A review of unplanned admissions in head and neck cancer patients undergoing oncological treatment.

AIM: Non-surgical treatment for head and neck cancer (HNC) often results in severe toxicities, which are detrimental to a patient's health and quality of life. There is limited published UK data on unplanned hospital admissions and reasons associated with admission. We aim to identify frequencies and reasons for unplanned hospital admissions, highlighting those patient groups who are most vulnerable. METHODS: A retrospective study of unplanned hospital admissions of HNC patients receiving non-surgical treatment was completed. An inpatient admission was defined as ≥ 1 night spent in the hospital. To test potential demographic and treatment predictors of inpatient admission, a multiple regression model was constructed using the endpoint measure (unplanned admission), as the dependent variable. RESULTS: A cohort of 216 patients was identified over a 7-month period, and 38 of these patients (17%) required an unplanned admission. Treatment type was the only statistically significant predictor of in-patient admission. The majority of admissions were patients receiving chemoradiotherapy (CRT) (58%) with predominant reasons for admission being nausea and vomiting (25.5%) and decreased oral intake/dehydration (30%). Of the patients admitted, 12 had a prophylactic PEG placed pre-treatment, and 18 of 26 admitted without prophylactic PEG required nasogastric tube feeding during their admission. DISCUSSION: Almost one-fifth of HNC patients over this time period required hospital admission; the majority of which can be attributed to treatment toxicities when receiving CRT. This is concurrent with other studies which review the impact of radiotherapy versus CRT. Increased support and monitoring, particularly focused on nutrition, are required for patients with HNC who receive CRT. KEY MESSAGE: This article describes a retrospective review of a patient undergoing non-surgical treatment for head and neck cancer. These patients frequently require unplanned hospital admission. The results indicate that patients undergoing (chemo)radiotherapy are most vulnerable to deterioration and additional support focused on nutrition for these patients is indicated.

Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach.

BACKGROUND: TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients. METHODS: HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV- patients was compared to p16 status. RESULTS: TNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV- (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16- patients (35%). Cancer stage was reduced in 95% of p16+/HPV- patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37-5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria. CONCLUSION: Given the significantly poorer survival of p16+/HPV- OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.

A protocol for the longitudinal investigation of cancer related fatigue in head and neck cancer with an emphasis on the role of physical activity.

BACKGROUND AND AIM: Cancer related fatigue significantly impairs the ability to undertake sustained physical activity across the domains of daily living, work and recreation. The purpose of this study is to monitor cancer related fatigue and the factors affected or caused by it for 12 months in head and neck cancer patients following their diagnosis. Their perceptions of how fatigue might affect their activity levels in addition to identifying avenues to improve engagement with physical activity will be also explored. METHODS: A single centre longitudinal mixed-methods study will be conducted. Forty head and neck cancer patients will be recruited over 6 months following the confirmation of their treatment plan, after which fatigue and physical activity will be assessed at four time points over 12 months. Additionally, other factors which influence fatigue such as body composition, blood counts, systemic inflammation levels, haemoglobin concentration, thyroid function, sleep quality, cardiorespiratory fitness and upper and lower extremity strength will be measured to understand how the multifactorial problem of fatigue may evolve over time and influence physical activity levels. Semi-structured interviews will be conducted after treatment completion and at end of twelve months which will analyse the participants fatigue experiences, understand how their perceived fatigue may have impacted physical activity and report the factors which may improve engagement with physical activity during cancer. Quantitative data will be analysed and reported using standard descriptive statistics and post-hoc pairwise comparisons. The changes in outcome measures across time will be analysed using the MIXED procedure in SPSS software. Statistical significance will be accepted at p<0.05. Qualitative data will be analysed using the Interpretative Phenomenological Approach using the NVivo software. DISCUSSION: The results from this study may help inform the planning and delivery of appropriately timed interventions for the management of cancer related fatigue.

ACTivity as medicine In Oncology for Head and Neck (ACTIOHN): Protocol for a feasibility study investigating a patient-centred approach to exercise for people with head and neck cancer.

BACKGROUND AND AIM: Attempts at personalisation of exercise programmes in head and neck cancer (HaNC) have been limited. The main aim of the present study is to investigate the feasibility and acceptability of introducing a remotely delivered, fully personalised, collaborative, and flexible approach to prescribing and delivering exercise programmes into the HaNC usual care pathway. METHODS: This is a single arm, feasibility study. Seventy patients diagnosed with HaNC will be recruited from two regional HaNC centres in the United Kingdom. Patients will undertake an 8-week exercise programme designed and delivered by cancer exercise specialists. The exercise programme will start any time between the time of diagnosis and up to 8 weeks after completing treatment, depending on patient preference. The content of the exercise programme will be primarily based on patient needs, preferences, and goals, but guided by current physical activity guidelines for people with cancer. The primary outcome measure is retention to the study. Secondary quantitative outcomes are uptake to the exercise programme, different measures of exercise adherence, pre- and post-intervention assessments of fatigue (Multidimensional Fatigue Symptom Inventory-Short Form), quality of life (SF-36), physical activity levels (International Physical Activity Questionnaire-Short Form), and various components of physical fitness. The outcomes of the nested qualitative study are acceptability and feasibility of the intervention evaluated via interviews with patients, health care professionals, and the cancer exercise specialists. Intervention and participant fidelity will be determined using checklists and scrutiny of each patient's logbook and the cancer exercise specialists' meeting notes. Analysis of quantitative data will be via standard summary statistics. Qualitative data will be analysed using thematic analysis. EXPECTED RESULTS: This feasibility study will inform the design and conduct of a future randomised controlled trial. Success will be defined according to a traffic light system for identifying the appropriateness of progression to a randomised controlled trial. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry (ISRCTN82505455).

Genetic variants associated with mandibular osteoradionecrosis following radiotherapy for head and neck malignancy.

BACKGROUND/AIM: Utilising radiotherapy in the management of head and neck cancer (HNC) often results in long term toxicities. Mandibular osteoradionecrosis (ORN) represents a late toxicity associated with significant morbidity. We aim to identify a panel of common genetic variants which can predict ORN to aid development of personalised radiotherapy protocols. METHOD: Single nucleotide polymorphism (SNP) arrays were applied to DNA samples from patients who had prior HNC radiotherapy and minimum two years follow-up. A case cohort of mandibular ORN was compared to a control group of participants recruited to CRUK HOPON clinical trial. Relevant clinical parameters influencing ORN risk (e.g. smoking/alcohol) were collected. Significant associations from array data were internally validated using polymerase chain reaction (PCR) and pyrosequencing. RESULTS: Following inclusion of 141 patients in the analysis (52 cases, 89 controls), a model predictive for ORN was developed; after controlling for alcohol consumption, smoking, and age, 4053 SNPs were identified as significant. This was reduced to a representative model of 18 SNPs achieving 92% accuracy. Following internal technical validation, a six SNP model (rs34798038, rs6011731, rs2348569, rs530752, rs7477958, rs1415848) was retained within multivariate regression analysis (ROC AUC 0.859). Of these, four SNPs (rs34798038 (A/G) (p 0.006), rs6011731 (C/T) (p 0.018), rs530752 (A/G) (p 0.046) and rs2348569 (G/G) (p 0.005)) were significantly associated with the absence of ORN. CONCLUSION: This is the first genome wide association study in HNC using ORN as the endpoint and offers new insight into ORN pathogenesis. Subject to validation, these variants may guide patient selection for personalised radiotherapy strategies.

Combining immunotherapy and radiotherapy in lung cancer.

Immunotherapy has become standard of care in advanced non-small cell lung cancer (NSCLC) in a number of settings. Radiotherapy remains an important and potentially curative treatment for localized and locally advanced NSCLC not amenable to surgery. While the principal cytotoxic effect of ionizing radiation is via DNA damage, the effect on tumour microenvironment, promoting dendritic cell presentation of tumour-derived antigens to T cells stimulating the host adaptive immune system to mount an immune response against tumours cells, has become of particular interest when combining immunomodulating agents with radiation. The 'abscopal effect' of radiation where non-irradiated metastatic lesions may respond to radiation may be immune-mediated, via radiation primed anti-tumour T cells. Immune priming by radiation offers the potential for increasing the efficacy of immunotherapy and this is subject to on-going clinical trials underpinned by immunological bioassays. Increasing understanding of the interaction between tumour, radiation and immune cells at a molecular level provides a further opportunity for intervention to enhance the potential synergy between radiation and immunotherapy. Applying the potential efficacy of combination therapy to clinical practice requires caution particularly to ensure the safety of the two treatment modalities in early phase clinical trials, many of which are currently underway. We review the biological basis for combining radiation and immunotherapy and examine the existing pre-clinical and clinical evidence and the challenges posed by the new combination of treatments.

Synthesis and SAR comparison of regioisomeric aryl naphthyridines as potent mGlu5 receptor antagonists.

We describe three novel regioisomeric series of aryl naphthyridine analogs, which are potent antagonists of the Class III GPCR mGlu5 receptor. The synthesis and in vitro and in vivo pharmacological activities of these analogs are discussed.

Synthesis and SAR of 2-aryl pyrido[2,3-d]pyrimidines as potent mGlu5 receptor antagonists.

A novel series of potent 2-aryl pyrido[2,3-d]pyrimidine mGlu5 receptor antagonists are described. The synthesis and pharmacological activities of these analogs are discussed.