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Planning target volume (PTV) to deliver the desired dose to the clinical target volume (CTV) accounts for systematic (∑) and random (σ) errors during the planning and execution of intensity modulated radiation therapy (IMRT). As these errors vary at different departments, this study was conducted to determine the 3-dimensional PTV (PTV 3D) margins for head and neck cancer (HNC) at our center. The same was also estimated from reported studies for a comparative assessment. A total of 77 patients with HNCs undergoing IMRT were included. Of these, 39 patients received radical RT and 38 received postoperative IMRT. An extended no action level protocol was implemented using on-board imaging. Shifts in the mediolateral (ML), anteroposterior (AP), and superoinferior (SI) directions of each patient were recorded for every fraction. PTV margins in each direction (ML, AP, SI) and PTV 3D were calculated using van Herk's equation. Weighted PTV 3D was also computed from the ∑ and σ errors in each direction published in the literature for HNC. Our patients were staged T 2-4 (66/77) and N 0 (39/77). In all, 2280 on-board images were acquired, and daily shifts in each direction were recorded. The PTV margins in the ML, AP, and SI directions were computed as 3.2 mm, 2.9 mm, and 2.6 mm, respectively. The PTV 3D margin was estimated to be 6.5 mm. This compared well with the weighted median PTV 3D of 7.2 mm (range: 3.2 to 9.9) computed from the 16 studies reported in the literature. To ensure ≥95% CTV dose coverage in 90% of HNC patients, PTV 3D margin for our department was estimated as 6.5 mm. This agrees with the weighted median PTV 3D margin of 7.2 mm computed from the 16 published studies in HNCs. Site-specific PTV 3D margin estimations should be an integral component of the quality assurance protocol of each department to ensure adequate coverage of dose to CTV during IMRT. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of sparing the dysphagia-aspiration-related structures (DARS) in various head and neck cancer sites treated with definitive DARS-optimized intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. Materials and Methods: Target volumes, organs at risk, and in addition, individual DARS were delineated, including the superior, middle, and inferior pharyngeal constrictor muscles, supraglottic and glottic larynx, the base of the tongue, esophageal inlet muscles and cervical esophagus in 35 patients with head and neck squamous cell carcinoma. Volume-based dose constraints were applied to the DARS outside the planning target volume (PTV). An IMRT plan was then generated to limit doses to DARS without compromising PTV dose coverage. Results: Twelve (34.3%) patients had an oropharyngeal primary (OPX), 18 (51.4%) had a laryngeal, and 5 (14.3%) patients had hypopharyngeal primary. The mean dose to the DARS was 47.93 Gy for the entire group, while it was 54.6 Gy in oropharyngeal primaries and 44.4 Gy in laryngopharyngeal primaries. DARS mean dose of ≤45 Gy could be achieved in a significantly lesser number of patients with oropharyngeal primaries (P < 0.02). Similarly, DARS mean dose was 42.25 Gy in patients with N0 disease, 49.6 Gy with ipsilateral involved nodes, and 55 Gy with bilateral disease. Sparing of DARS was feasible when the volume of PTV was ≤150 cc (P < 0.025). Conclusion: Sparing of DARS structures appears to be challenging in patients with oropharyngeal cancers without compromising the dose to the PTVs while it is feasible in laryngopharyngeal cancers. DARS sparing is feasible when the PTV volume is < 150 cc and in patients with negative or unilateral nodal disease. [ABSTRACT FROM AUTHOR]

Head and neck cancer is a significant public health concern in India and globally, with substantial social and economic consequences for affected individuals and their families. The study aimed to assess the socioeconomic impact of head and neck cancer. This paper presents the results of a questionnaire-based study involving 178 head and neck cancer patients who were evaluated at least two years post-completion of their treatment. The questionnaire data collected data on various factors, including site of cancer, treatment modality, speech and diet impairment, changes in earning capacity, occupation, and salary. This was collected from all patients visiting our tertiary cancer care center outpatient department in Ahmedabad, India, between January 2023 and August 2023. The findings highlight the diverse and profound socioeconomic consequences of head and neck cancer. The findings emphasize the need for comprehensive support systems for affected individuals and their families. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate whether malnutrition or nutrition impact symptoms (NIS) affect the possibility of returning to work after treatment for head and neck cancer. Methods: Patients of working age with head and neck cancer were followed up from treatment initiation to 3 months (n = 238), 1 year (n = 182), and 2 years (n = 130) after treatment completion. The observed decrease in the number of patients over time was due to retirement, lack of follow-up, or death. Returning to work was dichotomised as yes or no. Malnutrition was diagnosed 7 weeks after treatment initiation using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This time-point corresponds to the end of chemoradiotherapy or radiotherapy (with or without prior surgery), except for patients who underwent exclusive surgery. NIS were scored on a Likert scale (1–5) at each follow-up using the Head and Neck Patient Symptom Checklist© (HNSC©). Nonparametric tests were used to analyse the ability of patients with/without malnutrition and high/low NIS scores to return to work. Results: At 3 months, 1 year, and 2 years after treatment completion, 135/238 (56.7%), 49/182 (26.9%), and 23/130 (17.7%) patients had not returned to work. Patients with malnutrition at 7 weeks after treatment initiation were more likely to not return to work at 3 months than those without malnutrition, 70.5% compared to 47.1% (p < 0.001). At all three follow-up time-points, patients reporting high scores for a number of NIS had more often not returned to work, with this pattern being most distinct at 2 years. Conclusion: Malnutrition according to the GLIM criteria at 7 weeks after treatment initiation and NIS assessed by the HNSC© at subsequent follow-ups were predictors of the return-to-work process after treatment for up to 2 years. Trial registration number: ClinicalTrials.gov NCT03343236 (date of registration 17/11/2017). [ABSTRACT FROM AUTHOR]

The assessment of cancer patient outcomes is important for any oncology departments. In head and neck cancer, not all patients are suitable for clinical studies. Unfortunately not all oncology centres are well resourced to undertake all available head and neck cancer trials. As a tertiary oncology unit with catchment radius of 50 miles and diverse patient demographics, it remains vital to assess outcomes of patients not included in formal studies. The aim of this study was to gather real world survival data of patients treated with definitive (chemo) radiotherapy. As standard of care, head and neck cancer patients are referred from 7 district general hospitals via 2 regional supra-multidisciplinary teams (sMDT). The data of patients demographics, and the clinical details of the head and neck cancer, are as routine collected prospectively for the institution electronic database. The date of disease recurrence on any patients is prospectively recorded at the sMDT. Non-HPV mucosal head and neck cancer patients who received definitive radiotherapy outside clinical trials between Jan 2018 and May 2022 were retrospectively reviewed. All advanced stage patients (Stages III & IVa/b) were considered concomitant chemotherapy. Radiotherapy volume quality assurance was standard prior to radiation [1]. HPV-mediated oropharynx patients, as well those treated with post-operative or adjuvant radiation, were excluded. The progression free survival (PFS) were calculated from the prospective database, and the overall survival (OS) retrospectively from the institution main death register. A total of 267 patients were identified: 122 (46%) Larynx, 68 (25%) p16- Oropharynx, 34 (13%) Hypopharynx, 33 (12%) Nasopharynx, and 10 (4%) Nasal Cavity/Paranasal sinus patients. In terms of UICC 8th edition staging, there were 33 Stage I (12%), 55 Stage II (21%), 71 Stage III (27%), and 108 Stage IVa/b (40%) cases across all tumour sites. The median age was 65 (range 58 - 72). The male to female ratio was 3.2 to 1. Ninety percent (n = 240) of the patients had performance status of 0 or 1. Majority of the patients (n = 209, 78%) had had exposure to tobacco: 122 (46%) ex-smokers and 87 (33%) current smokers. The median smoking pack years for the tobacco exposed patients was 30 (range 10 - 40). As for alcohol consumption, 130 (49%) patients consumed at least 14 units per week, with 30 (11%) being non-drinkers. All patients received 65Gy in 30 fractions (f) over 6 weeks, unless they were T1/2N0M0 glottic cancer for which they received 55Gy in 20f over 4 weeks. A total of 107 patients (40%) had at least 1 cycle of concomitant chemotherapy with their radiation. The median follow up was 3 years. Across all tumour sites, the 2 and 3 year PFS was 60% and 55% respectively, while the 2 and 3 year OS was 74% and 65% respectively. The OS probability according to the UICC staging across all disease sites is shown in Figure 1. For the Larynx subsite, there were 26 Stage I (21%), 30 Stage II (25%), 51 Stage III (42%), and 15 Stage IVa/b (12%) patients. The 2 and 3 year PFS for larynx patients were 70% and 65% respectively, with the 2 and 3 year OS being 82% and 75% respectively. For the p16- oropharynx cohort, there were 3 Stage I (4%), 12 Stage II (18%), 3 Stage III (4%), and 50 Stage IVa/b (74%) patients. In comparison to the larynx cohort, there were higher proportion of advanced stage patients in the Oropharynx cohort. As a result, the 2 and 3 year PFS for the p16-Oropharynx was 44% and 40% respectively, while the 2 and 3 year OS was 60% and 50% respectively. As for the hypopharynx group, there were no Stage I (0%) but 3 Stage II (9%), 8 Stage III (24%), and 23 Stage IVa/b (68%) cases. The 2 and 3 year PFS was 40% and 25% respectively, while the 2 and 3 year OS was 55% and 42% respectively. Separately, there were 2 Stage I (6%), 8 Stage II (24%), 8 Stage III (24%), and 15 Stage IVa (45%) Nasopharynx patients. The 2 and 3 year PFS for nasopharynx cohort was 75% and 60% respectively, with the 2 and 3 year OS being 78% and 70% respectively. [Display omitted] Despite varying tumour sites, the OS of patients overall corresponded to the UICC Stage of their disease, indicating the importance of accurate initial staging as part of prognostication. [ABSTRACT FROM AUTHOR]

Using next-generation sequencing (NGS), we investigated DNA mutations in the plasma tumor cell-free circulating DNA (ctDNA) of 38 patients with inoperable squamous cell head neck cancer (SCHNC) before and after the completion of chemoradiotherapy (CRT). Baseline mutations of the TP53 were recorded in 10/38 (26.3%) and persisted in 4/10 patients after CRT. ΤP53 mutations were further detected post CRT in 7/38 additional patients with undetectable mutations at baseline (overall rate 44.7%). Furthermore, 4/38 patients exhibited baseline mutations of the EGFR, AR, FGFR3, and FBXW3, and four new gene mutations were detected after CRT (MTOR, EGFR3, ALK, and SF3B1). Τ4 stage was related with a significantly higher rate of mutations (TP53 and overall). Mutations were observed in 8/30 (26.6%) responders (complete/partial response) vs. in 6/8 (75%) of the rest of the patients (p = 0.03). Significant poorer LRFS was noted for patients with mutations detected before and after CRT (p = 0.02). Patients who had detectable mutations either before or after CRT had significantly worse DMFS (p = 0.04 overall, and p = 0.02 for TP53 mutations). It was concluded that assessment of mutations before and after the end of CRT is essential to characterize patients with a high risk of locoregional recurrence or metastatic progression. [ABSTRACT FROM AUTHOR]

Purpose: It is commonly recommended that tooth extraction should be performed prior to radiotherapy (RT) in patients with head neck cancer to prevent osteoradionecrosis (ORN). However, doctors still occasionally encounter patients who require tooth extraction during RT. This study aimed to determine the risk of ORN in patients who undergo tooth extraction during RT. Methods: Data were collected from Taiwan's National Health Insurance Research Database. We retrospectively enrolled 24,412 patients with head and neck cancer treated with radiotherapy between 2011 and 2017. The associations between ORN and demographic characteristics, timing of tooth extraction, and treatments were examined using univariate and multivariable Cox proportional hazards regression models. Results: A total of 24,412 head and neck cancer patients were enrolled; 133 patients underwent tooth extraction during RT and 24,279 patients did not undergo tooth extraction during RT. Tooth extraction during RT was not associated with a significantly higher risk of ORN (hazard ratio [HR] = 1.303, P = 0.4862). Tumor site, RT dose ≥ 60 Gy, age < 55 y/o, mandibulectomy, chronic periodontitis, and chemotherapy were significantly associated with a higher risk of ORN. Conclusion: The risk of ORN in head and neck cancer is not significantly different between patients who undergo tooth extraction during RT and patients who do not undergo tooth extraction during RT. [ABSTRACT FROM AUTHOR]

Purpose/objective: The purpose of the study is to externally validate published 18F-FDG-PET radiomic models for outcome prediction in patients with oropharyngeal cancer treated with chemoradiotherapy. Material/methods: Outcome data and pre-radiotherapy PET images of 100 oropharyngeal cancer patients (stage IV:78) treated with concomitant chemotherapy to 66–69 Gy/30 fr were available. Tumors were segmented using a previously validated semi-automatic method; 450 radiomic features (RF) were extracted according to IBSI (Image Biomarker Standardization Initiative) guidelines. Only one model for cancer-specific survival (CSS) prediction was suitable to be independently tested, according to our criteria. This model, in addition to HPV status, SUVmean and SUVmax, included two independent meta-factors (Fi), resulting from combining selected RF clusters. In a subgroup of 66 patients with complete HPV information, the global risk score R was computed considering the original coefficients and was tested by Cox regression as predictive of CSS. Independently, only the radiomic risk score RF derived from Fi was tested on the same subgroup to learn about the radiomics contribution to the model. The metabolic tumor volume (MTV) was also tested as a single predictor and its prediction performances were compared to the global and radiomic models. Finally, the validation of MTV and the radiomic score RF were also tested on the entire dataset. Results: Regarding the analysis of the subgroup with HPV information, with a median follow-up of 41.6 months, seven patients died due to cancer. R was confirmed to be associated to CSS (p value = 0.05) with a C-index equal 0.75 (95% CI=0.62–0.85). The best cut-off value (equal to 0.15) showed high ability in patient stratification (p=0.01, HR=7.4, 95% CI=1.6–11.4). The 5-year CSS for R were 97% (95% CI: 93–100%) vs 74% (56–92%) for low- and high-risk groups, respectively. RF and MTV alone were also significantly associated to CSS for the subgroup with an almost identical C-index. According to best cut-off value (RF>0.12 and MTV>15.5cc), the 5-year CSS were 96% (95% CI: 89–100%) vs 65% (36–94%) and 97% (95% CI: 88–100%) vs 77% (58–93%) for RF and MTV, respectively. Results regarding RF and MTV were confirmed in the overall group. Conclusion: A previously published PET radiomic model for CSS prediction was independently validated. Performances of the model were similar to the ones of using only the MTV, without improvement of prediction accuracy. [ABSTRACT FROM AUTHOR]

• For head and neck cancer, the significance of time intervals from surgery to post-op radiotherapy (PORT) is unclear. • Prior studies report inferior survival when PORT starts >8 weeks from surgery. • These studies dichotomize time variables; incorrect conclusions may be reached. • This study demonstrates time intervals as continuous variables and when adjusted for relevant patient and cancer factors, are not associated with inferior outcomes. • We suggest threshold time intervals are not used in patient selection for PORT. Studies reported inferior outcomes when radiotherapy starts >6–8 weeks post-surgery for head and neck squamous cell carcinoma (HNSCC) but are limited due to time variable dichotomization. We assessed the relationship between survival and the time between surgery and radiotherapy as a continuous variable, hypothesising there would be no change in patients' survival at 6–8 weeks post-surgery. Inclusion criteria: patients with HNSCC who underwent surgery and adjuvant (chemo)radiotherapy, Jan 2014-Dec 2020. A sub-cohort included patients with oral cavity squamous cell carcinoma (OCSCC) treated at the same institution, Jan 2016-Dec 2020. The primary endpoint was overall survival (OS); a multivariable Cox model was fitted. For the OCSCC sub-cohort, the endpoint of interest was progression-free survival (PFS); a multivariable competing risk regression model was fitted. 386 patients with HNSCC were included (main cohort). The median time between surgery and radiotherapy was 44 days (IQR: 14 days). Plotting time intervals vs log(hazard) did not demonstrate a threshold time where risk of death increases. The time interval between surgery and radiotherapy was not associated with OS (HR 1.00; 95 % CI 0.99–1.02; p = 0.4). In the sub-cohort of 208 patients with OCSCC, the time interval between surgery and radiotherapy was not associated with increased risk of cancer vs competing events (HR 1.01; 95 % CI 0.99–1.03; p = 0.5). Increasing time interval between surgery and radiotherapy was not associated with inferior survival outcomes. We suggest patients are considered for radiotherapy >6–8 weeks post-surgery and that no threshold is considered for patient selection. [ABSTRACT FROM AUTHOR]

Somatic copy number alterations (SCNAs), generally (1) losses containing interferons and interferon-pathway genes, many on chromosome 9p, predict immune-cold, immune checkpoint therapy (ICT)-resistant tumors (2); however, genomic regions mediating these effects are unclear and probably tissue specific. Previously, 9p21.3 loss was found to be an early genetic driver of human papillomavirus–negative (HPV– ) head and neck squamous cancer (HNSC), associated with an immune-cold tumor microenvironment (TME) signal, and recent evidence suggested that this TME-cold phenotype was greatly enhanced with 9p21 deletion size, notably encompassing band 9p24.1 (3). Here, we report multi-omic, -threshold and continuous-variable dissection of 9p21 and 9p24 loci (including depth and degree of somatic alteration of each band at each locus, and each gene at each band) and TME of four HPV– HNSC cohorts. Preferential 9p24 deletion, CD8 T-cell immune-cold associations were observed, driven by 9p24.1 loss, and in turn by an essential telomeric regulatory gene element, JAK2-CD274. Surprisingly, same genetic region gains were immune hot. Related 9p21-TME analyses were less evident. Inherent 9p-band-level influences on anti-PD1 ICT survival rates, coincident with TME patterns, were also observed. At a 9p24.1 whole-transcriptome expression threshold of 60th percentile, ICT survival rate exceeded that of lower expression percentiles and of chemotherapy; below this transcript threshold, ICT survival was inferior to chemotherapy, the latter unaffected by 9p24.1 expression level (P-values < 0.01, including in a PD-L1 immunohistochemistry-positive patient subgroup). Whole-exome analyses of 10 solid-tumor types suggest that these 9p-related ICT findings could be relevant to squamous cancers, in which 9p24.1 gain/immune-hot associations exist. [ABSTRACT FROM AUTHOR]

Investigating the expression and prognostic significance of adenovirus receptors DSG-2, CXADR and CD46 in head and neck cancer. 104 patients with HNSCC (77 OPSCC, 27 LSCC) were retrospectively included in the study. Immunohistochemical staining was performed on all selected slides to detect the expression of DSG-2, CXADR, CD46 and the immunoreactive score (IRS) was determined from the number of positively stained tumor cells and their staining intensity. Furthermore, the respective HPV status was determined by immunohistochemical staining against p16 and HPV-PCR. 81.7 % of the tumors showed DSG-2, 34.6 % of the tumors showed CXADR and 57.7 % of the tumors showed CD46 expression. A high DSG-2 IRS correlated significantly with an advanced tumor size (p= 0.003), increased grading (p=0.012) and positive HPV status (p=0.024) in OPSCC. A high CXADR IRS was significantly associated with a positive lymph node status (p= 0.041) in LSCC and an advanced AJCC stage (p= 0.012) and a positive HPV status (p= 0.009) in OPSCC. No significant correlation could be shown regarding CD46 expression and clinical tumor data. There was no effect of DSG-2, CXADR, and CD46 expression on 5-year overall and on 5-year disease-free survival. No prognostic significance of the expression of DSG-2, CXADR or CD46 in HNSCC was seen. DSG-2, CXADR and CD46 are expressed in HNSCC, so that optimization of oncotherapy with adenoviral vectors appears promising. Due to the significantly increased expression of DSG-2 and CXADR in advanced OPSCC tumors, there is potential for optimizing oncotherapy here in particular. • DSG-2, CXADR and CD46 are expressed in HNSCC. • High DSG-2 expression is correlated with advanced tumor size and grading in OPSCC. • High CXADR expression is associated with an advanced AJCC stage in OPSCC. • There is no prognostic significance of DSG-2, CXADR or CD46 in HNSCC. • Optimization of oncotherapy in HNSCC with adenoviral vectors appears promising. [ABSTRACT FROM AUTHOR]

Human papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have a favorable outcome, but upon relapse, survival is poor and new therapeutical options are needed. Recently, we found synergistic effects by combining the food and drug administration approved (FDA) phosphoinositide 3-kinase (PI3K) and fibroblast-growth-factor-receptor (FGFR) inhibitors BYL719 and JNJ-42756493 on TSCC cell lines. Here this approach was extended and Cyclin-Dependent-Kinase-4/6 (CDK4/6) and Poly-ADP-ribose-polymerase (PARP) and WEE1 inhibitors PD-0332991, and MK-1775 respectively were also examined. HPV+ CU-OP-2, -3, -20, and HPV− CU-OP-17 TSCC cell lines were treated with either BYL719 and JNJ-42756493, PD-0332991 BMN-673 and MK-1775 alone or in different combinations. Viability, proliferation, and cytotoxicity were followed by WST-1 assays and the IncuCyte S3 Live® Cell Analysis System. All inhibitors presented dose-dependent inhibitory effects on tested TSCC lines. Synergy was frequently obtained when combining CDK4/6 with PI3K inhibitors, but only sometimes or rarely when combining CDK4/6 with FGFR inhibitors or PARP with WEE1 inhibitors. To conclude, using CDK4/6 with PI3K or FGFR inhibitors, especially PD-0332991 with BYL719 presented synergy and enhanced the decrease of viability considerably, while although dose dependent responses were obtained with PARP and WEE1 inhibitors (BMN-673 and MK-1775 resp.), synergy was rarely disclosed. [ABSTRACT FROM AUTHOR]

Undifferentiated carcinoma of the nasopharynx (NPC) is a rare disease, which usually occurs in the Asian population. Due to its anatomic location, it is characterised by rich lymph node drainage and has a high incidence of cervical node metastasis. However, cervical nodal metastasis commonly involves retropharyngeal nodes and level II nodes, followed by level III nodes. In recent years, innovations in terms of systemic treatments and radiotherapy techniques have improved oncological outcome and treatment-related toxicities. Therefore, there is a growing interest in de-intensification strategies of reducing volumes and treatment-related side effects, especially in patients with NPC with N0–N1-stage disease. Proton therapy could represent a valid alternative to Intensity Modulated Radiotherapy (IMRT) in the management of NPC in this setting. With this Commentary, we aim to explore the feasibility of Intensity Modulated Proton Therapy (IMPT) in upper-neck irradiation of NPC N1-stage disease. We selected an NPC patient with N1 disease and compared the original IMRT plan with the IMPT plan in terms of dosimetric parameters. IMPT offers a minimal dosimetric advantage over IMRT in the bilateral lower-neck sparing. Clinical trials are needed to evaluate the significance of these proposed suggestions and their applicability in non-endemic areas. [ABSTRACT FROM AUTHOR]

This study presents multi-institutional individual data of reirradiation (ReRT) for head and neck cancer using brachytherapy (ReRT-BT) collected by national surveillance in Japan. We distributed an e-mail-based questionnaire to 153 institutions equipped with high-dose-rate (HDR) brachytherapy facilities and received responses from 76 institutions (49.7%). Of these 76 institutions, only four (5.2%) performed ReRT-BT for head and neck cancers, and three provided individual patient's data. Six ReRT-BT cases of patients with recurrent head and neck cancer, treated with HDR brachytherapy in seven ReRT sessions, were identified from three institutions. Three patients (two cases of lips and one case of gingiva) who underwent curative-intent treatment achieved complete response at the treated area. Three patients who received palliative treatment (one case of tongue and two cases of maxillary sinus) had sustained tumor growth at the treated site, but with improvement in symptoms. No grade ≥3 toxicity was found after HDR ReRT-BT. ReRT-BT for head and neck cancer using HDR brachytherapy is a safe and useful approach to treat recurrent cancer after initial radiotherapy with curative and palliative intent. However, the scarce availability of ReRT-BT is a barrier to the wider utility of this effective procedure. [ABSTRACT FROM AUTHOR]

Background: Anatomical variations in head and neck cancer during IMRT leads to volume shrinkage, results in dosimetric variations in tumour and normal tissue including parotid glands, with a risk of radiation toxicities. Methods: 30 patients with a stage II–IV head and neck squamous cell carcinoma (HNSCC) were treated with definitive IMRT‐SIB and concomitant chemotherapy. Volumetric and dosimetric variations were evaluated during the period of IMRT by recalculating and obtaining dose‐volume histograms of re‐contoured target volumes and parotid glands on repeat CT scans taken multiple times during treatment (CT1, CT2, CT3 and CT4). Results: Result showed significant (p < 0.001) mean decrease in both primary and nodal tumors volume with time whereas increase (p < 0.01 or p < 0.001) in respective V100 (%) and D2% (Gy). The mean parotid gland dose increased (p < 0.01 or p < 0.001) with time, whereas parotid gland volume and distance between plan isocenter and centre of mass of parotid glands decreased (p < 0.05 or p < 0.001) with time. Patient's mean weight and neck circumference both decrease (p < 0.001) with time whereas ECOG score increase (p < 0.001) with time. The mucosal toxicity increased significantly (p < 0.001) with time. The change in both weight and neck circumference showed significant (p < 0.001) and direct (positive correlation) association with change in parotid gland volume. Conclusion: If the PTV and normal anatomy are changing with time, adaptive IMRT would be beneficial radiation dose delivery where possible. [ABSTRACT FROM AUTHOR]

Purpose: Cancer patients are regarded as a group at risk for both COVID-19 infection and severe clinical course because of advanced age, comorbidities and iatrogenic immune impairment. Among them, patients with cancer of the upper and lower airways share other risk factors, mostly related to tobacco-smoke exposure, including male gender, airway epithelial damages, chronic obstructive respiratory disease (COPD), cardiovascular and cerebrovascular diseases. Clinical and pathophysiological factors shared by these conditions are reviewed. Methods: Review of the published literature since the beginning of 2020. Results: COVID-19 is a respiratory infectious disease and SARS-CoV-2 replication and shedding occurs in nasal and bronchial epithelial respiratory cells through the interaction with ACE2 and TMPRSS2 receptors, both overexpressed in smokers and former smokers. Tobacco-smoke airway exposure is also characterized by a chronic inflammation with activation of inflammatory cells and cytokine release including interleukin-6 (IL-6). A high release of cytokine in response to viral infection is documented in COVID-19 patients with adverse clinical outcomes and IL-6 is a key element of the cytokine storm syndrome leading to multi-organ damage. Conclusions: Patients with cancers of the upper and lower airways might be at increased risk of infection, morbidity and mortality from COVID-19 also because of tobacco exposure, a key factor in triggering inflammation, immunity and cancer. [ABSTRACT FROM AUTHOR]

Introduction: Advanced oncological defects of the face (AODF) involve the structures of the face in a threedimensional format, resulting in the communication of the upper aerodigestive tract, bones and facial soft tissues with the external environment.(1) The reconstructive microsurgery is the gold standard for rehabilitation of these defects, usually with vascularized fasciocutaneous and/or musculocutaneous free flaps. In the case of AODF, free flaps offer a better restoration of phonation and swallowing, resulting in increased quality of life and aesthetic satisfaction.(2) Despite the different classifications of AODF and the options for reconstruction, the type of free flap that promotes the best surgical and aesthetic results remains controversial.(3) Thus, we aimed to prospectively compare the results of AODF reconstructions with fasciocutaneous or musculocutaneous free flaps. Methods: A prospective randomized study was conducted with patients allocated in a 1:1 ratio to each group at an oncology reference center. Patients without previous treatment or with recurrent advanced oncologic disease of both genders, aged over 14 years and submitted to reconstructive microsurgery for the treatment of AODF were included. The patients were divided into two groups: Group A - fasciocutaneous free flap (anterolateral thigh flap) and Group B - musculocutaneous free flap (vertical rectus abdominis or latissimus dorsi flap). The groups were prospectively compared in terms of technical aspects of free flaps, morbidity in the donor site, nutritional status and postoperative aesthetic result. The results were expressed both as mean±standard deviation and as median and percentage. Fisher's exact test was used with a p<0.05 considered significant. The study was approved by an international IRB. Results: Of the twenty-eight patients selected, 23 completed the study, 12 allocated to Group A and 11 allocated to Group B. The length of the vascular pedicle of the free flap was significantly greater in Group A (p<0.001), while the time of flap dissection was lower in Group B (p=0.008). The rate of major complications in the donor area of the musculocutaneous flap group was significantly higher (p=0.037). The total flap survive was 91.30%, with one total loss in each group. There was a tendency for fasciocutaneous flaps to present better aesthetic results, however, when the statistical analysis of group comparison was carried out, there was no statistically significant difference (p=0.109). There was no statistically significant difference in relation to the nutritional status, minor complications of free flaps and minor complications of donor site. Table 1 describes the results. Conclusion: Both fasciocutaneous and musculocutaneous flaps proved to be effective for AODF reconstruction. The fasciocutaneous free flap proved to be an adequate option and was associated with less morbidity in the donor area, when compared to traditional musculocutaneous flaps. The fasciocutaneous free flaps and musculocutaneous free flaps have similar aesthetic results. [ABSTRACT FROM AUTHOR]

Introduction: Recently major efforts have been made to define the oligometastatic setting, but for head and neck cancer (HNC) limited data are available. We aimed to evaluate outcome of oligometastatic HNC treated with Stereotactic body radiotherapy (SBRT) as metastasis-directed therapy. Materials and methods: We analyzed patients treated with SBRT on a maximum of five oligometastases from HNC, in up to two organs. Concomitant treatment was allowed. End points were toxicity, local control of treated metastases (LC), progression-free survival (PFS) and overall survival (OS). Results: 48 consecutive patients and 71 lesions were treated. With a follow-up of 20.2 months, most common primary tumors were larynx (29.2%) and salivary glands (29.2%), while common site of metastases was lung (59.1%). Median dose was 48 Gy (21–75) in 3–8 fractions. Treatment was well tolerated, with two patients reporting mild pain and nausea. LC rates at 1 and 2 years were 83.1% and 70.2%. Previous local therapy (HR 4.97; p = 0.002), oligoprogression (HR 4.07; p = 0.031) and untreated metastases (HR 4.19; p = 0.027) were associated with worse LC. PFS at 1 and 2 years were 42.2% and 20.0%. Increasing age (HR 1.03; p = 0.010), non-adenoid cystic carcinoma (HR 2.57; p = 0.034) and non-lung metastases (HR 2.20; p = 0.025) were associated with worse PFS. One- and 2-years OS were 81.0% and 67.1%. Worse performance status (HR 2.91; p = 0.049), non-salivary primary (HR 19.9; p = 0.005), non-lung metastases (HR 2.96; p = 0.040) were correlated with inferior OS. Conclusions: SBRT can be considered a safe metastasis-directed therapy in oligometastatic HNC. Efficacy of the treatment seems to be higher when administered upfront in the management of metastatic disease; however, selection of patients need to be improved due to the relevant risk of appearance of new metastatic site after SBRT. [ABSTRACT FROM AUTHOR]

Drug resistance in antifungal therapy, a problem unknown until a few years ago, is increasingly assuming importance especially in immunosuppressed patients and patients receiving chemotherapy and radiotherapy. In the past years, the use of essential oils as an approach to improve the effectiveness of antifungal agents and to reduce antifungal resistance levels has been proposed. Our research aimed to evaluate the antifungal activity of Colombian rue, Ruta graveolens, essential oil (REO) against clinical strains of Candida albicans, Candida parapsilopsis, Candida glabrata, and Candida tropicalis. Data obtained showed that C. tropicalis and C. albicans were the most sensitive strains showing minimum inhibitory concentrations (MIC) of 4.1 and 8.2 µg/mL of REO. Time–kill kinetics assay demonstrated that REO showed a fungicidal effect against C. tropicalis and a fungistatic effect against C. albicans. In addition, an amount of 40% of the biofilm formed by C. albicans was eradicated using 8.2 µg/mL of REO after 1 h of exposure. The synergistic effect of REO together with some antifungal compounds was also investigated. Fractional inhibitory concentration index (FICI) showed synergic effects of REO combined with amphotericin B. REO Lead a disruption in the cellular membrane integrity, consequently resulting in increased intracellular leakage of the macromolecules, thus confirming that the plasma membrane is a target of the mode of action of REO against C. albicans and C. tropicalis. [ABSTRACT FROM AUTHOR]

Objective: To examine the patterns of care for octogenarian head and neck cancer patients. Methods: All newly diagnosed patients aged 80 years or older, who presented at our centre between June 2018 and October 2020, were included. Results: The total number of patients was 42. The median Charlson Comorbidity Index was 5 (range, 4–9). The larynx was the most common subsite (n = 12). Twenty-nine patients (66 per cent) were diagnosed at disease stage IV. Squamous cell carcinoma was the most common histology (86 per cent). Twenty-six patients (62 per cent) had radical treatment and 16 (38 per cent) had palliative treatment. The estimated six-month and one-year overall survival rates for the radical and palliative treatment cohorts were 92.3 per cent and 42.9 per cent (p = 0.001) and 65.4 per cent and 15.4 per cent (p = 0.003), respectively. Conclusion: This study provides useful information on octogenarian patients with head and neck cancer. This information may help in conducting prospective studies, especially those focusing on older patients with head and neck cancer, in order to define the ideal care of this patient population. [ABSTRACT FROM AUTHOR]

The article explores how global coronavirus (COVID-19) pandemic poses serious health challenges in oncologic clinics. It mentions that clinicians and patients need to be educated to continue to strictly follow the measures to limit viral transmission. It discusses that minimal requirements for proper head and neck cancer diagnosis and staging are assured and combined together to reduce hospital attendance.

Objectives: Tracheostomy is commonly used in intensive care units and in head and neck departments. Airway obstruction due to occluded cuffless tracheostomy tubes themselves remains unknown, although capping trials are commonly used before decannulation. The aim of this study was to evaluate the extent to which airway obstruction can be caused by occluded cuffless tubes in patients who underwent head and neck surgery. Design: Prospective Research Outcome. Settings: University teaching hospital. Participants: Fifty patients requiring transient tracheostomy after head and neck surgery. Main outcome measures: A flow‐volume loop (FVL) through the mouth using a portable spirometer, with the occluded fenestrated cuffless tube, was measured before and immediately after decannulation, by obstructing the orifice of tracheostomy tube. The measurement of FVL recorded the forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), forced expiratory flow at 50% of FVC, peak inspiratory flow (PIF) and forced inspiratory flow at 50% of FVC. Results: A statistically significant difference between all spirometric parameters was found. Mean PEF and PIF, respectively, increased from 2.8 to 4.5 L/s (P <.0001) and 2.3 to 2.7 L/s (P <.01) before and after decannulation, with a strong positive correlation (r = 0.7; P <.05). A mean expiratory (34%) and inspiratory (9%) airflow reduction was observed due to cannula. Conclusions: Occluded cuffless tracheostomy tubes cause a dramatic airflow obstruction, mainly in the expiratory phase of FVL. This should be taken into account during capping trials. [ABSTRACT FROM AUTHOR]

Chemo-radiotherapy and head and neck cancers are common adverse outcomes that impact patients' quality of life. The increasing cancer incidence and healthcare service shortages necessitate new strategies for optimal treatments and follow-ups. Digitalized healthcare, including digital health, telemedicine, and telemonitoring, is promising. HNC requires multidisciplinary team intervention, including speech language pathology telepractice models. Mobile health-based interventions can help cancer survivors increase physical activity and improve rehabilitation services. Effective self-management skills can improve outcomes. Advancements in communication technologies have led to telecommunication-based interventions incorporating swallowing exercises, education, monitoring, feedback, self-management, and communication. Home-based remote rehabilitation is urgent, especially during the COVID-19 pandemic, but the optimal strategy and effectiveness of remote interventions remain unclear. Telehealth interventions represent a possible novel approach to increase access to care across the cancer continuum, strengthen patients' knowledge and self-management, provide continuity of services, and enable remote monitoring of symptoms and response to treatment. Telehealth patients are typically younger, more likely to be English-speaking, and more likely to be female. These disparities widened slightly after the start of the pandemic but were also present prior to the pandemic. [ABSTRACT FROM AUTHOR]

Thyroid gland is irradiated to a considerable dose in conventional radiotherapy of head neck cancer and significant proportion of patients later develop hypothyroidism. This study is an effort to shed light on acute changes in thyroid function after irradiation those are less clearly defined. Values were recorded before radiation treatment, after 4 week of irradiation, after completion of treatment, 1 month after completion of treatment and after 4 months of completion of treatment. A repeated measures ANOVA with a Greenhouse–Geisser correction determined that mean T3, T4 and TSH levels differed statistically significantly between time points. Post hoc test using the Bonferroni correction revealed statistical significance difference in values of T3, T4 and TSH done at specific intervals. External irradiation in cancer therapeutic doses affects thyroid function and sets at a new point with increased TSH, but in reference ranges, to maintain required thyroxin level. [ABSTRACT FROM AUTHOR]

• Severe oral mucositis in head and neck cancer (HNC) represents a common entity. • Intensity modulated radiotherapy (IMRT) is nowadays the standard technique. • The role of oral-mucosa(OM)-sparing IMRT needs to be clarified. • This is the largest reported analysis of published data. • Further studies are necessary to standardize OM-sparing IMRT. Oral mucositis is a common dose-limiting toxicity during radiotherapy with or without chemotherapy in head and neck cancer patients. This potentially severe complication globally worsens quality of life and negatively impacts local control and survival's outcomes. Several studies have been published on feasibility and/or clinical benefit of intensity modulated radiotherapy (IMRT) mucosa-sparing technique. In 2017, the Italian Association of Radiation Oncology Head and Neck Cancer Working Group organized a study group to perform a systematic review. The aim was to verify if practical indications, including dose-constraints and demonstrated clinical benefit, could be proposed for oral mucosa (OM)-sparing IMRT in order to reduce the incidence of severe acute mucositis. Although dose to OM should be reduced as much as possible without compromising target volumes coverage, it is still tricky to firmly state that OM-sparing procedure should be considered the standard of care, especially due to high subjective variability in OM contour. [ABSTRACT FROM AUTHOR]

Background: Horner syndrome caused by metastatic squamous cell carcinoma of the head and neck is not common, and when diagnosed, may have serious clinical implications. We aim at highlighting the clinical significance of this finding. Methods: We retrospectively reviewed charts of 6 patients with Horner syndrome secondary to metastatic head and neck squamous cell carcinoma (HNSCC) in the neck. Results: All 6 patients had pathologically confirmed nodal metastatic HNSCC. There was one unknown primary and in the remaining 5 patients the primary tumor was identified in the oropharynx, larynx, and oral cavity. Three patients died within 1 month of diagnosis, before initiation of any treatment. One patient received radiation only while 2 patients received chemoradiation with cisplatin as the tumors were unresectable given carotid sheath involvement. Median survival was 4.5 months. Only 1 out of the 6 patients survived and had complete resolution of Horner syndrome after treatment. Conclusion: This is the first case series of neck metastasis from mucosal HNSCC as an unusual cause of Horner syndrome and is usually associated with very poor prognosis. [ABSTRACT FROM AUTHOR]

Cancer processes have been studied for over a century, but clinical care still relies on morphological and histological approaches. Modern diagnostic and therapy options include molecular characterisation of abnormal genes, cell surface indicators, hormonal/endocrine mediators, and signaling pathways. Targeted medicines, synthetic lethal targeting, and immune checkpoint inhibitors have spurred hope for molecular targets in cancer management. Precision medicine programs aim to transform population-based research into biomarker-driven clinical trials, but disparities in access to genetic profiling and inexpensive precision oncology drugs must be addressed to ensure cost-effective therapies are available to all patients. [ABSTRACT FROM AUTHOR]

The Second International Symposium on HPV Infection in Head and Neck Cancer was held on 3rd-4th November 2016 in Leipzig, Germany. The meeting brought together researchers and clinicians to share the latest knowledge on HPV infection in head and neck cancer and to join active and constructive scientific discussions. This report summarizes the major themes discussed during the symposium. [ABSTRACT FROM AUTHOR]

Abstract: We aimed to determine the prevalence and co‐occurrence of tobacco smoking, alcohol consumption, and depressive symptoms among a sample of head and neck cancer (HNC) patients undergoing radiotherapy. A total of 307 HNC patients participated in a multi‐site stepped‐wedge randomized controlled trial (RCT) evaluating the effectiveness of a dietitian‐delivered health behavior intervention in patients with HNC undergoing radiotherapy. During week one of radiotherapy patients completed measures of smoking, alcohol consumption, and level of depression. Approximately one‐fifth (21%) of patients had two or more co‐occurring problems: current smoking, hazardous alcohol use, and/or likely presence of a major depressive episode (MDE). Approximately one‐third (34%) of the sample were current smokers, one‐third (31%) were drinking hazardously and almost one‐fifth (19%) had likely cases of depression. Comorbidity of smoking, hazardous alcohol use, and MDE is high in HNC patients, and interventions need to address this cluster of cancer risk factors. [ABSTRACT FROM AUTHOR]

Modern standards of precision radiotherapy, primarily driven by the technological advances of intensity modulation and image guidance, have led to increased versatility in radiotherapy planning and delivery. The ability to shape doses around critical normal organs, while simultaneously “painting” boost doses to the tumor have translated to substantial therapeutic gains in head and neck cancer patients. Recently, dose adaptation (or adaptive radiotherapy) has been proposed as a novel concept to enhance the therapeutic ratio of head and neck radiotherapy, facilitated in part by the onset of molecular and functional imaging. These contemporary imaging techniques have enabled visualisation of the spatial molecular architecture of the tumor. Daily cone-beam imaging, besides improving treatment accuracy, offers another unique angle to explore radiomics – a novel high throughput feature extraction and selection workflow, for adapting radiotherapy based on real-time tumor changes. Here, we review the existing evidence of molecular and functional imaging in head and neck cancers, as well as the current application of adaptive radiotherapy in the treatment of this tumor type. We propose that adaptive radiotherapy can be further exploited through a systematic application of molecular and functional imaging, including radiomics, at the different phases of planning and treatment. [ABSTRACT FROM AUTHOR]

Background: WD repeat domain 5 (WDR5), a core member of Mixed lineage leukemia (MLL) and SET1 histone H3 lysine 4 (H3K4) methyltransferase complexes, is involved in multiple biological and pathological processes. Its deregulation in cancer and pro-tumorigenic roles has been increasingly appreciated. However, the expression pattern of WDR5 and its biological functions in head neck squamous cell carcinoma (HNSCC) have not been well established.Methods: The expression of WDR5 mRNA in HNSCC was determined by data mining and interrogation using publicly available databases. Its protein expression was measured by immunohistochemistry in a retrospective cohort of primary HNSCC samples. Moreover, the associations between WDR5 expression and various clinicopathological parameters and patient survival were assessed. The pro-tumorigenic roles of WDR5 in HNSCC were further delineated in vitro by loss-of-function assay.Results: Our bioinformatics analyses revealed that WDR5 mRNA was significantly overexpressed in 3 HNSCC cohorts. WDR5 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with large tumor size, advanced clinical stage (chi-square test, P = .048, .006) and reduced overall and disease-free survival (Kaplan-Mier analyses, Log-rank test, P = .0137, .0154). Univariate and multivariate survival analyses further revealed WDR5 protein abundance as an independent prognostic factor for patients' overall survival. Moreover, WDR5 knockdown significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis in HNSCC cells.Conclusions: Our findings reveal that WDR5 is aberrantly overexpressed in HNSCC and associates with aggressiveness and unfavorable prognosis, thus representing a novel diagnostic and prognostic biomarker for HNSCC. [ABSTRACT FROM AUTHOR]

Background: Shoulder dysfunction is common after neck dissection for head and neck cancer (HNC). Brief electrical stimulation (BES) is a novel technique that has been shown to enhance neuronal regeneration after nerve injury by modulating the brain-derived neurotrophic growth factor (BDNF) pathways. The objective of this study was to evaluate the effect of BES on postoperative shoulder function following oncologic neck dissection. Methods: Adult participants with a new diagnosis of HNC undergoing Level IIb +/- V neck dissection were recruited. Those in the treatment group received intraoperative BES applied to the spinal accessory nerve (SAN) after completion of neck dissection for 60 min of continuous 20 Hz stimulation at 3-5 V of 0.1 msec balanced biphasic pulses, while those in the control group received no stimulation (NS).The primary outcome measured was the Constant-Murley Shoulder (CMS) Score, comparing changes from baseline to 12 months post-neck dissection. Secondary outcomes included the change in the Neck Dissection Impairment Index (ANDII) score and the change in compound muscle action potential amplitude (ACMAP) over the same period. Results: Fifty-four patients were randomized to the treatment or control group with a 1:1 allocation scheme. No differences in demographics, tumor characteristics, or neck dissection types were found between groups. Significantly lower ACMS scores were observed in the BES group at 12 months, indicating better preservation of shoulder function (p = 0.007). Only four in the BES group compared to 17 patients in the NS groups saw decreases greater than the minimally important clinical difference (MICD) of the CMS (p = 0.023). However, NDII scores (p = 0.089) and CMAP amplitudes (p = 0.067) between the groups did not reach statistical significance at 12 months. BES participants with Level IIb + V neck dissections had significantly better ACMS and ACMAP scores at 12 months (p = 0.048 and p = 0.025, respectively). Conclusions: Application of BES to the SAN may help reduce impaired shoulder function in patients undergoing oncologic neck dissection, and may be considered a viable adjunct to functional rehabilitation therapies. Trial registration: Clinicaltrials.gov (NCT02268344, October 17, 2014). [ABSTRACT FROM AUTHOR]

The aim of the present study was to elucidate the effect of intratumoral abscess/necrosis (AN) on the outcome of patients with recurrent head and neck cancer (HNC) treated by stereotactic radiotherapy. The records of 67 patients treated with CyberKnife® in four institutes between August 2000 and July 2010 were reviewed. The frequency of AN appeared to be increased in younger postoperative patients with large ulcerative tumors. The AN+ group exhibited a better initial response rate compared with the AN- group (64 vs. 33%, respectively; P=0.04). The 1-year local control rate was 51 and 75% in the AN+ and AN- groups, respectively (P=0.01), while the respective 1-year overall survival rates were 53 and and 71% (P=0.0004). A total of 21 patients (31%) experienced grade ≥ 3 toxicities, and carotid blowout syndrome (CBOS) was found in 11 patients, resulting in 8 deaths. A significantly larger proportion of patients in the AN+ group developed CBOS (8/18; 44%) compared with the AN- group (3/49; 6%) (P=0.001). Therefore, AN may be an important prognostic factor for patients with recurrent HNC, as well as a predictor of lethal toxicity due to CBOS. [ABSTRACT FROM AUTHOR]

Head neck cancer (HNC) is generally treated with a multimodality approach. Loco-regional-distant control is often worst, due to the advantage stage disease at diagnosis and the optimal treatment option remains an unresolved issue. Metronomic chemotherapy (MCHT) is an emerging therapeutic option in clinical oncology and it may prove useful in HNC patients. [ABSTRACT FROM AUTHOR]

Although surgery, radiotherapy, chemotherapy, or combined treatment often elicits an initial satisfactory response, relapses are frequently observed within two years. Current surveillance methods, including clinical exams and imaging evaluations, have not unambiguously demonstrated a survival benefit, most probably due to a lack of sensitivity in detecting very early recurrence. Current guidelines advise post-treatment surveillance of head and neck cancer (HNC) patients should involve scheduled appointments with a variety of practitioners. The benefits of prolonged routine follow-up on survival have not been proven. Increasing numbers of HNC survivors raise the burden to provide efficient and effective care. [ABSTRACT FROM AUTHOR]

Background: Dysphagia is a significant side-effect following treatment for head and neck cancers, yet poor adherence to swallowing exercises is frequently reported in intervention studies. Behaviour change techniques (BCTs) can be used to improve adherence, but no review to date has described the techniques or indicated which may be more associated with improved swallowing outcomes.Methods: A systematic review was conducted to identify behavioural strategies in swallowing interventions, and to explore any relationships between these strategies and intervention effects. Randomised and quasi-randomised studies of head and neck cancer patients were included. Behavioural interventions to improve swallowing were eligible provided a valid measure of swallowing function was reported. A validated and comprehensive list of 93 discrete BCTs was used to code interventions. Analysis was conducted via a structured synthesis approach.Results: Fifteen studies (8 randomised) were included, and 20 different BCTs were each identified in at least one intervention. The BCTs identified in almost all interventions were: instruction on how to perform the behavior, setting behavioural goals and action planning. The BCTs that occurred more frequently in effective interventions, were: practical social support, behavioural practice, self-monitoring of behaviour and credible source for example a skilled clinician delivering the intervention. The presence of identical BCTs in comparator groups may diminish effects.Conclusions: Swallowing interventions feature multiple components that may potentially impact outcomes. This review maps the behavioural components of reported interventions and provides a method to consistently describe these components going forward. Future work may seek to test the most effective BCTs, to inform optimisation of swallowing interventions. [ABSTRACT FROM AUTHOR]

The aims of this study were to evaluate clinical outcomes and to determine their predictive factors in patients with oral cavity squamous cell carcinoma (OCSCC) invading the mandibular bone (T4) who underwent primary radical surgery and fibula free-flap reconstruction. Between 2001 and 2013, all patients who underwent primary surgery and mandibular fibula free-flap reconstruction for OCSCC were enrolled in this retrospective study. Predictive factors of oncologic and functional outcomes were assessed in univariate and multivariate analysis. 77 patients (55 men and 22 women, mean age 62 ± 10.6 years) were enrolled in this study. Free-flap failure and local and general complication rates were 9, 31, and 22 %, respectively. In multivariate analysis, ASA score ( p = 0.002), pathologic N-stage ( p = 0.01), and close surgical margins ( p = 0.03) were independent predictors of overall survival. Six months after therapy, oral diet, speech intelligibility, and mouth opening functions were normal or slightly impaired in, respectively, 79, 88, and 83 % of patients. 6.5 % of patients remaining dependent on enteral nutrition 6 months after therapy. With acceptable postoperative outcomes and satisfactory oncologic and functional results, segmental mandibulectomy with fibula free-flap reconstruction should be considered the gold standard primary treatment for patients with OCSCC invading mandible bone. Oncologic outcomes are dependent on three main factors: ASA score, pathologic N-stage, and surgical margin status. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness and tolerability profile of tapentadol prolonged release (PR) in a cohort of head and neck cancer (HNC) patients affected by background pain due to painful mucositis during intensity modulated radiation therapy with or without cisplatin with definitive and adjuvant intent.Materials and Methods: Tapentadol PR was administered at the moment of pain onset in opioid-naive patients at the dosage of 50 mg BID. The dosage was increased 50 mg twice a day until the optimal dose of no more than 500 mg/day of tapentadol PR. Primary endpoint of the analysis was the evaluation of improved assessment using the numerical rating scale (NRS). Secondary endpoints were as follows: (1) assessment of the treatment received using the patients' global impression of change (PGIC) scale; (2) weight increase/stability; (3) sleep quality; and (4) tolerability. The period of observation was 90 days from the start of antineoplastic treatment.Results: Between September 2014 and May 2015, 30 HNC patients were observed. The average age was 64.9 years (range, 36-80). Twenty-two days after the start of antineoplastic treatment, tapentadol PR was administered to 25 % of patients. This percentage was increased to 50 % after 39 days and to 75 % after 43 days. Considering the efficacy of tapentadol PR on daily pain, there was a reduction of 30 % (95 % C.I. 69.3 ÷ 96.2 %) in the pain score in 26 patients (86.7 %), and a reduction of 50 % (95 % C.I. 57.7 ÷ 90.1 %) in 23 patients (76.7 %).Conclusion: The use of tapentadol PR is feasible and well tolerated in HNC patients affected by background pain due to painful mucositis during intensity modulated radiotherapy with or without cisplatin. Further studies are needed to enhance current findings. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to analyse the impact of surgical margins on tumour recurrence and survival of patients with carcinomas of the head and neck.Material and Methods: A cohort of 156 patients with primary squamous cell carcinoma of the head and neck treated by local resection with negative margins and neck dissection between 2004 and 2012 was investigated. Margin status in frozen sections and permanent paraffin tissues were analysed and compared to clinical and histopathological parameters as well as to tumour recurrence (local, regional and distant) and disease-specific survival (DSS).Results: Close margins (<5mm) on permanent sections were correlated to high-grade differentiation (p=0.070), lymphangiosis (p=0.009) and positive neck nodes (p=0.025) implicating regional and distant recurrence (p=0.001) as well as unfavorable DSS (p=0.002). Positive margins on initial frozen section analysis revised into negative margins during further surgery were the strongest predictor for local recurrence in uni- and multivariate analysis (p<0.001, hazard ratio 3.34). However, positive frozen section margins were not significantly predictive for DSS (p=0.150). Significant predictors for DSS in univariate analysis were local recurrence (p=0.026), T-stage (p=0.02), N-stage (p<0.001), grading (p=0.02) and lymphangiosis (p=0.001). Multivariate DSS analysis revealed lymph node metastasis (p=0.005) and local recurrence (p=0.017) as significant negative predictors.Conclusion: Close margins on permanent sections are associated with aggressive tumour characteristics, regional and distant metastasis implicating worse DSS. The accuracy of frozen section analysis seems limited as positive frozen section margins revised into negative margins bear a high risk of local recurrence. [ABSTRACT FROM AUTHOR]

Background The prevalence of overweight and obesity defined as BMI ≥ 25 kg/m 2 is increasing, also among head and neck cancer patients. It is unknown whether the presence of high BMI influences disease-related mortality, overall survival and recurrence in these patients. Methods We reviewed available literature using Pubmed and Web of Science. Human observational studies were included if they reported the impact of high BMI on mortality, recurrence or survival for head and neck cancer. Results Eleven full articles and two abstracts met the inclusion criteria: six prospective and seven retrospective cohort studies, which comprised 8.306 patients. Patients with higher BMI had increased overall survival and decreased disease-related mortality and recurrence rate compared with underweight and normal weight patients. Most studies were adjusted for potentially confounding variables, such as stage of disease and smoking habits. Conclusion High BMI is associated with a better outcome in head and neck cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the factors associated with infection at the recipient site of pectoralis major myocutaneous flap (PMMF) of head and neck cancer patients. We retrospectively reviewed head and neck cancer patients who underwent PMMF reconstruction and identified those with recipient site infection. Variables of patients with and without infection were compared and associated factors were investigated by logistic regression model. A total of 478 patients were included in the final analysis and 183 patients (38.3 %) developed recipient site infection. Lower margin of skin island, concurrent tracheotomy, diabetes mellitus, mandibular plate reconstruction, prior radiation, and peri-operative blood transfusion were independent factors associated with recipient site infection of PMMF. Skin island of PMMF beyond the eighth intercostal space markedly increased the risk of recipient site infection after major head and neck cancer surgery. Recognition of relevant factors associated with infection may help surgeons to identify those at risk. [ABSTRACT FROM AUTHOR]

Background: This study aimed to elucidate the influence of skin invasion in patients with recurrent head and neck cancer treated with re-irradiation using stereotactic radiotherapy.Materials: We reviewed 104 patients treated using CyberKnife in four institutions.Results: Nine cases of skin invasion were recognized (8.6 %). Larger tumors tended to exhibit skin invasion. The skin invasion (+) group showed a lower response rate (0/9, 0 %) than the skin invasion (-) group (56/95, 59 %) (p = 0.002). The skin invasion (+) group showed lower local control (LC) and progression free survival (PFS) rates, both 0 % at 6 months, than the skin invasion (-) group, which had a LC of 69 % (p = 0.0001) and a PFS of 48 % at 1 year (p = 0.0157). Median survival time and one-year survival rates for the skin invasion (+) and (-) groups were 6.6 vs. 15.3 months and 14 % vs. 59 % (p = 0.0005), respectively. No patient with skin invasion survived more than 14.4 months. The percentage of patients who developed grade 3 or higher toxicity was 44 % in the skin invasion (+) group and 18 % in the skin invasion (-) group (p = 0.14).Conclusions: Skin invasion is an important predictor of poor prognosis in recurrent head and neck cancer after re-irradiation with stereotactic radiation therapy. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer (HNC) is a debilitating disease due in part to its effects on function, including speech, swallowing, and cosmesis. Previous studies regarding depression in HNC have focused on demographic predictors, incidence, and quality of life studies. There is, however, a paucity of studies that objectively address depressive symptoms in HNC patients and the resultant effects on post-treatment functional performance status. The aim of this study was to assess the relationship between preoperative depressive symptoms (PDS) and postoperative functional performance status (PFPS), in addition to other predictors of rehabilitation and survival. Methods: A prospective cohort study was undertaken at the University of Alberta, including all new adult HNC patients undergoing surgery as primary therapy for HNC from May 2013 to January 2014. Baseline depressive symptoms were measured on the Quick Inventory of Depressive Symptoms (QIDS) questionnaire 2 weeks preoperatively and PFPS was assessed 12 months postoperatively on the Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scale. Secondary outcomes included completion of adjuvant therapy, narcotic dependence, return to detrimental habits, loss of follow-up, and length of hospital stay (LOHS). Differences between the Normal-Mild and Moderate-Severe QIDS groups were assessed using Mann--Whitney and Fischer Exact statistical analyses. Results: Seventy-one patients were included in the study. Mild and Moderate-Severe PDS were 35.2 % and 18.3 %, respectively. Significantly lower FACT-HN scores were noted in the Moderate-Severe group at 12 months (p = 0.03). The risk ratio (RR) for FACT-HN score < 50 % at 12 months in the Moderate-Severe group was 5.66. In addition, significantly lower completion of adjuvant treatment (p = 0.03), significantly higher incidence of narcotic dependence (p = 0.004), and significantly higher LOHS (24 days vs. 18 days; p = 0.02) was observed in the Moderate-Severe group. There was no significant difference in loss of follow-up between the 2 groups (p = 0.64). Conclusions: The incidence and severity of PDS in HNC patients treated with surgery is high (53.5 %). Patients with Moderate-Severe PDS have significantly decreased PFPS, increased narcotic use, decreased completion of adjuvant therapy, and a longer LOHS. HNC patients should be monitored closely for depressive symptoms. [ABSTRACT FROM AUTHOR]

Primary human tumor culture models allow for individualized drug sensitivity testing and are therefore a promising technique to achieve personalized treatment for cancer patients. This would especially be of interest for patients with advanced stage head and neck cancer. They are extensively treated with surgery, usually in combination with high-dose cisplatin chemoradiation. However, adding cisplatin to radiotherapy is associated with an increase in severe acute toxicity, while conferring only a minor overall survival benefit. Hence, there is a strong need for a preclinical model to identify patients that will respond to the intended treatment regimen and to test novel drugs. One of such models is the technique of culturing primary human tumor tissue. This review discusses the feasibility and success rate of existing primary head and neck tumor culturing techniques and their corresponding chemo- and radiosensitivity assays. A comprehensive literature search was performed and success factors for culturing in vitro are debated, together with the actual value of these models as preclinical prediction assay for individual patients. With this review, we aim to fill a gap in the understanding of primary culture models from head and neck tumors, with potential importance for other tumor types as well. [ABSTRACT FROM AUTHOR]

Background: Shoulder pain and dysfunction are common after oncologic neck dissection for head and neck cancer (HNC), due to traction, compression, and devascularization injuries to the spinal accessory nerve (SAN). Shoulder pain and dysfunction can hinder postoperative rehabilitation and hygiene, activities of daily living (ADLs), and return to work after treatment for HNC. Due to the rising incidence of human papillomavirus (HPV)-associated oropharyngeal cancer, patients are often diagnosed in the third or fourth decade of life, leaving many potential working years lost if shoulder dysfunction occurs. Brief electrical stimulation (BES) is a novel technique that has been shown to enhance and accelerate neuronal regeneration after injury through a brain-derived neurotrophic growth factor (BDNF)-driven molecular pathway in multiple peripheral nerves in both humans and animals. Methods/Design: This is a randomized controlled trial testing the effect of intraoperative BES on postoperative shoulder pain and dysfunction. All adult participants with a new diagnosis of HNC undergoing surgery with neck dissection, including Level IIb and postoperative radiotherapy, will be enrolled. Participants will undergo intraoperative BES after completion of neck dissection for 60 min continuously at 20 Hz, 3 to 5 V, in 100-msec pulses. Postoperatively, participants will be evaluated using the Constant-Murley Shoulder Score, a scale that assesses shoulder pain, ADLs, strength, and range of motion. Secondary outcomes measured will include nerve conduction studies (NCS) and electromyographic (EMG) studies, as well as scores on the Oxford Shoulder Score (OSS), the Neck Dissection Impairment Index (NDII), and the University of Washington Quality of Life (UW-QOL) score. Primary and secondary outcomes will be assessed at 6 weeks, 3 months, 6 months, and 12 months. Discussion: The objective of this study is to evaluate the effect of BES on postoperative clinical and objective shoulder functional outcomes and pain after oncologic neck dissection. BES has been shown to be successful in accelerating peripheral nerve regeneration in both animal and human participants in multiple different peripheral nerves. If successful, this technique may provide an adjunctive prevention option for shoulder pain and dysfunction in HNC patients. Trial registration: NCT02268344: 17 October 2014. [ABSTRACT FROM AUTHOR]

BACKGROUND An evaluation system was established for measuring physician performance. This study was designed to determine whether an initial evaluation with surgeon feedback improved subsequent performance. METHODS After an evaluation of an initial cohort of procedures (2004-2008), surgeons were given risk-adjusted individual feedback. Procedures in a postfeedback cohort (2009-2010) were then assessed. Both groups were further stratified into high-acuity procedure (HAP) and low-acuity procedure (LAP) groups. Negative performance measures included the length of the perioperative stay (2 days or longer for LAPs and 11 days or longer for HAPs); perioperative blood transfusions; a return to the operating room within 7 days; and readmission, surgical site infections, and mortality within 30 days. RESULTS There were 2618 procedures in the initial cohort and 1389 procedures in the postfeedback cohort. Factors affecting performance included the surgeon, the procedure's acuity, and patient comorbidities. There were no significant differences in the proportions of LAPs and HAPs or in the prevalence of patient comorbidities between the 2 assessment periods. The mean length of stay significantly decreased for LAPs from 2.1 to 1.5 days ( P = .005) and for HAPs from 10.5 to 7 days ( P = .003). The incidence of 1 or more negative performance indicators decreased significantly for LAPs from 39.1% to 28.6% ( P < .001) and trended downward for HAPs from 60.9% to 53.5% ( P = .081). CONCLUSIONS Periodic assessments of performance and outcomes are essential for continual quality improvement. Significant decreases in the length of stay and negative performance indicators were seen after feedback. Therefore, an audit and feedback system may be an effective means of improving quality of care and reducing practice variability within a surgical department. Cancer 2015;121:1581-1587. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background and purpose Although reirradiation has attracted attention as a potential therapy for recurrent head and neck tumors with the advent of modern radiotherapy, severe rate toxicity such as carotid blowout syndrome (CBOS) limits its potential. The aim of this study was to identify the risk factors of CBOS after hypofractionated stereotactic radiotherapy (SBRT). Methods and patients We conducted a matched-pair design examination of pharyngeal cancer patients treated by CyberKnife reirradiation in four institutes. Twelve cases with CBOS were observed per 60 cases without CBOS cases. Prognostic factors for CBOS were analyzed and a risk classification model was constructed. Results The median prescribed radiation dose was 30 Gy in 5 fractions with CyberKnife SBRT after 60 Gy/30 fractions of previous radiotherapy. The median duration between reirradiation and CBOS onset was 5 months (range, 0–69 months). CBOS cases showed a median survival time of 5.5 months compared to 22.8 months for non-CBOS cases (1-year survival rate, 36% vs.72%; p = 0.003). Univariate analysis identified an angle of carotid invasion of >180°, the presence of ulceration, planning treatment volume, and irradiation to lymph node areas as statistically significant predisposing factors for CBOS. Only patients with carotid invasion of >180° developed CBOS (12/50, 24%), whereas no patient with tumor involvement less than a half semicircle around the carotid artery developed CBOS (0/22, 0%, p = 0.03). Multivariate Cox hazard model analysis revealed that the presence of ulceration and irradiation to lymph nodes were statistically significant predisposing factors. Thus, we constructed a CBOS risk classification system: CBOS index = (summation of risk factors; carotid invasion >180°, presence of ulceration, lymph node area irradiation). This system sufficiently separated the risk groups. Conclusion The presence of ulceration and lymph node irradiation are risk factors of CBOS. The CBOS index, including carotid invasion of >180°, is useful in classifying the risk factors and determining the indications for reirradiation. [ABSTRACT FROM AUTHOR]

Background: To investigate tumor response and toxicities in head and neck squamous cell cancer (HNSCC) upon hypofractionated radiotherapy compared with conventional fractionation. Settings and Design: Data from patients with squamous cell cancer of oral cavity, oropharynx, hypopharynx, and larynx (AJCC, 2010 Stage II to IVB); who received hypofractionated (n = 30) or conventionally fractionated (n = 30) radiotherapy, with or without chemotherapy, between January 2010 to June 2011 were retrieved and retrospectively analyzed. Materials and Methods: In conventional arm (Arm A), each patient received 70 Gy at 2 Gy per fraction over 7 weeks, along with concurrent cisplatin (100 mg/m²) on days 1, 22, and 43 for locally advanced stage. In hypofractionated arm (Arm B), each patient received 55 Gy at 2.75 Gy per fraction over 4 weeks, along with concurrent cisplatin (100 mg/m2) on days 1 and 22 for locally advanced stage. The end points were tumor response, acute and late toxicities, overall survival (OS), and diseases-free survival (DFS). Results: The tumor response distribution was comparable - 24 (80%) patients in arm A and 23 (76%) in arm B achieved a complete response. Significant differences in frequencies of acute grade = 2 skin toxicity, mucositis were found, with higher frequencies in Arm B. Higher frequencies of late grade = 2 dysphagia, laryngeal edema, xerostomia, and confluent mucositis were encountered in Arm B at 6 months from start of chemoradiation. However, OS, DFS, and loco-regional recurrence rates were comparable between the two arms. Conclusions: Hypofractionated radiotherapy can achieve similar tumor response to conventionally fractionated radiotherapy in HNSCC, although with some increase of toxicity. [ABSTRACT FROM AUTHOR]