An exploratory assessment of the impact of a novel risk assessment test on breast cancer clinic waiting times and workflow: a discrete event simulation model.

BACKGROUND: Breast cancer clinics across the UK have long been struggling to cope with high demand. Novel risk prediction tools - such as the PinPoint test - could help to reduce unnecessary clinic referrals. Using early data on the expected accuracy of the test, we explore the potential impact of PinPoint on: (a) the percentage of patients meeting the two-week referral target, and (b) the number of clinic 'overspill' appointments generated (i.e. patients having to return to the clinic to complete their required investigations). METHODS: A simulation model was built to reflect the annual flow of patients through a single UK clinic. Due to current uncertainty around the exact impact of PinPoint testing on standard care, two primary scenarios were assessed. Scenario 1 assumed complete GP adherence to testing, with only non-referred cancerous cases returning for delayed referral. Scenario 2 assumed GPs would overrule 20% of low-risk results, and that 10% of non-referred non-cancerous cases would also return for delayed referral. A range of sensitivity analyses were conducted to explore the impact of key uncertainties on the model results. Service reconfiguration scenarios, removing individual weekly clinics from the clinic schedule, were also explored. RESULTS: Under standard care, 66.3% (95% CI: 66.0 to 66.5) of patients met the referral target, with 1,685 (1,648 to 1,722) overspill appointments. Under both PinPoint scenarios, > 98% of patients met the referral target, with overspill appointments reduced to between 727 (707 to 746) [Scenario 1] and 886 (861 to 911) [Scenario 2]. The reduced clinic demand was sufficient to allow removal of one weekly low-capacity clinic [N = 10], and the results were robust to sensitivity analyses. CONCLUSION: The findings from this early analysis indicate that risk prediction tools could have the potential to alleviate pressure on cancer clinics, and are expected to have increased utility in the wake of heightened pressures resulting from the COVID-19 pandemic. Further research is required to validate these findings with real world evidence; evaluate the broader clinical and economic impact of the test; and to determine outcomes and risks for patients deemed to be low-risk on the PinPoint test and therefore not initially referred.

Diagnosing myeloma in general practice: how might earlier diagnosis be achieved?

Smith et al describe the issues with the current diagnostic process for myeloma in general practice, explore the potential impact of the COVID-19 pandemic, and identify alternative strategies that may improve the early diagnosis. Around half of myeloma patients have three or more pre-referral consultations and around one-third are diagnosed through emergency presentation. Improving the timeliness of myeloma diagnosis is vital to improving patient outcomes, but is difficult to achieve because of complex, non-specific, and varied presentations. Improving GP education on the salient features of multiple myeloma presentation and the investigations required for diagnosis, alongside ensuring adequate safety netting for patients with persistent, unexplained symptoms, should be urgent priorities. Changes to general practice consultations following the COVID-19 pandemic have made myeloma diagnosis more difficult, and, over the longer term, research is required to develop intelligent and technological strategies that support physician decision making and reduce diagnostic delay.

Development and validation of multivariable machine learning algorithms to predict risk of cancer in symptomatic patients referred urgently from primary care: a diagnostic accuracy study.

OBJECTIVES: To develop and validate tests to assess the risk of any cancer for patients referred to the NHS Urgent Suspected Cancer (2-week wait, 2WW) clinical pathways. SETTING: Primary and secondary care, one participating regional centre. PARTICIPANTS: Retrospective analysis of data from 371 799 consecutive 2WW referrals in the Leeds region from 2011 to 2019. The development cohort was composed of 224 669 consecutive patients with an urgent suspected cancer referral in Leeds between January 2011 and December 2016. The diagnostic algorithms developed were then externally validated on a similar consecutive sample of 147 130 patients (between January 2017 and December 2019). All such patients over the age of 18 with a minimum set of blood counts and biochemistry measurements available were included in the cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: sensitivity, specificity, negative predictive value, positive predictive value, Receiver Operating Characteristic (ROC) curve Area Under Curve (AUC), calibration curves RESULTS: We present results for two clinical use-cases. In use-case 1, the algorithms identify 20% of patients who do not have cancer and may not need an urgent 2WW referral. In use-case 2, they identify 90% of cancer cases with a high probability of cancer that could be prioritised for review. CONCLUSIONS: Combining a panel of widely available blood markers produces effective blood tests for cancer for NHS 2WW patients. The tests are affordable, and can be deployed rapidly to any NHS pathology laboratory with no additional hardware requirements.

Acceptance and Commitment Therapy to support medication decision-making and quality of life in women with breast cancer: protocol for a pilot randomised controlled trial.

BACKGROUND: Adherence to adjuvant endocrine therapy is affected by medication side-effects and associated distress. Previous interventions focused on educating women to enhance adherence have proved minimally effective. We co-designed an Acceptance and Commitment Therapy (ACT) intervention to enhance medication decision-making and quality of life by targeting a broader range of factors, including side-effect management and psychological flexibility. This study aims to establish key trial parameters, assess the acceptability of the intervention and the extent to which it can be delivered with fidelity, and to demonstrate "proof of principle" regarding its efficacy on primary and process outcomes. METHODS: The ACTION intervention includes an individual 1:1 ACT session followed by three group sessions involving 8-10 women and two practitioner psychologists. Participants are also provided with access to a website containing evidence-based methods for self-managing side-effects. The ACT sessions were adapted during the COVID-19 pandemic to be remotely delivered via video conferencing software. To evaluate the feasibility and acceptability of this intervention, a multi-site, exploratory, two-arm, individually randomised external pilot trial with a nested qualitative study will be undertaken. Eighty women with early stage breast cancer prescribed adjuvant endocrine therapy will be randomised (1:1) to receive treatment as usual or treatment as usual plus the ACTION intervention. The planned future primary outcome is medication adherence assessed by the ASK-12 measure. Progression to a phase III RCT will be based on criteria related to recruitment and follow-up rates, acceptability to patients, competency and fidelity of delivery, and proof of principle for change in medication adherence. DISCUSSION: This external pilot trial will be used to ascertain the feasibility of undertaking a future phase III RCT to definitively evaluate an ACT-based intervention to support medication taking behaviour and quality of life in women with early stage breast cancer on adjuvant endocrine therapy. TRIAL REGISTRATION: ISRCTN: 12027752. Registered 24 December 2020, https://doi.org/10.1186/ISRCTN12027752.

Protocol for a feasibility study incorporating a randomised pilot trial with an embedded process evaluation and feasibility economic analysis of ThinkCancer!: a primary care intervention to expedite cancer diagnosis in Wales.

BACKGROUND: Compared to the rest of Europe, the UK has relatively poor cancer outcomes, with late diagnosis and a slow referral process being major contributors. General practitioners (GPs) are often faced with patients presenting with a multitude of non-specific symptoms that could be cancer. Safety netting can be used to manage diagnostic uncertainty by ensuring patients with vague symptoms are appropriately monitored, which is now even more crucial due to the ongoing COVID-19 pandemic and its major impact on cancer referrals. The ThinkCancer! workshop is an educational behaviour change intervention aimed at the whole general practice team, designed to improve primary care approaches to ensure timely diagnosis of cancer. The workshop will consist of teaching and awareness sessions, the appointment of a Safety Netting Champion and the development of a bespoke Safety Netting Plan and has been adapted so it can be delivered remotely. This study aims to assess the feasibility of the ThinkCancer! intervention for a future definitive randomised controlled trial. METHODS: The ThinkCancer! study is a randomised, multisite feasibility trial, with an embedded process evaluation and feasibility economic analysis. Twenty-three to 30 general practices will be recruited across Wales, randomised in a ratio of 2:1 of intervention versus control who will follow usual care. The workshop will be delivered by a GP educator and will be adapted iteratively throughout the trial period. Baseline practice characteristics will be collected via questionnaire. We will also collect primary care intervals (PCI), 2-week wait (2WW) referral rates, conversion rates and detection rates at baseline and 6 months post-randomisation. Participant feedback, researcher reflections and economic costings will be collected following each workshop. A process evaluation will assess implementation using an adapted Normalisation Measure Development (NoMAD) questionnaire and qualitative interviews. An economic feasibility analysis will inform a future economic evaluation. DISCUSSION: This study will allow us to test and further develop a novel evidenced-based complex intervention aimed at general practice teams to expedite the diagnosis of cancer in primary care. The results from this study will inform the future design of a full-scale definitive phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04823559 .

Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study.

OBJECTIVES: To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer. METHODS: We employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England. RESULTS: Declines in urgent referrals (median=-70.4%) and chemotherapy attendances (median=-41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=-44.5%) and chemotherapy attendances (median=-31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity. CONCLUSIONS: Dramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.