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Competing Interests: HH serves without remuneration on an external advisory board of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, on the International Advisory Board of the University of Vienna, and on the external Executive Advisory Committee of the Sylvester Comprehensive Cancer Center, University of Miami Health System, and as a member of the Standing Advisory Group on Nuclear Applications of the International Atomic Energy Agency. Until Oct 31, 2024, HH also served without remuneration on the Scientific Committee of the German Cancer Research Center (DKFZ) and the Board of Trustees of the DKFZ. She is remunerated for serving on the Board of Directors of Ion Beam Applications and receives stock options for serving on the Board of Directors of iCAD. Her work is partly supported by funding to her institution (Memorial Sloan-Kettering Center support grant/core grant P30 CA008748) from the US National Institutes of Health (NIH)–National Cancer Institute (NCI). JOP reports uncompensated service as President of the Swiss Society of Nuclear Medicine, service to the World Federation of Nuclear Medicine and Biology as the focal point for technical collaboration with WHO, and service as the President of Section and Board of Nuclear Medicine of the European Union of Medical Specialists. AM reports that her work is partly supported by funding to her institution (Memorial Sloan-Kettering Center support grant/core grant P30 CA008748) from NIH–NCI. BA reports support for attending meetings or travel from the International Society of Radiology and the American College of Radiology. AMS reports institutional research funding from the Australian National Health and Medical Research Council, Medical Research Future Fund, and National Imaging Facility; patents planned, issued or pending for his role as an inventor of antibodies to HER2, ADAMs, EGFR, and Ephs; uncompensated participation on data safety monitoring or advisory boards for Telix and ImunOs; uncompensated service as a board member for the Australia and New Zealand Society of Nuclear Medicine and World Federation of Nuclear Medicine and Biology and as theme chair of the National Imaging Facility; stock holdings as founder and Director of Certis Therapeutics; and research and trial funding to his institution from Telix, Clarity, Fusion, Antengene, EMD Serono, ITM, Avid/Lily, Medimmune, and Cyclotek. All other authors declare no competing interests.

Competing Interests: We declare no competing interests.

Following on from the 2015 Lancet Oncology Commission on expanding global access to radiotherapy, Radiotherapy and theranostics: a Lancet Oncology Commission was created to assess the access and availability of radiotherapy to date and to address the important issue of access to the promising field of theranostics at a global level. A marked disparity in the availability of radiotherapy machines between high-income countries and low-income and middle-income countries (LMICs) has been identified previously and remains a major problem. The availability of a suitably trained and credentialled workforce has also been highlighted as a major limiting factor to effective implementation of radiotherapy, particularly in LMICs. We investigated initiatives that could mitigate these issues in radiotherapy, such as extended treatment hours, hypofractionation protocols, and new technologies. The broad implementation of hypofractionation techniques compared with conventional radiotherapy in prostate cancer and breast cancer was projected to provide radiotherapy for an additional 2·2 million patients (0·8 million patients with prostate cancer and 1·4 million patients with breast cancer) with existing resources, highlighting the importance of implementing new technologies in LMICs. A global survey undertaken for this Commission revealed that use of radiopharmaceutical therapy-other than 131 I-was highly variable in high-income countries and LMICs, with supply chains, workforces, and regulatory issues affecting access and availability. The capacity for radioisotope production was highlighted as a key issue, and training and credentialling of health professionals involved in theranostics is required to ensure equitable access and availability for patient treatment. New initiatives-such as the International Atomic Energy Agency's Rays of Hope programme-and interest by international development banks in investing in radiotherapy should be supported by health-care systems and governments, and extended to accelerate the momentum generated by recognising global disparities in access to radiotherapy. In this Commission, we propose actions and investments that could enhance access to radiotherapy and theranostics worldwide, particularly in LMICs, to realise health and economic benefits and reduce the burden of cancer by accessing these treatments., Competing Interests: Declaration of interests HH serves (unpaid) on an external advisory board of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, on the International Advisory Board of the University of Vienna, on the Scientific Committee of the German Cancer Research Center (DKFZ), on the Board of Trustees of the DKFZ, and on the advisory board of The Lancet Oncology; is remunerated for serving on the Board of Directors of Ion Beam Applications; receives stock options for serving on the Board of Directors of iCAD; and reports research funding to their institution (Memorial Sloan-Kettering Center Support Grant/Core Grant P30 CA008748) from the National Institutes of Health (NIH)–National Cancer Institute (NCI). AA reports funding to their institution from the National Institute for Health and Care Research (NIHR) and the NIH. GB reports research funding to their institution from the Science and Technology Facilities Council UK and reports travel support from International Council Expert Corps. MD reports research funding to their institution from Science and Technology Facilities Council UK and reports travel support from International Council Expert Corps. TE reports honoraria from the University of Washington and the Japanese Society for Radiation Oncology (JASTRO) and reports receiving travel support to attend meetings from JASTRO, the Turkish Society for Radiation Oncology, and the American Society for Radiation Oncology (ASTRO). SGr reports receiving grants from the NCI; reports consulting fees from Lumonus and the Sustainable Dialogue on Peaceful Uses; and has stock options in Harbinger Health. KH reports research funding to their institution from Novartis and Sofie Biosciences; reports consulting fees from Advanced Accelerator Applications, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curiun, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien Munchen, Janssen, Merck, Molecular Partners, Nvision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Telix, Theragnostics, and Ymabs; reports honoraria for lectures from PeerVoice; serves on paid advisory boards for Fusion and GE Healthcare; reports travel support from Janssen; and has stock options from Sofie Biosciences, Pharma15, Nvision, Convergent, Aktis Oncology, and AdvanCell. MSH reports research funding to their institution from the Prostate Cancer Foundation, the US Department of Defence, Movember, and the Peter MacCallum Foundation; reports clinical trial funding to their institution from Bayer and Isotopia; reports clinical trial support to their institution from the Australian Nuclear Science and Technology Organisation; reports consulting fees from Merck Sharp & Dohme and Novartis; reports speaker fees from Janssen and AstraZeneca; reports fees to their institution for serving on the advisory board on Novartis; reports unremunerated participation in the Scientific Committee at the Australian Friends of Sheba; and is supported by a National Health and Medical Research Council (NHMRC) Investigator grant. DJ reports royalties from Elekta Oncology System, Precision X-ray System, and Modus Medical; reports license of technology to iRT; reports board membership on Break Through Cancer; reports being an advisor to ACS BrightEdge; and is a founder and stockholder in Nanovista. JK reports participation on a data safety monitoring board and advisory board from Novartis (personal fees) and reports lecture honoraria from Monrol. JSL reports research support from Clarity Pharmaceuticals and Avid Radiopharmaceuticals; has acted as an adviser of Alpha-9 Theranostics, Clarity Pharmaceuticals, Earli, Evergreen Theragnostics, Suba Therapeutics, Inhibrx, Precirix, Solve, Goldman Sachs, TPG Capital, Curie Therapeutics, NextTech Invest, and Telix Pharmaceuticals; is secretary/treasurer of the Society of Nuclear Medicine and Molecular Imaging (SNMMI); holds equity in Curie Therapeutics, Summit Biomedical Imaging, Telix Pharmaceuticals, and Evergreen Theragnostics; and is supported by NIH R35 CA232130. YL reports funding to their institution for the European Society for Radiotherapy and Oncology (ESTRO) Chair on Health Economics in Radiation Oncology (HERO)–Value-Based Radiation Oncology, for a proton beam project from the Research Foundation Flanders (FWO)–Applied Biomedical Research with a Primary Finality, and for the ARCHERY trial; reports unpaid positions on advisory boards for the HALT trial and PROSECCA trial; is a member of the ESTRO Scientific Council and the Belgian Board of Oncology; is co-chair of the ESTRO-HERO project; and is principal investigator of the E2-Radiate trial, a joint project of ESTRO, and the European Organisation for Research and Treatment of Cancer (EORTC). JRP reports being an unpaid chair of the American Association of Physicists in Medicine (AAPM) International Council. AAR received consulting fees from Novartis; received honoraria for lectures from the European Society for Medical Oncology, Sociedade Brasileira de Mastologia, and Instituto Oncoclinicas; received financial support for attending meetings from ASTRO, Congresso Gramado, and Congresso Oncolinicas; reports an unpaid leadership position at the Sociedade Brasileira de Radioterapia; and has stock and stock options in Grupo Oncoclinicas. MMS reports research funding to their institution from Aktis, Point Biopharma, and Telix Pharmaceuticals; reports speaker honoraria from Novartis, Ion Beam Applications, and Johnson and Johnson; and holds positions in the Africa Health Research Institute and Adcock. VV holds positions as editor of the Journal of Clinical Oncology/Global Oncology and Translational Oncology and is a member of the board for City Cancer Challenge. RLW reports research funding to their institution from Siemens Healthineers, White Rabbit AI, Fusion, Perspective Therapeutics, Rayze, and Bayer; provides consulting services to Voximetry, Molecular Targeting Technologies (MTT), Perspective, Siemens, Abdera, and Seno; reports speaker payment from Hamad Health Qatar; reports travel support from Rayze and Hamad Health Qatar; has stock options in Voximetry and MTT; is a stockholder in Clarity Pharmaceuticals; participates on advisory boards for Perspective and Fusion; is a member of the SNMMI Mars Shot Board; and was a past president of SNMMI. JSY reports funding to their institution from the NIH, the IVY Foundation, and the Falk Research Medical Trust; reports honoraria from the University of Maryland and the Dana Farber/Harvard Cancer Center; and holds an unpaid position in the Clinical Advisory Council at the American Brain Tumor Association. AMS reports trial funding to their institution from EMD Serono, ITM, Telix Pharmaceuticals, AVID Radiopharmaceuticals, Fusion Pharmaceuticals, and Cyclotek; reports research funding to their institution from Medimmune, Antengene, Humanigen, and Telix Pharmaceuticals; is on advisory boards of Imagion and ImmunOs; reports unpaid board membership of the Australian and New Zealand Society of Nuclear Medicine and the World Federation of Nuclear Medicine and Biology; and is supported by a NHMRC Investigator grant (number 1177837). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The number of new cancer cases in Commonwealth countries rose by 35% between 2008 and 2018, but progress in cancer control has been slow in many low-income and lower-middle-income member states. We aimed to examine cancer outcomes and priority areas in the Commonwealth to provide insight and guidance on prioritisation of efforts to improve cancer survival and make the best use of scarce resources., Methods: We adapted a previously developed microsimulation model of global cancer survival for 11 cancer sites (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate). All 56 Commonwealth countries were included and classified based on the 2020 World Bank Income groups (low-income, lower-middle-income, upper-middle-income, and high-income countries) and Commonwealth geographical areas. We modelled the number of incident cancer cases in each Commonwealth country in 2020, based on age group-specific estimates of incidence rates from GLOBOCAN 2020. We simulated 5-year net survival for each patient, accounting for the stage at diagnosis (I-IV), availability of specific treatment and imaging modalities, and quality of care (based on residual differences in expected versus observed survival after accounting for the availability and effectiveness of treatment and imaging modalities). We also simulated counterfactual policy scenarios, in which we scaled up various aspects of cancer care to the mean level of high-income countries to estimate the comparative effectiveness of different policies., Findings: Incident cancers in the Commonwealth accounted for an estimated 14·3% of global diagnosed cancer cases in 2020 among the 11 cancers modelled (1 610 000 Commonwealth cases [95% UI 1 556 000-1 674 000] of 11 227 000 global cases [11 069 000-11 406 000]) and are estimated to increase to 17·3% in 2050 due to population growth (3 330 000 [3 154 000-3 539 000] of 19 308 000 [18 706 000-19 911 000]). The 5-year net survival across 11 cancers combined in 2020 was 30·7% (95% UI 22·4-38·6) in Commonwealth countries, ranging from 4·1% (0·04-15·2) in low-income countries, 17·8% (3·7-30·9) in lower-middle-income countries, 33·1% (23·7-46·0) in upper-middle-income countries, to 59·0% (57·8-60·2) in high-income countries. Among single treatment policies, scaling up access to radiotherapy had the largest survival impact in low-income countries, surgery had the largest impact in lower-middle-income and upper-middle-income countries, and targeted therapy had the largest impact in high-income countries. By geographical area, improving radiotherapy availability was estimated to have the largest impact in Africa, surgery in Asia, targeted therapy in the Caribbean and the Americas and Europe, and quality of care in the Pacific Commonwealth countries. Comparing packages of scaling up the availability of all treatment modalities versus imaging modalities, expanding availability of imaging yielded the largest benefits in high-income countries, and in the Caribbean and the Americas, Europe, and the Pacific, whereas expanding treatment yielded larger benefits in all other income groups and geographical areas., Interpretation: We found large variation in 5-year net survival, with a nearly 15-times difference in cancer survival by country income group within the Commonwealth. Efforts to improve the availability of treatment and imaging modalities and quality of care will be crucial to reduce these disparities, with specific priorities of scale-up policies varying by setting. The Commonwealth could leverage a broad range of knowledge and resources and have an important role in supporting member countries with setting-specific priorities to improve cancer outcomes., Funding: Harvard T H Chan School of Public Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Cancer is a leading cause of disease burden globally, with more than 19·3 million cases and 10 million deaths recorded in 2020. Research is crucial to understanding the determinants of cancer and the effects of interventions, and to improving outcomes. We aimed to analyse global patterns of public and philanthropic investment in cancer research., Methods: In this content analysis, we searched the UberResearch Dimensions database and Cancer Research UK data for human cancer research funding awards from public and philanthropic funders between Jan 1, 2016, and Dec 31, 2020. Included award types were project and programme grants, fellowships, pump priming, and pilot projects. Awards focused on operational delivery of cancer care were excluded. Awards were categorised by cancer type, cross-cutting research theme, and research phase. Funding amount was compared with global burden of specific cancers, measured by disability-adjusted life-years, years lived with disability, and mortality using data from the Global Burden of Disease study., Findings: We identified 66 388 awards with total investment of about US$24·5 billion in 2016-20. Investment decreased year-on-year, with the largest drop observed between 2019 and 2020. Pre-clinical research received 73·5% of the funding across the 5 years ($18 billion), phase 1-4 clinical trials received 7·4% ($1·8 billion), public health research received 9·4% ($2·3 billion), and cross-disciplinary research received 5·0% ($1·2 billion). General cancer research received the largest investment ($7·1 billion, 29·2% of the total funding). The most highly funded cancer types were breast cancer ($2·7 billion [11·2%]), haematological cancer ($2·3 billion [9·4%]), and brain cancer ($1·3 billion [5·5%]). Analysis by cross-cutting theme revealed that 41·2% of investment ($9·6 billion) went to cancer biology research, 19·6% ($4·6 billion) to drug treatment research, and 12·1% ($2·8 billion) to immuno-oncology. 1·4% of the total funding ($0·3 billion) was spent on surgery research, 2·8% ($0·7 billion) was spent on radiotherapy research, and 0·5% ($0·1 billion) was spent on global health studies., Interpretation: Cancer research funding must be aligned with the global burden of cancer with more equitable funding for cancer research in low-income and middle-income countries (which account for 80% of cancer burden), both to support research relevant to these settings, and build research capacity within these countries. There is an urgent need to prioritise investment in surgery and radiotherapy research given their primacy in the treatment of many solid tumours., Funding: None., Competing Interests: Declaration of interests SAMcI reports honoraria from MSD, Roche, and Becton, Dickinson & Company; is on advisory boards for Roche, Lilly, and MSD; reports conference travel and support from Roche, Lilly, and MSD; and institutional research funding from Novartis. RIC reports institutional research funding from Astra Zeneca and SECA. EC reports institutional research funding from Astra Zeneca and SECA; and honoraria from Roche, Astra Zeneca, Lilly, Novartis, Pfizer, and Daiichi-Sankyo; and conference travel and support from Roche and Novartis. RA reports institutional research funding from Novo Nordisk, Novartis, Roche, and Union for International Cancer Control, and honoraria from Merck, Hoffman-La Roche, and Novartis. AM reports payments from the British Medical Association as a committee member. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies and planning to mitigate the forthcoming cancer-related health impacts of the pandemic in Chile., Methods: We developed a microsimulation model of five cancers in Chile (breast, cervix, colorectal, prostate, and stomach) for which reliable data were available, which simulates cancer incidence and progression in a nationally representative virtual population, as well as stage-specific cancer detection and survival probabilities. We calibrated the model to empirical data on monthly detected cases, as well as stage at diagnosis and 5-year net survival. We accounted for the impact of COVID-19 on excess mortality and cancer detection by month during the pandemic, and projected diagnosed cancer cases and outcomes of stage at diagnosis and survival up to 2030. For comparison, we simulated a no COVID-19 scenario in which the impacts of COVID-19 on excess mortality and cancer detection were removed., Findings: Our modelling showed a sharp decrease in the number of diagnosed cancer cases during the COVID-19 pandemic, with a large projected short-term increase in future diagnosed cases. Due to the projected backlog in diagnosis, we estimated that in 2021 there will be an extra 3198 cases (95% uncertainty interval [UI] 1356-5017) diagnosed among the five modelled cancers, an increase of nearly 14% compared with the no COVID-19 scenario, falling to a projected 10% increase in 2022 with 2674 extra cases (1318-4032) diagnosed. As a result of delayed diagnosis, we found a worse stage distribution for detected cancers in 2020-22, which is estimated to lead to 3542 excess cancer deaths (95% UI 2236-4816) in 2022-30, compared with the no COVID-19 scenario, among the five modelled cancers, most of which (3299 deaths, 2151-4431) are projected to occur before 2025., Interpretation: In addition to a large projected surge in diagnosed cancer cases, we found that delays in diagnosis will result in worse cancer stage at presentation, leading to worse survival outcomes. These findings can help to inform surge capacity planning and highlight the importance of ensuring appropriate health system capacity levels to detect and care for the increased cancer cases in the coming years, while maintaining the timeliness and quality of cancer care. Potential delays in treatment and adverse impacts on quality of care, which were not considered in this model, are likely to contribute to even more excess deaths from cancer than projected., Funding: Harvard TH Chan School of Public Health., Translations: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Female breast cancer is the most commonly diagnosed cancer in the world, with wide variations in reported survival by country. Women in low-income and middle-income countries (LMICs) in particular face several barriers to breast cancer services, including diagnostics and treatment. We aimed to estimate the potential impact of scaling up the availability of treatment and imaging modalities on breast cancer survival globally, together with improvements in quality of care., Methods: For this simulation-based analysis, we used a microsimulation model of global cancer survival, which accounts for the availability and stage-specific survival impact of specific treatment modalities (chemotherapy, radiotherapy, surgery, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single-photon emission computed tomography [SPECT]), and quality of cancer care, to simulate 5-year net survival for women with newly diagnosed breast cancer in 200 countries and territories in 2018. We calibrated the model to empirical data on 5-year net breast cancer survival in 2010-14 from CONCORD-3. We evaluated the potential impact of scaling up specific imaging and treatment modalities and quality of care to the mean level of high-income countries, individually and in combination. We ran 1000 simulations for each policy intervention and report the means and 95% uncertainty intervals (UIs) for all model outcomes., Findings: We estimate that global 5-year net survival for women diagnosed with breast cancer in 2018 was 67·9% (95% UI 62·9-73·4) overall, with an almost 25-times difference between low-income (3·5% [0·4-10·0]) and high-income (87·0% [85·6-88·4]) countries. Among individual treatment modalities, scaling up access to surgery alone was estimated to yield the largest survival gains globally (2·7% [95% UI 0·4-8·3]), and scaling up CT alone would have the largest global impact among imaging modalities (0·5% [0·0-2·0]). Scaling up a package of traditional modalities (surgery, chemotherapy, radiotherapy, ultrasound, and x-ray) could improve global 5-year net survival to 75·6% (95% UI 70·6-79·4), with survival in low-income countries improving from 3·5% (0·4-10·0) to 28·6% (4·9-60·1). Adding concurrent improvements in quality of care could further improve global 5-year net survival to 78·2% (95% UI 74·9-80·4), with a substantial impact in low-income countries, improving net survival to 55·3% (42·2-67·8). Comprehensive scale-up of access to all modalities and improvements in quality of care could improve global 5-year net survival to 82·3% (95% UI 79·3-85·0)., Interpretation: Comprehensive scale-up of treatment and imaging modalities, and improvements in quality of care could improve global 5-year net breast cancer survival by nearly 15 percentage points. Scale-up of traditional modalities and quality-of-care improvements could achieve 70% of these total potential gains, with substantial impact in LMICs, providing a more feasible pathway to improving breast cancer survival in these settings even without the benefits of future investments in targeted therapy and advanced imaging., Funding: Harvard T H Chan School of Public Health, and National Cancer Institute P30 Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The diagnosis and treatment of patients with cancer requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified substantial shortages in equipment and workforce, particularly in low-income and middle-income countries (LMICs). A microsimulation model of 11 cancers showed that the scale-up of imaging would avert 3·2% (2·46 million) of all 76·0 million deaths caused by the modelled cancers worldwide between 2020 and 2030, saving 54·92 million life-years. A comprehensive scale-up of imaging, treatment, and care quality would avert 9·55 million (12·5%) of all cancer deaths caused by the modelled cancers worldwide, saving 232·30 million life-years. Scale-up of imaging would cost US$6·84 billion in 2020-30 but yield lifetime productivity gains of $1·23 trillion worldwide, a net return of $179·19 per $1 invested. Combining the scale-up of imaging, treatment, and quality of care would provide a net benefit of $2·66 trillion and a net return of $12·43 per $1 invested. With the use of a conservative approach regarding human capital, the scale-up of imaging alone would provide a net benefit of $209·46 billion and net return of $31·61 per $1 invested. With comprehensive scale-up, the worldwide net benefit using the human capital approach is $340·42 billion and the return per dollar invested is $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In addition to increased availability of treatment modalities, advanced imaging modalities are increasingly recommended to improve global cancer care. However, estimates of the costs and benefits of investments to improve cancer survival are scarce, especially for low-income and middle-income countries (LMICs). In this analysis, we aimed to estimate the costs and lifetime health and economic benefits of scaling up imaging and treatment modality packages on cancer survival, both globally and by country income group., Methods: Using a previously developed model of global cancer survival, we estimated stage-specific cancer survival and life-years gained (accounting for competing mortality) in 200 countries and territories for patients diagnosed with one of 11 cancers (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate) representing 60% of all cancer diagnoses between 2020 and 2030 (inclusive of full years). We evaluated the costs and health and economic benefits of scaling up packages of treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, single-photon emission CT), and quality of care to the mean level of high-income countries, separately and in combination, compared with no scale-up. Costs and benefits are presented in 2018 US$ and discounted at 3% annually., Findings: For the 11 cancers studied, we estimated that without scale-up (ie, with current availability of treatment, imaging, and quality of care) there will be 76·0 million cancer deaths (95% UI 73·9-78·6) globally for patients diagnosed between 2020 and 2030, with more than 70% of these deaths occurring in LMICs. Comprehensive scale-up of treatment, imaging, and quality of care could avert 12·5% (95% UI 9·0-16·3) of these deaths globally, ranging from 2·8% (1·8-4·3) in high-income countries to 38·2% (32·6-44·5) in low-income countries. Globally, we estimate that comprehensive scale-up would cost an additional $232·9 billion (95% UI 85·9-422·0) between 2020 and 2030 (representing a 6·9% increase in cancer treatment costs), but produce $2·9 trillion (1·8-4·0) in lifetime economic benefits, yielding a return of $12·43 (6·47-33·23) per dollar invested. Scaling up treatment and quality of care without imaging would yield a return of $6·15 (2·66-16·71) per dollar invested and avert 7·0% (3·9-10·3) of cancer deaths worldwide., Interpretation: Simultaneous investment in cancer treatment, imaging, and quality of care could yield substantial health and economic benefits, especially in LMICs. These results provide a compelling rationale for the value of investing in the global scale-up of cancer care., Funding: Harvard TH Chan School of Public Health and National Cancer Institute., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Accurate survival estimates are important for cancer control planning. Although observed survival estimates are unavailable for many countries, where they are available, wide variations are reported. Understanding the impact of specific treatment and imaging modalities can help decision makers to effectively allocate resources to improve cancer survival in their local context., Methods: We developed a microsimulation model of stage-specific cancer survival in 200 countries and territories for 11 cancers (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate) comprising 60% of global diagnosed cancer cases. The model accounts for country-specific availability of treatment (chemotherapy, surgery, radiotherapy, and targeted therapy) and imaging modalities (ultrasound, x-ray, CT, MRI, PET, single-photon emission CT), as well as quality of care. We calibrated the model to reported survival estimates from CONCORD-3 (which reports global trends in cancer survival in 2000-14). We estimated 5-year net survival for diagnosed cancers in each country or territory and estimated potential survival gains from increasing the availability of individual treatment and imaging modalities, and more comprehensive packages of scale-up of these interventions. We report the mean and 95% uncertainty intervals (UIs) for all outcomes, calculated as the 2·5 and 97·5 percentiles of the simulation results., Findings: The estimated global 5-year net survival for all 11 cancers combined is 42·6% (95% uncertainty interval 40·3-44·3), with survival in high-income countries being an average of 12 times (range 4-17) higher than that in low-income countries. Expanding availability of surgery or radiotherapy or improving quality of care would yield the largest survival gains in low-income (2·5-3·4 percentage point increase in survival) and lower-middle-income countries (2·4-6·1 percentage point increase), whereas upper-middle-income and high-income countries are more likely to benefit from improved availability of targeted therapy (0·7 percentage point increase for upper-middle income and 0·4 percentage point increase for high income). Investing in medical imaging will also be necessary to achieve substantial survival gains, with traditional modalities estimated to provide the largest gains in low-income settings, while MRI and PET would yield the largest gains in higher-income countries. Simultaneous expansion of treatment, imaging, and quality of care could improve 5-year net survival by more than ten times in low-income countries (3·8% [95% UI 0·5-9·2] to 45·2% [40·2-52·1]) and could more than double 5-year net survival in lower-middle-income countries (20·1% [7·2-31·7] to 47·1% [42·8-50·8])., Interpretation: Scaling up both treatment and imaging availability could yield synergistic survival gains for patients with cancer. Expanding traditional modalities in lower-income settings might be a feasible pathway to improve survival before scaling up more modern technologies., Funding: Harvard T H Chan School of Public Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cervical cancer is the fourth most common cancer among women worldwide, causing more than 300 000 deaths globally each year. In addition to screening and prevention, effective cancer treatment is needed to reduce cervical cancer mortality. We discuss the role of imaging in cervical cancer management and estimate the potential survival effect of scaling up imaging in several different contexts., Methods: Using a previously developed microsimulation model of global cancer survival, we estimated stage-specific cervical cancer 5-year net survival in 200 countries and territories. We evaluated the potential survival effect of scaling up treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), and imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single photon emission CT [SPECT]) to the mean level of high-income countries, both individually and in combination., Findings: We estimate global cervical cancer 5-year net survival as 42·1% (95% uncertainty interval [UI] 33·8-48·5). Among individual imaging modalities, expanding MRI would yield the largest 5-year survival gains globally (data are absolute percentage point increase in survival 0·6, 95% UI 0·1-2·1), scaling up ultrasound would yield the largest gains in low-income countries (0·5, 0·0-3·7), expanding CT and x-ray would have the greatest effect in Latin America (0·8, 0·0-3·4) and Oceania (0·4, 0·0-3·2), and expanding PET would yield the largest gains in high-income countries (0·2, 0·0-0·8). Scaling up SPECT did not show major changes in any region. Among individual treatment modalities, scaling up radiotherapy would yield the largest absolute percentage point gains in low-income countries (5·2, 0·3-13·5), and expanding surgery would have the largest effect in lower-middle-income countries (7·4, 0·3-21·1) and upper-middle-income countries (0·8, 0·0-2·9). Estimated survival gains in high-income countries were very modest. However, the gains from expanding any single treatment or imaging modality individually were small across all income levels and geographical settings. Scaling up all treatment modalities could improve global 5-year net survival to 52·4% (95% UI 44·6-62·0). In addition to expanding treatment, improving quality of care could raise survival to 57·5% (51·2-63·5), and the cumulative effect of scaling up all imaging modalities together with expanded treatment and quality of care could improve 5-year net survival for cervical cancer to 62·5% (57·7-67·8)., Interpretation: Comprehensive scale-up of treatment, imaging, and quality of care could substantially improve global cervical cancer 5-year net survival, with quality of care and imaging improvements each contributing about 25% of the total potential gains. These findings suggest that a narrow focus on the availability of treatment modalities could forgo substantial survival gains. Investments in imaging equipment, personnel, and quality of care efforts will also be needed to successfully scale up cervical cancer treatment worldwide., Funding: Harvard T H Chan School of Public Health and National Cancer Institute., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Childhood cancers caused an estimated 75 000 deaths in children aged 0-14 years in 2018, of which 90% were in low-income and middle-income countries, and yet this group is missing from global health agendas. We examined global patterns in public and philanthropic funding for childhood cancer research-a proxy for global research activity-to address the critical gaps in knowledge. We used data from the Dimensions database to systematically search for and analyse 3414 grants from 115 funders across 35 countries between 2008 and 2016, organised by funding source, recipient, tumour type, research focus, and pipeline categories, to investigate trends over time. During this period, global funding for childhood cancer research was US$2 billion, of which $772 million (37·9%) was for general childhood cancer, $449 million (22·0%) was for leukaemias, and $330 million (16·2%) was for CNS tumours. $1·6 billion (77·7%) of funding was awarded from, and to, institutions based in the USA. Preclinical research received $1·2 billion (59·3%), and around $525 million (25·7%) included support for clinical trials, but only $113 million (5·5%) supported health-care delivery research. Overall, funding was inadequate and geographically inequitable, and new commitments to funding have declined since 2011., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Accurate childhood cancer survival estimates are crucial for policy makers and clinicians for priority-setting and planning decisions. However, observed survival estimates are lacking for many countries, and when available, wide variation in outcomes is reported. Understanding the barriers to optimising survival can help improve childhood cancer outcomes. We aimed to provide estimates of global childhood cancer survival, accounting for the impact of multiple factors that affect cancer outcomes in children., Methods: We developed a microsimulation model to simulate childhood cancer survival for 200 countries and territories worldwide, accounting for clinical and epidemiologic factors, including country-specific treatment variables, such as availability of chemotherapy, radiation, and surgery. To ensure model results were consistent with reported survival data, we calibrated the model to estimates from the CONCORD-2 and CONCORD-3 studies using an Approximate Bayesian Computation approach. We estimated 5-year net survival for diagnosed cases of childhood cancer in each country and territory and estimated potential survival gains of seven policy interventions focused on improving treatment availability and delivery (ie, increasing the availability of chemotherapy, radiation, general surgery, neurosurgery, or ophthalmic surgery, reducing treatment abandonment, and improving the quality of care to the mean of high-income countries) implemented in isolation or as packages., Findings: Our model estimated that, for diagnosed cases, global 5-year net childhood cancer survival is currently 37·4% (95% uncertainty interval 34·7-39·8), with large variation by region, ranging from 8·1% (4·4-13·7) in eastern Africa to 83·0% (81·6-84·4) in North America. Among the seven policy interventions modelled, each individually provided small gains, increasing global 5-year net survival to between 38·4% (35·8-40·9) and 44·6% (41·7-47·4). 5-year net survival increased more substantially when policy interventions were bundled into packages that improved service delivery (5-year net survival 50·2% [47·3-53·0]) or that expanded treatment access (54·1% [50·1-58·5]). A comprehensive systems approach consisting of all policy interventions yielded superadditive gains with a global 5-year net survival of 53·6% (51·5-55·6) at 50% scale-up and 80·8% (79·5-82·1) at full implementation., Interpretation: Childhood cancer survival varies widely by region, with especially poor survival in Africa. Although expanding access to treatment (chemotherapy, radiation, and surgery) and addressing financial toxicity are essential, investments that improve the quality of care, at both the health-system and facility level, are needed to improve childhood cancer outcomes globally., Funding: Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard TH Chan School of Public Health, Harvard Medical School, National Cancer Institute, SickKids, St Jude Children's Research Hospital, Union for International Cancer Control, Children with Cancer UK Davidson and O'Gorman Fellowship., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination., Methods: We applied the Global Task Force on Radiotherapy for Cancer Control investment framework to model the health and economic benefits of scaling up external-beam radiotherapy and brachytherapy for cervical cancer in upper-middle-income, lower-middle-income, and low-income countries between 2015 and 2035. We estimated the unique costs of external-beam radiotherapy and brachytherapy and included a specific valuation of women's caregiving contributions. Model outcomes life-years gained and the human capital and full income net present value of investment. We estimated the effects of stage at diagnosis, radiotherapy delivery system, and simultaneous HPV vaccination (75% coverage) up to a time horizon set at 2072., Findings: For the period from 2015 to 2035, we estimated that 9·4 million women in low-income and middle-income countries required treatment with external-beam radiotherapy, of which 7·0 million also required treatment with brachytherapy. Incremental scale-up of radiotherapy in these countries from 2015 to meet optimal radiotherapy demand by 2035 yielded 11·4 million life-years gained, $59·3 billion in human capital net present value (-$1·5 billion in low-income, $19·9 billion in lower-middle-income, and $40·9 billion in upper-middle-income countries), and $151·5 billion in full income net present value ($1·5 billion in low-income countries, $53·6 billion in lower-middle-income countries, and $96·4 billion in upper-middle-income countries). Benefits increased with advanced stage of cervical cancer and more efficient scale up of radiotherapy. Bivalent HPV vaccination of 12-year-old girls resulted in a 3·9% reduction in incident cases from 2015-2035. By 2072, when the first vaccinated cohort of girls reaches 70 years of age, vaccination yielded a 22·9% reduction in cervical cancer incidence, with 38·4 million requiring external-beam radiotherapy and 28·8 million requiring brachytherapy., Interpretation: Effective cervical cancer control requires a comprehensive strategy. Even with HPV vaccination, radiotherapy treatment scale-up remains essential and produces large health benefits and a strong return on investment to countries at different levels of development., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Accurate estimates of childhood cancer incidence are important for policy makers to inform priority setting and planning decisions. However, many countries do not have cancer registries that quantify the incidence of childhood cancer. Moreover, even when registries do exist, they might substantially underestimate the true incidence, since children with cancer might not be diagnosed. We therefore aimed to provide estimates of total childhood cancer incidence accounting for underdiagnosis., Methods: We developed a microsimulation model to simulate childhood cancer incidence for 200 countries and territories worldwide, taking into account trends in population growth and urbanicity, geographical variation in cancer incidence, and health system barriers to access and referral that contribute to underdiagnosis. To ensure model results were consistent with epidemiological data, we calibrated the model to publicly available cancer registry data using a Bayesian approach in which the observed data are fixed and the model parameters (cancer incidence and probabilities of health system access and referral) are random variables. We estimated the total incidence of childhood cancer (diagnosed and undiagnosed) in each country in 2015 and projected the number of cases from 2015 to 2030., Findings: Our model estimated that there were 397 000 (95% uncertainty interval [UI] 377 000-426 000) incident cases of childhood cancer worldwide in 2015, of which only 224 000 (95% UI 216 000-237 000) were diagnosed. This finding suggests that 43% (172 000 of 397 000) of childhood cancer cases were undiagnosed globally, with substantial variation by region, ranging from 3% in western Europe (120 of 4300) and North America (300 of 10 900) to 57% (43 000 of 76 000) in western Africa. In south Asia (including southeastern Asia and south-central Asia), the overall proportion of undiagnosed cases was estimated to be 49% (67 000 of 137 000). Taking into account population projections, we estimated that there will be 6·7 million (95% UI 6·3-7·2) cases of childhood cancer worldwide from 2015 to 2030. At current levels of health system performance, we estimated that 2·9 million (95% UI 2·7-3·3) cases of childhood cancer will be missed between 2015 and 2030., Interpretation: Childhood cancer is substantially underdiagnosed, especially in south Asia and sub-Saharan Africa (including western, eastern, and southern Africa). In addition to improving treatment for childhood cancer, health systems must be strengthened to accurately diagnose and effectively care for all children with cancer. As countries expand universal health coverage, these estimates of total incidence will hopefully help guide efforts to appropriately increase health system capacity to ensure access to effective childhood cancer care., Funding: Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard T H Chan School of Public Health, Harvard Medical School, National Cancer Institute, SickKids, St Jude Children's Research Hospital, and Union for International Cancer Control., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

5-year net survival of children and adolescents diagnosed with cancer is approximately 80% in many high-income countries. This estimate is encouraging as it shows the substantial progress that has been made in the diagnosis and treatment of childhood cancer. Unfortunately, scarce data are available for low-income and middle-income countries (LMICs), where nearly 90% of children with cancer reside, suggesting that global survival estimates are substantially worse in these regions. As LMICs are undergoing a rapid epidemiological transition, with a shifting burden from infectious diseases to non-communicable diseases, cancer care for all ages has become a global focus. To improve outcomes for children and adolescents diagnosed with cancer worldwide, an accurate appraisal of the global burden of childhood cancer is a necessary first step. In this Review, we analyse four studies of the global cancer burden that included data for children and adolescents. Each study used various overlapping and non-overlapping statistical approaches and outcome metrics. Moreover, to provide guidance on improving future estimates of the childhood global cancer burden, we propose several recommendations to strengthen data collection and standardise analyses. Ultimately, these data could help stakeholders to develop plans for national and institutional cancer programmes, with the overall aim of helping to reduce the global burden of cancer in children and adolescents., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries-a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015-35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015-35 (-$14·9 billion in low-income countries; -$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (-$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits., (Copyright © 2015 Elsevier Ltd. All rights reserved.)