Title: The use of existing healthcare datasets to determine whether the survival of teenagers and young adults with cancer is associated with the dose and intensity of chemotherapy that they receive.
Funder: Department of Health and Social Care

Abstract: Background Cancer is the most common disease related cause of death in the teenage and young adult (TYA) population. Over the last 20 years the unique needs of TYAs with cancer have been recognised and it has become a growing field of research. Despite this, survival rates still lag behind those of children and older adults with the same cancers. Improving the survival of TYAs is therefore an important clinical and societal need due to the loss of social structure and productivity that is associated with poor outcomes in these individuals. The reason that TYAs have worse outcomes is multifactorial but it is the variation in treatment protocols which this study will address. Dose matters in cancer chemotherapy if we are to cure the cancer. For many cancers common in TYAs there is the evidence that maintaining dose intensity improves outcomes. This can be problematic as the more intense regimes carry greater toxicity. In TYAs this is further complicated by the physiological changes that occur during puberty influencing the efficacy of drugs. The literature surrounding dose intensity in the TYA population is limited, often reliant on retrospective clinical trial data with limited relation to clinical practice. This study will use existing health data and novel data linkage methods to investigate the impact of dose intensity, and the toxicity caused, using actual doses administered in routine NHS practice. Research questions This study will address: Whether the dose intensity of systemic anticancer agents received by TYA cancer patients is associated with survival outcome. What factors aid/ prevent TYA patients receiving the optimum dose intensity of systemic anticancer agent. Whether existing healthcare datasets can be used to answer these questions.Methods Existing datasets spanning regional, national and international sources will be identified, requested, linked, cleaned and analysed.Descriptive statistics will be used to look at how dose intensity of each chemotherapy drug delivered differs according to the following confounding variables; tumour type, stage at diagnosis, grade of tumour, age at diagnosis, gender, ethnicity, socioeconomic status, distance from treatment centre, previous treatment, grade of toxicity experienced and clinical trial participation. Linear regression will be used to assess the effect of each variable on the actual dose of chemotherapy delivered. Survival analysis will be performed using Cox-proportional hazards regression in conjunction with Kaplan-Meier curves. Causal inference modelling will enable identification of the causal relationships between variables so that confounding can be adequately controlled for. Anticipated impact and dissemination This research has the potential to improve survival outcomes and minimise side-effects for TYA patients receiving chemotherapy. Where dose matters for outcomes, identification of barriers to patients receiving optimal chemotherapy will help inform NHS interventions to optimise the treatment that patients receive.Dissemination will be through conference presentations, peer-reviewed journal articles and public engagement channels such as the annual University of Leeds Be Curious event and social media. Findings will be reported to commercial companies including Cis-Healthcare and the pharmaceutical industry who will be able to exploit the findings when designing clinical trials incorporating the TYA population.

Lay abstract: Background Teenagers and young adults (TYA), 13 to 24 year olds, have poorer survival outcomes than children and many older adults with the same type of cancer. Recent research suggests that one possible reason for this is that these patients are not receiving enough chemotherapy. This may be because optimal doses of chemotherapy are often high and can cause significant side effects resulting in a poor quality of life for the patient. Aim This study will use existing, routinely-collected NHS data and international clinical trial data to investigate whether the dose of chemotherapy that TYAs receive affects their length of life. It will also determine whether any factors exist which influence a patient's ability to receive the ideal amount of chemotherapy.Methods This study will analyse three different data sources, spanning local, national and international populations. The local population relates to the Yorkshire Specialist Register of Cancer in Children and Young People (YSRCCYP), a register of over 10,500 patients diagnosed with cancer in the region. Existing treatment records will be enhanced through a unique, secure link to hospital electronic prescribing systems, providing vital information on actual doses received and any changes to the original planned dosing schedule that were made. The results of any blood tests taken at around the time the chemotherapy was given will also be obtained and will provide an indication of the toxicity caused by the chemotherapy.The national data source will comprise the Systemic Anti-Cancer Therapy (SACT) dataset which collects chemotherapy prescribing data from all hospitals in England. This will be linked to data from the National Cancer Registry and Analysis Service (NCRAS) to create the first national TYA treatment dataset for all individuals treated with chemotherapy since data collection began in 2014. This dataset will provide bigger patient numbers, enabling analysis according to cancer subtypes and allowing comparisons between specialist and non-specialist treatment centres. It will also demonstrate the usefulness of this national dataset for health research. The third component of the study will use an international dataset derived from clinical trials, enabling a comparison to be made between outcomes for patients treated in clinical trials, compared with everyday practice. Inclusion criteriaPatients aged 12-29 years old across all tumour types who have received at least one dose of an anti-cancer agent. Inclusion in the clinical trials analysis will be determined by the trial entrance criteria. Patient and Public Involvement An online questionnaire was posted on social media networks locally and nationally through the charity CLIC Sargent, to obtain TYA patients' experiences of undergoing chemotherapy. This helped to identify factors for investigation. A research advisory group containing patient volunteers and representatives from the national useMydata group will help to interpret the analysis throughout the project and with ideas on disseminating the results. Distribution of Results The findings of this study have the potential to generate the evidence required to change the management of TYA cancer patients receiving chemotherapy. By identifying barriers to optimal delivery or patient groups at higher risk of chemotherapy side effects, care and outcomes can be improved. The usefulness of the different datasets examined will be discussed and areas for improvement highlighted. This will be relevant to healthcare professionals across a range of disciplines. Results will be disseminated via peer-reviewed journals and conference presentations, and communicated to patients and the public through charities, the media and public engagement events. The results will also be presented to drug companies to inform the development of clinical trials involving TYA patients. Dissemination to the companies who develop the chemotherapy electronic prescribing systems will build relationships to help facilitate their future use in research.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS