National Cancer Registration And Analysis Service Research Articles

Systemic anti-cancer therapy in gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC): insights from national cancer registration and analysis service (NCRAS)

Systemic anti-cancer therapy in gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC): insights from national cancer registration and analysis service (NCRAS)

Prognostic determinants in cancer survival: a multidimensional evaluation of clinical and genetic factors across 10 cancer types in the participants of Genomics England’s 100,000 Genomes Project

BackgroundCancer is a complex disease, caused and impacted by a combination of genetic, demographic, clinical, environmental and lifestyle factors. Analysis of cancer characteristics, risk factors, treatment options and the heterogeneity across cancer types has been the focus of medical research for years. The aim of this study is to describe and summarise genetic, clinicopathological, behavioural and demographic characteristics and their differences across ten common cancer types and evaluate their impact on overall survival outcomes.MethodsThis study included data from 9977 patients with bladder, breast, colorectal, endometrial, glioma, leukaemia, lung, ovarian, prostate, and renal cancers. Genetic data collected through the 100,000 Genomes Project was linked with clinical and demographic data provided by the National Cancer Registration and Analysis Service (NCRAS), Hospital Episode Statistics (HES) and Office for National Statistics (ONS). Descriptive and Kaplan Meier survival analyses were performed to visualise similarities and differences across cancer types. Cox proportional hazards regression models were applied to identify statistically significant prognostic factor associations with overall survival.Results161 clinical and 124 genetic factors were evaluated for prognostic association with overall survival. Of these, 116 unique factors were found to have significant prognostic effect for overall survival across ten cancer types when adjusted for age, sex and stage. The findings confirmed prognostic associations with overall survival identified in previous studies in factors such as multimorbidity, tumour mutational burden, and mutations in genes BRAF, CDH1, NF1, NRAS, PIK3CA, PTEN, TP53. The results also identified new prognostic associations with overall survival in factors such as mental health conditions, female health-related conditions, previous hospital encounters and mutations in genes FANCE, FBXW7, GATA3, MSH6, PTPN11, RB1, RNF43.ConclusionThis study provides a comprehensive view of clinicopathological and genetic prognostic factors across different cancer types and draws attention to less commonly known factors which might help produce more precise prognosis and survival estimates. The results from this study contribute to the understanding of cancer disease and could be used by researchers to develop complex prognostic models, which in turn could help predict cancer prognosis more accurately and improve patient outcomes.

Sex Differences in the Survival of Patients with Neuroendocrine Neoplasms: A Comparative Study of Two National Databases.

Neuroendocrine neoplasms (NENs) are increasing in incidence globally. Previous analysis of the UK cancer database (National Cancer Registration and Analysis Service (NCRAS)) showed a notable female survival advantage in most tumour sites. This study aims to compare NCRAS to the Surveillance, Epidemiology, and End Results Program (SEER) to validate these results using the same statistical methods. A total of 14,834 and 108,399 patients with NENs were extracted from NCRAS and SEER, respectively. Sixty-months survival for both males and females for each anatomical site of NENs were calculated using restricted mean survival time (RMST) and Kaplan-Meier Survival estimates. The sixty-month RMST female survival advantage (FSA) was calculated. FSA was similar in NCRAS and SEER. The highest FSA occurred in lung and stomach NENs. The data from SEER confirm the findings published by NCRAS. Female survival advantage remains unexplained.

Identification of people with Lynch syndrome from those presenting with colorectal cancer in England: baseline analysis of the diagnostic pathway

It is believed that >95% of people with Lynch syndrome (LS) remain undiagnosed. Within the National Health Service (NHS) in England, formal guidelines issued in 2017 state that all colorectal cancers (CRC) should be tested for DNA Mismatch Repair deficiency (dMMR). We used a comprehensive population-level national dataset to analyse implementation of the agreed diagnostic pathway at a baseline point 2 years post-publication of official guidelines. Using real-world data collected and curated by the National Cancer Registration and Analysis Service (NCRAS), we retrospectively followed up all people diagnosed with CRC in England in 2019. Nationwide laboratory diagnostic data incorporated somatic (tumour) testing for dMMR (via immunohistochemistry or microsatellite instability), somatic testing for MLH1 promoter methylation and BRAF status, and constitutional (germline) testing of MMR genes. Only 44% of CRCs were screened for dMMR; these figures varied over four-fold with respect to geography. Of those CRCs identified as dMMR, only 51% underwent subsequent diagnostic testing. Overall, only 1.3% of patients with colorectal cancer had a germline MMR genetic test performed; up to 37% of these tests occurred outside of NICE guidelines. The low rates of molecular diagnostic testing in CRC support the premise that Lynch syndrome is underdiagnosed, with significant attrition at all stages of the testing pathway. Applying our methodology to subsequent years’ data will allow ongoing monitoring and analysis of the impact of recent investment. If the diagnostic guidelines were fully implemented, we estimate that up to 700 additional people with LS could be identified each year.

Second Primary Malignancies in Patients with a Neuroendocrine Neoplasm in England

Introduction: Patients with neuroendocrine neoplasms (NENs) may often develop other malignancies. This study aimed to identify the frequency at which these second malignancies occurred in England. Methods: Data were extracted from the National Cancer Registration and Analysis Service (NCRAS) on all patients diagnosed with a NEN at one of eight NEN site groups between 2012 and 2018: appendix, caecum, colon, lung, pancreas, rectum, small intestine, and stomach. WHO International Classification of Disease Edition-10 (ICD-10) codes were used to identify patients who had been diagnosed with an additional non-NEN cancer. Standardized incidence ratios (SIRs) for tumours diagnosed after the index NEN were produced for each non-NEN cancer type by sex and site. Results: A total of 20,579 patients were included in the study. The most commonly occurring non-NEN cancers after NEN diagnosis were the prostate (20%), lung (20%), and breast (15%). Statistically significant SIRs were observed for non-NEN cancer of the lung (SIR = 1.85, 95% CI: 1.55–2.22), colon (SIR = 1.78, 95% CI: 1.40–2.27), prostate (SIR = 1.56, 95% CI: 1.31–1.86), kidney (SIR = 3.53, 95% CI: 2.72–4.59), and thyroid (SIR = 6.31, 95% CI: 4.26–9.33). When stratified by sex, statistically significant SIRs remained for the lung, renal, colon, and thyroid tumours. Additionally, females had a statistically significant SIR for stomach cancer (2.65, 95% CI: 1.26–5.57) and bladder cancer (SIR = 2.61, 95% CI: 1.36–5.02). Conclusion: This study found that patients with a NEN experienced a metachronous tumour of the lung, prostate, kidney, colon, and thyroid at a higher rate than the general population of England. Surveillance and engagement in existing screening programmes are required to enable earlier diagnosis of second non-NEN tumours in these patients.

Primary renal neuroendocrine neoplasms: A systematic literature review, report of four local cases, and original survival analysis of 63 patients from a national registry 2012-2018.

Primary renal neuroendocrine neoplasms (NEN) are rare. We aimed to conduct a systematic review, present local cases, and analyse data from the England's National Cancer Registration and Analysis Service (NCRAS) to provide comprehensive evidence on clinical experience, incidence, and survival to better characterize these tumours. First, a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method; second, a synthesis of local cases; and, finally, a retrospective population-based cohort analysis of renal NEN recorded between 2012 and 2018 on NCRAS were performed. Kaplan-Meier estimator was used to calculate overall survival and Cox proportional hazard regression to identify prognostic factors. Systematic review identified 48 articles and the evidence was summarized and presented. We reported data from four local cases presenting with abdominal and back pain but without carcinoid syndrome. In population-based analysis, we identified 63 cases of renal NEN between 2012 and 2018 from the registry. Age-standardized incidence was 0.09-0.32 per million with a median age of 64 years (interquartile range=48-72 years). Survival was worse in males and those aged 64 years and over. Five-year survival for renal neuroendocrine tumours (NET) was 69.8% (95% confidence interval=66.6-72.7) and neuroendocrine carcinomas (NEC) was 38.4% (95% confidence interval=34.6-42.0). No independent predictive factor was identified in the multivariable analyses. We have given a systematic review of evidence, published local experience, and reported incidence and survival of renal NEN in England for the first time. We have provided clinicians with evidence on diagnosis and proposed a treatment algorithm of theses rare tumours. The incidence and median age of presentation in England is similar to other published series. Renal NET has better survival than renal NEC as expected. A uniform classification system would reduce inconsistencies in reporting and standardize treatment decisions for this neoplasia.

Incidence and Outcome of Breast Sarcomas in England (2013–2018): An analysis from the National Cancer Registration and Analysis Service

BackgroundBreast sarcomas (BS) are rare cancers originating from mesenchymal breast tissue with a paucity of national population level data detailing their incidence and outcomes. MethodsWe performed an analysis of data collected by National Cancer Registration and Analysis Service (NCRAS) for patients diagnosed with BS between 2013 and 2018. Chi-square test was used to compare groups. Overall survival (OS) was calculated by Kaplan–Meier. Specialist sarcoma centres (SSC) were defined as centres with a sarcoma multidisciplinary team (MDT). ResultsThere were 684 patients with BS (357 malignant phyllodes tumours [PTs], 238 vascular tumours, 93 other morphology) with a median age of 64 (range 14–96); 187 (27%) had received breast radiotherapy for a prior malignancy; 633 (92%) had resection of the tumour within 12 months of diagnosis. Five-year OS was 82%, 54% and 48% in patients with PT, vascular tumours and other sarcomas, respectively, and 55% for those with radiation-induced BS. Patients managed within SSC more frequently had a biopsy prior to surgery 83% versus 72%, p < 0.05) and were less likely to require multiple operations (26% versus 41%, p < 0.05). Tumour stage and grade data were not available. ConclusionThis is the first population series evaluating incidence and outcomes for BS. Patients treated at non-specialist sarcoma centres (NSSCs) are less likely to have a biopsy prior to surgery and more likely to require multiple operations. Based on these observational data, we would recommend all BS are discussed at a sarcoma MDT meeting early in their pathway and surgery to be considered at SSC where possible.

Health service planning to assess the expected impact of centralising specialist cancer services on travel times, equity, and outcomes: a national population-based modelling study

Centralisation of specialist cancer services is occurring in many countries, often without evaluating the potential impact before implementation. We developed a health service planning model that can estimate the expected impacts of different centralisation scenarios on travel time, equity in access to services, patient outcomes, and hospital workload, using rectal cancer surgery as an example. For this population-based modelling study, we used routinely collected individual patient-level data from the National Cancer Registration and Analysis Service (NCRAS) and linked to the NHS Hospital Episode Statistics (HES) database for 11 888 patients who had been diagnosed with rectal cancer between April 1, 2016, and Dec 31, 2018, and who subsequently underwent a major rectal cancer resection in 163 National Health Service (NHS) hospitals providing rectal cancer surgery in England. Five centralisation scenarios were considered: closure of lower-volume centres (scenario A); closure of non-comprehensive cancer centres (scenario B); closure of centres with a net loss of patients to other centres (scenario C); closure of centres meeting all three criteria in scenarios A, B, and C (scenario D); and closure of centres with high readmission rates (scenario E). We used conditional logistic regression to predict probabilities of affected patients moving to each of the remaining centres and the expected changes in travel time, multilevel logistic regression to predict 30-day emergency readmission rates, and linear regression to analyse associations between the expected extra travel time for patients whose centre is closed and five patient characteristics, including age, sex, socioeconomic deprivation, comorbidity, and rurality of the patients' residential areas (rural, urban [non-London], or London). We also quantified additional workload, defined as the number of extra patients reallocated to remaining centres. Of the 11 888 patients, 4130 (34·7%) were women, 5249 (44·2%) were aged 70 years and older, and 5005 (42·1%) had at least one comorbidity. Scenario A resulted in closures of 43 (26%) of the 163 rectal cancer surgery centres, affecting 1599 (13·5%) patients; scenario B resulted in closures of 112 (69%) centres, affecting 7029 (59·1%) patients; scenario C resulted in closures of 56 (34%) centres, affecting 3142 (26·4%) patients; scenario D resulted in closures of 24 (15%) centres, affecting 874 (7·4%) patients; and scenario E resulted in closures of 16 (10%) centres, affecting 1000 (8·4%) patients. For each scenario, there was at least a two-times increase in predicted travel time for re-allocated patients with a mean increase in travel time of 23 min; however, the extra travel time did not disproportionately affect vulnerable patient groups. All scenarios resulted in significant reductions in 30-day readmission rates (range 4-48%). Three hospitals in scenario A, 41 hospitals in in scenario B, 13 hospitals in scenario C, no hospitals in scenario D, and two hospitals in scenario E had to manage at least 20 extra patients annually. This health service planning model can be used to to guide complex decisions about the closure of centres and inform mitigation strategies. The approach could be applied across different country or regional health-care systems for patients with cancer and other complex health conditons. National Institute for Health Research.

A prospective evaluation of the fourth national Be Clear on Cancer 'Blood in Pee' campaign in England.

ObjectiveTo assess the impact of the fourth Be Clear on Cancer (BCoC) ‘Blood in Pee’ (BiP) campaign (July to September 2018) on bladder and kidney cancer symptom awareness and outcomes in England.MethodsIn this uncontrolled before and after study, symptom awareness and reported barriers to GP attendance were assessed using panel and one‐to‐one interviews. The Health Improvement Network (THIN), National Cancer Registration and Analysis Service (NCRAS) and NHS Cancer Waiting Times (CWT) data were analysed to assess the impact on GP attendances, urgent cancer referrals, cancer diagnoses and 1‐year survival. Analyses used Poisson, negative binomial and Cox regression.ResultsSymptom awareness and intention to consult a GP after one episode of haematuria increased following the campaign. GP attendance with haematuria (rate ratio (RR) 1.17, 95% confidence interval (CI): 1.07–1.28) and urgent cancer referrals (RR 1.18 95% CI: 1.08–1.28) increased following the campaign. Early‐stage diagnoses increased for bladder cancer (difference in percentage 2.8%, 95% CI: −0.2%–5.8%), but not for kidney cancer (difference −0.6%, 95% CI: −3.2%–2.1%).ConclusionsThe fourth BCoC BiP campaign appears to have been effective in increasing bladder cancer symptom awareness and GP attendances, although long‐term impacts are unclear.

Enrolment and Outcomes of Ethnic Minorities with Multiple Myeloma Treated in UK Myeloma Research Alliance (UK-MRA) Clinical Trials over 18 Years

Enrolment and Outcomes of Ethnic Minorities with Multiple Myeloma Treated in UK Myeloma Research Alliance (UK-MRA) Clinical Trials over 18 Years

Real-World Study of the Treatment Patterns of Patients Diagnosed with Therapy-Related AML or AML-MRC in England between 2013 and 2020 Using the Cancer Analysis System Database

Introduction: Patients with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) are a known high-risk AML subgroup with historically poor outcomes. In December 2018, CPX-351 (Vyxeos ® Liposomal) received a positive reimbursement decision in England for the treatment of adults with newly diagnosed t-AML or AML-MRC. The objective of this retrospective study was to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics, clinical characteristics, and treatment pathways for patients with t-AML or AML-MRC in England from 2013 to 2020, including the use of CPX-351.Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with t-AML or AML-MRC between January 2013 and March 2020 were identified either directly using International Classification of Diseases for Oncology, Third Edition(ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with a record of prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC; other AML-MRC subtypes could not be distinguished from de novo AML). First-line and second-line treatments identified included clinical trials, intensive chemotherapy (IC) treatments (CPX-351; daunorubicin plus cytarabine [DA]; fludarabine, cytarabine, idarubicin and granulocyte-colony stimulating factor [FLAG-Ida]; or “other IC” consisting of mitoxantrone-based therapy or high-dose cytarabine alone), or less-intensive therapies (azacitidine, low-dose cytarabine [LDAC], or hydroxycarbamide alone). Patients who did not receive active systemic therapy (ie, those who received best supportive care alone) were not included.Results: A total of 2,891 patients with t-AML or AML-MRC were identified. Most patients were male (62%), white (91%), and aged ≥60 years (80%). Overall, 590 (20%) patients received first-line treatment in a clinical trial, 1,474 (51%) received less-intensive therapy, and 827 (29%) received an IC regimen. Patients aged ≥60 years at diagnosis were less likely than those aged <60 years to either enter a clinical trial (18% vs 32%, respectively) or receive IC (22% vs 54%). In patients treated with IC, those who received CPX-351 were slightly older (mean [standard deviation] age: 63.9 years [8.3]) than those who received DA (60.5 years [11.4]) or FLAG-Ida (55.6 years [12.6]); 28% of patients treated with CPX-351 were aged <60 years compared to 37% for DA and 55% for FLAG-Ida.When treatment patterns were analyzed per annum, utilization of less-intensive therapies remained stable over time (Figure 1A). Azacitidine was the most common less-intensive therapy both overall (64%) and across all yearly time points, followed overall by LDAC (22%) then hydroxycarbamide alone (14%). In contrast, the IC treatment patterns were more dynamic over time (Figure 1B). DA chemotherapy was the most common IC overall (48%), followed by FLAG-Ida (23%) and other ICs (18%). However, CPX-351 uptake started in 2018 (5% of all IC) and by the end of 2019 had displaced DA chemotherapy as standard-of-care IC (40% vs 22%, respectively). Excluding patients who were alive but had not received subsequent therapy (ie, censored), most patients who received front-line azacitidine or LDAC died without receiving salvage therapy (89% and 92%, respectively). In comparison, non-censored patients who received front-line DA chemotherapy or FLAG-Ida were more likely to receive salvage treatment (52% and 34%, respectively). Key salvage treatments following DA included azacitidine alone and FLAG-based therapy. Key salvage treatments following front-line CPX-351 included FLAG-Ida or DA ± hematopoietic cell transplant and azacitidine.Conclusions: This large population-level, retrospective analysis of CAS data provides a detailed overview of the management of patients with t-AML and AML-MRC. Historically, a high proportion of these high-risk patients have received less-intensive treatment. Since 2018, CPX-351 has been rapidly adopted into the IC treatment pathway, displacing DA chemotherapy. These analyses will be repeated after the CAS database has been updated to determine the impact of COVID-19. [Display omitted] DisclosuresLegg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Muzwidzwa: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Adamson: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Wilkes: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.

Real-World Study of CPX-351 Treatment Outcomes for Acute Myeloid Leukemia (AML) in England

Introduction: CPX-351 (US: Vyxeos ®; Europe: Vyxeos ® Liposomal) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. Since November 2018, the National Institute for Health and Care Excellence (NICE) has recommended its use for adults with newly diagnosed, therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) due to either prior myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) or de novo AML with myelodysplasia-related cytogenetic changes. The key aims of this study were to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics and clinical characteristics of adults with AML in England who have received CPX-351, as well as to estimate overall survival (OS) and survival within stratifications of interest.Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with AML and treated with CPX-351 were included in this study. A diagnosis of t-AML or AML-MRC between January 2013 and March 2020 was determined either directly using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with either prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC; other AML-MRC subtypes could not be specifically identified and are included within the de novo AML subgroup). OS was measured from the date of diagnosis; a separate analysis of OS landmarked from the date of hematopoietic cell transplant (HCT) was also performed. Within this preliminary analysis, no OS adjustments have been made to account for any COVID-19-related deaths.Results: A total of 172 patients with AML who were treated with CPX-351 were identified: 37 (22%) had t-AML, 57 (33%) had AML-MRC, and 78 (45%) had de novo AML. At diagnosis, the mean (standard deviation) age was 62.8 years (10.1), with 49/172 (28%) patients aged <60 years; 66% of patients were male; 87% were white; and most had an Eastern Cooperative Oncology Group performance status of 0 or 1 (68%). Six (3%) patients had received azacitidine treatment for a prior malignancy. To date, 43/172 (25%) patients had undergone HCT overall, including 43/97 (44%) patients with ≥3 months of follow-up.The cut-off date for OS was December 31, 2020, giving a median (interquartile range) follow-up of 11.2 months (3.6, 16.9). Overall, 91 patients had died, with an estimated median OS (95% confidence interval [CI]) of 16.6 months (11.0, not estimable) and probability of survival (95% CI) at 1 and 2 years of 0.54 (0.47, 0.62) and 0.39 (0.30, 0.50), respectively (Figure 1). Early mortality rates were 7% at 30 days and 15% at 60 days. When OS was landmarked from the date of HCT, median OS was not reached, with a probability of survival (95% CI) at 1 year of 0.74 (0.62, 0.89; Figure 2). When stratified by age, estimated median OS (95% CI) was not reached for patients aged <60 years and 12.8 months (8.9, 17.6) for patients aged ≥60 years. In a treatment patterns analysis that evaluated second-line treatments after CPX-351, 68 patients died without salvage therapy and 64 were alive without receiving subsequent therapy by the end of the study period. The most common salvage treatments were fludarabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor (FLAG-Ida; n = 15), daunorubicin plus cytarabine (DA)-based therapy (n = 6), and azacitidine alone (n = 7). Of the 43 patients who received an HCT, 6 (14%) underwent HCT following salvage therapy.Conclusions: This is the largest study to date examining the real-world outcomes for patients with AML who were treated with CPX-351. The estimated median OS of 16.6 months is consistent with reported real-world outcomes for CPX-351 in French and Italian studies. Median OS has not been reached in patients aged <60 years or when landmarked from the date of HCT. Once the CAS database has been updated, these analyses will be repeated to increase follow-up and patient numbers and to determine the impact of COVID-19 on OS following CPX-351 treatment. [Display omitted] DisclosuresLegg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Doubleday: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Reich: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Lambova: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.

P14.45 The incidence of major subtypes of primary brain tumours in adults in England 1995–2017

Abstract BACKGROUND Primary brain tumours are a complex heterogenous group of benign and malignant tumours. Reports on their occurrence in the English population by sex, age, and morphological subtype and on their incidence are currently not available. Using data from the National Cancer Registration and Analysis Service (NCRAS), the incidence of adult primary brain tumour by major subtypes in England will be described. METHODS Data on all adult English patients diagnosed with primary brain tumour between 1995 and 2017, excluding spinal, endocrinal and other CNS tumours, were extracted from NCRAS. Incidence rates were standardised to the 2013 European Standard Population. Results are presented by sex, age, and morphological subtype. RESULTS Between 1995 and 2017, a total of 133,669 cases of adult primary brain tumour were registered in England. Glioblastoma was the most frequent tumour subtype (31.8%), followed by meningioma (27.3%). The age-standardised incidence for glioblastoma increased from 3.27 per 100,000 population per year in 1995 to 7.34 in men in 2013 and from 2.00 to 4.45 in women. Meningioma incidence also increased from 1.89 to 3.41 per 100,000 in men and from 3.40 to 7.46 in women. The incidence of other astrocytic and unclassified brain tumours declined between 1995 and 2007 and remained stable thereafter. CONCLUSION Part of the increase in the incidence of major subtypes of brain tumours in England could be explained by advances in clinical practice including the adoption of new diagnostic tools, classifications and molecular testing, and improved cancer registration practices.

Machine learning to guide the use of adjuvant therapies for breast cancer

Accurate prediction of the individualized survival benefit of adjuvant therapy is key to making informed therapeutic decisions for patients with early invasive breast cancer. Machine learning technologies can enable accurate prognostication of patient outcomes under different treatment options by modelling complex interactions between risk factors in a data-driven fashion. Here, we use an automated and interpretable machine learning algorithm to develop a breast cancer prognostication and treatment benefit prediction model—Adjutorium—using data from large-scale cohorts of nearly one million women captured in the national cancer registries of the United Kingdom and the United States. We trained and internally validated the Adjutorium model on 395,862 patients from the UK National Cancer Registration and Analysis Service (NCRAS), and then externally validated the model among 571,635 patients from the US Surveillance, Epidemiology, and End Results (SEER) programme. Adjutorium exhibited significantly improved accuracy compared to the major prognostic tool in current clinical use (PREDICT v2.1) in both internal and external validation. Importantly, our model substantially improved accuracy in specific subgroups known to be under-served by existing models. Adjutorium is currently implemented as a web-based decision support tool ( https://vanderschaar-lab.com/adjutorium/ ) to aid decisions on adjuvant therapy in women with early breast cancer, and can be publicly accessed by patients and clinicians worldwide. Methods are available to support clinical decisions regarding adjuvant therapies in breast cancer, but they have limitations in accuracy, generalizability and interpretability. Alaa et al. present an automated machine learning model of breast cancer that predicts patient survival and adjuvant treatment benefit to guide personalized therapeutic decisions.

Accessing routinely collected health data to improve clinical trials: recent experience of access

BackgroundRoutinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders.MethodsThis is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams’ application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718).ResultsThe Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years.ConclusionsOur experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials.

08. Incidence and outcome of breast sarcomas in NHS England (2013-2018): An analysis from Public Health England (PHE) National Cancer Registration and Analysis Service (NCRAS)

Background: Breast sarcomas (BS) are rare cancers originating from mesenchymal breast tissue with a paucity of national population level data detailing their incidence and outcomes.

The incidence of major subtypes of primary brain tumors in adults in England 1995-2017.

BackgroundPrimary brain tumors are a complex heterogenous group of benign and malignant tumors. Reports on their occurrence in the English population by sex, age, and morphological subtype and on their incidence are currently not available. Using data from the National Cancer Registration and Analysis Service (NCRAS), the incidence of adult primary brain tumor by major subtypes in England will be described.MethodsData on all adult English patients diagnosed with primary brain tumor between 1995 and 2017, excluding spinal, endocrinal, and other CNS tumors, were extracted from NCRAS. Incidence rates were standardized to the 2013 European Standard Population. Results are presented by sex, age, and morphological subtype.ResultsBetween 1995 and 2017, a total of 133 669 cases of adult primary brain tumor were registered in England. Glioblastoma was the most frequent tumor subtype (31.8%), followed by meningioma (27.3%). The age-standardized incidence for glioblastoma increased from 3.27 per 100 000 population per year in 1995 to 7.34 in men in 2013 and from 2.00 to 4.45 in women. Meningioma incidence also increased from 1.89 to 3.41 per 100 000 in men and from 3.40 to 7.46 in women. The incidence of other astrocytic and unclassified brain tumors declined between 1995 and 2007 and remained stable thereafter.ConclusionPart of the increase in the incidence of major subtypes of brain tumors in England could be explained by advances in clinical practice including the adoption of new diagnostic tools, classifications and molecular testing, and improved cancer registration practices.

Retrospective cohort study evaluating clinical, biochemical and pharmacological prognostic factors for prostate cancer progression using primary care data

ObjectivesTo confirm the association of previously reported prognostic factors with future progression of localised prostate cancer using primary care data and identify new potential prognostic factors for further assessment in...

PCN329 Utilising Public Health England Datasets to Establish a Standing Cohort of Patients with Metastatic Bladder Cancer: Initial Results and Algorithm Defining Disease Progression

Bladder (i.e. urothelial) cancer is the tenth most common UK cancer with survival prospects that vary by disease stage. Late diagnosis and metastatic progression lead to significantly poorer prognosis. Disease pathways are rapidly evolving and real-world evidence on treatment of metastatic urothelial cancer (mUC) and respective health outcomes would enable better understanding of current NHS clinical management. This descriptive, non-interventional study established an open-ended and population-based standing cohort of patients with mUC using routine clinical datasets linked within Public Health England’s National Cancer Registration and Analysis Service (NCRAS). In total, 14,951 patients were diagnosed with UC between January 2016 and June 2017. Of these, 2,543 (17%) had metastases at diagnosis. Patients with metastasis had a mean age of 74 years (SD=11.1) and were predominantly male (64%) with a C67 diagnosis (76%) and a transitional cell morphology (73%). Hypertension (24%) and type-2 diabetes (9%) were the most common comorbidities. Within the first follow-up period, 19% of patients underwent a primary tumour site resection. Systemic therapy was received by 27% of patients with a median of 8 administrations (IQR=4.0-11.0) per patient, lasting a median 84 days (IQR=49.0-133.0). Median overall survival was 5.8 months (95%CI=5.4-6.3) with the most common cause of death being C679, ‘malignant neoplasm of bladder, unspecified’ (67%, n=1,355). Initial results provide insight into the management of patients with mUC who are already metastatic at diagnosis in England, and improve our understanding of both the disease pathway and the NCRAS datasets. Completeness of the mUC cohort will improve over time through refresh of linked and quality-assured data. Additionally, an algorithm for disease progression has been developed through collaboration between data analysts and clinical experts to enable the inclusion of patients diagnosed with UC who subsequently progress to mUC, as well as those with metastases at diagnosis.

2017 Cancer Prevalence Dashboard for London.

As cancer incidence increases and survival improves, the number of people living with a cancer diagnosis is increasing. People living with cancer have 50% more contact with GPs 15 months after diagnosis than a population of similar age, sex and locality; 70% have another long-term condition. To aid service providers' understanding of the cancer prevalent population by creating a publicly available visualisation tool that both describes patients' demographics and length of time lived with cancer, and compares counts of nationally registered cancer survivors to GP-maintained registers. Using National Cancer Registration and Analysis Service (NCRAS) data, prevalence rates and counts were generated for London patients diagnosed 1995-2017 and alive 31 December 2017, overall and for lower-level geographies. GP-recorded Quality and Outcomes Framework (QOF) prevalence at Clinical Commissioning Group (CCG) level was compared to NCRAS counts for the same period. On 31 December 2017, 231 740 (2.6%) people were living with cancer in London; 33% were diagnosed 5-9 years prior and 31% were diagnosed ≥10 years prior. Prevalence was higher in women (P<0.001) and dramatically increased with age for London (P<0.001); >12% of >75 year olds were living with a cancer diagnosis in every lower-level geography. Completeness of GP QOF cancer registers against NCRAS prevalence counts ranged from 75-108% across CCGs. Local understanding of the cancer prevalent population is needed, with a concerted effort to interpret large discrepancies between QOF and NCRAS registers, which may arise from differences in coding practice. Ensuring patients are identified in primary care is a first key step to managing cancer as a long-term condition.