (≥6 months) assessments to 16.4 % (95 %CI = 12.6 %-21.0 %). Anxiety symptoms continuously decreased from baseline (pooled prevalence 29.9 % [95 %CI = 27.3 %-32.7 %]) to 17.4 % (95 %CI = 12.1 %-24.5 %) in the long-term. Female and married patients showed higher prevalence of depressive symptoms. Those who underwent surgery showed a lower prevalence of anxiety symptoms., Conclusions: High prevalence of clinically significant depressive and anxiety symptoms were found in patients with HNC undergoing RT, from baseline to long-term follow-up. The weeks following completion of RT are key, as depressive symptoms increase in this period. Screening and interventions prior to, during, and especially immediately post-RT would be beneficial., Competing Interests: Declaration of competing interest PJ received personal fees or grants from Roche, Merck, MSD Merck Sharp & Dohme, and Novartis outside the current work. CA received personal fees or grants from Janssen Cilag and Neuraxpharm outside the current work and is supported by the Alicia Koplowitz Foundation. IB received personal fees from Merck sharp & Dohme, Sanofi, Achilles Therapeutics, eTheRNA Immunotherapies, Cancer Expert Now, Boehringer Ingelheim as a Speakers’ Bureau: Bristol Myers Squibb, Merck Serono, Roche, MSD. Lastly, as a research Funding: AstraZeneca (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Gliknik (Inst), GlaxoSmithKline (Inst), Janssen Oncology (Inst), Kura Oncology (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), Pfizer (Inst), Roche (Inst), Shattuck labs (Inst), Nanobiotix (Inst), Seattle Genetics (Inst), Immutep (Inst), Debiopharm Group (Inst), Regeneron (Inst), Boehringer Ingelheim (Inst), ISA Pharmaceuticals (Inst), Merck Serono (Inst), Seattle Genetics (Inst), Northern Biologics (Inst), VCN Biosciences (Inst), and for travel, accommodations and expenses: MSD Oncology. CN reports research funding paid to their institution from Cancer Research UK. KN received honoraria as a speaker's bureau from Eisai. KJH received honoraria from Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys Biopharma (Inst), Pfizer (Inst), Replimune (Inst), Inzen Therapeutics (Inst) and Codiak Biosciences (Inst). Consulting or Advisory Role: Arch Oncology (Inst), AstraZeneca (Inst), BMS (Inst), Boehringer Ingelheim (Inst), Merck Serono (Inst), MSD (Inst), Oncolys BioPharma (Inst), Replimune (Inst), Inzen Therapeutics (Inst) Speakers’ Bureau: BMS (Inst), Merck Serono (Inst), MSD (Inst) Research Funding: AstraZeneca (Inst), Merck Sharp & Dohme (Inst), Replimune (Inst), Boehringer Ingelheim (Inst). AC received personal fees or grants from Janssen Cilag, ROVI, and Lundbeck outside the current work. All other authors have declared no conflicts of interest (AR, JC)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: An intact sense of taste provides pleasure, supports sustenance and alerts the body to toxins. Head and neck cancer (HNC) patients who receive radiotherapy (RT) are high-risk for developing radiation-induced taste dysfunction. Advances in RT offer opportunities for taste-preserving strategies by reducing dose to the gustatory organs-at-risk., Methods: PubMed, Medline and EMBASE were searched for publications reporting on taste, RT and HNC. Randomised trials, cohort studies and cross-sectional studies were included., Results: 31 studies were included in this review. Meta-analysed prevalence of acute taste dysfunction following RT was approximately 96% (95% CI 64 to 100%) by objective measures and 79% (95% CI 65 to 88%) by subjective measures, with the majority of patients showing at least partial recovery. Long-term dysfunction was seen in ~25% of patients. Taste dysfunction was associated with sequalae including weight loss and reduced quality-of-life (QoL). Taste dysfunction was more common when the oral cavity, and specifically the anterior two-thirds of the tongue, was irradiated, suggesting a dose constraint for taste preservation might be feasible. Proton beam therapy and customised bite blocks reduced dose to the gustatory field and subsequent loss of taste., Conclusions: Taste dysfunction following RT is common and negatively affects patients' nutritional status and QoL. Decisions about treatment strategies, including choice of RT modality, dose distribution across the gustatory field and the use of adjuncts like bite blocks may be beneficial. However, evidence is limited. There is a pressing need for randomised studies or large prospective cohort studies with sufficient adjustment for confounders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: This phase III, non-blinded, parallel-group, randomised controlled study evaluated the efficacy of Caphosol mouthwash in the management of radiation-induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radical (chemo)radiotherapy., Patients and Methods: Eligible patients were randomised at 1:1 to Caphosol plus standard oral care (intervention) or standard oral care alone (control), stratified by radiotherapy technique and use of concomitant chemotherapy. Patients in the intervention arm used Caphosol for 7weeks: 6weeks during and 1-week post-radiotherapy. The primary endpoint was the incidence of severe OM (CTCAE ⩾grade 3) during and up to week 8 post-radiotherapy. Secondary endpoints include pharyngeal mucositis, dysphagia, pain and quality of life., Results: The intervention (n=108) and control (n=107) arms were well balanced in terms of patient demographics and treatment characteristics. Following exclusion of patients with missing data, 210 patients were available for analysis. The incidence of severe OM did not differ between the intervention and control arms (64.1% versus 65.4%, p=0.839). Similarly, no significant benefit was observed for other secondary endpoints. Overall, compliance with the recommended frequency of Caphosol was low., Conclusion: Caphosol did not reduce the incidence or duration of severe OM during and after radiotherapy in HNC., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning., Materials and Methods: Predictive models of severe acute mucositis were generated using radiotherapy dose (dose-volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models., Results: The dose-volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis., Conclusions: The RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Purpose: Current oral mucositis normal tissue complication probability models, based on the dose distribution to the oral cavity volume, have suboptimal predictive power. Improving the delineation of the oral mucosa is likely to improve these models, but is resource intensive. We developed and evaluated fully-automated atlas-based segmentation (ABS) of a novel delineation technique for the oral mucosal surfaces., Material and Methods: An atlas of mucosal surface contours (MSC) consisting of 46 patients was developed. It was applied to an independent test cohort of 10 patients for whom manual segmentation of MSC structures, by three different clinicians, and conventional outlining of oral cavity contours (OCC), by an additional clinician, were also performed. Geometric comparisons were made using the dice similarity coefficient (DSC), validation index (VI) and Hausdorff distance (HD). Dosimetric comparisons were carried out using dose-volume histograms., Results: The median difference, in the DSC and HD, between automated-manual comparisons and manual-manual comparisons were small and non-significant (-0.024; p=0.33 and -0.5; p=0.88, respectively). The median VI was 0.086. The maximum normalised volume difference between automated and manual MSC structures across all of the dose levels, averaged over the test cohort, was 8%. This difference reached approximately 28% when comparing automated MSC and OCC structures., Conclusions: Fully-automated ABS of MSC is suitable for use in radiotherapy dose-response modelling., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Purpose: Fatigue during head and neck radiotherapy may be related to radiation dose to the central nervous system (CNS). The impact of patient, tumour, and dosimetric variables on acute fatigue was assessed in nasopharyngeal cancer patients undergoing chemoradiotherapy., Material and Methods: Radiation dose to the following retrospectively-delineated CNS structures; brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia (BG) and clinical variables were related to incidence of ⩾ grade 2 fatigue in 40 patients., Results: Sixty per cent of patients reported fatigue during and following radiotherapy. Dmean and D2 to the BG and Dmean to the pituitary gland were significantly associated with fatigue during radiation (P<0.01). Dmean to the cerebellum was associated with fatigue following radiotherapy and at any time (P < 0.01). After adjusting for clinical factors, an association remained between fatigue during radiotherapy and mean dose and D2 to the pituitary gland and BG (P = 0.012, 0.036, 0.009 and 0.018) and mean dose to the cerebellum following radiation and at any time (P = 0.042 and 0.029)., Conclusion: Disruption of connections between BG, cerebellum, and higher cortical centres or disruption of pituitary-regulated hormonal balance may be implicated in the pathophysiology of radiation-related fatigue., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To determine whether concomitant chemotherapy increases the incidence of high grade xerostomia following parotid-sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced head and neck squamous cell cancer., Materials and Methods: The incidence of high grade (≥G2) acute (CTCAEv3.0) and late (LENTSOMA and RTOG) xerostomia was compared between patients treated with either IMRT or concomitant chemo-IMRT (c-IMRT) in 2 prospective studies. Parotid gland mean tolerance doses (D₅₀) were reported using non-linear logistic regression analysis., Results: Thirty-six patients received IMRT alone and 60 patients received c-IMRT. Patients received 65 Gy in 30 daily fractions to the primary site and involved nodal groups and 54 Gy in 30 fractions to elective nodal groups, mean doses to the parotid glands were comparable. Concomitant cisplatin 100mg/m(2) was administered on days 1 and 29 of IMRT. The incidence of ≥G2 subjective xerostomia was similar in both groups; acute-64.7% (IMRT) versus 60.3% (c-IMRT), p=0.83; late-43% (IMRT) versus 34% (c-IMRT), p=0.51. Recovery of parotid salivary flow at 1 year was higher with IMRT (64% vs 50%), but not statistically significant (p=0.15). D₅₀ for absence of parotid saliva flow at 1 year was 23.2 Gy (95% CI: 17.7-28.7) for IMRT and 21.1 Gy (11.8-30.3) for c-IMRT., Conclusion: Concomitant c-IMRT does not increase the incidence of acute or late xerostomia relative to IMRT alone., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To describe the dose-response relationships for the different measures of salivary gland recovery following radical radiotherapy for locally advanced head and neck squamous cell cancers (LA-HNSCC)., Methods and Materials: Dosimetric analysis of data from the PARSPORT trial, a Phase III study of conventional RT (RT) and intensity modulated radiotherapy (IMRT) for LA-HNSCC was undertaken to determine the relationship between parotid gland mean dose and toxicity endpoints: high-grade subjective and objective xerostomia and xerostomia-related quality of life scores. LKB-NTCP parameters (TD50, m and n) were generated and tolerance doses (D50) reported using non-linear logistic regression analysis., Results: Data were available on 63 patients from the PARSPORT trial. Parotid saliva flow rate provided the strongest association between mean dose and recovery, D50=23.4 Gy (20.6-26.2) and k=3.2 (1.9-4.5), R(2)=0.85. Corresponding LKB parameters were TD50=26.3 Gy (95% CI: 24.0-30.1), m=0.25 (0.18-1.0 and n=1). LENTSOMA subjective xerostomia also demonstrated a strong association D50=33.3 Gy (26.7-39.8), k=2.8 (91.4-4.4), R(2)=0.77)., Conclusion: We recommend using the LENT SOMA subjective xerostomia score to predict recovery of salivation due to its strong association with dosimetry and ease of recording., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Magnetic resonance imaging (MRI) provides superior diagnostic accuracy over computed tomography (CT) in oropharyngeal tumours. Precise delineation of the gross tumour volume (GTV) is mandatory in radiotherapy planning when a GTV boost is required. CT volume definition in this regard is poor. We studied the feasibility of using flexible surface (flex-L) coils to obtain MR images for MR-CT fusion to assess the benefit of MRI over CT alone in planning base of tongue tumours., Methods: Eight patients underwent CT and MRI radiotherapy planning scans with an immobilisation device. Distortion-corrected T1-weighted post-contrast MR scans were fused to contrast-enhanced planning CT scans. GTV, clinical target and planning target volumes (CTV, PTV) and organs at risk (OAR) were delineated on CT, then on MRI with blinding to the CT images. The volumetric and spatial differences between MRI and CT volumes for GTV, CTV, PTV and OAR were compared. MR image distortions due to field inhomogeneity and non-linear gradients were corrected and the need for such correction was evaluated., Results: The mean primary GTV was larger on MRI (22.2 vs. 9.5 cm(3), p=0.05) than CT. The mean primary and nodal GTV (i.e. BOT and macroscopic nodes) was significantly larger on MRI (27.2 vs. 14.4 cm(3), p=0.05). The volume overlap index (VOI) between MRI and CT for the primary was 0.34 suggesting that MRI depicts parts of the primary tumour not detected by CT. There was no significant difference in volume delineation between MR and CT for CTV, PTV, nodal CTV and nodal PTV. MRI volumes for brainstem and spinal cord were significantly smaller due to improved organ definition (p=0.002). Susceptibility and gradient-related distortions were not found to be clinically significant., Conclusion: MRI improves the definition of tongue base tumours and neurological structures. The use of MRI is recommended for GTV dose-escalation techniques to provide precise depiction of GTV and improved sparing of spinal cord and brainstem., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Aim of this study was to correlate dose to pharyngeal constrictors (PC) with subjective and observer-based assessments of swallowing in patients with head and neck cancer undergoing concomitant chemo-IMRT., Materials and Methods: Dose-volume histograms (DVHs) for superior constrictor (SC), middle constrictor (MC) and inferior constrictor (IC) were generated for 37 patients. Mean doses to SC, MC and IC were correlated to objective dysphagia grade (1 year, RTOG scoring) and global, total physical (TP) and most relevant components of the physical section (P6, P8) of the MD Anderson dysphagia inventory (MDADI) which was evaluated post-treatment. Odds ratios of dysphagia (>grade 0), poor global (<3), TP (<32), P6 (<3) and P8 (<3) for patients with mean dose>60 Gy to SC and IC were calculated., Results: There was no significant correlation between mean dose to PC and any of the analysed MDADI parameters and observer-assessed dysphagia grade. Odds ratio of dysphagia (>grade 0), poor global (<3), TP (<32), P6 (<3) and P8 (<3) for patients with mean dose>60 Gy to IC and SC were not significantly higher than those for patients receiving <60 Gy., Conclusion: This study did not find a statistically significant correlation between radiation dose to the PC and observer-assessed dysphagia grade or patient-reported MDADI questionnaire at 1 year.

Background and Purpose: To measure voice outcomes following accelerated hypofractionated radiotherapy for larynx cancer., Materials and Methods: Twenty-five patients with T1/T2 glottic cancer underwent serial electroglottographic and acoustic analysis (sustained vowel/i/ and connected speech) before radiotherapy and 1, 6 and 12 months post-treatment. Twenty-five normal subjects served as a reference control population., Results: Pre-treatment measures were significantly worse for larynx cancer patients. Median jitter (0.23% vs 0.97%, p=0.001) and shimmer (0.62dB vs 0.98dB, p=0.05) and differences in data ranges reflected greater frequency and amplitude perturbation in the larynx cancer patients. Pre-treatment Mean Phonation Time (MPT) was significantly reduced (21s vs 14.8s, p=0.002) in larynx cancer patients. There was a trend towards improvement of jitter, shimmer and normalized noise energy at 12 months post-treatment. MPT improved but remained significantly worse than for normal subjects (21s vs 16.4s, p=0.013). Average fundamental frequency resembled normal subjects, including improvement of the measured range (91.4-244.6Hz in controls vs 100-201Hz in post-treatment larynx cancer patients)., Conclusions: This non-invasive technique effectively measures post-treatment vocal function in larynx cancer patients. This study demonstrated improvement of many key parameters that influence voice function over 12 months after radiotherapy.