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Non-melanoma skin cancers (NMSCs) are the most common form of skin cancer worldwide. The global incidence of cutaneous squamous cell carcinoma (CSCC) is rising, with an estimated 2.4 million cases diagnosed in 2019. Chronic exposure to ultraviolet (UV) radiation is a major risk factor for developing CSCC. Most early-stage CSCCs are treated successfully with surgery or radiotherapy; however, locally advanced or metastatic disease can be associated with significant morbidity or mortality. Recently, the treatment paradigm for advanced CSCC has been revolutionised by the introduction of immunotherapy, which can achieve a response rate of approximately 50% with durable cancer control, and significant improvement in quality of life. With the regulatory approval of programmed death-1 (PD-1)-targeting drugs since 2018, immunotherapy is now recognised as the standard of care for first-line systemic therapy in advanced or metastatic CSCC. [ABSTRACT FROM AUTHOR]

This study explored associative relationships between radiotherapy dose volumes delivered to the dysphagia aspiration risk structures (DARS) and swallowing physiological disturbance at 3 months post treatment in a homogenous cohort of patients who received (chemo)radiotherapy ((C)RT) for oropharyngeal head and neck cancer (HNC). Participants(n = 53) were a subgroup of patients previously recruited as part of a prospective randomised trial, and had undergone physiological swallowing assessment using videofluroscopic swallowing study (VFSS) at 3 months post (C)RT. The extended oral cavity (EOC), supraglottic larynx (SGL), glottic larynx (GL), cricopharyngeal inlet (CI), and pharyngeal constrictor muscles (PCM) were contoured as per international consensus guidelines and dose volume histograms (DVHs) were generated for each structure. Each DVH was analysed to reveal mean, maximum and partial radiotherapy doses of V40, V50 and V60 for each structure. Physiological swallowing function on VFSS was rated using the Modified Barium Swallow Impairment Profile (MBSImP). A binary logistic regression model was used to establish associative relationships between radiotherapy dose to the DARS and physiological changes within the swallowing mechanism. Structures that received the largest volumes of radiotherapy dose were the PCM and SGL. Significant relationships were found between the proportion of the EOC, SGL, GL and PCMs that received radiotherapy doses > 40 Gy, > 50 Gy and > 60 Gy and the likelihood of a moderate-severe physiological swallowing impairment (on the MBSImP). Whilst the current study was exploratory in nature, these preliminary findings provide novel evidence to suggest structure-specific associative relationships between radiotherapy dose and impacts to corresponding swallow physiology in patients with oropharyngeal HNC. [ABSTRACT FROM AUTHOR]

Purpose: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model.Methods: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data.Results: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation.Conclusions: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated heterogeneous disease and is characterized by peritumoral immune infiltrate. Adoptive T-cell therapy (ACT) has emerged as a potential therapeutic strategy for NPC. However, the tumor microenvironment remains a major roadblock for the successful implementation of ACT in clinical settings. Expression of checkpoint molecules by malignant cells can inhibit the effector function of adoptively transferred EBV-specific T cells. Here we present a novel case report of a patient with metastatic NPC who was successfully treated with a combination of EBV-specific ACT and programmed cell death-1 blockade therapy. Following combination immunotherapy, the patient showed complete resolution of metastatic disease with no evidence of disease relapse for 22 months. Follow-up immunological analysis revealed dramatic restructuring of the global T-cell repertoire that was coincident with the clinical response. This case report provides an important platform for translating these findings to a larger cohort of NPC patients. [ABSTRACT FROM AUTHOR]

Background: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). Results: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. Conclusions: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC. [ABSTRACT FROM AUTHOR]

Treatment personalisation remains an unmet need in oropharynx cancer (OPC). We aimed to determine whether gene expression signatures improved upon clinico-pathological predictors of outcome in OPC. The clinico-pathological predictors, AJCC version 7 (AJCC 7), AJCC 8, and a clinical algorithm, were assessed in 4 public series of OPC (n = 235). Literature review identified 16 mRNA gene expression signatures of radiosensitivity, HPV status, tumour hypoxia, and microsatellite instability. We quality tested signatures using a novel sigQC methodology, and added signatures to clinico-pathological variables as predictors of survival, in univariate and multivariate analyses. AJCC 7 Stage was not predictive of recurrence-free survival (RFS) or overall survival (OS). AJCC 8 significantly predicted RFS and OS. Gene signature quality was highly variable. Among HPV-positive cases, signatures for radiosensitivity, hypoxia, and microsatellite instability revealed significant underlying inter-tumour biological heterogeneity, but did not show prognostic significance when adjusted for clinical covariates. Surprisingly, among HPV-negative cases, a gene signature for HPV status was predictive of survival, even after adjustment for clinical covariates. Across the whole series, several gene signatures representing HPV and microsatellite instability remained significant in multivariate analysis. However, quality control and independent validation remain to be performed to add prognostic information above recently improved clinico-pathological variables. [ABSTRACT FROM AUTHOR]

Intensive, prophylactic swallowing therapy programs have been developed to improve dysphagia outcomes for patients with head/neck cancer (HNC) receiving (chemo)radiotherapy ([C]RT). Across studies, variable therapy adherence rates have been reported. Preliminary research suggests that service-delivery mode and demographic factors may influence adherence. This study examined patient adherence to a prophylactic swallowing therapy protocol across three service-delivery models: (1) clinician-directed face-to-face therapy, (2) technology-assisted therapy using the telepractice application, SwallowIT and (3) independent patient-directed therapy. The secondary aim explored the impact of patient factors on adherence. Patients with oropharyngeal HNC receiving definitive (C)RT were randomised to receive the Pharyngocise exercise protocol via clinician-directed (n = 26), patient-directed (n = 27) or SwallowIT-assisted (n = 26) models. Adherence was calculated as the percentage of prescribed exercise completed. Multiple patient factors were recorded at baseline. Adherence across the 6 weeks in all groups was low (27%), and declined from week 4 of (C)RT. The clinician-directed model yielded significantly (p = 0.014) better adherence than patient-directed therapy in weeks 1-3. There was also a trend for higher adherence in the SwallowIT group compared to patient-directed in weeks 1-3 (p = 0.064). Multivariable linear modelling identified active smoking at baseline (p < 0.001) and concomitant chemotherapy (p = 0.040) as significant negative predictors of adherence, with baseline reduced motivation trending towards significance. Although (C)RT-related toxicities will impact adherence, adopting service-delivery models with greater structure/support and providing extra assistance to patients with known risk factors may help optimise therapy adherence to prophylactic therapy programs. Telepractice may provide an alternate model to support adherence where service constraints limit intensive clinician-directed therapy. [ABSTRACT FROM AUTHOR]

Research advocates for the use of intensive, prophylactic swallowing therapy to help reduce the severity of dysphagia in patients receiving (chemo)radiotherapy ([C]RT) for head/neck cancer (HNC). Unfortunately, the intensity of this therapy, coupled with growing patient numbers and limited clinical resources, provides challenges to many international cancer facilities. Telepractice has been proposed as a potential method to provide patients with greater support in home-practice, whilst minimising burden to the health service. This study investigated the clinical and patient-attributable costs of delivering an intensive, prophylactic swallowing therapy protocol via a new telepractice application "SwallowIT" as compared to clinician-directed FTF therapy and independent patient self-directed therapy. Patients (n = 79) with oropharyngeal HNC receiving definitive (C)RT were randomised to receive therapy via a: clinician-directed (n = 26), patient-directed (n = 27), or SwallowIT-assisted (n = 26) model of care. Data pertaining to health service costs (service time, consumables, therapy resources), patient-attributable costs (travel and wages) and patient-reported health-related quality of life (QoL) (AQoL-6D) were collected. SwallowIT provided a cost-efficient model of care when compared to the clinician-directed model, with significant cost savings to both the health service and to HNC consumers (total saving of $1901.10 AUD per patient; p < 0.001). The SwallowIT model also proved more cost-effective than the patient-directed model, yielding clinically significantly superior QoL at the end of (C)RT, for comparable costs. Overall, when compared to the alternate methods of service-delivery, SwallowIT provided a financially viable and cost-effective method for the delivery of intensive, prophylactic swallowing therapy to patients with HNC during (C)RT. [ABSTRACT FROM AUTHOR]

Purpose: There is a growing association of human papillomavirus (HPV) with some cases of mucosal squamous cell carcinoma of the head and neck (HNSCC), particularly of the oropharynx. Persistent oral HPV infection is believed to increase the likelihood of malignancy, and it is possible that host genetic factors can determine susceptibility to persistent HPV infection. Polymorphisms in the two EV genes (EVER1 and EVER2, also known as transmembrane channel protein (TMC) 6 and 8) have been identified as strong candidate genes, since a small number of critical mutations in these genes have been shown to cause profound and florid skin HPV infections, and some of them have been linked to susceptibility to cervical cancer. Methods: We sought to determine whether there was a difference in the frequency of single nucleotide polymorphisms (SNPs) in EVER1 (rs2613516, rs12449858) and EVER2 (rs7205422, rs12452890) between HNSCC patients with HPV-positive and HPV-negative tumors, and healthy controls. We used logistic regression to analyze SNPs in 219 patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx, or larynx, and 321 healthy controls. Results: We did not find any associations with the EVER1/EVER2 SNPs and HPV status or being a HNSCC case or a control. Conclusions: The present data do not provide evidence for a role of genetic variations in EVER1 or EVER2 for HPV status of mucosal HNSCC or between HNSCC patients and controls. [ABSTRACT FROM AUTHOR]

Purpose: Dysphagia is a common and debilitating side effect for head and neck cancer (HNC) patients undergoing radiotherapy (RT) with or without chemotherapy ([C]RT) and is associated with nutritional and emotional comorbidities. Emotional sequelae and distress are also known to affect carers of HNC patients. A weekly, joint speech pathology/dietetic (SP/DN) service-delivery model has been employed to manage swallowing/nutritional and associated emotional issues during (C)RT. This study aimed to conduct a service evaluation of the weekly SP/DN clinical model.Methods: Cross-sectional sampling of core service metrics and perceptions of key stakeholders (70 HNC patients, 30 carers, and 10 clinicians) were collated from the Metro South Radiation Oncology Service in Brisbane, Australia. Data from each source was examined separately and then triangulated.Results: An average of 28 patients (SD = 5.54) attended SP/DN appointments per week, with 58% reporting swallowing and/or nutritional issues. Distress was reported by 27% of patients and 30% of carers. Clinicians felt able to adequately identify and manage swallowing and nutrition 90% of the time but only 10% of the time for distress. Seventy-six percent of scheduled SP/DN sessions were perceived as necessary by either patients, clinicians or both.Conclusions: Findings demonstrated a third of patients and their carers had a high level of distress during HNC [C]RT, supporting need for the provision of a weekly SP/DN service in a select cohort. However, the routine weekly SP/DN assessment model for all patients undergoing HNC treatment demonstrates the potential for over-servicing. Alternative service-delivery models warrant further evaluation. [ABSTRACT FROM AUTHOR]

The International Classification of Functioning, Disability, and Health (ICF) is an internationally recognized framework which allows its user to describe the consequences of a health condition on an individual in the context of their environment. With growing recognition that dysphagia can have broad ranging physical and psychosocial impacts, the aim of this paper was to identify the ICF domains and categories that describe the full functional impact of dysphagia following non-surgical head and neck cancer (HNC) management, from the perspective of the person with dysphagia. A secondary analysis was conducted on previously published qualitative study data which explored the lived experiences of dysphagia of 24 individuals with self-reported swallowing difficulties following HNC management. Categories and sub-categories identified by the qualitative analysis were subsequently mapped to the ICF using the established linking rules to develop a set of ICF codes relevant to the impact of dysphagia following HNC management. The 69 categories and sub-categories that had emerged from the qualitative analysis were successfully linked to 52 ICF codes. The distribution of these codes across the ICF framework revealed that the components of Body Functions, Activities and Participation, and Environmental Factors were almost equally represented. The findings confirm that the ICF is a valuable framework for representing the complexity and multifaceted impact of dysphagia following HNC. This list of ICF codes, which reflect the diverse impact of dysphagia associated with HNC on the individual, can be used to guide more holistic assessment and management for this population. [ABSTRACT FROM AUTHOR]

The implication of dysphagia for people treated nonsurgically for head and neck cancer (HNC) and its detrimental effects on functioning and quality of life has been well documented. To date, however, there has been a paucity of research on the effects of dysphagia following HNC on carers, independent of the consequences of a gastrostomy. The objective of this qualitative study was to report on the experiences of carers of people with dysphagia (non-gastrostomy dependent) following nonsurgical treatment for HNC and to identify the support needs of this group. A purposive, maximum-variation sampling technique was adopted to recruit 12 carers of people treated curatively for HNC since 2007. Each participated in an in-depth interview, detailing their experience of caring for someone with dysphagia and the associated impact on their life. Thematic analysis was adopted to search the transcripts for key phases and themes that emerged from the discussions. Analysis of the transcripts revealed four themes: (1) dysphagia disrupts daily life, (2) carers make adjustments to adapt to their partner's dysphagia, (3) the disconnect between carers' expectations and the reality of dysphagia, and (4) experiences of dysphagia-related services and informal supports. Carers generally felt ill-prepared for their role in dysphagia management. The qualitative methodology successfully described the impact of dysphagia on the everyday lives of carers, particularly in regard to meal preparation, social events, and family lifestyle. Clinicians should provide adequate and timely training and support to carers and view carers as copartners in dysphagia management. [ABSTRACT FROM AUTHOR]

With no long-term data available in published research to date, this study presents details of the swallowing outcomes as well as barriers to and facilitators of oral intake and weight maintenance at 2 years after altered fractionation radiotherapy with concomitant boost (AFRT-CB). Twelve patients with T1-T3 oropharyngeal cancer who received AFRT-CB were assessed at baseline, 6 months, and 2 years post-treatment for levels of dysphagia and salivary toxicity, food and fluid tolerance, functional swallowing outcomes, patient-reported function, and weight. At 2 years, participants were also interviewed to explore barriers and facilitators of oral intake. Outcomes were significantly worse at 2 years when compared to baseline for late toxicity, functional swallowing, and patient-rated physical aspects of swallowing. Most patients (83%) tolerated a full diet pretreatment, but the rate fell to 42% (remainder tolerated soft diets) at 2 years. Multiple barriers to oral intake that impacted on activity and participation levels were identified. Participants lost 11 kg from baseline to 2 years, which was not regained between 6 months and 2 years. Global, social, and emotional domains of patient-reported function returned to pretreatment levels. At 2 years post AFRT-CB, worsening salivary and dysphagia toxicity, declining functional swallowing, and multiple reported ongoing barriers to oral intake had a negative impact on participants' activity and participation levels relating to eating. These ongoing deficits contributed to significant deterioration in physical swallowing functioning determined by the MDADI. In contrast, patients perceived their broader functioning had improved at 2 years, suggesting long-term adjustment to ongoing swallowing deficits. [ABSTRACT FROM AUTHOR]

Purpose: Altered fractionation radiotherapy with concomitant boost (AFRT-CB) may be considered an alternative treatment for patients not appropriate for chemoradiation (CRT). As functional outcomes following AFRT-CB have been minimally reported, this exploratory paper describes the outcomes of patients managed with AFRT-CB or CRT at 6 months post-treatment. Methods: Using a cross-sectional analysis design, functional outcomes of 14 AFRT-CB and 17 CRT patients with T1-T3 oropharyngeal cancers were explored at 6 months post-treatment. Clinical and instrumental swallow assessments, weight and nutritional status, and the functional impact of treatment were examined. Results: Inferior outcomes were observed for the CRT patients on the RBHOMS ( p = 0.03) which was reflected in diet and fluid restrictions with 18% of the CRT group requiring modified fluids and diets. Although a trend ( p = 0.07) was noted for increased lingual deficits and aspiration risk for fluids in the CRT group, no other significant differences were observed. Both groups experienced an average of 10 kg weight loss and reported reduced general and swallowing-related function. Conclusions: These preliminary data suggest functional outcomes following AFRT-CB and CRT were largely comparable at 6 months post-treatment. Treatment intensification in any form may contribute to impaired function which requires multidimensional intervention. Larger cohort investigations with systematic methodology are needed to further examine these initial findings. [ABSTRACT FROM AUTHOR]

Altered fractionation radiotherapy for head and neck cancer has been associated with improved locoregional control, overall survival, and heightened toxicity compared with conventional treatment. Swallowing, nutrition, and patient-perceived function for altered fractionation radiotherapy with concomitant boost (AFRT-CB) for T1-T3 oropharyngeal squamous cell carcinoma (SCC) have not been previously reported. Fourteen consecutive patients treated with AFRT-CB for oropharyngeal SCC were recruited from November 2006 to August 2009 in a tertiary hospital in Brisbane, Australia. Swallowing, nutrition, and patient-perceived functional impact assessments were conducted pretreatment, at 4-6 weeks post-treatment, and at 6 months post-treatment. Deterioration from pretreatment to 4-6 weeks post-treatment in swallowing, nutrition, and functional impact was evident, likely due to the heightened toxicity associated with AFRT-CB. There was significant improvement at 6 months post-treatment in functional swallowing, nutritional status, patient-perceived swallowing, and overall function, consistent with recovery from acute toxicity. However, weight and patient perception of physical function and side effects remained significantly worse than pretreatment scores. The ongoing deficits related to weight and patient-perceived outcomes at 6 months revealed that this treatment has a long-term impact on function possibly related to the chronic effects of AFRT-CB. [ABSTRACT FROM AUTHOR]