A change in cis-regulatory logic underlying obligate versus facultative muscle multinucleation in chordates.

Vertebrates and tunicates are sister groups that share a common fusogenic factor, Myomaker (Mymk), that drives myoblast fusion and muscle multinucleation. Yet they are divergent in when and where they express Mymk. In vertebrates, all developing skeletal muscles express Mymk and are obligately multinucleated. In tunicates, Mymk is only expressed in post-metamorphic multinucleated muscles, but is absent from mononucleated larval muscles. In this study, we demonstrate that cis-regulatory sequence differences in the promoter region of Mymk underlie the different spatiotemporal patterns of its transcriptional activation in tunicates and vertebrates. While in vertebrates Myogenic Regulatory Factors (MRFs) like MyoD1 alone are required and sufficient for Mymk transcription in all skeletal muscles, we show that transcription of Mymk in post-metamorphic muscles of the tunicate Ciona requires the combinatorial activity of MRF/MyoD and Early B-Cell Factor (Ebf). This macroevolutionary difference appears to be encoded in cis, likely due to the presence of a putative Ebf binding site adjacent to predicted MRF binding sites in the Ciona Mymk promoter. We further discuss how Mymk and myoblast fusion might have been regulated in the last common ancestor of tunicates and vertebrates, for which we propose two models.

Metal-Mediated, Autolytic Amide Bond Cleavage: A Strategy for the Selective, Metal Complexation-Catalyzed, Controlled Release of Metallodrugs.

Activation of metalloprodrugs or prodrug activation using transition metal catalysts represents emerging strategies for drug development; however, they are frequently hampered by poor spatiotemporal control and limited catalytic turnover. Here, we demonstrate that metal complex-mediated, autolytic release of active metallodrugs can be successfully employed to prepare clinical grade (radio-)pharmaceuticals. Optimization of the Lewis-acidic metal ion, chelate, amino acid linker, and biological targeting vector provides means to release peptide-based (radio-)metallopharmaceuticals in solution and from the solid phase using metal-mediated, autolytic amide bond cleavage (MMAAC). Our findings indicate that coordinative polarization of an amide bond by strong, trivalent Lewis acids such as Ga3+ and Sc3+ adjacent to serine results in the N, O acyl shift and hydrolysis of the corresponding ester without dissociation of the corresponding metal complex. Compound [68Ga]Ga-10, incorporating a cleavable and noncleavable functionalization, was used to demonstrate that only the amide bond-adjacent serine effectively triggered hydrolysis in solution and from the solid phase. The corresponding solid-phase released compound [68Ga]Ga-8 demonstrated superior in vivo performance in a mouse tumor model compared to [68Ga]Ga-8 produced using conventional, solution-phase radiolabeling. A second proof-of-concept system, [67Ga]Ga-17A (serine-linked) and [67Ga]Ga-17B (glycine-linked) binding to serum albumin via the incorporated ibuprofen moiety, was also synthesized. These constructs demonstrated that complete hydrolysis of the corresponding [68Ga]Ga-NOTA complex from [67Ga]Ga-17A can be achieved in naïve mice within 12 h, as traceable in urine and blood metabolites. The glycine-linked control [68Ga]Ga-17B remained intact. Conclusively, MMAAC provides an attractive tool for selective, thermal, and metal ion-mediated control of metallodrug activation compatible with biological conditions.

Evolution of a chordate-specific mechanism for myoblast fusion.

Vertebrate myoblast fusion allows for multinucleated muscle fibers to compound the size and strength of mononucleated cells, but the evolution of this important process is unknown. We investigated the evolutionary origins and function of membrane-coalescing agents Myomaker and Myomixer in various groups of chordates. Here, we report that Myomaker likely arose through gene duplication in the last common ancestor of tunicates and vertebrates, while Myomixer appears to have evolved de novo in early vertebrates. Functional tests revealed a complex evolutionary history of myoblast fusion. A prevertebrate phase of muscle multinucleation driven by Myomaker was followed by the later emergence of Myomixer that enables the highly efficient fusion system of vertebrates. Evolutionary comparisons between vertebrate and nonvertebrate Myomaker revealed key structural and mechanistic insights into myoblast fusion. Thus, our findings suggest an evolutionary model of chordate fusogens and illustrate how new genes shape the emergence of novel morphogenetic traits and mechanisms.

Association Between Medicaid Expansion Under the Affordable Care Act and Survival Among Newly Diagnosed Cancer Patients.

BACKGROUND: Medicaid expansion under the Affordable Care Act (ACA) is associated with increased insurance coverage among patients with cancer. Whether these gains translate to improved survival is largely unknown. This study examines changes in 2-year survival among patients newly diagnosed with cancer following the ACA Medicaid expansion. METHODS: Patients aged 18-62 years from 42 states' population-based cancer registries diagnosed pre (2010-2012) and post (2014-2016) ACA Medicaid expansion were followed through September 30, 2013, and December 31, 2017, respectively. Difference-in-differences (DD) analysis of 2-year overall survival was stratified by sex, race and ethnicity, census tract-level poverty, and rurality. RESULTS: A total of 2 555 302 patients diagnosed with cancer were included from Medicaid expansion (n = 1 523 585) and nonexpansion (n = 1 031 717) states. The 2-year overall survival increased from 80.58% pre-ACA to 82.23% post-ACA in expansion states and from 78.71% to 80.04% in nonexpansion states, resulting in a net increase of 0.44 percentage points (ppt) (95% confidence interval [CI] = 0.24ppt to 0.64ppt) in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer (DD = 0.90ppt, 95% CI = 0.19ppt to 1.60ppt), lung cancer (DD = 1.29ppt, 95% CI = 0.50ppt to 2.08ppt), non-Hodgkin lymphoma (DD = 1.07ppt, 95% CI = 0.14ppt to 1.99ppt), pancreatic cancer (DD = 1.80ppt, 95% CI = 0.40ppt to 3.21ppt), and liver cancer (DD = 2.57ppt, 95% CI = 1.00ppt to 4.15ppt). The improvement in 2-year overall survival was larger among non-Hispanic Black patients (DD = 0.72ppt, 95% CI = 0.12ppt to 1.31ppt) and patients residing in rural areas (DD = 1.48ppt, 95% CI= -0.26ppt to 3.23ppt), leading to narrowing survival disparities by race and rurality. CONCLUSIONS: Medicaid expansion was associated with greater increase in 2-year overall survival, and the increase was prominent among non-Hispanic Blacks and in rural areas, highlighting the role of Medicaid expansion in reducing health disparities. Future studies should monitor changes in longer-term health outcomes following the ACA.

Impact of including second and later cancers in cause-specific survival estimates using population-based registry data.

BACKGROUND: Second or later primary cancers account for approximately 20% of incident cases in the United States. Currently, cause-specific survival (CSS) analyses exclude these cancers because the cause of death (COD) classification algorithm was available only for first cancers. The authors added rules for later cancers to the Surveillance, Epidemiology, and End Results cause-specific death classification algorithm and evaluated CSS to include individuals with prior tumors. METHODS: The authors constructed 2 cohorts: 1) the first ever primary cohort, including patients whose first cancer was diagnosed during 2000 through 2016) and 2) the earliest matching primary cohort, including patients with any cancer who matched the selection criteria irrespective of whether it was the first or a later cancer diagnosed during 2000 through 2016. The cohorts' CSS estimates were compared using follow-up through December 31, 2017. The new rules were used in the second cohort for patients whose first cancers during 2000 through 2016 were their second or later cancers. RESULTS: Overall, there were no statistically significant differences in CSS estimates between the 2 cohorts. Estimates were similar by age, stage, race, and time since diagnosis, except for patients with leukemia and those aged 65 to 74 years (3.4 percentage point absolute difference). CONCLUSIONS: The absolute difference in CSS estimates for the first cancer ever cohort versus earliest of any cancers cohort in the study period was small for most cancer types. As the number of newly diagnosed patients with prior cancers increases, the algorithm will make CSS more inclusive and enable estimating survival for a group of patients with cancer for whom life tables are not available or life tables are available but do not capture other-cause mortality appropriately.

Determining Fitness for Use of SEER Cause-Specific Cause of Death in Analyses of Cause-Specific Survival.

Background: Net and crude cancer survival statistics can be calculated using cause of death or expected survival from life tables. In some instances, using cause of death information may be advantageous. The Surveillance, Epidemiology, and End Results (SEER) Program cause-specific cause of death variable (North American Association of Central Cancer Registries [NAACCR] item #1914) designates that a patient died of their cancer. We evaluated how miss-ingness in NAACCR item #1914 impacted survival estimates to determine fitness for use in NAACCR Cancer in North America (CiNA) products. Methods: We used CiNA survival and prevalence data (November 2020 submission) to calculate 60-month cause-specific survival among persons aged 15-99 years at time of diagnosis using NAACCR item #1914. We treated missing/unknown causes of death in 3 ways: excluded from analysis, included as dead from this cancer, or included as censored at time of last follow-up. Autopsy/death-certificate-only cases were excluded from survival analyses. We calculated the proportion of deaths with unknown/missing cause of death by registry and demographic variables. Results: Generally, 60-month cause-specific survival estimates differed by <1% between the 3 approaches when NAACCR item #1914 was missing/unknown for <3% of deaths. When applying a <3% fit-for-use standard to SEER cause-specific cause of death, data from 34 registries were included in cause-specific survival analyses. The proportion of deaths with missing/unknown cause of death varied by primary site, age at diagnosis, race/ethnicity, year of diagnosis, and registry. Conclusion: We have identified missingness cut points for NAACCR item #1914, which strike a balance between scientific integrity and registry inclusiveness, to designate data in NAACCR CiNA data products as fit for use in cause-specific survival analyses.

Time from breast cancer diagnosis to treatment among Idaho's National Breast and Cervical Cancer Early Detection Program population, 2011-2017.

PURPOSE: Idaho's Women's Health Check (WHC) Program provides breast and cervical cancer screening to under- and uninsured women via funding from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Because WHC serves populations with less access to health care, this study evaluated time from breast cancer diagnosis to treatment for women enrolled in the WHC program and linked to Cancer Data Registry of Idaho (CDRI) case data (WHC-linked) and the remainder of female Idaho resident breast cases. METHODS: Among Idaho residents aged 50-64 years diagnosed during 2011-2017 with ductal carcinoma in situ or invasive breast cancer, we assessed differences in the median time from definitive diagnosis to treatment initiation overall and by demographic and tumor characteristics, and differences in the distribution of demographic and tumor-related variables between 231 WHC-linked and 3,040 non-linked breast cancer cases. RESULTS: WHC-linked cases were significantly less likely to be non-Hispanic white, and more likely to live in poorer census tracts, be diagnosed at a later stage, and be treated with mastectomy. Most WHC-linked (92%) and non-linked women (94%) began treatment within 60 days of diagnosis; no differences in time to treatment were observed. CONCLUSION: Disparities in the interval from definitive diagnosis to breast cancer treatment initiation were not observed for women enrolled in the WHC program relative to other Idaho women.

Cancer among Refugees Resettled to Idaho during 2008-2019: A Proof-of-Concept Study.

BACKGROUND: Disparities in cancer burden and outcomes according to socioeconomic characteristics have been extensively characterized for US populations. The cancer experience of refugees, who may share characteristics of other socioeconomically disadvantaged populations and also experience distinct barriers to care, has not been described previously. We conducted a proof-of-concept study evaluating our ability to characterize cancer incidence in refugees resettled to Idaho via a novel linkage of cancer data and administrative data characterizing refugee arrivals to Idaho. METHODS: In July 2021, the Cancer Data Registry of Idaho probabilistically linked cancer surveillance data and refugee arrival data (2008- 2019 diagnosis and arrival years) collected through the Centers for Disease Control and Prevention's Electronic Disease Notification (EDN) System. We used SEER*Stat to calculate standardized incidence ratios (SIR) for malignant tumors and benign/borderline malignant brain and other nervous system (ONS) tumors using Idaho-specific and Surveillance, Epidemiology, and End Results (SEER) Program referent incidence rates. RESULTS: 60 malignant and 7 benign brain and ONS tumors were diagnosed among 9,499 refugees resettled to Idaho. Refugees had fewer than expected malignant tumors overall (57 observed vs 96.0 expected; SIR, 0.60; 95% CI, 0.45-0.77). An excess of tumors of the esophagus were diagnosed among Southeast Asian refugees (4 observed vs 0.64 expected; SIR, 6.3; 95% CI, 1.7-16.0). We also used EDN data to update country of birth for linked persons. CONCLUSIONS: Linking EDN refugee data to cancer surveillance data presented unique challenges. However, we used a novel data source to augment cancer data and characterize incidence in refugees, potentially improving our ability to serve this vulnerable population.

Homologous Structural, Chemical, and Biological Behavior of Sc and Lu Complexes of the Picaga Bifunctional Chelator: Toward Development of Matched Theranostic Pairs for Radiopharmaceutical Applications.

The radioactive isotopes scandium-44/47 and lutetium-177 are gaining relevance for radioimaging and radiotherapy, resulting in a surge of studies on their coordination chemistry and subsequent applications. Although the trivalent ions of these elements are considered close homologues, dissimilar chemical behavior is observed when they are complexed by large ligand architectures due to discrepancies between Lu(III) and Sc(III) ions with respect to size, chemical hardness, and Lewis acidity. Here, we demonstrate that Lu and Sc complexes of 1,4-bis(methoxycarbonyl)-7-[(6-carboxypyridin-2-yl)methyl]-1,4,7-triazacyclononane (H3mpatcn) and its corresponding bioconjugate picaga-DUPA can be employed to promote analogous structural features and, subsequently, biological properties for coordination complexes of these ions. The close homology was evidenced using potentiometric methods, computational modeling, variable temperature mass spectrometry, and pair distribution function analysis of X-ray scattering data. Radiochemical labeling, in vitro stability, and biodistribution studies with Sc-47 and Lu-177 indicate that the 7-coordinate ligand environment of the bifunctional picaga ligand is compatible with biological applications and the future investigation of ß-emitting, picaga-chelated Sc and Lu isotopes for radiotherapy.

Disparate survival of late-stage male oropharyngeal cancer in Appalachia.

The United States Appalachian region harbors a higher cancer burden than the rest of the nation, with disparate incidence of head and neck squamous cell carcinomas (HNSCC), including oral cavity and pharynx (OC/P) cancers. Whether elevated HNSCC incidence generates survival disparities within Appalachia is unknown. To address this, HNSCC survival data for 259,737 tumors from the North American Association for Central Cancer Registries 2007-2013 cohort were evaluated, with age-adjusted relative survival (RS) calculated based on staging, race, sex, and Appalachian residence. Tobacco use, a primary HNSCC risk factor, was evaluated through the Behavioral Risk Factor Surveillance System from Appalachian states. Decreased OC/P RS was found in stage IV Appalachian white males within a subset of states. The survival disparity was confined to human papillomavirus (HPV)-associated oropharyngeal cancers, specifically the oropharynx subsite. This correlated with significantly higher smoking and male smokeless tobacco use in most Appalachian disparity states. Lower survival of Appalachian males with advanced-stage HPV-associated oropharyngeal cancers suggests pervasive tobacco consumption likely generates more aggressive tumors at HPV-associated oropharynx subsites than national averages. Comprehensive tobacco and HPV status should therefore be evaluated prior to considering treatment de-intensification regimens for HPV-associated oropharyngeal cancers in populations with high tobacco consumption.

Breast and colorectal cancer recurrence and progression captured by five U.S. population-based registries: Findings from National Program of Cancer Registries patient-centered outcome research.

OBJECTIVES: Cancer recurrence is a meaningful patient outcome that is not captured in population-based cancer surveillance. This project supported National Program of Cancer Registries central cancer registries in five U.S. states to determine the disease course of all breast and colorectal cancer cases. The aims were to assess the feasibility of capturing disease-free (DF) status and subsequent cancer outcomes and to explore analytic approaches for future studies. METHODS: Data were obtained on 11,769 breast and 6033 colorectal cancer cancers diagnosed in 2011. Registry-trained abstractors reviewed medical records from multiple sources for up to 60 months to determine documented DF status, recurrence, progression and residual disease. We described the occurrence of these patient-centered outcomes along with analytic considerations when determining time-to-event outcomes and recurrence-free survival. RESULTS: Disease-free status was determined on all but 3.8 % of cancer cases. Among 14,458 cases that became DF, 6.1 % of breast and 13.0 % of colorectal cancer cases had a documented recurrence. Recurrence-free survival varied by stage; for stage II-III cancers at 48 months, 83.2 % of female breast and 69.2 % of colorectal cancer patients were alive without recurrence. The ability to distinguish between progression and residual disease among never disease-free patients limited our ability to examine progression as an outcome. CONCLUSIONS: This study demonstrated that population-based registries given intense support and resources can capture recurrence and offer a generalizable picture of cancer outcomes. Further work on refining definitions, sampling strategies, and novel approaches to capture recurrence could advance the ability of a national cancer surveillance system to contribute to patient-centered outcomes research.

Impact of Linkage to the Social Security Administration on Follow-up Completeness and Cancer Relative Survival Estimates in 2 New SEER Registries: 2000-2016 Diagnosis Years.

BACKGROUND: The Social Security Administration Service to Epidemiological Researchers (SSA-SER) can help central cancer registries meet the contractual follow-up requirements of the Surveillance, Epidemiology, and End Results (SEER) Program and improve survival estimate accuracy. We evaluated the impact of first-time SSA-SER linkage on follow-up rates and survival estimates for 2 SEER registries. Methods: In May 2019, cancer registries in Idaho (Cancer Data Registry of Idaho [CDRI]) and New York (New York State Cancer Registry [NYSCR]) used results from an SSA-SER linkage to update date of last contact and vital status for patients with a SEER-reportable tumor diagnosed during 2000-2016. We compared follow-up completeness through 2017 between pre-SSA-SER linkage and post-SSA-SER linkage data. Among individuals with a first primary tumor diagnosed during 2009-2015, we calculated 60-month age-standardized all sites and site-specific relative survival ratio (RSR) estimates via the presumed alive method using pre-SSA linkage data, and survival time calculated from last known date of contact using post-SSA linkage data. Results: SSA-SER linkage improved overall followup completeness from 79.0% to 97.4% and 55.7% to 92.6% for CDRI and NYSCR, respectively. Follow-up completeness improved most for laboratory-only reported tumors, in situ tumors, melanomas of the skin, prostate cancers, and benign and borderline brain and other central nervous system tumors. Post-SSA linkage RSRs were lower than pre-SSA presumed alive RSRs by an average -0.47% and -2.16% for Idaho and New York, respectively. Conclusions: SSA-SER linkage greatly and efficiently improved follow-up completeness for the 2 participating registries and revealed small difference in survival estimates by method. Use of the SSA-SER by all US registries would standardize and improve US survival estimates.

Five-Year U.S. Trends in the North American Cancer Survival Index, 2005-2014.

INTRODUCTION: Progress in U.S. 5-year survival trends for all cancers combined was assessed using the North American Cancer Survival Index, a sum of age-, sex-, and cancer site-standardized relative survival ratios. METHODS: In January 2019, authors calculated 5-year cancer survival indices and 95% CIs by race and sex for 2005-2011, 2006-2012, 2007-2013, and 2008-2014 diagnosis cohorts with data from 42 cancer registries. RESULTS: Overall 5-year survival increased from 63.5% (95% CI=63.4, 63.5) in 2005-2011 to 64.1% (95% CI=64.1, 64.2) in 2008-2014. Survival increased 0.9 and 0.5 percentage points in female and male patients, respectively; the survival disparity among blacks versus whites decreased by 0.5%. In 2008-2014, the Cancer Survival Index was 7.7% higher for whites (64.6%; 95% CI=64.6, 64.7) than for blacks (56.9%; 95% CI=56.7, 57.1). CONCLUSIONS: Cancer Survival Index survival estimates increased among all race and sex subpopulations during 2005-2014. A substantial but decreasing survival gap persisted between blacks and whites. The Cancer Survival Index can assist decision makers and others in comparing cancer survival among populations and over time and in monitoring progress toward national cancer surveillance objectives.

General Approach to Direct Measurement of the Hydration State of Coordination Complexes in the Gas Phase: Variable Temperature Mass Spectrometry.

The formation of ternary aqua complexes of metal-based diagnostics and therapeutics is closely correlated to their in vivo efficacy but approaches to quantify the presence of coordinated water ligands are limited. We introduce a general and high-throughput method for characterizing the hydration state of para- and diamagnetic coordination complexes in the gas phase based on variable-temperature ion trap tandem mass spectrometry. Ternary aqua complexes are directly observed in the mass spectrum and quantified as a function of ion trap temperature. We recover expected periodic trends for hydration across the lanthanides and distinguish complexes with several inner-sphere water ligands by inspection of temperature-dependent speciation curves. We derive gas-phase thermodynamic parameters for discernible inner- and second-sphere hydration events, and discuss their application to predict solution-phase behavior. The differences in temperature at which water binds in the inner and outer spheres arise primarily from entropic effects. The broad applicability of this method allows us to estimate the hydration states of Ga, Sc, and Zr complexes under active preclinical and clinical study with as-yet undetermined hydration number. Variable-temperature mass spectrometry emerges as a general tool to characterize and quantitate trends in inner-sphere hydration across the periodic table.

Geographical, racial and socio-economic variation in life expectancy in the US and their impact on cancer relative survival.

PURPOSE: Despite gains in life expectancy between 1992 to 2012, large disparities in life expectancy continue to exist in the United States between subgroups of the population. This study aimed to develop detailed life tables (LT), accounting for mortality differences by race, geography, and socio-economic status (SES), to more accurately measure relative cancer survival and life expectancy patterns in the United States. METHODS: We estimated an extensive set of County SES-LT by fitting Poisson regression models to deaths and population counts for U.S. counties by age, year, gender, race, ethnicity and county-level SES index. We reported life expectancy patterns and evaluated the impact of the County SES-LT on relative survival using data from the Surveillance Epidemiology and End Results (SEER) Program cancer registries. RESULTS: Between 1992 and 2012, the largest increase in life expectancy was among black men (6.8 years), however there were still large geographical differences. Life expectancy was highest for Asian or Pacific Islanders (API), and lowest for American Indians and Alaskan Natives (AIAN). In 2010, life expectancies by state ranged from 73 to 82 years for white males, 78 to 86 years for white females, 66 to 75 for black males, and 75 to 81 for black females. Comparisons of relative survival using National LT and the new County SES-LT showed that relative survival using County SES-LT improved relative survival estimates for some demographic groups, particularly in low and high SES areas, among Hispanics and AIAN, and among older male cancer patients. Relative survival using County SES-LT was 7.3% and 6.7% survival points closer to cause-specific survival compared to the National LT relative survival for AIAN and Hispanic cancer patients diagnosed between ages 75 and 84 years, respectively. Importantly, the County SES-LT relative survival estimates were higher in lower SES areas and lower in higher SES areas, reducing differences in relative survival comparisons. CONCLUSION: The use of these new socio-economic life tables (County SES-LT) can provide more accurate estimates of relative survival, improve comparisons of relative survival among registries, better illustrate disparities and cancer control efforts, and should be used as default for cancer relative survival using U.S. data.

Capture of tobacco use among population-based registries: Findings from 10 National Program of Cancer Registries states.

BACKGROUND: Tobacco use data are important when the epidemiology and prognosis of tobacco-associated cancers are being defined. Central cancer registries in 10 National Program of Cancer Registries states pilot-tested the collection of standardized tobacco use variables. This study evaluated the capture of tobacco use data and examined smoking prevalence among cancer patients. METHODS: Participating registries collected data about the use of tobacco-cigarettes, other smoked tobacco, and smokeless tobacco-for cases diagnosed during 2011-2013. The percentage of cases with known tobacco variable values was calculated, and the prevalence of tobacco use was analyzed by the primary cancer site and state. RESULTS: Among 1,646,505 incident cancer cases, 51% had known cigarette use data: 18% were current users, 31% were former users, and 51% reported never using. The percentage of cases with a known status for both other smoked tobacco and smokeless tobacco was 43%, with 97% and 98% coded as never users, respectively. The percent known for cigarette use ranged from 27% to 81% by state and improved from 47% in 2011 to 59% in 2013 for all 10 states combined. The percent known for cigarette use and the prevalence of ever smoking cigarettes were highest for laryngeal cancer and tracheal, lung, and bronchus cancer. CONCLUSIONS: Cancer registrars ascertained cigarette use for slightly more than half of all new cancer cases, but other tobacco-related fields were less complete. Studies to evaluate the validity of specific tobacco-related variables and the ability of cancer registries to capture this information from the medical record are needed to gauge the usefulness of collecting these variables through cancer surveillance systems. Cancer 2018;124:2381-9. © 2018 American Cancer Society.

Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries.

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.

Population-based cancer survival in the United States: Data, quality control, and statistical methods.

BACKGROUND: Robust comparisons of population-based cancer survival estimates require tight adherence to the study protocol, standardized quality control, appropriate life tables of background mortality, and centralized analysis. The CONCORD program established worldwide surveillance of population-based cancer survival in 2015, analyzing individual data on 26 million patients (including 10 million US patients) diagnosed between 1995 and 2009 with 1 of 10 common malignancies. METHODS: In this Cancer supplement, we analyzed data from 37 state cancer registries that participated in the second cycle of the CONCORD program (CONCORD-2), covering approximately 80% of the US population. Data quality checks were performed in 3 consecutive phases: protocol adherence, exclusions, and editorial checks. One-, 3-, and 5-year age-standardized net survival was estimated using the Pohar Perme estimator and state- and race-specific life tables of all-cause mortality for each year. The cohort approach was adopted for patients diagnosed between 2001 and 2003, and the complete approach for patients diagnosed between 2004 and 2009. RESULTS: Articles in this supplement report population coverage, data quality indicators, and age-standardized 5-year net survival by state, race, and stage at diagnosis. Examples of tables, bar charts, and funnel plots are provided in this article. CONCLUSIONS: Population-based cancer survival is a key measure of the overall effectiveness of services in providing equitable health care. The high quality of US cancer registry data, 80% population coverage, and use of an unbiased net survival estimator ensure that the survival trends reported in this supplement are robustly comparable by race and state. The results can be used by policymakers to identify and address inequities in cancer survival in each state and for the United States nationally. Cancer 2017;123:4982-93. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Colon cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study.

BACKGROUND: In the first CONCORD study (2008), 5-year survival for patients diagnosed with colon cancer between 1990 and 1994 in the United States was among the highest in the world (60%), but there were large racial disparities in most participating states. The CONCORD-2 study (2015) enabled the examination of survival trends between 1995 and 2009 for US states by race and stage. METHODS: The authors analyzed data from 37 state population-based cancer registries, covering approximately 80% of the US population, for patients who were diagnosed with colon cancer between 2001 and 2009 and were followed through 2009. Survival up to 5 years was corrected for background mortality (net survival) using state-specific and race-specific life tables and age-standardized using the International Cancer Survival Standard weights. Survival is presented by race (all, black, white), stage, state, and calendar period (2001-2003 and 2004-2009) to account for changes in methods used to collect stage. RESULTS: Five-year net survival increased by 0.9%, from 63.7% between 2001 and 2003 to 64.6% between 2004 and 2009. More black than white patients were diagnosed with distant-stage disease between 2001 and 2003 (21.5% vs 17.2%) and between 2004 and 2009 (23.3% vs 18.8%). Survival improved for both blacks and whites, but 5-year net survival was 9-10% lower for blacks than for whites both between 2001 and 2003 (54.7% vs 64.5%) and between 2004 and 2009 (56.6% vs 65.4%). The absolute difference between blacks and whites decreased by only 1% during the decade. CONCLUSIONS: Five-year net survival from colon cancer increased slightly over time. Survival among blacks diagnosed between 2004 and 2009 had still not reached the level of that among whites diagnosed between 1990 and 1994, some 15 to 20 years earlier. These findings suggest a need for more targeted efforts to improve screening and to ensure timely, appropriate treatment, especially for blacks, to reduce this large and persistent disparity in survival. Cancer 2017;123:5014-36. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.