Adolescents and young adults' (AYA) views on their cancer knowledge prior to diagnosis: Findings from a qualitative study involving AYA receiving cancer care.

BACKGROUND: Cancer is rare amongst adolescents and young adults (AYA). Previous research has reported (healthy) AYA's knowledge of risk factors and symptoms as limited, with this potentially leading to delays in help-seeking and diagnosis. OBJECTIVES: We explored AYA's views on their cancer knowledge prior to diagnosis and if/how they perceived this as having affected their experiences of diagnosis and care. METHODS: We interviewed 18 AYA diagnosed with cancer (aged 16-24 years). Interviews were recorded and transcribed verbatim. We undertook qualitative descriptive analysis, exploring both a priori topics and emergent themes, including cancer knowledge prior to diagnosis. RESULTS: Adolescents and young adults characterized their knowledge of cancer and treatment prior to diagnosis and treatment initiation as limited and superficial. AYA perceived gaps in their knowledge as having profound consequences throughout their cancer journey. These included: hindering recognition of symptoms, thereby delaying help-seeking; impeding understanding of the significance of tests and referrals; amplifying uncertainty on diagnosis; and affording poor preparation for the harsh realities of treatment. CONCLUSIONS: Adolescents and young adults perceived their limited cancer knowledge prior to diagnosis as affecting experiences of diagnosis and initial/front-line care. These findings prompt consideration of whether, when and how, AYA's knowledge of cancer might be improved. Two broad approaches are discussed: universal education on AYA cancer and/or health; and targeted education (enhanced information and counselling) at and after diagnosis. PATIENT OR PUBLIC CONTRIBUTION: Our work was informed throughout by discussions with an advisory group, whose membership included AYA treated for cancer.

Strategies for improving access to clinical trials by teenagers and young adults with cancer: A qualitative study of health professionals' views.

OBJECTIVE: Few teenagers and young adults (TYA) with cancer participate in clinical trials. Lack of opportunity has been identified as a major barrier. We canvassed health professionals' views on how TYA's access to trials might be improved. METHODS: We interviewed 35 professionals with responsibility for delivering or facilitating cancer care and/or clinical trials. We analysed data using a qualitative descriptive approach. RESULTS: Interviewees viewed improving TYA's access to trials as challenging, but possible. They reframed the problem as one of rare disease and surmised that modifying the organisation, administration and resourcing of research (and care) might expand opportunities for both TYA and other patients with low volume conditions. Proposals coalesced around four themes: consolidating the pool of patients; streamlining bureaucratic requirements; investing in the research workforce; and promoting pragmatism in trial design. CONCLUSION: Accounts suggest there is scope to improve access to trials by TYA with cancer and other patients with rare diseases. Though re-configuring care, research and resource frameworks would present substantial challenges, doing nothing would also have costs. Change will require the support of a range of stakeholders, and agreement as to the best way forward. Further work, such as priority setting exercises, may be necessary to reach a consensus.

The challenges of making informed decisions about treatment and trial participation following a cancer diagnosis: a qualitative study involving adolescents and young adults with cancer and their caregivers.

BACKGROUND: Limited attention has been paid to adolescents and young adults' (AYA's) experiences in the aftermath of a cancer diagnosis, despite this being a time when potentially life-changing decisions are made. We explored AYA's and caregivers' experiences of, and views about, making treatment and trial participation decisions following a cancer diagnosis, in order to understand, and help facilitate, informed treatment decision-making in this age group. METHODS: Interviews were undertaken with 18 AYA diagnosed, or re-diagnosed, with cancer when aged 16-24 years, and 15 parents/caregivers. Analysis focused on the identification and description of explanatory themes. RESULTS: Most AYA described being extremely unwell by the time of diagnosis and, consequently, experiencing difficulties processing the news. Distress and acceleration in clinical activity following diagnosis could further impede the absorption of treatment-relevant information. After referral to a specialist cancer unit, many AYA described quickly transitioning to a calm and pragmatic mind-set, and wanting to commence treatment at the earliest opportunity. Most reported seeing information about short-term side-effects of treatment as having limited relevance to their recovery-focused outlook at that time. AYA seldom indicated wanting to make choices about front-line treatment, with most preferring to defer decisions to health professionals. Even when charged with decisions about trial participation, AYA reported welcoming a strong health professional steer. Parents/caregivers attempted to compensate for AYA's limited engagement with treatment-relevant information. However, in seeking to ensure AYA received the best treatment, these individuals had conflicting priorities and information needs. CONCLUSION: Our study highlights the challenging context in which AYA are confronted with decisions about front-line treatment, and reveals how their responses make it hard to ensure their decisions are fully informed. It raises questions about the direct value, to AYA, of approaches that aim to promote decision-making by improving understanding and recall of information, though such approaches may be of value to caregivers. In seeking to improve information-giving and involvement in treatment-related decision-making at diagnosis, care should be taken not to delegitimize the preference of many AYA for a directive approach from trusted clinicians.

Circulating tumour DNA sequencing to determine therapeutic response and identify tumour heterogeneity in patients with paediatric solid tumours.

OBJECTIVE: Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind. METHODS: To address this, we have developed a clinically relevant (67 gene) NGS capture panel and accompanying workflow that enables sensitive and reliable detection of low-frequency genetic variants in cell-free DNA (cfDNA) from children with solid tumours. We combined gene panel sequencing with low pass whole-genome sequencing of the same library to inform on genome-wide copy number changes in the blood. RESULTS: Analytical validity was evaluated using control materials, and the method was found to be highly sensitive (0.96 for SNVs and 0.97 for INDEL), specific (0.82 for SNVs and 0.978 for INDEL), repeatable (>0.93 [95% CI: 0.89-0.95]) and reproducible (>0.87 [95% CI: 0.87-0.95]). Potential for clinical application was demonstrated in 39 childhood cancer patients with a spectrum of solid tumours in which the single nucleotide variants expected from tumour sequencing were detected in cfDNA in 94.4% (17/18) of cases with active extracranial disease. In 13 patients, where serial samples were available, we show a close correlation between events detected in cfDNA and treatment response, demonstrate that cfDNA analysis could be a useful tool to monitor disease progression, and show cfDNA sequencing has the potential to identify targetable variants that were not detected in tumour samples. CONCLUSIONS: This is the first pan-cancer DNA sequencing panel that we know to be optimised for cfDNA in children for blood-based molecular diagnostics in paediatric solid tumours.

Clinician-researchers and custodians of scarce resources: a qualitative study of health professionals' views on barriers to the involvement of teenagers and young adults in cancer trials.

BACKGROUND: Equipoise and role conflict have been previously identified as important factors in professionals' engagement with trials, inducing behaviours which can impact on recruitment. We explored these phenomena as potential explanations for the low levels of involvement of teenagers and young adults (TYA) with cancer in clinical trials in oncology. METHODS: We report findings from interviews with 30 purposively sampled direct-care professionals involved in delivering cancer care and/or facilitating clinical trials in Scotland. We undertook qualitative descriptive analysis, focussed on identifying key issues and themes. RESULTS: Interviewees largely identified as clinician-researchers and portrayed oncology as a specialty in which research was integral to care. They saw their primary responsibility as ensuring patients received the best treatment, but asserted that, in general, trials provided a vehicle for optimal care. Role conflict in its traditional form was rarely evident; however, other tensions were manifest. Professionals found the significant time costs of delivering trials difficult to reconcile with the increasing pressures on clinical services. They felt a responsibility to make prudent choices about the trials with which to engage. Guided by utilitarian principles, these choices were oriented towards benefiting the largest number of patients. This favoured trials in high volume diseases; as TYA tend to have rarer forms of cancer, professionals' support for-and TYA's access to-relevant trials was, by default, more limited. CONCLUSIONS: Neither lack of individual equipoise nor experiences of traditional forms of role conflict accounted for the low levels of involvement of TYA with cancer in clinical trials. However, prominent tensions around the management of scarce resources provided an alternative explanation for TYA's limited access to cancer trials. The prevailing approach to decision-making about whether and which trials to support was recognised as contributing to inequalities in access and care. Professionals' choices, however, were made in the context of scarcity, and structured by incentives and sanctions understood by them as signalling governmental priorities. A franker discussion of the extent and distribution of the costs and benefits of trials work is needed, for change to be achieved.