#Progress towards the #WHO Global Initiative for #Childhood #Cancer target of 60% 5-year survival for all childhood cancers combined, 1990–2019 (CONCORD-4): ...

 

Summary

Background

CONCORD is a global public health programme for long-term surveillance of population-based cancer survival. The first three cycles of this programme focused primarily on adults. In CONCORD-4, for the first time, we also included all cancers in children. The WHO Global Initiative for Childhood Cancer (GICC), published in 2018, set a target for 5-year survival for all childhood cancers combined, worldwide, to reach 60% by 2030. We designed the protocol for CONCORD-4 to assess progress towards this target in as many countries as possible.

Methods

We identified population-based cancer registries from the members of the International Association of Cancer Registries and other sources. We invited 513 registries in 101 countries to submit anonymised individual records for all children (aged 0–14 years) living in their territory who were diagnosed with any form of cancer during the 30-year period 1990–2019, or later years. The data included demographic variables, the morphological type and anatomical location of the tumour, and the follow-up for the vital status of each child. We used the data for 2010–19 to construct a set of weights that reflect the global frequency distribution of childhood cancers, by age, sex, and subtype, both for the 12 major groups in the third edition of the International Classification of Childhood Cancer (ICCC-3) and for the six WHO tracer cancers prioritised in the GICC. We estimated 5-year net survival for children diagnosed during 1990–2019 by age, sex, and type of cancer, using the Pohar Perme estimator. We then used the weights to construct a Cancer Survival Index (CSI) as a weighted average of these survival estimates, for each country and each 5-year period during 1990–2019 for the 12 ICCC-3 groups and separately for the six WHO tracer cancers.

Findings

We received 679 776 individual records for children diagnosed with cancer during 1990–2022 from 307 population-based cancer registries in 68 countries and territories, 52 with 100% national coverage. We produced two sets of weights, by age, sex, and type of cancer, reflecting the global distribution of cancer in children, both for all childhood cancers and for the six WHO tracer cancers. We restricted survival analyses to 613 021 children diagnosed during 1990–2019. The 5-year CSI for all childhood cancers combined increased in most countries between 1990 and 2019. For children diagnosed during 2015–19, the CSI was more than 80% in most high-income countries, in the range 60–80% in most upper-middle-income countries, and in the range 50–60% in the five participating lower-middle-income countries.

Interpretation

The new CSI enables quantitative international comparison of trends in survival for all childhood cancers combined and for the six WHO tracer cancers, through a simple three-way standardisation by age, sex and subtype. The CSI should be a useful tool to monitor future trends. In most high-income, upper-middle-income, and lower-middle-income countries participating in CONCORD-4, the all-cancers CSI was either close to or had already passed the GICC target to reach 60% 5-year survival for all childhood cancers combined, worldwide, by 2030. The GICC target therefore may not be ambitious enough.

Funding

Cancer Research UK, Institut National du Cancer (France), St Jude Children's Research Hospital (USA), US National Cancer Institute, and Dell Technologies.

Research in context

Evidence before this study

Survival differs widely between the various types of cancer in children, and between countries defined by their World Bank national income group. In 2018, WHO published the Global Initiative for Childhood Cancer (GICC), with the central target of reaching 60% survival (presumed to be 5 years) for all childhood cancers combined, worldwide, by 2030. 

No single metric exists to enable monitoring of progress towards this target. We searched PubMed for articles published in English, without date limits, using the following search string: “Population-based cancer regist*”[tiab] OR population-based registr* OR “population-based study”[tiab:~0] OR “EUROCARE”[tiab] AND “case-mix-standardised survival”[tiab:~0] OR “all cancers combined survival”[tiab:~0] OR “case-mix by cancer “[tiab:~0] OR “cancer survival index”[tiab:~0] OR “one-number index”[tiab:~0] OR “all cancers survival”[tiab:~0] OR “patient survival for all cancers combined”[ti:~0]”. 

At present, the only attempt to evaluate progress towards the GICC target is derived from simulation-based model estimates of net survival for 197 countries. In most of these countries, real-world data from population-based cancer registries are not available. The estimates include all types of cancer combined in the age range 0–14 years in a single pool, despite the well known differences in survival by age, sex, and type of cancer. Some large comparisons of survival for all cancers combined were produced by the EUROCARE project, in Europe, or by NORDCAN, in northern Europe only, or in single countries (Canada, China, Denmark, and the USA). 

In these studies, an estimate of survival for all cancers combined, in adults or in children, was based on a double standardisation, starting from the usual standardisation by age, followed by a further standardisation by case-mix or cancer type, and sex. This approach implies the use of two sets of weights, one for age-standardisation and another to reflect the cancer type and sex distribution of the patients included in each study. These distributions are not representative of the global population of cancer patients—in this context, children. The cancer survival indices derived for all these studies are not directly comparable either between countries or over time.

Added value of this study

The current cycle of the CONCORD programme for global surveillance of trends in population-based cancer survival (CONCORD-4) has extended coverage to include data for adults diagnosed with one of 22 malignancies, and for the first time, also includes data on all children diagnosed with a cancer during 1990–2022. 

CONCORD-4 provides the largest global real-world database on childhood cancer, including data from 307 population-based cancer registries in 68 countries, 52 with 100% national coverage. We created two sets of weights that reflect the global frequency distribution of childhood cancers by age, sex, and subtype: one set for the 12 major groups defined in the 3rd edition of the International Classification of Childhood Cancer, and another for the six tracer cancers prioritised by WHO in 2021. 

For each country and 5-year calendar period during the three decades 1990–2019, we then constructed a Cancer Survival Index (CSI), which enables quantitative comparisons of net survival for all childhood cancers combined, between countries and over time. Both sets of weights, which allow for a simple three-way standardisation by age, sex, and subtype, are now available for national and international research on childhood cancer survival. 30-year trends in the CSI offer a robust, long-term baseline against which to evaluate progress towards the GICC 2030 target.

Implications of all the available evidence

The CSI will facilitate monitoring of real-world progress towards the GICC target for childhood cancer survival. The CSI that includes all childhood cancers is a better indicator than the CSI based on the six WHO tracer cancers, especially for lower-middle-income countries, where diagnostic facilities are often inadequate, and the need to improve survival is even more urgent. WHO should devote even greater efforts to increase the coverage of population-based cancer registries worldwide and to facilitate data sharing for international research. In most high-income and upper-middle-income countries, impressive trends in survival for all childhood cancers combined since 1990 have already exceeded the GICC target for 2030, suggesting that a more ambitious target could be set. In low-income countries and lower-middle-income countries, where 60% of the world's children live, late presentation, abandonment of treatment, and suboptimal health-care systems are major contributors to poor survival.

Source: 

Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00189-3/fulltext?rss=yes

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The #global, regional, and national burden of #cancer, 1990–2023, with #forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023

 

Summary

Background

Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050.

Methods

Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer.

Findings

In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by –5·6% (–12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3).

Interpretation

Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment.

Funding

Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.

Source: The Lancet, https://www.sciencedirect.com/science/article/abs/pii/S0140673625016356?dgcid=rss_sd_all

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#COVID19 #pandemic resulted in more metastatic #breast #cancer cases at #diagnosis

Abstract

The study aimed to assess the impact of the COVID-19 pandemic on breast cancer diagnosis, tumor characteristics, and staging in an Eastern-European country. This retrospective study included 11,635 breast cancer patients and clients presenting between March 2019 and March 2022. Patients were categorized into pre-pandemic, pandemic, and post-pandemic groups. Data included age, sex, pathology, tumor characteristics (histologic type, grade, ER/PR/HER2 status), and TNM staging. Statistical analysis compared these parameters across the three-time intervals. During the pandemic, breast cancer diagnosis decreased significantly compared to the pre-pandemic period (9.1% vs. 13.17%, p < 0.001) but increased post-pandemic (11%, p = 0.013). Invasive ductal carcinoma of non-special type (IDC-NST) was predominant in all three-time periods. Aggressive tumors (Nottingham grade 3, ER negative) increased during the pandemic and post-pandemic times. Molecular subtypes showed variations across time intervals, with triple-negative tumors rising significantly. Larger tumors, increased lymph node involvement (9–19%), and distant metastasis characterized the pandemic and post-pandemic periods. Compared to pre-pandemic patients, post-pandemic ones were 7 times more likely to be metastatic at diagnosis (p < 0.05). The COVID-19 pandemic led to a significant decrease in breast cancer diagnosis, particularly during the pandemic period. Tumors appeared more aggressive, with higher lymph node and distant metastatic involvement. The long-term prognosis and healthcare cost implications remain uncertain. These findings emphasize the need for adapted cancer screening programs and healthcare system readiness during pandemics. COVID-19 pandemic has resulted in a lower detection rate among patients diagnosed with breast cancer and increased TNM stage.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-14582-z

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#Genome #integration of human #DNA #oncoviruses

ABSTRACT

Tumors of infectious origin globally represent 13%. Oncogenic DNA viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV) are responsible for approximately 60% of these tumors. These oncoviruses are extensively studied to understand their role in cancer development, particularly through viral genome integration into the host DNA. Retroviruses require integration mediated by viral integrase for persistence, whereas DNA oncoviruses do not need integration for replication; instead, integration occurs incidentally. This process often targets fragile sites in the human genome, causing structural rearrangements that disrupt genes, activate proto-oncogenes, and increase genomic instability, all contributing to tumorigenesis. Integration near promoter regions and active genes is closely linked to carcinogenesis, highlighting its importance in developing diagnostic and therapeutic strategies. This review summarizes viral integration’s role in oncogenesis, mechanisms of integration, and methods to study this process, focusing on DNA tumor viruses such as HBV, EBV, HPV, and Merkel cell polyomavirus.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00562-25?af=R

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#Geographic and #age #variations in mutational processes in #colorectal #cancer

Abstract

Colorectal cancer incidence rates vary geographically and have changed over time1. Notably, in the past two decades, the incidence of early-onset colorectal cancer, affecting individuals under the age of 50 years, has doubled in many countries2-5. The reasons for this increase are unknown. Here, we investigate whether mutational processes contribute to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries. No major differences were found in microsatellite unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases. Multiple signatures, most with unknown etiologies, exhibited varying prevalence in Argentina, Brazil, Colombia, Russia, and Thailand, indicating geographically diverse levels of mutagenic exposure. Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin6,7, had higher mutation loads in countries with higher colorectal cancer incidence rates. SBS88 and ID18 were also enriched in early-onset colorectal cancers, being 3.3 times more common in individuals diagnosed before age 40 than in those over 70, and were imprinted early during colorectal cancer development. Colibactin exposure was further linked to APC driver mutations, with ID18 responsible for about 25% of APC driver indels in colibactin-positive cases. This study reveals geographic and age-related variations in colorectal cancer mutational processes, and suggests that early-life mutagenic exposure to colibactin-producing bacteria may contribute to the rising incidence of early-onset colorectal cancer.

Source: Nature, https://www.nature.com/articles/s41586-025-09025-8

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