G-8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy

Background: Evidence-based guidelines concerning the older head and neck cancer (HNCA) patient are lacking. Accurate patient selection for optimal care management is therefore challenging. We examined if geriatric assessment is indicative of long-term health-related quality of life (HRQOL) and overall survival in this unique population. Methods: All HNCA patients, aged >= 65 years, eligible for curative radio(chemo) therapy were evaluated with the Geriatric-8 (G-8) questionnaire and a comprehensive geriatric assessment (CGA). Euroqol-5 dimensions (EQ-5D) and survival were collected until 36 months post treatment start. Repeated measures ANOVA was applied to analyse HRQOL evolution in 'fit' and 'vulnerable' patients, defined by G-8. Kaplan-Meier curves and cox proportional hazard analysis were established for determination of the prognostic value of geriatric assessments. Quality-adjusted survival was calculated in both patient subgroups. Results: One hundred patients were recruited. Seventy-two percent of patients were considered vulnerable according to CGA (>= 2 abnormal tests). Fit patients maintained a relatively acceptable long-term HRQOL, whilst vulnerable patients showed significantly lower median health states. The difference remained apparent at 36 months. Vulnerability, as classified by G-8 or CGA, came forward as independent predictor for lower EQ-5D index scores. After consideration of confounders, a significantly lower survival was observed in patients defined vulnerable according to G-8, compared to fit patients. A similar trend was seen based on CGA. Calculation of quality-adjusted survival showed significantly less remaining life months in perfect health in vulnerable patients, compared to fit ones. Conclusions: G-8 is indicative of quality-adjusted survival, and should be considered at time of treatment decisions for the older HNCA patient

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service

Background: Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. Methods: Over a 6-year period (2008–2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address ‘ad hoc’ pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. Results: A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. Conclusion: Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research

Serial comprehensive geriatric evaluation in older head and neck cancer patients undergoing radiotherapy

Downregulating transcription of the oncogene <i>c-MYC</i> is a feasible strategy for cancer therapy. Stabilization of the G-quadruplex structure present in the <i>c-MYC</i> promoter can suppress <i>c-MYC</i> transcription. Thus, far, several ligands targeting this structure have been developed. However, most have shown no selectivity for the <i>c-MYC</i> G-quadruplex over other G-quadruplexes, leading to uncertain side effects. In this study, through structural modification of aryl-substituted imidazole/carbazole conjugates, a brand-new, four-leaf clover-like ligand called <b>IZCZ-3</b> was found to preferentially bind and stabilize the <i>c-MYC</i> G-quadruplex. Further intracellular studies indicated that <b>IZCZ-3</b> provoked cell cycle arrest and apoptosis and thus inhibited cell growth, primarily by blocking <i>c-MYC</i> transcription through specific targeting of the promoter G-quadruplex structure. Notably, <b>IZCZ-3</b> effectively suppressed tumor growth in a mouse xenograft model. Accordingly, this work provides an encouraging example of a selective small molecule that can target one particular G-quadruplex structure, and the selective ligand might serve as an excellent anticancer agent

Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial

Background: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. Methods: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. Results: Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs −5%) and n-6 GLA (42% vs −20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs −1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. Conclusions: Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. Trial registration: ClinicalTrials.gov Identifier NCT01596933

Omega-3 fatty acids : physiology, biological sources and potential applications in supportive cancer care

The impact of the Western diet on chronic diseases, such as cancer, has been well recognized. Dietary saturated and trans fatty acids have been found to play a negative role in obesity, heart disease, diabetes and cancer, while the beneficial health effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) have become widely accepted. Despite the current knowledge, n-3 PUFA intake is still under recommended daily intake levels in Europe. As wild fish, currently still the major source of n-3 PUFA, are facing a decline, alternative sources such as marine and plant (both natural and transgenic) sources are being explored. In this review we aim to provide an overview of the current biological sources of n-3 PUFAs, their part in normal physiology, as well as their emerging application in supportive cancer care, and more specifically in cancer cachexia, therapy-related neurocognitive dysfunction and distress. In addition, we provide a brief summary of currently ongoing clinical trials examining potential beneficial effects of n-3 PUFAs in reducing cancer(therapy)-related side effects, and describe future research directions