There is growing interest in the use of routinely collected electronic health records to enhance service delivery and facilitate clinical research. It should be possible to detect and measure patterns of care and use the data to monitor improvements but there are methodological and data quality challenges. Driven by the desire to model the impact of a patient self-test blood count monitoring service in patients on chemotherapy, we aimed to (i) establish reproducible methods of process-mining electronic health records, (ii) use the outputs derived to define and quantify patient pathways during chemotherapy, and (iii) to gather robust data which is structured to be able to inform a cost-effectiveness decision model of home monitoring of neutropenic status during chemotherapy. Electronic Health Records at a UK oncology centre were included if they had (i) a diagnosis of metastatic breast cancer and received adjuvant epirubicin and cyclosphosphamide chemotherapy or (ii) colorectal cancer and received palliative oxaliplatin and infusional 5-fluorouracil chemotherapy, and (iii) were first diagnosed with cancer between January 2004 and February 2013. Software and a Markov model were developed, producing a schematic of patient pathways during chemotherapy. Significant variance from the assumed care pathway was evident from the data. Of the 535 patients with breast cancer and 420 with colorectal cancer there were 474 and 329 pathway variants respectively. Only 27 (5%) and 26 (6%) completed the planned six cycles of chemotherapy without having unplanned hospital contact. Over the six cycles, 169 (31.6%) patients with breast cancer and 190 (45.2%) patients with colorectal cancer were admitted to hospital. The pathways of patients on chemotherapy are complex. An iterative approach to addressing semantic and data quality issues enabled the effective use of routinely collected patient records to produce accurate models of the real-life experiences of chemotherapy patients and generate clinically useful information. Very few patients experience the idealised patient pathway that is used to plan their care. A better understanding of real-life clinical pathways through process mining can contribute to care and data quality assurance, identifying unmet needs, facilitating quantification of innovation impact, communicating with stakeholders, and ultimately improving patient care and outcomes.

Purpose: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. Patients and Methods: Patients received either G+C (guadecitabine 30 mg/m² s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). Results: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. Conclusions: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.

A randomised phase III trial was conducted to assess the role of interferon-alpha (INFα) 2a as maintenance therapy following surgery and/or chemotherapy in patients with epithelial ovarian carcinoma. Patients were randomised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment. A total of 300 patients were randomised within the study between February 1990 and July 1997. No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival. We conclude that INF-α is not effective as a maintenance therapy in the management of women with ovarian cancer. The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains.

Objectives: To characterize treatment patterns and survival outcomes for patients with locally advanced or metastatic malignancy of the urothelial tract during a period immediately preceding the widespread use of immune checkpoint inhibitors in the UK. Patients and Methods: We retrospectively examined the electronic case notes of patients attending the Leeds Cancer Center, UK with locally advanced or metastatic urothelial carcinoma, receiving chemotherapy between January 2003 and March 2017. Patient characteristics, treatment patterns, and outcomes were collected. Summary and descriptive statistics were calculated for categorical and continuous variables as appropriate. The Kaplan–Meier method was used to estimate median survival and Cox regression proportional hazards model was used to explore relationships between clinical variables and outcome. Results: Two hundred and sixteen patients made up the study cohort, with a median age of 66 years (range: 35–83) and 72.7% being male. First-line treatment consisted of either a cisplatin- (44%) or carboplatin-based regimen (48%) in the majority of patients. Twenty seven percent of patients received a second-line of treatment (most commonly single-agent paclitaxel) following a first-line platinum containing regimen. Grade 4 neutropenia was observed in 19 and 27% of those treated with a first-line cisplatin- and carboplatin-based regimen, respectively. The median overall survival (mOS) of the study cohort was estimated to be 16.2 months (IQR: 10.6–28.3 months). Receipt by patients of cisplatin-based chemotherapy was associated with a longer mOS and this association persisted when survival analysis was adjusted for age, sex, performance status and presence of distant metastases. Conclusions: This study provides a useful benchmark for outcomes achieved in a real-world setting for patients with locally advanced or metastatic UC treated with chemotherapy in the immediate pre-immunotherapy era.

Background: Cancer is treated using multiple modalities (e.g. surgery, radiotherapy and systemic therapies) and is frequently associated with adverse events that affect treatment delivery and quality of life. Regular adverse event reporting could improve care and safety through timely detection and management. Information technology provides a feasible monitoring model, but applied research is needed. This research programme developed and evaluated an electronic system, called eRAPID, for cancer patients to remotely self-report adverse events. Objectives: The objectives were to address the following research questions: is it feasible to collect adverse event data from patients’ homes and in clinics during cancer treatment? Can eRAPID be implemented in different hospitals and treatment settings? Will oncology health-care professionals review eRAPID reports for decision-making? When added to usual care, will the eRAPID intervention (i.e. self-reporting with tailored advice) lead to clinical benefits (e.g. better adverse event control, improved patient safety and experiences)? Will eRAPID be cost-effective? Design: Five mixed-methods work packages were conducted, incorporating co-design with patients and health-care professionals: work package 1 – development and implementation of the electronic platform across hospital centres; work package 2 – development of patient-reported adverse event items and advice (systematic and scoping reviews, patient interviews, Delphi exercise); work package 3 – mapping health-care professionals and care pathways; work package 4 – feasibility pilot studies to assess patient and clinician acceptability; and work package 5 – a single-centre randomised controlled trial of systemic treatment with a full health economic assessment. Setting: The setting was three UK cancer centres (in Leeds, Manchester and Bristol). Participants: The intervention was developed and evaluated with patients and clinicians. The systemic randomised controlled trial included 508 participants who were starting treatment for breast, colorectal or gynaecological cancer and 55 health-care professionals. The radiotherapy feasibility pilot recruited 167 patients undergoing treatment for pelvic cancers. The surgical feasibility pilot included 40 gastrointestinal cancer patients. Intervention: eRAPID is an online system that allows patients to complete adverse event/symptom reports from home or hospital. The system provides immediate severity-graded advice based on clinical algorithms to guide self-management or hospital contact. Adverse event data are transferred to electronic patient records for review by clinical teams. Patients complete an online symptom report every week and whenever they experience symptoms. Main outcome measures: In systemic treatment, the primary outcome was Functional Assessment of Cancer Therapy – General, Physical Well-Being score assessed at 6, 12 and 18 weeks (primary end point). Secondary outcomes included cost-effectiveness assessed through the comparison of health-care costs and quality-adjusted life-years. Patient self-efficacy was measured (using the Self-Efficacy for Managing Chronic Diseases 6-item Scale). The radiotherapy pilot studied feasibility (recruitment and attrition rates) and selection of outcome measures. The surgical pilot examined symptom report completeness, system actions, barriers to using eRAPID and technical performance. Results: eRAPID was successfully developed and introduced across the treatments and centres. The systemic randomised controlled trial found no statistically significant effect of eRAPID on the primary end point at 18 weeks. There was a significant effect at 6 weeks (adjusted difference least square means 1.08, 95% confidence interval 0.12 to 2.05; p = 0.028) and 12 weeks (adjusted difference least square means 1.01, 95% confidence interval 0.05 to 1.98; p = 0.0395). No between-arm differences were found for admissions or calls/visits to acute oncology or chemotherapy delivery. Health economic analyses over 18 weeks indicated no statistically significant difference between the cost of the eRAPID information technology system and the cost of usual care (£12.28, 95% confidence interval –£1240.91 to £1167.69; p > 0.05). Mean differences were small, with eRAPID having a 55% probability of being cost-effective at the National Institute for Health and Care Excellence-recommended cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained. Patient self-efficacy was greater in the intervention arm (0.48, 95% confidence interval 0.13 to 0.83; p = 0.0073). Qualitative interviews indicated that many participants found eRAPID useful for support and guidance. Patient adherence to adverse-event symptom reporting was good (median compliance 72.2%). In the radiotherapy pilot, high levels of consent (73.2%) and low attrition rates (10%) were observed. Patient quality-of-life outcomes indicated a potential intervention benefit in chemoradiotherapy arms. In the surgical pilot, 40 out of 91 approached patients (44%) consented. Symptom report completion rates were high. Across the studies, clinician intervention engagement was varied. Both patient and staff feedback on the value of eRAPID was positive. Limitations: The randomised controlled trial methodology led to small numbers of patients simultaneously using the intervention, thus reducing overall clinician exposure to and engagement with eRAPID. Furthermore, staff saw patients across both arms, introducing a contamination bias and potentially reducing the intervention effect. The health economic results were limited by numbers of missing data (e.g. for use of resources and EuroQol-5 Dimensions). Conclusions: This research provides evidence that online symptom monitoring with inbuilt patient advice is acceptable to patients and clinical teams. Evidence of patient benefit was found, particularly during the early phases of treatment and in relation to self-efficacy. The findings will help improve the intervention and guide future trial designs. Future work: Definitive trials in radiotherapy and surgical settings are suggested. Future research during systemic treatments could study self-report online interventions to replace elements of traditional follow-up care in the curative setting. Further research during modern targeted treatments (e.g. immunotherapy and small-molecule oral therapy) and in metastatic disease is recommended. Trial registration: The systemic randomised controlled trial is registered as ISRCTN88520246. The radiotherapy trial is registered as ClinicalTrials.gov NCT02747264. Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 1. See the NIHR Journals Library website for further project information.