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

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

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 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [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. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society

A collaborative model to implement flexible, accessible and efficient oncogenetic services for hereditary breast and ovarian cancer : the C-MOnGene study

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust)

Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust)

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

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)