Premature mortality trends in 183 countries by cancer type, sex, WHO region, and World Bank income level in 2000-19: a retrospective, cross-sectional, population-based study.

BACKGROUND: Cancer is a leading cause of mortality worldwide. By 2040, over 30 million new cancers are predicted, with the greatest cancer burden in low-income countries. In 2015, the UN passed the Sustainable Development Goal 3.4 (SDG 3.4) to tackle the rising burden of non-communicable diseases, which calls for a reduction by a third in premature mortality from non-communicable diseases, including cancer, by 2030. However, there is a paucity of data on premature mortality rates by cancer type. In this study, we examine annual rates of change for cancer-specific premature mortality and classify whether countries are on track to reach SDG 3.4 targets. METHODS: This is a retrospective, cross-sectional, population-based study investigating premature mortality trends from 2000-19 using the WHO Global Health Estimates data. All cancers combined and thirteen individual cancers in 183 countries were examined by WHO region, World Bank income level, and sex. The risk of premature mortality was calculated for ages 30-69 years, independent of other competing causes of death, using standard life table methods. The primary objective was to compute average annual rate of change in premature mortality from 2000 to 2019. Secondary objectives assessed whether this annual rate of change would be sufficient to reach SDG 3.4. targets for premature mortality by 2030. FINDINGS: This study was conducted using data retrieved for the years 2000-19. Premature mortality rates decreased in 138 (75%) of 183 countries across all World Bank income levels and WHO regions, however only eight (4%) countries are likely to meet the SDG 3.4 targets for all cancers combined. Cancers where early detection strategies exist, such as breast and colorectal cancer, have higher declining premature mortality rates in high-income countries (breast cancer 48 [89%] of 54 and colorectal cancer 45 [83%]) than in low-income countries (seven [24%] of 29 and four [14%]). Cancers with primary prevention programmes, such as cervical cancer, have more countries with declining premature mortality rates (high-income countries 50 [93%] of 54 and low-income countries 26 [90%] of 29). Sex-related disparities in premature mortality rates vary across WHO regions, World Bank income groups, and by cancer type. INTERPRETATION: There is a greater reduction in premature mortality for all cancers combined and for individual cancer types in high-income countries compared with lower-middle-income and low-income countries. However, most countries will not reach the SDG 3.4 target. Cancers with early detection strategies in place, such as breast and colorectal cancers, are performing poorly in premature mortality compared with cancers with primary prevention measures, such as cervical cancer. Investments toward prevention, early detection, and treatment can potentially accelerate declines in premature mortality. FUNDING: WHO.

Evolution and current trends in the management of colorectal cancer liver metastasis.

Metastatic colorectal cancer (mCRC) is a major cause of cancer-related death, with a 5-year relative overall survival of up to 20%. The liver is the most common site of distant metastasis in colorectal cancer (CRC), with about 50% of CRC patients metastasizing to their liver over the course of their disease. Complete liver resection is the primary modality of treatment for resectable colorectal cancer liver metastasis (CRLM), with an overall 5-year survival rate of up to 58%. However, only 15% to 20% of patients with CRLM are deemed suitable for resection at presentation. For unresectable diseases, the median survival of patients remains low even with the best chemotherapy. In recent decades, the management of CRLM has continued to evolve with the expansion of resection criteria, novel targeted systemic therapies, and improved locoregional therapies. However, due to the heterogeneity of the CRC patient population, the optimal evaluation of treatment options for CRLM remains complex. Therefore, effective management requires a multidisciplinary team to help define resectability and devise a personalized treatment approach, from the initial diagnosis to the final treatment.

Series on the Lancet Oncology Commission on Global Cancer Surgery: Introduction-Intent and Content.

BACKGROUND: Surgery plays a key role in the multi-disciplinary cancer care pathway. Nearly 80% of patients with solid tumors will require surgical intervention during the course of their disease. Unfortunately, the vast majority of these patients do not have access to safe, timely, high-quality, and affordable cancer surgical care. The first Lancet Oncology Commission on Global Cancer Surgery shone a light on this grave situation and outlined some strategies to address them. The second Lancet Oncology Commission on Global Cancer Surgery (TLO- II) was conceived to continue the work of its predecessor by developing a roadmap of practical solutions to propel improvements in cancer surgical care globally. METHODS: The Commission was developed by involving approximately 50 cancer care leaders and experts from different parts of the world to ensure diversity of input and global applicability. RESULTS: The Commission identified nine solutional domains that are considered essential to deliver safe, timely, high-quality, and affordable cancer surgical care. These nine domains were further refined to develop solutions specific to each of the six World Health Organization regions. Based on the above solutions, we developed eight action items that are intended to propel improvements in cancer surgical care on the global stage. CONCLUSIONS: The second Lancet Oncology Commission on Global Cancer Surgery builds on the first Commission by developing a pragmatic roadmap of practical solutions that we hope will ensure access to safe, timely, high-quality, and affordable cancer surgical care for everyone regardless of their socioeconomic status or geographic location.

Incorporation of Simulation in Graduate Medical Education: Historical Perspectives, Current Status, and Future Directions.

Technological advancement and improved training strategies have transformed the healthcare practice environment in the last few decades. Simulation has evolved as one of the leading training models for the next generation of healthcare professionals. Simulation-based training enables healthcare professionals to acquire knowledge and skills in a safe and educationally oriented environment and can be a valuable tool for improving clinical practice and patient outcomes. The field of healthcare simulation has been rapidly growing, and various graduate medical education programs around the world have started incorporating this modality into their curricula. In graduate medical education, simulation-based training helps implement an outcome-based curriculum that tests the trainee's actual skill level as the primary factor for the trainee's competency rather than relying on the current model of a predetermined training period. However, the major challenge revolves around developing an educational curriculum incorporating a simulation-based educational model, understanding the value of this new technology, the overall cost factor, and the lack of adequate infrastructure. Hence, embracing the full potential of simulation technology in graduate medical education curricula requires an innovative approach with participation from institutions and stakeholders.

PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.

In the last decade, pathway-specific targeted therapy has revolutionized colorectal cancer (CRC) treatment strategies. This type of therapy targets a tumor-vulnerable spot formed primarily due to an alteration in an oncogene and/or a tumor suppressor gene. However, tumor heterogeneity in CRC frequently results in treatment resistance, underscoring the need to understand the molecular mechanisms involved in CRC for the development of novel targeted therapies. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/Akt/mTOR) signaling pathway axis is a major pathway altered in CRC. The aberrant activation of this pathway is associated with CRC initiation, progression, and metastasis and is critical for the development of drug resistance in CRC. Several drugs target PI3K/Akt/mTOR in clinical trials, alone or in combination, for the treatment of CRC. This review aims to provide an overview of the role of the PI3K/Akt/mTOR signaling pathway axis in driving CRC, existing PI3K/Akt/mTOR-targeted agents against CRC, their limitations, and future trends.

Cancer surgery on the global stage: Updates and progress.

Over 5 billion people lack access to basic surgical procedures, and it is estimated, the number of surgical procedures needed for cancer care will increase by 5 million from 2018 to 2040. The greatest increase in demand will occur in low- and middle-income countries. In this article, we highlight progress made in surgical cancer care globally and gaps that still needs to be addressed. We highlight political support, workforce progress and shortages, impact of the COVID-19 pandemic, and the importance of high value cancer care.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

From ChatGPT to Treatment: the Future of AI and Large Language Models in Surgical Oncology.

This paper explores the transformative potential of Large Language Models (LLMs) within the context of surgical oncology and outlines the foundational mechanisms behind these models. LLMs, such as GPT-4, have rapidly evolved in terms of scale and capabilities, with profound implications for their applications in healthcare. These models, rooted in the Generative Pretrained Transformer architecture, exhibit advanced natural language understanding and generation skills. Within surgical oncology, LLMs, when integrated into a Generalist Medical AI (GMAI) framework, hold great promise in offering real-time support throughout the cancer journey. However, alongside these opportunities, this paper underscores the importance of ethical, privacy, and efficacy considerations, especially in light of issues like data drift and potential biases. Collaborative efforts among healthcare providers, AI developers, and regulatory bodies are pivotal in ensuring responsible and effective use of LLMs in surgical oncology, thereby contributing to enhanced patient care and safety. As LLMs continue to advance, they are poised to become indispensable tools in the delivery of high-quality, efficient care in this specialized medical field.

Education of the cancer surgical workforce: Gaps, priorities, and strategies.

Cancer is a leading cause of noncommunicable disease-related mortality. The predicted number of new cancer cases will increase from 19.3 million in 2020 to 30.2 million by 2040. To mitigate the cancer burden, it is critical to build capacity of the cancer workforce, especially in systems with limited resources. We provide a global overview of gaps and implementation strategies that can increase the quality and quantity of the global surgical cancer workforce.

Global trends in the incidence and mortality of pancreatic cancer based on geographic location, socioeconomic status, and demographic shift.

BACKGROUND: Pancreatic cancer (PC) is a lethal malignancy with a significantly rising rate of incidence and mortality. This study aims to describe the influence of geography, socioeconomic development (based on the Human Development Index [HDI]), gender, and demographic shift on the temporal trends in the global burden of PC. METHODS: Data (2020-2040) relating to the incidence, mortality of PC, and demographic shifts based on continents and HDI areas were extracted from GLOBOCAN 2020. RESULTS: PC was associated with a higher socioeconomic status. Asia contributed to the majority of the burden, led by China. Advanced age (≥65 years) contributed to the majority of the burden in all socioeconomic regions except in Medium HDI and Low HDI countries, where the younger population (<65 years) contributed more. Females contributed to a higher burden in certain countries. Future trends for 2040 showed a >60% increase in the incidence and mortality of PC with an associated demographic shift. CONCLUSION: The global burden of PC is expected to rise significantly over the next few decades regardless of geography, socioeconomic development, age, and gender. Advance knowledge of this data can help to formulate strategies and public health policies to specifically target countries and populations at risk.

Global epidemiological trends and variations in the burden of gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is a rare but lethal malignancy with a dismal prognosis. The aim of this study is to analyze the burdens and trends of GBC across the world based on geography, socioeconomic development (based on human development index [HDI]), and gender. METHODS: GLOBOCAN 2020 database was used to extract data (2020-2040) relating to the incidence and mortality of GBC across the world. RESULTS: Asia had the highest burden of GBC with India and China contributing to majority of the absolute burden. The burden of GBC by age standardized rate was highest in Latin America (Bolivia and Chile) and Southeast Asia (Bangladesh and Nepal). Medium HDI countries had a higher mortality rate compared to very high HDI countries. Females had a higher predilection for GBC across different regions and socioeconomic groups. GBC burden is expected to significantly increase across the world by 2040 with variable trends across different regions, age groups, and genders. CONCLUSION: The global burden of GBC will significantly increase over the next two decades with marked regional and demographic variations. The results of this study will empower national and global health leaders to develop policies to address the increasing burden of this lethal malignancy.

Inequities in cancer surgical research capacity in the global south and strategies to address them.

Globally, cancer is a leading cause of premature mortality and incidence is rising rapidly. To mitigate the cancer burden establishing research programs that are country and/or region specific will inform evidence-based cancer control policies and programs. However inequities in surgical cancer research in the global south exist and in this article we discuss gaps and potential solutions through frameworks focusing on research training, building infrastructure, economic strategies, and research ethics.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Impact of COVID-19 on cancer services and patients' outcomes: a retrospective single-center study.

Background: Our main objective was to assess the impact of the coronavirus disease 2019 (COVID-19) on cancer services and cancer patients in terms of disease severity, morbidity and mortality. Secondary objectives were to characterize cancer type, affected age groups, gender, comorbidities, infectivity, and to identify cancer treatment delay and its complications after COVID-19 infection. Methods: A retrospective analysis of electronic health records of polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected cancer patients from April 2020 to March 2021 was done. The following parameters were investigated upon-new and follow-up cases during the pandemic and its preceding years (2018-2019, 2019-2020), age, sex, type of cancer, comorbidities, presentation, symptomatology and treatment for COVID-19, time to recovery, complications, delay in treatment and survival outcome. Statistical analysis using chi-square testing was done on the above variables. Results: There was a 50.49% reduction in the number of new and follow-up cases as compared to that of the previous years. Seventy-four out of 310 (23.87%) COVID-19 positive cancer patients were aged in their sixth decade with the commonest type being hematological malignancies. A proportion of 84.8% (n=263) patients were asymptomatic. Univariate analysis was statistically significant for mortality with regard to age ≥60 years (P=0.034), type of malignancy (P=0.000178), hypertension (P=0.0028), symptomatology of COVID-19 infection (P=0.0016), site of treatment and oxygen/intervention (P<0.0001). There was an average delay in treatment time of 5 to 6 weeks. Multivariate analysis showed that gastrointestinal (GI) and hepato-pancreato-biliary (HPB) malignancies and oxygen requirement (>2 L/min) were responsible for the 20.65% mortality rate. Conclusions: The pandemic significantly affected the care of cancer patients with decreased cases, late presentation, delayed treatment with potentially worse mortality outcome. Although they have decreased immunity, majority were asymptomatic. Most of the fatalities were in the GI and HPB malignancies.

Competency-Based Medical Education (CBME): an Overview and Relevance to the Education of Future Surgical Oncologists.

In the next two decades, the global cancer burden is expected to rise by 47%, and the demand for global cancer surgery will increase by 52%. At present, only 25% of the estimated 80% of patients needing surgical intervention have access to timely surgical care. The shortage of a trained workforce of surgical oncologists is one of the main barriers to providing the optimal surgical intervention needed for cancer patients. Some of the contributing factors to the shortage of trained surgical oncologists are variations in the current global educational platforms, long training programs, and physician burnout. Therefore, the availability of a credible training framework and a sustainable certification pipeline for future surgical oncologists is critical to meet the global demand for an adequate healthcare workforce. The current surgical oncology educational program is a time-based construct that trains surgeons to function seamlessly in the multidisciplinary care of cancer patients. However, there is a lack of flexibility in the training framework and timeline despite differences in trainees' abilities. Developing a globally acceptable standard curriculum for surgical oncology training based on the competency-based medical education (CBME) framework and tailoring it to local needs can increase the surgical oncology workforce ready to tackle the rising cancer burden. However, successful implementation of the global CBME-based surgical oncology training curriculum requires an innovative approach to ensure that this framework produces a competent surgical oncologist that meets the local needs.

Colorectal cancer: Review of signaling pathways and associated therapeutic strategies.

Tumor profiling and targeted therapy revolutionized the treatment strategies of metastatic colorectal cancer (mCRC) in the last decade. The heterogeneity of CRC tumors plays a critical role in the development of treatment resistance, which underscores the need to understand the molecular mechanism involved in CRC to develop novel targeted therapeutic strategies. This review provides an overview of the signaling pathways driving CRC, the existing targeted agents, their limitations, and future trends.

Factors associated with pathologic complete response following neoadjuvant chemoradiation and esophagectomy for carcinoma of esophagus and gastroesophageal junction.

BACKGROUND AND OBJECTIVES: The aim of this study was to analyze factors associated with pathologic complete response (pCR) following neoadjuvant chemoradiation (NCRT) and esophagectomy for carcinoma of the esophagus (EC) and gastroesophageal junction (GEJ). METHODS: Patients with EC and GEJ tumors who received NCRT and underwent esophagectomy between January 2010 to March 2021 were included. Univariate and multivariate analyses were performed to evaluate the factors associated with pCR by comparing the patients who achieved pCR (pCR group) with those who did not achieve pCR (non-pCR group). RESULTS: A total of 321 patients were included in the study, with squamous cell carcinoma (SCC) accounting for the majority of cases (76%). One hundred and sixty (49.8%) patients had pCR. SCC histology and pretreatment radiographic node-negative status (cN0) were associated with pCR. Patients in the pCR group had significantly better overall and disease-free survival compared with patients in the non-pCR group. CONCLUSIONS: SCC histology and pretreatment radiographic node-negative status were associated with pCR. For patients with tumors of EC and GEJ who received NCRT and underwent esophagectomy, pCR was associated with improved prognosis compared with those not achieving pCR.