Human papillomavirus associated oropharyngeal cancer now the most common mucosal head and neck cancer in Queensland.

INTRODUCTION: The profile and outcomes of head and neck cancer throughout Australia has changed over the past decade. The aim of this study was to perform a population-based analysis of incidence, demographics, stage, treatments and outcomes of patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC), with a particular focus on HPV-associated disease. METHODS: This was a retrospective analysis of prospectively collected data within the Queensland Oncology Repository (QOR) and analysed by the Queensland Cancer Control Analysis Team. The cohort included patients diagnosed in Queensland between 1 January 2015 and 31 December 2019. Outcome measures included incidence of new OPSCC cases, age-standardised rates (ASR) (3-year average), demographics, p16 status, stage (8th Edition American Joint Commission on Cancer), treatments, and 2- and 5-year overall survival. RESULTS: There were 1527 newly diagnosed OPSCC, representing 96% (1527/1584) of all oropharyngeal cancers. It was the most common head and neck cancer diagnosed, with oral cavity cancer being the second most common (n = 1171). Seventy-seven percent were p16 positive (1170/1527), of which 87% (1019/1170) were male. The median age was 61 years and 49% (568/1170) presented with Stage I disease. The ASR was 6.3/100,000, representing a 144% incidence increase since 1982 (2.6/100,000). Radiotherapy was utilised in 91% of p16+ cases with 2- and 5- year overall survival of 89% and 79%, respectively. CONCLUSION: OPSCC is now the most common mucosal head and neck cancer diagnosed in Queensland, having surpassed oral cavity cancer. The majority are HPV-associated (p16+), presenting with early-stage disease with a favourable prognosis.

Characterising B cell expression and prognostic significance in human papillomavirus positive oropharyngeal cancer.

OBJECTIVES: The incidence of human papillomavirus positive oropharyngeal cancer (HPV+OPC) is increasing, and new biomarkers are required to better define prognostic groups and guide treatment. Infiltrating T cells have been well studied in head and neck cancer, however the presence and role of B cells and tertiary lymphoid structures (TLS) in the tumor microenvironment has not, even though the interplay between T and B cells is increasingly being recognised. MATERIALS AND METHODS: Using CD20 immunohistochemistry (IHC) to identify B cells and TLS in a cohort of 159 HPV + OPC patients, we semi-quantitatively scored abundance and location (intra-tumoral or stromal) and correlated findings with patient survival. RESULTS: 32% (51/157) of patients had high intra-tumoral (IT) abundance of CD20+ B cells (≥5%) and this was prognostic for improved overall survival (OS) with an adjusted hazard ratio (HR) of 0.2 (95 % CI 0.0-0.7, p = 0.014). We validated our results in an independent cohort comprising 171 HPV + OPC where 14% (23/171) were IT CD20+ high, again showing improved survival with an adjusted HR for OS of 0.2 (95 % CI 0.0-1.4, p = 0.003). Neither stromal abundance nor the presence of TLS were prognostic in either cohort. B cells were subtyped by multispectral IHC, identifying CD20+CD27+ cells, consistent with memory B cells, as the predominant subtype. Combined with validated biomarker CD103, a marker of tissue-resident memory T cells, IT CD20+ B cells abundance was able to prognostically stratify patients further. CONCLUSIONS: CD20+ B cell abundance has the potential to be used as a biomarker to identify good and poor prognosis HPV + OPC patients.

The Current Treatment Landscape of Cutaneous Squamous Cell Carcinoma.

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.

Epidemiology and treatment outcomes of cutaneous squamous cell carcinoma extending to the temporal bone.

BACKGROUND: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking. METHODS: Retrospective analysis of 167 Australian patients with primary and peri-temporal bone cSCC. RESULTS: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post-operative radiotherapy (n = 146, 87.4%), 5-year disease-free survival, locoregional recurrence-free survival, disease-specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre-auricular tumors, salvage surgery, tumor size (≥40 mm medial-lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis. CONCLUSION: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre-auricular cancers is required given poorer associated survival outcomes.

Facial nerve perineural spread from cutaneous squamous cell carcinoma of the head and neck: A single institution analysis of epidemiology, treatment, survival outcomes, and prognostic factors.

BACKGROUND: This study aimed to examine patients with facial nerve (VII) perineural spread (PNS) from cutaneous squamous cell carcinoma of the head and neck. METHODS: Retrospective analysis of patients managed by an Australian tertiary center between 2000 and 2019. RESULTS: Seventy three patients were included. Most presented with recurrent disease (89.0%) and simultaneous trigeminal nerve (V) involvement (67.1%). Of the 55 patients (75.3%) who received curative intent treatment, 48 received surgery plus/minus post-operative radiotherapy. In these patients, 5-year disease-free survival, disease-specific survival, and overall survival was 50.7%, 68.7%, and 58.1%, respectively. Pathological nodal disease, involved margins, increasing VII zonal extent, and concurrent zone 2 V PNS significantly worsened outcomes. CONCLUSION: High rates of recurrent disease reflects the importance of adequate treatment of the primary. Surgery and post-operative radiotherapy remains the mainstay treatment. Outcomes are improved in early-stage disease and with clear surgical margins, reinforcing the need for prompt diagnosis and intervention.

Outcomes of Post-Operative Treatment with Concurrent Chemoradiotherapy (CRT) in High-Risk Resected Oral Cavity Squamous Cell Carcinoma (OCSCC): A Multi-Institutional Collaboration.

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

Malignancies requiring temporal bone resection: An Australian single-institution experience.

BACKGROUND: Malignancies in and around the temporal bone are aggressive and difficult to manage. In Queensland (Australia), where skin cancer rates are exceedingly high, tumours extending to the temporal bone from surrounding structures occur more commonly than primary cancers. Yet, a paucity of evidence exists as to their management and outcomes. This study aimed to review an Australian centre's experience of managing temporal and peritemporal bone malignancies, reporting on patient and tumour characteristics, treatment, and survival outcomes. METHODS: Retrospective analysis of patients with primary temporal bone cancer and cancers extending to the temporal bone managed by the Queensland Skull Base Unit (Princess Alexandra Hospital) between 2000 and 2019. RESULTS: A total of 222 patients were identified, of which 203 (91.4%) had cutaneous primaries, with 167 (75.2%) being squamous cell carcinoma (SCC). 73.9% presented with locoregionally recurrent or residual disease. Secondary tumours (92.8%) were 12 times more frequent than primary malignancies (7.2%), with the preauricular subsite the most common (45.5%). In the 201 patients (90.5%) who underwent curative intent surgery, 5-year overall survival, disease-free survival (DFS), and disease-specific survival was 46.6%, 52.2%, and 65.9%, respectively. The preauricular subsite (p = 0.004), melanoma (vs. SCC, p = 0.027), involved margins (p < 0.001), and pathologically involved nodes (p < 0.001) were associated with significantly worse DFS. CONCLUSION: This is one of the largest studies of temporal bone malignancy in the literature, comprised primarily of secondary cutaneous malignancies. Although clear differences in epidemiological characteristics exist around the world, survival remains poor. Treatment should focus on achieving a clear margin of resection to optimize outcomes.

Indications and limits of postoperative radiotherapy for skin malignancies.

PURPOSE OF REVIEW: To provide a summary of the current evidence, with a focus on recent publications, pertaining to indications for postoperative radiation therapy for cutaneous squamous-cell carcinoma (cSCC), basal-cell carcinoma, Merkel-cell carcinoma and melanoma of the head and neck. RECENT FINDINGS: Meta-analyses in cSCC and Merkel-cell carcinoma have shown an association between postoperative radiation therapy and overall survival. Prospective phase III data in head and neck cSCC has shown excellent locoregional control following surgery and postoperative radiation therapy. The addition of concurrent cytotoxic chemotherapy to postoperative radiation therapy has not improved outcomes in either of these two entities. Postoperative immune checkpoint inhibition or combined BRAF and MEK blockade in stage-III melanoma improves progression-free survival whereas postoperative radiation therapy does not. SUMMARY: Further improvement in outcomes with high-risk cSCC and Merkel-cell carcinoma might be achieved with concurrent or sequential immune checkpoint inhibition and postoperative radiation therapy. Postoperative radiation therapy for cutaneous melanoma should be reserved for patients in whom novel systemic therapies are not a treatment option.

A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

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.

A prospective study monitoring carer distress during (chemo)radiotherapy for head and neck cancer via an electronic platform.

INTRODUCTION: Research has shown that electronic platforms can assist data capture of patient-reported outcome measures (PROMs) to guide clinical care. In comparison, routine collection of carer-reported outcome measures (CROMs) to support the patient-carer dyad during cancer treatment has had limited attention. The current study utilised a novel electronic CROM (eCROM) system, ScreenIT Carer, to monitor the prevalence and nature of distress in carers of patients undergoing (chemo)radiotherapy ((C)RT) for head/neck cancer (HNC), and explore factors associated with carer distress. METHODS: Carers completed ScreenIT Carer weekly when attending patients' (C)RT treatment sessions from planning to 2 weeks post-treatment. ScreenIT Carer included the Distress Thermometer (DT) and Problem List, and a purpose-built Mealtime-Specific DT and Problem list. Data were first examined descriptively, then associations between demographic/treatment-related factors and distress severity were analysed using mixed-effects general linear modelling. RESULTS: 135 carers provided 434 ScreenIT Carer entries during the study period (mean entries = three/carer; yielding average adherence rate of 41% (range 11-100%)). A high prevalence of general (59%) and mealtime-specific distress (46%) was reported by carers. Nature of distress was multifactorial, with emotional problems and the patients' physical condition/symptoms common contributing factors. Based on multivariate analysis, tumour site, geographical location of residence and time during (C)RT when ScreenIT Carer was completed were significant predictors of carer distress severity. CONCLUSIONS: Carer distress is prevalent and multifactorial during (C)RT. This study highlights the feasibility of utilising eCROM platforms such as ScreenIT Carer, to monitor carer wellbeing and guide supportive care services as part of a holistic care pathway.

Number of nodal metastases and the American Joint Committee on cancer staging of head and neck cutaneous squamous cell carcinoma: A multicenter study.

OBJECTIVES: We aimed to determine if the number of nodal metastases is an independent predictor of survival in HNcSCC, whether it provides additional prognostic information to the AJCC N and TNM stage and identify optimal cut-points for risk stratification. MATERIALS AND METHODS: Retrospective multi-institutional cohort study of patients with parotid and/or cervical nodal metastases from HNcSCC treated with curative intent by surgery ±â€¯adjuvant therapy. The impact of number of nodal metastases on disease-specific and overall survival was assessed using multivariate Cox regression. Optimal cut-points for prognostic discrimination modelled using the AIC, BIC, C-index and PVE. RESULTS: The study cohort included 1128 patients, with 962 (85.3%) males, median age of 72.9 years (range: 18-100 years) and median follow-up 3.4 years. Adjuvant radiotherapy was administered to 946 (83.9%) patients. Based on objective measures of model performance, number of nodal metastases was classified as 1-2 (N = 816), 3-4 (N = 162) and ≥5 (N = 150) nodes. In multivariate analyses, the risk of disease-specific mortality progressively increased with 3-4 nodes (HR, 1.58; 95% CI: 1.03-2.42; p = 0.036) and ≥5 nodes (HR, 2.91; 95% CI: 1.99-4.25; p < 0.001) with similar results for all-cause mortality. This simple categorical variable provided superior prognostic information to the TNM stage. CONCLUSION: Increasing number of nodal metastases is an independent predictor of mortality in HNcSCC, with categorization as 1-2, 3-4 and ≥5 nodes optimizing risk stratification and providing superior prognostic information to TNM stage. These findings may aid in the development of future staging systems as well as identification of high-risk patients in clinical trials.

Dysregulation of Stemness Pathways in HPV Mediated Cervical Malignant Transformation Identifies Potential Oncotherapy Targets.

Human papillomavirus (HPV) infection is associated with a range of malignancies that affect anogenital and oropharyngeal sites. α-HPVs dominantly infect basal epithelial cells of mucosal tissues, where they dysregulate cell division and local immunity. The cervix is one of the mucosal sites most susceptible to HPV infections. It consists of anatomically diverse regions, and the majority of cervical intraepithelial neoplasia and cancers arise within the cervical squamo-columnar junction where undifferentiated basal progenitor cells with stem cell properties are found. The cancer stem cell theory particularly associates tumorigenesis, invasion, dissemination, and metastasis with cancer cells exhibiting stem cell properties. In this perspective, we discuss evidence of a cervical cancer stem cell niche and explore the association of stemness related genes with 5-year survival using a publicly available transcriptomic dataset of a cervical cancer cohort. We report that poor prognosis in this cohort correlates with overexpression of a subset of stemness pathway genes, a majority of which regulate the central Focal Adhesion pathway, and are also found to be enriched in the HPV infection pathway. These observations support therapeutic targeting of stemness genes overexpressed by mucosal cells infected with high-risk HPVs.

Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

Head and Neck Cancer International Group (HNCIG) Consensus Guidelines for the Delivery of Postoperative Radiation Therapy in Complex Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN).

Radiation therapy (RT) consensus contouring guidelines in the postoperative setting for complex cutaneous squamous cell carcinoma of the head and neck have been developed by expert clinicians in the field of head and neck and dermato-oncology and members of the Head and Neck Cancer International Group to assist radiation oncologists involved in the management of this disease. These guidelines present a set of principles used to define postoperative RT volumes and corresponding minimum doses after resection of all macroscopic tumor with or without microscopic residual disease. It is anticipated they will promote the harmonization of postoperative RT globally and contribute to a reduction in treatment variation among clinicians, allowing for RT quality and outcomes assessment across institutions.

Prophylactic swallowing therapy for patients with head and neck cancer: A three-arm randomized parallel-group trial.

BACKGROUND: Intensive prophylactic swallowing therapy can mitigate dysphagia in patients with oropharyngeal (OP) SCC, however, presents service challenges. This trial investigated the clinical efficacy of three service models delivering prophylactic swallowing therapy during (chemo)radiotherapy ([C]RT). METHODS: Patients (n = 79) with OPSCC receiving (C)RT were were randomized to: (a) clinician-directed face-to-face therapy (n = 26); (b) telepractice therapy via "SwallowIT" (n = 26); or (c) patient self-directed therapy (n = 27). Swallowing, nutritional, and functional status were compared at baseline, 6-weeks, and 3-months post-(C)RT. Patients' perceptions/preferences for service-delivery were collated posttreatment. RESULTS: Service-delivery mode did not affect clinical outcomes, with no significant (P > .05) between-group differences or group-by-time interactions observed for swallowing, nutrition, or functional measures. Therapy adherence declined during (C)RT in all groups. SwallowIT and clinician-directed models were preferred by significantly (P = .002) more patients than patient-directed. CONCLUSIONS: SwallowIT provided clinically equivalent outcomes to traditional service models. SwallowIT and clinician-directed therapy were preferred by patients, likely due to higher levels of therapy support.

A prospective examination of mask anxiety during radiotherapy for head and neck cancer and patient perceptions of management strategies.

INTRODUCTION: Distress related to wearing an immobilisation mask for radiotherapy treatment (RT) is a common experience for the person undergoing RT for head and neck cancer (HNC). Described as 'mask anxiety', there is little known about the patterns of this distress through the course of the treatment or what strategies are being used by people to help alleviate mask anxiety. METHODS: The study used a prospective cohort design to examine the patterns of patient-reported mask anxiety during the course of RT, using a modified Distress Thermometer (DT) and a survey to explore strategies patients used to assist their mask anxiety. RESULTS: Thirty-five participants, who identified as experiencing mask anxiety, were followed throughout RT treatment. At baseline, females were more likely to experience higher mask anxiety (P = 0.03). Across the course of treatment, mask anxiety significantly (P < 0.001) reduced within the total cohort. In 72% of participants, the level of initial distress was found to reduce over time. Only 22% experienced mask anxiety that remained constant. Few (6%) experienced an increase in mask anxiety across the course of RT. Participants reported relying on intervention from health professionals, self-taught strategies, music, visualisation and medication to manage their mask anxiety. CONCLUSIONS: Due to its high prevalence and variable patterns over time, it is recommended that routine screening for mask anxiety be implemented as standard care throughout the course of RT for HNC. Multiple, diverse strategies are being used by patients and studies are needed to develop effective interventions for managing mask anxiety.

An Ex Vivo Human Tumor Assay Shows Distinct Patterns of EGFR Trafficking in Squamous Cell Carcinoma Correlating to Therapeutic Outcomes.

EGFR overexpression is associated with squamous cell carcinoma development. Altered endocytosis and polarization of receptor tyrosine kinases, including EGFR, affect migration and invasion in three-dimensional culture. These studies have been completed via genetic sequencing, cell line, or three-dimensional in vitro and in vivo murine models. Here, we describe an imaging method that allows ex vivo examination of ligand-induced endocytosis of EGFR in non-dissociated human tumors. We analyzed sets of tumor samples from advanced cutaneous squamous cell carcinoma and head and neck squamous cell carcinoma, actinic keratosis, intraepidermal carcinoma, and cutaneous squamous cell carcinoma. We show that EGFR endocytosis is dysregulated in advanced SCC and correlates with anti-EGFR monoclonal antibody therapy outcomes. In actinic keratosis, intraepidermal carcinoma, and well-differentiated cutaneous squamous cell carcinoma, different patterns of epidermal growth factor ligand uptake and binding were observed at the leading edge of different dysplastic lesions, suggesting that these differences in EGFR endocytosis might influence the metastatic potential of dysplastic squamous epithelium. These studies in live ex vivo human tumors confirm that endocytosis dysregulation is a physiological event in human tumors and has therapeutic implications.

Economic Analysis of a Three-Arm RCT Exploring the Delivery of Intensive, Prophylactic Swallowing Therapy to Patients with Head and Neck Cancer During (Chemo)Radiotherapy.

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.

Treating Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Unsuitable to Receive Cisplatin-Based Therapy.

Concurrent chemoradiotherapy with high-dose cisplatin (100 mg/m2 every 3 weeks) is the preferred regimen with curative intent for patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). This treatment is associated with acute and late toxicities, including myelosuppression, severe nausea/vomiting, irreversible renal failure, hearing loss, and neurotoxicity. Because of cisplatin's safety profile, treatment adherence to high-dose cisplatin can be suboptimal. Patients commonly receive less than the total cumulative target dose of 300 mg/m2 or the minimum recommended dose of 200 mg/m2, which can have a negative impact on locoregional control and survival. Alternatively, cetuximab plus radiotherapy may be most suitable for patients at high risk of non-adherence to high-dose cisplatin. We discuss the baseline characteristics dictating the unsuitability/borderline unsuitability of cisplatin and the available alternative evidence-based treatment regimens for patients with LA SCCHN. We non-systematically reviewed published phase II and III trials and retrospective analyses of high-dose cisplatin-based chemoradiation in LA SCCHN conducted between 1987 and 2018, focusing on recent key phase III studies. We defined the baseline characteristics and associated prescreening tests to determine unsuitability and borderline unsuitability for high-dose cisplatin in combination with radiotherapy in patients with LA SCCHN. Patients with any pre-existing comorbidities that may be exacerbated by high-dose cisplatin treatment can be redirected to a non-cisplatin-based option to minimize the risk of treatment non-adherence. High-dose cisplatin plus radiotherapy remains the preferred treatment for fit patients with unresected LA SCCHN; patients who are unsuitable or borderline unsuitable for high-dose cisplatin could be identified using available tests for potential comorbidities and should be offered alternative treatments, such as cetuximab plus radiotherapy.

Exploring the prevalence and experience of mask anxiety for the person with head and neck cancer undergoing radiotherapy.

INTRODUCTION: While use of a thermoplastic mask during radiotherapy (RT) treatment for head and neck cancer (HNC) is an essential component of safe patient care, there is little understanding of the extent to which this evokes anxiety (i.e. "mask anxiety") for the person undergoing treatment. METHODS: A mixed method, convergent design was used to examine the prevalence and experience of mask anxiety using two clinical cohorts. In phase one, a cohort of 100 patients undergoing RT for HNC were assessed for self-perceived mask anxiety using a modified distress thermometer screening tool. In phase two, a separate cohort of 20 patients who identified as having mask anxiety participated in individual interpretative descriptive interviews to explore the nature of their experience. RESULTS: In phase one, 26% of participants self-identified as being anxious about the use of a thermoplastic mask. In phase two thematic analysis of the interviews revealed two over-arching themes relating to the person's experience of mask anxiety: contributors to the mask anxiety (vulnerability, response to experience and expectations); and how the person was going to manage the mask anxiety during treatment (strategies and mindset). CONCLUSIONS: Mask anxiety impacted a quarter of participants undergoing radiotherapy for HNC. In line with the themes elicited from the participants, implementation of routine screening to ensure early identification, and patient education to assist preparation for wearing the mask during RT are strategies that could improve current management of mask anxiety.