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.

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.

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.

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.

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.

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.

Geographic variation in attitudes regarding management of locally advanced pancreatic cancer.

Background: Recent literature suggests wide variations exist in the international management of locally advanced pancreatic cancer. This study sought to evaluate how geography contributes to variations in management of locally advanced pancreatic cancer. Methods: An electronic survey investigating preferences for the evaluation and management of locally advanced pancreatic cancer was distributed to an international cohort of pancreatic surgeons. Surgeons were classified according to geographic location of practice, and survey responses were compared across locations. Results: A total of 153 eligible responses were received from 4 continents: North and South America (n = 94, 61.4%), Europe (n = 25, 16.3%), and Asia (n = 34, 22.2%). Preferences for the use and duration of neoadjuvant chemotherapy and radiotherapy varied widely. For example, participants in Asia commonly preferred 2 months of neoadjuvant chemotherapy (61.8%), whereas North and South American participants preferred 4 months (52.1%), and responses in Europe were mixed (P = .006). Participants in Asia were less likely to consider isolated liver or lung metastases contraindications to exploration and consequently had a greater propensity to consider exploration in a vignette of oligometastatic disease (56.7% vs North and South America: 25.6%, Europe: 43.5%; P = .007). Conclusion: In an international survey of pancreatic surgeons, attitudes regarding locally advanced pancreatic cancer and metastatic disease management varied widely across geographic locations. Better evidence is needed to define optimal management of locally advanced pancreatic cancer.

Thyroid Cancer: Global Burden and Trends.

The incidence of thyroid cancer continues to increase, representing the 5th most common cancer type in the USA today (Sherman, Lancet 361(9356):501-11, 2003). The current study sought to analyze the global burden of thyroid cancer utilizing the publicly accessible GLOBOCAN database. An estimated 586,202 cases of thyroid cancer were reported in 2020, making thyroid cancer the 10th most common cancer worldwide. The majority of thyroid cancer cases occurred in countries with a high or very high Human Development Index (HDI), accounting for 91% of new cases. With respect to the World Health Organization (WHO) regions, the Western Pacific had the highest incidence of thyroid cancer accounting for 47.6% of cases despite representing only 25.4% of the world's population. Thyroid cancer incidence and mortality are expected to increase by 29.9% and 67%, respectively, by the year 2040. The African region is projected to experience the highest increase in both incidence (84.3%) and mortality (100.3%) over this time period. The results of our study demonstrate that the incidence and mortality of thyroid cancer vary by the geographic location and socio-economic status. Although the incidence was noted to be the highest in very high HDI countries and the Western Pacific region, mortality was noted to be disproportionately higher in the low HDI countries and African region. This may be due to discrepancies in access to care and/or environmental exposures such as ionizing radiation and iodine deficiency. Further measures are required to improve the outcomes from thyroid cancer regardless of the geographic location or socio-economic status.

Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Radical surgery for de novo gallbladder carcinoma-Single-center analysis of prognostic factors and survival outcomes from an endemic region.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is an aggressive malignancy where curative resection is possible in few and survival is poor. There are limited data on outcomes in patients with de novo GBC from endemic regions undergoing surgery for curative intent. We report survival outcomes in this group of patients from a region with high incidence of disease. METHODS: We reviewed the records of all GBC patients (2014-2018) and included those who underwent radical cholecystectomy (RC) for de novo GBC. Univariable and multivariable analyses were performed to identify factors influencing recurrence and survival. RESULTS: A total of 649 patients with GBC were evaluated for surgery and curative intent surgery was attempted in 246 (38%) patients. Of these 246 patients, RC was performed in 115 patients, with histologically confirmed de novo GBC. Locally advanced disease (≥stage IIIB) was present in 52 (45.2%) patients. Median time to recurrence and overall survival (OS) were 31 and 36 months, respectively. Lymph node positivity (p = 0.005) and grade significantly influenced OS on multivariable analysis. CONCLUSION: Satisfactory survival outcomes are possible after RC for de novo GBC. Extended resections performed in high volume centers combined with appropriate adjuvant treatment can offer significant survival benefits, with acceptable morbidity and mortality rates.

The interdisciplinary and psychosocial gap in cancer survivorship: A longitudinal study in a Latin American Cancer Center.

BACKGROUND AND OBJECTIVES: There is lack of information on the quality of care provided to the rapidly increasing population of cancer survivors in Latin America. Our study attempts to address this gap and to identify areas needed to be improved. METHODS: A random sample of 210 breast and colorectal cancer survivors were selected from a hospital-based registry in Chile. Cancer registry information, electronic chart review, and personal interviews were used to assess medical and nonmedical care over a 5-year period. Survivorship care practices were compared to a standardized reference based on the US Institute of Medicine domains and the American Cancer Association guidelines. RESULTS: Over 80% of breast and colorectal cancer survivors received appropriate medical care, ongoing testing surveillance and risk factors assessment. Only a third of survivors were assessed for psychosocial disorders and 25% of them received interdisciplinary care. Overall, 66.1% of breast and 58.6% of colorectal cancer survivors reached the expected quality level of cancer survivorship care according to the reference standard (p < .001). CONCLUSION: Medical care practices reached a high standard in a leading cancer center in Latin America. However, a much stronger psychosocial assessment and interdisciplinary care is needed to improve survivorship cancer quality care.