Neck stiffness and its correlation with dysphagia after radiotherapy in head and neck cancer.

Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

Background Radiation-induced fibrosis (RIF) is a common side effect in head and neck cancer (HNC) patients treated with radiotherapy. A validated tool to measure RIF does not currently exist. In this study, we evaluate the ability of shear wave elastography (SWE) to measure RIF in HNC survivors. Methods HNC patients treated with surgery and adjuvant radiation between January and September 2022 at a single tertiary medical center were enrolled with age and gender-matched control patients. Median tissue stiffness was recorded with SWE at the sternocleidomastoid (SCM) muscle, overlying subcutaneous tissues (ST), and the base of the tongue (BOT). Results A total of 20 patients were included. Tissue stiffness was significantly higher among HNC patients at the SCM ipsilateral (53.7 kPa vs. 17.5 kPa, p=0.002) and contralateral (44.1 kPa vs. 21.6 kPa, p=0.027) than the side of treatment. Tissue stiffness was not significantly different in ST ipsilateral (6.6 kPa vs. 5.3 kPa, p=0.922) or contralateral (8.0 kPa vs. 6.4 kPa, p=0.426) to treatment. Tissue stiffness at the BOT was not significantly different (19.1 kPa vs. 13.1 kPa, p=0.084). Conclusion SWE is a noninvasive method for measuring tissue fibrosis and is a promising tool for the measurement of RIF in patients with HNC. SWE measurements were taken from the SCM, ST, and BOT in HNC patients at least one year out from treatment with surgery and adjuvant radiation as well as age and gender-matched control patients. HNC patients showed significantly higher levels of tissue stiffness at the SCM both ipsilateral and contralateral to radiotherapy. SWE may be useful for tracking the progression of RIF in HNC patients.

Carotid Artery Stenosis and Ischemic Stroke in Patients With Head and Neck Cancer Treated With Radiation Therapy: A Critical Review

Automated dysphagia characterization in head and neck cancer patients using videofluoroscopic swallowing studies.

BackgroundRadiotherapy is an indispensable treatment modality in head and neck cancer (HNC), while radioresistance is the major cause of treatment failure. The aim of this study is to identify a prognostic molecular signature associated with radio-resistance in HNC for further clinical applications.MethodsAffymetrix cDNA microarrays were used to globally survey different transcriptomes between HNC cell lines and isogenic radioresistant sublines. The KEGG and Partek bioinformatic analytical methods were used to assess functional pathways associated with radioresistance. The SurvExpress web tool was applied to study the clinical association between gene expression profiles and patient survival using The Cancer Genome Atlas (TCGA)-head and neck squamous cell carcinoma (HNSCC) dataset (n = 283). The Kaplan-Meier survival analyses were further validated after retrieving clinical data from the TCGA-HNSCC dataset (n = 502) via the Genomic Data Commons (GDC)-Data-Portal of National Cancer Institute. A panel maker molecule was generated to assess the efficacy of prognostic prediction for radiotherapy in HNC patients.ResultsIn total, the expression of 255 molecules was found to be significantly altered in the radioresistant cell sublines, with 155 molecules up-regulated 100 down-regulated. Four core functional pathways were identified to enrich the up-regulated genes and were significantly associated with a worse prognosis in HNC patients, as the modulation of cellular focal adhesion, the PI3K-Akt signaling pathway, the HIF-1 signaling pathway, and the regulation of stem cell pluripotency. Total of 16 up-regulated genes in the 4 core pathways were defined, and 11 over-expressed molecules showed correlated with poor survival (TCGA-HNSCC dataset, n = 283). Among these, 4 molecules were independently validated as key molecules associated with poor survival in HNC patients receiving radiotherapy (TCGA-HNSCC dataset, n = 502), as IGF1R (p = 0.0454, HR = 1.43), LAMC2 (p = 0.0235, HR = 1.50), ITGB1 (p = 0.0336, HR = 1.46), and IL-6 (p = 0.0033, HR = 1.68). Furthermore, the combined use of these 4 markers product an excellent result to predict worse radiotherapeutic outcome in HNC (p < 0.0001, HR = 2.44).ConclusionsFour core functional pathways and 4 key molecular markers significantly contributed to radioresistance in HNC. These molecular signatures may be used as a predictive biomarker panel, which can be further applied in personalized radiotherapy or as radio-sensitizing targets to treat refractory HNC.

The Presence of Second Primary Esophageal Tumor (Spet) is Still an Independent Negative Prognostic Factor for Head and Neck Cancer (Hnc) Patients: a Retrospective Study

Background: Bone metastasis (BM) is one of the typical metastatic types of head and neck cancer (HNC). The occurrence of BM prevents the HNC patients from obtaining a long survival period. Early assessment of the possibility of BM could bring more therapy options for HNC patients, as well as a longer overall survival time. This study aims to identify independent BM risk factors and develop a diagnostic nomogram to predict BM risk in HNC patients. Methods: Patients diagnosed with HNC between 2010 and 2015 were retrospectively evaluated in the Surveillance, Epidemiology, and End Results (SEER) database, and then eligible patients were enrolled in our study. First, those patients were randomly assigned to training and validation sets in a 7:3 ratio. Second, univariate and multivariate logistic regression analyses were used to determine the HNC patients’ independent BM risk factors. Finally, the diagnostic nomogram’s risk prediction capacity and clinical application value were assessed using calibration curves, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Results: 39,561 HNC patients were enrolled in the study, and they were randomly divided into two sets: training (n = 27,693) and validation (n = 11,868). According to multivariate logistic regression analysis, race, primary site, tumor grade, T stage, N stage, and distant metastases (brain, liver, and lung) were all independent risk predictors of BM in HNC patients. The diagnostic nomogram was created using the above independent risk factors and had a high predictive capacity. The training and validation sets’ area under the curves (AUC) were 0.893 and 0.850, respectively. The AUC values of independent risk predictors were all smaller than that of the constructed diagnostic nomogram. Meanwhile, the calibration curve and DCA also proved the reliability and accuracy of the diagnostic nomogram. Conclusion: The diagnostic nomogram can quickly assess the probability of BM in HNC patients, help doctors allocate medical resources more reasonably, and achieve personalized management, especially for HNC patients with a potentially high BM risk, thus acquiring better early education, early detection, and early diagnosis and treatment to maximize the benefits of patients.

Acute and late toxicities in patients treated with (chemo)radiotherapy for head and neck cancer (HNC) is common and can negatively impact quality of life and performance. Performance status instruments measure the functional ability to perform daily life activities and are important tools in the oncologic population. Since Dutch performance status scales for the HNC population are lacking, we conducted this study to translate the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) into Dutch (D-PSS-HN) and to validate this version. The D-PSS-HN was translated into Dutch according to the internationally described cross-cultural adaptation process. It was administered to HNC patients and together with the Functional Oral Intake Scale completed by a speech and language pathologist at five different time points during the first 5 weeks of (chemo)radiotherapy. Patients were asked each time to complete the Functional Assessment of Cancer Therapy and the Swallowing Quality of Life Questionnaire. Pearson correlation coefficients were used to calculate convergent and discriminant validity and the evolution of D-PSS-HN scores was assessed by means of linear mixed models. A total of 35 patients were recruited and > 98% of the clinician-rated scales were completed. Convergent and discriminant validity were demonstrated, with all correlations rs between 0.467 and 0.819, and between 0.132 and 0.256, respectively. The subscales of the D-PSS-HN are sensitive to detect changes through time. The D-PSS-HN is a valid and reliable instrument to assess performance status in patients with HNC treated with (chemo)radiotherapy. It is a useful tool to measure HNC patients' current diet level and functional abilities to perform daily life activities. What is already known on the subject Acute and late toxicities in patients treated with (chemo)radiotherapy for HNC are common and can negatively impact quality of life and performance. Performance status instruments measure the functional ability to perform daily life activities and are important tools in the oncologic population. However, Dutch performance status scales for the HNC population are lacking. Therefore, we translated the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) into Dutch (D-PSS-HN) and validated this version. What this paper adds to existing knowledge We translated the PSS-HN and demonstrated its convergent and discriminant validity. The subscales of the D-PSS-HN are sensitive to detect changes through time. What are the potential or actual clinical implications of this work? The D-PSS-HN is a useful tool to measure HNC patients' functional abilities to perform daily life activities. The tool can easily be used in clinical settings: since data collection duration is very short, this facilitates clinical (and research-related) implementation of the scale. Patients' individual needs could be identified by using the D-PSS-HN, resulting in more appropriate approaches and (early) referrals if needed. Interdisciplinary communication could be facilitated.

Poor nutritional status is common and associated with mortality and morbidity in patients with head and neck cancer (HNC). While there are several established clinical risk factors for poor nutritional status during HNC radiotherapy, the complete aetiology is not known. The association of malnutrition with psychological factors has been recognised in other chronic illnesses but has not been studied in HNC patients who have higher levels of malnutrition and psychological disorder than many other patient populations. Patients with HNC were assessed at three time points: week 1 of radiotherapy treatment (T1, n = 72), end of radiotherapy treatment (T2, n = 64) and 4 weeks post-radiotherapy treatment (T3, n = 58). Nutritional outcome was measured using the Patient-Generated Subjective Global Assessment, and psychological factors measured were depression, anxiety and adjustment style. Linear mixed models indicated that a model containing the variables time, tumour site and baseline depression best explained malnutrition at T2 and T3 (-2 restricted log likelihood = 695.42). The clinical risk factors: cancer stage, number of radiotherapy fractionations, a PEG feeding tube, availability of a care giver and dietitian's informal clinical assessment did not predict later nutritional status. Depression is a modifiable risk factor for malnutrition among HNC patients undergoing radiation therapy, offering the potential to ameliorate malnutrition in this group. While the nature of any causal relationship between depression and malnutrition in HNC is yet to be understood, the utility of a short depression screen in predicting malnutrition has been demonstrated and could be adopted in clinical practice.

Osteoradionecrosis (ORN), or bone death, is a multifactorial late complication caused by radiotherapy (RT), that diminishes the bone’s ability to withstand trauma and avoid infection. In head and neck cancer (HNC), ORN most commonly manifests in the mandible. It is influenced by RT-induced factors and patient-related parameters. The most effective way to limit RT-induced ORN is to reduce mandibular volumes receiving high RT doses. However, this strategy may also result in a reduced dose to the tumor due to its proximity to the mandible, and therefore must be restricted to only the patients deemed most vulnerable to mandibular ORN. The objective of this study was to design a prognostic model based on RT-planning CT-derived radiomic features extracted from mandible contours along with the patient’s clinical features to predict the probability of mandibular ORN from the end of RT to the onset of ORN in HNC patients. We hypothesized that these features are related to mandibular ORN and that incorporating them into a prediction model will help to identify patients at risk of mandibular ORN after HNC RT. Patient data was retrospectively collected from the Princess Margaret Cancer Centre, University Health Network and based on the following inclusion criteria: patients had (1) had status regarding radiation-induced bone toxicity, (2) the time to the toxicity event was recorded, and (3) head RT-planning CT images in addition to mandible contours. Then, the patient’s history was reviewed by radiation oncologists to collect clinical features. Quantitative image features were then extracted from the segmented mandible for each patient. Finally, multivariable models, a binary classifier, and a regressor were independently trained on three sets of features (radiomic, demo-clinical, and both) to predict the patient’s risk of ORN and the time between the end of RT and the start of ORN respectively. In total, we analyzed CT images from 92 OPC patients with known ORN status (55 positive, 37 negative). We extracted a total of 1877 radiomic features from the manually-segmented Mandible from each patient. Initially, cases were labelled with their status regarding presence and time to radiation toxicity. Top 50, most relevant and least redundant, features were with mRMRe were used for both binary classification and regression models to predict time to the mandibular ORN. Model training upon radiomics and clinical features resulted in the higher accuracy value of 0.93 (AUCROC) compared to the only radiomics features (0.92) and clinical model (0.74). The distribution of AUC values was significantly wider in models trained on clinical features than radiomics or radiomics plus clinical features. Citation Format: Reza Reiazi, Mattea Welch, Scott V. Bratman, Andrew J. Hope, Benjamin Haibe-Kains. The prediction of mandibular osteoradionecrosis in head and neck cancer patients using CT-derived radiomics features [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-034.

Denture use and dental risk factors associated developing osteoradionecrosis after head and neck radiotherapy: A retrospective analysis of hospital records

Abnormal speech function caused by radiotherapy will affect the normal communication of patients with head and neck cancer (HNC) and even interrupt their social life. Rehabilitation Training is widely used to improve articulatory abnormalities in patients with HNC. However, the effectiveness of these rehabilitation measures in restoring the voice function of HNC patients is still unknown. This study aimed to systematically examine the effects of rehabilitation training on radiotherapy-related voice function and quality of life in patients with HNC. The databases PubMed, Web of Science, EMBASE, Cochrane Library, CINAHL, CNKI, Wan Fang, and SinoMed were searched for studies published from inception through October 2024. Randomized controlled trials of rehabilitation training to improve voice function abnormalities associated with radiotherapy for HNC were included, and two investigators independently performed the literature review. Meta-analysis was performed using RevMan 5.4 software to determine statistical heterogeneity based on P-values and I2 values. 13 randomized controlled trials involving 710 participants were included. Meta-analysis showed that rehabilitation training significantly affected the patients' maximum phonation time(MD=1.53, 95%CI=[0.83, 2.23], P<0.0001, Grade Moderate), smoothed cepstral peak prominence(MD=-0.59, 95%CI=[-0.89, -0.29], P=0.0001, Grade Moderate), social communication abilities(MD=-2.60, 95%CI=[-5.14, -0.07], P=0.04, Grade Moderate), and quality of life(MD=8.49, 95%CI=[3.06, 13.92], P=0.002, Grade Moderate). Rehabilitation training is an effective approach for ameliorating abnormal voice functions after radiotherapy for HNC. However, there is no consensus on the optimal frequency, periodicity, and follow-up of interventions for rehabilitation training. More studies are still required to determine the optimal intervention effect for ameliorating speech function abnormalities in patients with HNC after radiotherapy.

Worldwide head and neck cancer (HNC) is the sixth most frequently diagnosed cancer in men and is associated with significant morbidity, mortality and economic loss. African Americans (AA) experience significantly more HNC compared to Caucasian Americans (CA) and they have markedly reduced 5-year survival rates, 40% compared to 61% among CA. AA bear a disproportionate burden of HNC for reasons that are incompletely understood, but likely due to the complex interplay of environmental, genetic and health care access issues. An inverse association for vitamin (vit) D status and HNC cancer has been reported and hypovitaminosis D in AA is well documented; yet, vit D status has not been assessed in HNC patients stratified by race. Thus, objective of this prospective pilot study is to access vit D status in newly diagnosed AA and CA HNC patients by measuring the circulating metabolite of vit D, vit-D 25-OH and by assessing dietary levels utilizing the Block vit D/Calcium screener. Circulating calcium, parathyroid, and 1,25-Dihydroxy vit D are also being measured. In addition, to improve our understanding of mechanisms associated with the potential cancer protective effects of vit D in the context of HNC two HNC cell lines were treated with 2 µM cholecalciferol for 6 hours and protein harvested for proteome profiling. To date, 18 HNC patients have been evaluated, 8 AA and 10 CA. Mean circulating vit D 25-OH levels were 27.3 (+ 9.9) and 20.0 (+ 5.9) ng/mL in CA and AA, respectively supporting that vit D levels are suppressed to a greater extent in AA compared to CA HNC patients, even in sunny Florida. Dietary vit D estimates were non-significantly higher in AA HNC patients compared to CA who had higher total vit D levels, supporting differences in metabolism or potentially supplement use. None of the AA patients had vit D 25-OH levels &amp;gt; 30 ng/mL, a level suggested for optimum regulation of PTH, calcium absorption and bone density; 30% of CA patients expressed levels above 30 ng/mL. Proteome profiling of CAL27 and SSC25 HNC cell lines following vit D treatment revealed inverse modulation of proteins linked to HNC. Proteins down-regulated by vit D treatment included nucleophosmin (NPM), lactoylglutathione, heat shock protein beta-1 (HSPB1) Peroxiredoxin-1 (PRDX1) and Ras-related protein Rap-2b. Recent reports have linked NPM with the regulation of the oncogene FOXM1, also a potential biomarker for early detection. Disease-free survival rate is improved in HNC patients with low NPM expression. Similarly, HSPB1 has been shown to be over expressed in HNC and silencing of HSPB1 has been shown to decrease metastatic behavior in HSNCC. PRDX1 displays upregulation in oral premalignancy and is an indicator for local recurrence. Histone H2A type was up-regulated by Vitamin D. Study results support that newly diagnosed AA HNC patients have depressed vit D levels compared to CA cases and that vit D treatment inversely targets select proteins dysregulated in HNC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 669. doi:1538-7445.AM2012-669

Tooth Failure Post-Radiotherapy in Head and Neck Cancer: Primary Report of the Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad) Study

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: Results of a survey in EORTC institutes