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Legislative and technological advancements over the past decade have given rise to the proliferation of healthcare data generated from routine clinical practice, often referred to as real‐world data (RWD). These data have piqued the interest of healthcare stakeholders due to their potential utility in generating evidence to support clinical and regulatory decision making. In the oncology setting, studies leveraging RWD offer distinct advantages that are complementary to randomized controlled trials (RCTs). They also permit the conduct of investigations that may not be possible through prospective designs due to ethics or feasibility. Despite its promise, the use of RWD for the generation of clinical evidence remains controversial due to concerns of unmeasured confounding and other sources of bias that must be carefully addressed in the study design and analysis. To facilitate a better understanding of when RWD can provide reliable conclusions on drug effectiveness, we seek to conduct 10 RWD‐based studies that emulate RCTs in oncology using a systematic, protocol‐driven approach described herein. Results of this investigation will help inform clinical, scientific, and regulatory stakeholders on the applications of RWD in the context of product labeling expansion, drug safety, and comparative effectiveness in oncology. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) accounts for the majority of all lung cancer diagnoses, and approximately 35% of patients with NSCLC are diagnosed at an early stage (I–IIIA). This study aimed to describe epidermal growth factor receptor (EGFR) testing, patient characteristics, and overall survival (OS) among patients with early‐stage NSCLC in Denmark. Patients with early‐stage NSCLC registered in the Danish Lung Cancer Registry in 2013–2018 were followed through 2019. We described EGFR testing, descriptively summarised patient characteristics, and calculated OS by EGFR testing and mutation status. The association between EGFR mutation (EGFRm) and all‐cause mortality was estimated using Cox proportional‐hazards regression, in subgroups defined by stage at diagnosis, age at diagnosis, comorbidity, and receipt of surgery. In 2013–2018, 21,282 patients with NSCLC were registered in the Danish Lung Cancer Registry, of whom 8758 were diagnosed at an early stage. Of those, 4071 (46%) were tested for EGFRm at diagnosis. Median OS was 5.7 years among patients with EGFRm‐positive status (n = 361) and 4.4 years among patients with EGFRm‐negative status (n = 3710). EGFRm‐positive status was associated with lower all‐cause mortality in all subgroups. This study contributes to population‐based evidence on the epidemiology of early‐stage NSCLC treated in routine clinical practice. [ABSTRACT FROM AUTHOR]

Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care even more urgent. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3,554 CMM patients from the Stockholm Melanoma Register were included. Information on comorbidities, progression, death, and treatments was obtained from nationwide registers and hospital electronic medical records. Unadjusted 5-year survival varied from 91.4% for stage I to 24.6% for stage IV patients. Stage, age and gender were predictors of survival, with gender an independent predictor of survival for stages IA and IIA. 74.6% of patients remained recurrence/progression-free during follow-up, with 5-year recurrence/progression-free survival rates varying from 85.3% to 12.9% among stages I and IV patients, respectively. In addition to stage, male gender, and age, circulatory system comorbidities increased the risk for recurrence/progression. No statistically significant differences in progression rate for operated and non-operated patients could be detected, possibly due to high rate (98.9%) of surgery. Our estimates of survival and recurrence rates are consistent with historical and global expectations and can serve as a baseline to gauge population-level improvements with use of novel melanoma treatments. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (population-based cohort study) Level of Evidence 2b OBJECTIVES To estimate the risk of a second primary tumour (SPT) of the bladder in a cohort of childhood cancer survivors, investigate factors associated with a bladder SPT developing, and compare the risk observed with that expected from the general population. PATIENTS AND METHODS The analysis included 17 981 individuals diagnosed with childhood cancer, between 1940 and 1991 in Britain, and surviving for ≥5 years. Ascertainment of a bladder SPT was primarily through the National Health Service Central Registers (NHSCR). RESULTS From the NHSCR, 17 bladder SPTs were ascertained; this corresponded to four times (95% confidence interval 2.5-6.4) the expected number of bladder tumours. Standardized incidence ratios (SIRs) varied significantly ( P < 0.05) by first primary tumour (FPT) type, follow-up period, attained age and chemotherapy. The highest SIRs were in those: with heritable retinoblastoma (31.4); treated with chemotherapy (12.0); 0-9 years of follow-up (10.8); and aged 0-19 years (9.3). The absolute excess risk (AER) for a bladder SPT was 3.7 cases/100 000 survivors per year. The AER varied significantly by FPT type, follow-up period, attained age and gender. The highest AERs were in those: diagnosed with heritable retinoblastoma (34.0); 20-29 years of follow-up (14.2); aged 40-49 years (13.0); and male (5.8). Using multivariable Cox regression, FPT and chemotherapy were significantly associated with the risk of a bladder SPT developing. By the age of 55 years, 0.4% of survivors developed a bladder SPT. CONCLUSION Although the absolute risk of a bladder tumour within childhood cancer survivors was low, the risk was four times that expected from the general population. Specific groups, e.g. survivors of heritable retinoblastoma and those treated with chemotherapy, were at the highest risk. [ABSTRACT FROM AUTHOR]

Second primary neoplasms (SPNs) are a recognised late effect of treatment for childhood cancer. Thyroid SPNs can develop after exposure to low-dose radiation, due to the radio-sensitivity of the thyroid gland. The British Childhood Cancer Survivor Study (BCCSS) was set up to directly monitor the late effects of treatment, including risk of SPNs, in childhood cancer survivors and includes 17,980 5-year survivors. We carried out a cohort analysis to determine the risk of thyroid SPNs in the BCCSS, and estimated risk using standardised incidence ratios (SIRs), relative risk (RR) using multivariate Poisson regression and cumulative incidence curves. There were 340,202 person years at risk subsequent to a 5-year survival, median follow-up 17.4 years per survivor. We identified 50 thyroid SPNs including 31 (62%) papillary carcinomas, 15 (30%) follicular carcinomas and 4 (8%) other types. 88% of thyroid SPNs developed after exposure to radiotherapy in or around the thyroid gland. SIR overall was 18.0 (95% confidence interval 13.4-23.8). Risk of thyroid cancer was highest after Hodgkin's disease: RR 3.3 (1.1-10.1) and Non Hodgkin's Lymphoma: RR 3.4 (1.1-10.7) relative to leukaemia (RR 1.0) ( p < 0.001). Survivors treated with radiotherapy in childhood had a RR of 4.6 (1.4-15.1) relative to survivors not treated with radiotherapy (RR 1.0), p = 0003. In conclusion, the risk of thyroid cancer in childhood cancer survivors is relatively high in this cohort of childhood cancer survivors. These results will be of use in counselling survivors of childhood cancer exposed to radiation in or around the thyroid area. © 2009 UICC [ABSTRACT FROM AUTHOR]

Previous studies have reported substantially increased risks of breast cancer among survivors of childhood cancer at 10-20 years posttreatment. Whether these excess risks are sustained beyond 40 years of age when general population incidence of breast cancer begins its steep increase is largely unknown. We quantified the risk of breast cancer in adult female survivors with considerably more survivors followed-up beyond 40 years of age than previously available. Standardized Incidence Ratios (SIR), Excess Absolute Risks (EAR), and cumulative incidence were calculated within a population-based cohort of 8,093 female survivors of childhood cancer. Poisson regression models were used to model SIRs and EARs in a multivariable setting. Eighty-one survivors developed a primary breast cancer, where 37.5 were expected (SIR= 2.2, 95% CI: 1.7-2.7). SIRs decreased significantly with increasing attained age ( p [ABSTRACT FROM AUTHOR]

A British population-based cohort study was carried out to determine the risk of second primary neoplasms in survivors of Wilms' tumour. The cohort was obtained from the British Childhood Cancer Survivor Study, a population-based cohort study of treatment toxicities in 18,044 individuals diagnosed with childhood cancer, at an age of less than 15 years, between 1940 and 1991 in Britain. There were 1,441 Wilms' tumour survivors in the cohort: 732 males (50.8%) and 709 females (49.2%). Total follow-up from 5-year survival was 27,841 person years, mean follow-up of 19.3 years per survivor. There were 81 second primary neoplasms, including 52 solid neoplasms, 3 acute myeloid leukaemias and 26 basal cell carcinomas. Thirty-five of the 39 solid neoplasms that developed in the thoracic, abdominal or pelvic region occurred within irradiated tissue. The standardised incidence ratio for all solid second primary neoplasms was 6.7 (95% CI: 5.0-8.8). Cumulative incidence for all solid second primary neoplasms by ages 30, 40 and 50 years was 2.3% (1.4-3.5%), 6.8% (4.6-9.5%) and 12.2% (7.3-18.4%). The overall risk of second primary neoplasms in survivors of Wilms' tumour treated between 1940 and 1991 was substantial, and solid second tumours tended to develop in the irradiated tissue. Continued follow-up of these survivors is important to monitor such late effects of treatment. It is also important to evaluate the risk of second primary neoplasms following more recent lower radiation dose treatment practices. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]