John Broggio

Survival in diffuse large B-cell lymphoma (DLBCL) has improved, raising interest in mortality from nonlymphoma causes in patients with DLBCL, which is known to be increased compared with the general population. We investigate excess mortality after DLBCL, quantifying both the absolute magnitude of the total nonlymphoma excess and the contributions of major disease groups. All 58 221 patients aged 18 to 79 years diagnosed with DLBCL as their first lymphoma in England during 1997 to 2020 were identified and followed for up to 25 years (median, 10.2 years). Absolute excess mortality rates (AERs) and standardized mortality ratios (SMRs) were estimated. A total of 30 596 patients died, 35.6% from lymphoma and 17.0% from other causes. The nonlymphoma mortality rate was 58% higher than that of the general population (SMR, 1.58; 95% confidence interval [CI], 1.55-1.61), with >100 excess nonlymphoma deaths per 10 000 person-years (AER, 103.8; 95% CI, 98.2-109.4). The nonlymphoma AER was substantial during the first year after diagnosis (AER, 369.1; 95% CI, 349.1-389.7). It subsequently fell but remained significantly elevated throughout follow-up, even beyond 10 years (AER, 93.7; 95% CI, 80.5-107.3). Disease groups with the biggest contributions to the AER were infection <1 year after diagnosis, constituting 29%; hematological causes excluding lymphoma (eg, leukemia) during years 1 to 4, 38%; and solid tumors thereafter, 31% in years 5 to 9 and 34% in years 10 to 25. Deaths from circulatory disease were elevated overall, but the SMR diminished in more recent calendar years of diagnosis. These insights may help guide treatment developments, interventions, and screening strategies toward reducing excess nonlymphoma deaths in the future.

Breast cancer can be categorised into a number of histological types, based on microscopic appearances. There is some evidence that the different breast cancer histological types are associated with different patient and tumour characteristics, but few previous studies have been large enough to investigate this systematically, especially for rare histological types. National cancer registration data were used to describe trends in the incidence of specific histological types of invasive breast cancer in women diagnosed when aged 18–89 years in England from January 1988 to December 2016, and to investigate associations between breast cancer histological types and patient and tumour characteristics. There were 838,776 women diagnosed with a first primary invasive breast cancer in this 29‐year period, including 614,698 (73%) cases of ductal carcinoma NST [no special type (NST)], 90,028 (11%) cases of lobular carcinoma, and more than 16,000 (2%) cases each of tubular and mucinous carcinomas. Rarer histological types included medullary, papillary, metaplastic, and cribriform carcinomas, with >1000 cases of each type. Data quality and completeness improved substantially during the study period. The different histological types of breast cancer showed different patterns in incidence by calendar period of diagnosis, age at diagnosis, and screen‐detection status, as well as different associations with tumour characteristics such as grade, stage at diagnosis, and molecular subtype. This large nationwide study provides an overview of the changing incidence of the different histological types of invasive breast cancer in England over almost 30 years. It also gives an opportunity to investigate the characteristics of rare histological types, which smaller studies have been unable to explore. In addition, the results demonstrate the continuing value of histological types defined by microscopic morphology, alongside newer molecular classifications.

Purpose The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of National Disease Registration Service in National Health Service England, quality assures, curates and analyses individual data on the pregnancies, fetuses, babies, children and adults with congenital anomalies and rare diseases across England. The congenital anomaly (CA) register provides a resource for patients and their families, clinicians, researchers and public health professionals in furthering the understanding of CAs. Participants NCARDRS registers CAs occurring in babies born alive and stillborn, fetal losses and terminations in England. NCARDRS collects data from secondary and tertiary healthcare providers, private providers and laboratories covering fetal medicine, maternity or paediatric services. Data describe the pregnancy, mother, baby and anomaly. Established in 2015, NCARDRS expanded CA registration coverage from 22% of total births in England in 2015 to national coverage, which was achieved in 2018. Prior to 2015, data collection was performed independently by regional registers in England; these data are also held by NCARDRS. Findings to date NCARDRS registers approximately 21 000 babies with CAs per year with surveillance covering around 600 000 total births, the largest birth coverage for a CA register globally. Data on prevalence, risk factors and survival for children with CAs are available. Data have been used in several peer-reviewed publications. Birth prevalence statistics, including public health indicators such as the association with maternal age, infant and perinatal mortality, are published annually. NCARDRS supports clinical audit for screening programmes and service evaluation. Future plans NCARDRS provides a valuable resource for the understanding of the epidemiology, surveillance, prevention and treatment of CAs. Currently, approximately 21 000 new registrations of babies or fetuses with suspected or confirmed CAs are added each year. Identifiers are collected, enabling linkage to routinely collected healthcare and population statistics, further enhancing the value of the data.

Background Childhood cancer survival figures have improved between 2002 and 2019. However, these overall figures may mask differences in survival for children living in different socioeconomic conditions as seen in adult cancer survival. Methods We estimated 5- and 10-year survival figures for children diagnosed with cancer between 2002 and 2019 using data from the National Cancer Registration and Analysis Service. Where full follow-up information was available survival was estimated using the cohort approach; where full follow-up was not available estimates of survival used the period approach, which assumes that people will experience the most recently observed conditional probabilities of survival in each year up to 5 or 10 years since diagnosis. Survival estimates were stratified based on an area based measure of deprivation in which postcode of residence was mapped to quintiles of the Index of Multiple Deprivation (IMD). All estimates are age-standardised using equal weights for each of the 5-year age groups (0–4, 5–9 and 10–14years). Locally weighted regression smoothing was applied to highlight trends over time. Results Consistently lower 5- and 10- year survival estimates were seen for children diagnosed with cancer living in the most deprived quintile compared with those living in the least deprived quintile. 5-year survival was between 0.4 and 5.8 percentage points lower, and 10-year survival between 0.1 and 7.9 percentage points lower, in children living in the most deprived quintile compared with those living in the least deprived quintile. The most pronounced differences in trends in survival estimates were seen for 10-year survival which showed a sharp divergence for children diagnosed with cancer between 2008–2011 dependent on their deprivation quintile. Children living in the least deprived quintile showed an increase in 10-year survival from 75.5% in children diagnosed in 2002 to 82.9% in those diagnosed in 2010, and a marginal increase to 83.8% in those diagnosed in 2019. In contrast, children living in the most deprived quintile showed an increase in survival from 72.7% to 79.1% for those diagnosed in 2002 to those diagnosed in 2007, followed by a decrease to a low of 75.3% for those diagnosed in 2011, with survival estimates only reaching 2007 levels again for those diagnosed in 2019 (79.3%). Conclusion Stark inequalities in both 5- and 10-year survival appeared for children diagnosed around 2008–2011 with children living in the most deprived quintiles having lower survival estimates than those living in the least deprived quintiles. Inequalities in survival estimates were seen throughout the 2010s.

Involved margins after surgery for early breast cancer increase the risk of local recurrence (LR), but international guidelines suggest that’ no tumour’ on ink is sufficient margin clearance after breast conserving surgery (BCS). Data on the effect of margin clearance on distant recurrence (DR) are lacking. Our aim was to determine the association between margin involvement, recurrence (DR) and breast cancer deaths. Methods Data from breast cancer units in Greater Manchester (GM) and the UK National Cancer Registry (NCRAS) were analysed. Margin status was prospectively recorded after surgery according to National Health Service Breast Screening Pathology (NHSBSP) minimum pathology data standards All patients underwent curative surgery and received adjuvant therapy according to local guidelines. Patients not undergoing curative surgery(T4, inflammatory or metastatic cancer) were excluded .Cox-proportional hazards models investigated factors associated with LR, DR and risk of breast cancer death.NCRAS records breast cancer deaths . Results GM analysis included 3270 patients from 2010 to 2014, 2295 (70.2%) had margins (>2mm) ,302 (9.2%) close (1-2mm) margin clearance and 673 (20.6%) involved (Citation Format: Nigel James Bundred, Sarah Michael, John Broggio, Anne Armstrong, Glen Martin, Mohamed Absar, Jane Ooi. Increased distant recurrence following margin involvement in early invasive breast cancer in two large UK cohorts [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-01.

The first UK national COVID‐19 lockdown began 23rd March 2020. Immediately, almost all outpatient healthcare service requests temporarily focused exclusively on urgent referrals and two‐week‐wait urgent cancer referrals with restrictions due to staff sickness, redeployment and changing work environments. Additionally, patient anxiety regarding attending appointments and perceived overburdening of healthcare resources resulted in fewer presentations.² Technological advancements have arisen from challenging circumstances. The National Cancer Registration and Analysis Service (NCRAS), England, has developed a Rapid Cancer Registration Dataset (RCRD). Utilising automated datafeeds, lag‐time from diagnosis to registration is reduced from 18 to 4 months, however, data has not been quality assured to the same standards and completeness.⁴ We identify how the pandemic has affected skin cancer.

Objective To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic. Design We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2–6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19–related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008–2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval. Results Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk–benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%. Conclusions Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.

Objective To evaluate the long term risks of invasive breast cancer and death from breast cancer after ductal carcinoma in situ (DCIS) diagnosed through breast screening. Design Population based observational cohort study. Setting Data from the NHS Breast Screening Programme and the National Cancer Registration and Analysis Service. Participants All 35 024 women in England diagnosed as having DCIS by the NHS Breast Screening Programme from its start in 1988 until March 2014. Main outcome measures Incident invasive breast cancer and death from breast cancer. Results By December 2014, 13 606 women had been followed for up to five years, 10 998 for five to nine years, 6861 for 10-14 years, 2620 for 15-19 years, and 939 for at least 20 years. Among these women, 2076 developed invasive breast cancer, corresponding to an incidence rate of 8.82 (95% confidence interval 8.45 to 9.21) per 1000 women per year and more than double that expected from national cancer incidence rates (ratio of observed rate to expected rate 2.52, 95% confidence interval 2.41 to 2.63). The increase started in the second year after diagnosis of DCIS and continued until the end of follow-up. In the same group of women, 310 died from breast cancer, corresponding to a death rate of 1.26 (1.13 to 1.41) per 1000 women per year and 70% higher than that expected from national breast cancer mortality rates (observed:expected ratio 1.70, 1.52 to 1.90). During the first five years after diagnosis of DCIS, the breast cancer death rate was similar to that expected from national mortality rates (observed:expected ratio 0.87, 0.69 to 1.10), but it then increased, with values of 1.98 (1.65 to 2.37), 2.99 (2.41 to 3.70), and 2.77 (2.01 to 3.80) in years five to nine, 10-14, and 15 or more after DCIS diagnosis. Among 29 044 women with unilateral DCIS undergoing surgery, those who had more intensive treatment (mastectomy, radiotherapy for women who had breast conserving surgery, and endocrine treatment in oestrogen receptor positive disease) and those with larger final surgical margins had lower rates of invasive breast cancer. Conclusions To date, women with DCIS detected by screening have, on average, experienced higher long term risks of invasive breast cancer and death from breast cancer than women in the general population during a period of at least two decades after their diagnosis. More intensive treatment and larger final surgical margins were associated with lower risks of invasive breast cancer.

Background: The COVID-19 pandemic has caused disruption across cancer pathways for diagnosis and treatment. In England, 32% of colorectal cancer (CRC) is diagnosed via urgent symptomatic referral from primary care, the “2-week-wait” (2WW) pathway. Access to routine endoscopy is likely to be a critical bottleneck causing delays in CRC management due to chronic limitation in capacity, acute competition for physician time, and safety concerns. Methods: We used age-specific, stage-specific 10 year CRC survival for England 2007–2017 and 2WW CRC cases volumes. We used per-day hazard ratios of CRC survival generated from observational studies of CRC diagnosis-to-treatment interval to model the effect of different durations of per-patient delay. We utilised data from a large London observational study of faecal immunochemical testing (FIT) in symptomatic patients to model FIT-triage to mitigate delay to colonoscopy. Findings: Modest delays result in significant reduction in survival from CRC with a 4-month delay resulting across age groups in ≥20% reduction in survival in Stage 3 disease and in total over a year, 1,419 attributable deaths across the 11,266 CRC patients diagnosed via the 2WW pathway. FIT triage of >10 ug Hb/g would salvage 1,292/1,419 of the attributable deaths and reduce colonoscopy requirements by >80%. Diagnostic colonoscopy offers net survival in all age groups, providing nosocomial COVID-19 infection rates are kept low (<2·5%). Interpretation: To avoid significant numbers of avoidable deaths from CRC, normal diagnostic and surgical throughput must be maintained. An accrued backlog of cases will present to primary care following release of lockdown, supranormal endoscopy capacity will be required to manage this without undue delays. FIT-triage of symptomatic cases provides a rational approach by which to avoid patient delay and mitigate pressure on capacity in endoscopy. This would also reduce exposure to nosocomial COVID-19 infection, relevant in particular to older patient groups. Funding: Breast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR).

Background: Cancer diagnostics and surgery have been disrupted by the response of healthcare services to the COVID-19 pandemic. Progression of cancers during delay will impact on patient long-term survival. Methods: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of three months and six months and periods of disruption of one year and two years. Using healthcare resource costing, we contextualise attributable lives saved and life years gained from cancer surgery to equivalent volumes of COVID-19 hospitalisations. Findings: Per year, 94,912 resections for major cancers result in 80,406 long-term survivors and 1,717,051 life years gained. Per-patient delay of six months would cause attributable death of 10,555 of these individuals with loss of 205,024 life years. For cancer surgery, average life years gained (LYGs) per patient are 18·1 under standard conditions and 15·9 with a delay of six months (a loss of 2·3 LYG per patient). Taking into account units of healthcare resource (HCRU), surgery results on average per patient in 2·25 resource-adjusted life years gained (RALYGs) under standard conditions and 1·98 RALYGs following delay of six months. For 94,912 hospital COVID-19 admissions, there are 474,505 LYGs requiring of 1,097,937 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5·0 LYG and 0·43 RALYGs. Interpretation: Delay of six months in surgery for incident cancers would mitigate 43% of life years gained by hospitalisation of an equivalent volume of admissions for community acquired COVID-19. This rises to 62% when considering resource-adjusted life-years gained. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued. Funding: Breast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR)