Performance of two formal tests based on martingales residuals to check the proportional hazard assumption and the functional form of the prognostic factors in flexible parametric excess hazard models.

: Net survival, the one that would be observed if the disease under study was the only cause of death, is an important, useful, and increasingly used indicator in public health, especially in population-based studies. Estimates of net survival and effects of prognostic factor can be obtained by excess hazard regression modeling. Whereas various diagnostic tools were developed for overall survival analysis, few methods are available to check the assumptions of excess hazard models. We propose here two formal tests to check the proportional hazard assumption and the validity of the functional form of the covariate effects in the context of flexible parametric excess hazard modeling. These tests were adapted from martingale residual-based tests for parametric modeling of overall survival to allow adding to the model a necessary element for net survival analysis: the population mortality hazard. We studied the size and the power of these tests through an extensive simulation study based on complex but realistic data. The new tests showed sizes close to the nominal values and satisfactory powers. The power of the proportionality test was similar or greater than that of other tests already available in the field of net survival. We illustrate the use of these tests with real data from French cancer registries.<br/

Multi-state models and arthroplasty histories after unilateral total hip arthroplasties: Introducing the Summary Notation for Arthroplasty Histories

Background and purpose: An increasing number of patients have several joint replacement procedures during their lifetime. We investigated the use and suitability of multi-state model techniques in providing a more comprehensive analysis and description of complex arthroplasty histories held in arthroplasty registries than are allowed for with traditional survival methods. Patients and methods: We obtained data from the Australian Orthopaedic Association National Joint Replacement Registry on patients (n = 84,759) who had undergone a total hip arthroplasty for osteoarthritis in the period 2002–2008. We set up a multi-state model where patients were followed from their first recorded arthroplasty to several possible states: revision of first arthroplasty, either a hip or knee as second arthroplasty, revision of the second arthroplasty, and death. The Summary Notation for Arthroplasty Histories (SNAH) was developed in order to help to manage and analyze this type of data. Results: At the end of the study period, 12% of the 84,759 patients had received a second hip, 3 times as many as had received a knee. The estimated probabilities of having received a second arthroplasty decreased with age. Males had a lower transition rate for receiving a second arthroplasty, but a higher mortality rate. Interpretation: Multi-state models in combination with SNAH codes are well suited to the management and analysis of arthroplasty registry data on patients who experience multiple joint procedures over time. We found differences in the progression of joint replacement procedures after the initial total hip arthroplasty regarding type of joint, age, and sex.Marianne H Gillam, Philip Ryan, Amy Salter, Stephen E Grave

Cancer incidence and mortality trends in France over 1990-2018 for solid tumors: the sex gap is narrowing

OBJECTIVE: To analyze trends in cancer incidence and mortality (France, 1990-2018), with a focus on men-women disparities. METHODS: Incidence data stemmed from cancer registries (FRANCIM) and mortality data from national statistics (CépiDc). Incidence and mortality rates were modelled using bidimensional penalized splines of age and year (at diagnosis and at death, respectively). Trends in age-standardized rates were summarized by the average annual percent changes (AAPC) for all-cancers combined, 19 solid tumors, and 8 subsites. Sex gaps were indicated using male-to-female rate ratios (relative difference) and male-to-female rate differences (absolute difference) in 1990 and 2018, for incidence and mortality, respectively. RESULTS: For all-cancers, the sex gap narrowed over 1990-2018 in incidence (1.6 to 1.2) and mortality (2.3 to 1.7). The largest decreases of the male-to-female incidence rate ratio were for cancers of the lung (9.5 to 2.2), lip - oral cavity - pharynx (10.9 to 3.1), esophagus (12.6 to 4.5) and larynx (17.1 to 7.1). Mixed trends emerged in lung and oesophageal cancers, probably explained by differing risk factors for the two main histological subtypes. Sex incidence gaps narrowed due to increasing trends in men and women for skin melanoma (0.7 to 1, due to initially higher rates in women), cancers of the liver (7.4 to 4.4) and pancreas (2.0 to 1.4). Sex incidence gaps narrowed for colon-rectum (1.7 to 1.4), urinary bladder (6.9 to 6.1) and stomach (2.7 to 2.4) driven by decreasing trends among men. Other cancers showed similar increasing incidence trends in both sexes leading to stable sex gaps: thyroid gland (0.3 to 0.3), kidney (2.2 to 2.4) and central nervous system (1.4 to 1.5). CONCLUSION: In France in 2018, while men still had higher risks of developing or dying from most cancers, the sex gap was narrowing. Efforts should focus on avoiding risk factors (e.g., smoking) and developing etiological studies to understand currently unexplained increasing trends

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

National cancer incidence is estimated using the incidence/mortality ratio in countries with local incidence data: is this estimation correct?

BACKGROUND: In countries with local cancer registration, the national cancer incidence is usually estimated by multiplying the national mortality by the incidence/mortality (I/M) ratio from pooled registries. This study aims at validating this I/M estimation in France, by a comparison with estimation obtained using the ratio of incidence over hospital discharge (I/HD) or the ratio of incidence over health insurance data (long-duration diseases, I/LDD). METHODS: This comparison was performed for 22 cancer sites over the period 2004-2006. In France, a longitudinal I/M approach was developed relying on incidence and mortality trend analyses; here, the corresponding estimations of national incidence were extracted for 2004-2006. The I/HD and I/LDD estimations were performed using a common cross-sectional methodology. RESULTS: The three estimations were found similar for most cancers. The relative differences in incidence rates (vs. I/M) were below 5% for numerous cancers and below 10% for all cancers but three. The highest differences were observed for thyroid cancer (up to +21% in women and +8% in men), skin melanoma (up to +13% in women and +8% in men), and Hodgkin disease in men (up to +15%). Differences were also observed in women aged over 60 for cervical cancer. Except for thyroid cancer, differences were mainly due to the smoothing performed in the I/M approach. CONCLUSION: Our results support the validity of I/M approaches for national estimations, except for thyroid cancer. The longitudinal version of this approach has, furthermore, the advantage of providing smoothed estimations and trend analyses, including useful birth-cohort indicators, and should thus be preferred