Search

Background: Design, results, and interpretation of oncology randomised controlled trials (RCTs) have changed substantially over the past decade. In this study, we describe all RCTs evaluating anticancer therapies in haematological cancers published globally during 2014-2017 with comparisons with solid tumours RCTs., Methods: A PubMed literature search identified all phase 3 RCTs of anticancer therapy for haematological cancers and solid tumours published globally during 2014-2017. Descriptive statistics, chi-square tests and the Kruskal-Wallis test were used to compare RCT design results, and output between haematological cancers and solid tumours as well as for different haematological cancer subtypes., Results: 694 RCTs were identified; 124 in haematological cancers and 570 in solid tumours. Overall survival (OS) was the primary endpoint in only 12% (15/124) of haematological cancer trials compared to 35% (200/570) in solid tumours ( p < 0.001). Haematological cancer RCTs evaluated the systemic novel therapy more often than the solid tumour RCT (98% versus 84%, p = 0.002). Use of surrogate endpoints like progression-free survival (PFS) and time to treatment failure (TTF) were more common in haematological cancers than solid tumours (47% versus 31%, p < 0.001). Within haematological cancers, the use of PFS and TTF was more prevalent in chronic lymphocytic leukaemia and multiple myeloma as compared to others (80%-81% versus 0%-41%, p < 0.001). Seventy-eight percent of haematologic trials were funded by industry as compared to 70% of solid tumour trials. Only 4% (5/124) of haematologicalcancer trials were led by investigators in upper-middle and lower-middle-income countries as compared to the 9% of solid tumour trials., Conclusion: The fact that only 12% of haematological cancer RCTs are designed to show improvements in OS is of grave concern for the field and the care of future patients. This is further compounded by the highly prevalent use of alternative primary endpoints that are rarely valid surrogates for OS in haematological cancers., Competing Interests: Manju Sengar, Wilma M. Hopman, Ghulam Rehman Mohyuddin, Nazik Hammad, CS Pramesh, Ajay Aggarwal, Richard Sullivan, Christopher M. Booth- None Aaron Goodman: Consultant and speaker for Seattle Genetics and EUSA Pharma Bishal Gyawali: Consulting fees from Vivio Health, unrelated to the manuscript Deborah Mukherjee: Astellas, Invited Speaker, Personal, Astra Zeneca, Invited Speaker, Personal, Bayer, Invited Speaker, Personal, BMS, Invited Speaker, Personal, Janssen, Invited Speaker, Personal, MSD, Invited Speaker, Personal, Pfizer, Advisory Board, Personal, Astellas, Research Grant, Institutional, No financial interest, BMS, Research Grant, Institutional, No financial interest, Janssen, Research Grant, Institutional, No financial interest, Novartis, Research Grant, Institutional, No financial interest., (© the authors; licensee ecancermedicalscience.)

Background: In many low-and middle-income countries (LMICs), childhood overweight is increasing, while underweight remains a problem. This study aimed to investigate the association between socio-economic status (SES) and nutritional status among Nepalese school children., Methods: This cross-sectional study used a multistage random cluster sampling method and included 868 students aged 9-17 years from both public and private schools located in a semi-urban area of Pokhara Metropolitan City, Nepal. SES was determined based on a self-reported questionnaire. Body weight and height were measured by health professionals and body mass index (BMI) was categorized based on the World Health Organization BMI-for-age cut-offs. The association between Lower and Upper SES and BMI was assessed using mixed-effects logistic regression model estimating the adjusted odds ratio (aOR) with a corresponding 95% confidence interval (CI) and compared to Middle SES., Results: The proportion of obesity, overweight, underweight, and stunting among school children was 4%, 12%, 7%, and 17%, respectively. More girls were overweight/obese compared with boys (20% vs. 13%). The mixed-effects logistic regression model showed that both participants from Lower SES households and Upper SES households had a higher tendency to be overweight compared to participants from Middle SES; aOR = 1.4; 95% CI 0.7-3.1 and aOR = 1.1; 95% CI 0.6-2.1, respectively. Furthermore, stunting and overweight occurred simultaneously., Conclusions: This study found that about one out of four children and adolescents in the study setting was malnourished. There was a tendency that both participants from Lower SES and Upper SES had higher odds of being overweight compared to participants from Middle SES. Furthermore, both stunting and overweight were present simultaneously in some individuals. This emphasizes the complexity and importance of awareness of childhood malnutrition in LMICs like Nepal., (© 2023. The Author(s).)

This paper introduces CORE, a widely used scholarly service, which provides access to the world's largest collection of open access research publications, acquired from a global network of repositories and journals. CORE was created with the goal of enabling text and data mining of scientific literature and thus supporting scientific discovery, but it is now used in a wide range of use cases within higher education, industry, not-for-profit organisations, as well as by the general public. Through the provided services, CORE powers innovative use cases, such as plagiarism detection, in market-leading third-party organisations. CORE has played a pivotal role in the global move towards universal open access by making scientific knowledge more easily and freely discoverable. In this paper, we describe CORE's continuously growing dataset and the motivation behind its creation, present the challenges associated with systematically gathering research papers from thousands of data providers worldwide at scale, and introduce the novel solutions that were developed to overcome these challenges. The paper then provides an in-depth discussion of the services and tools built on top of the aggregated data and finally examines several use cases that have leveraged the CORE dataset and services., (© 2023. The Author(s).)

Background: Criticisms have emerged that cancer medicines offer modest benefits at increasingly high prices. Reimbursement decisions made by health technology assessment (HTA) agencies have become a complex endeavour for cancer medicines. Most high-income countries (HICs) use HTA criteria to identify high-value medicines for reimbursement under public drug coverage plans. We compared HTA criteria specific for cancer medicines in economically similar HICs, to understand how these criteria contribute to reimbursement decisions., Methods: We did an international, cross-sectional analysis in collaboration with author investigators across eight HICs, from the Group of Seven (known as G7; Canada, England, France, Germany, Italy, and Japan) and Oceania (Australia and New Zealand). Publicly available data from HTA agency reports and official documentation were extracted and analysed between Aug 15, 2021, and July 31, 2022. We collected data pertaining to the decision-making criteria used by the national HTA agency; HTA reimbursement status for 34 medicine-indication pairs corresponding to 15 unique US top-selling cancer medicines; and HTA reimbursement status for 18 cancer medicine-indication pairs (13 unique medicines) with minimal clinical benefit (score of 1 on the European Society of Medical Oncology Magnitude of Clinical Benefit Scale). Descriptive statistics were used to compare HTA decision criteria and drug reimbursement recommendations (or for Germany and Japan, final reimbursement status) across the eight countries., Findings: Therapeutic impact related to clinical outcomes of the new medicine was a uniform criterion across the eight countries, whereas quality of evidence (under the remit of therapeutic impact assessment) and equity were infrequently cited criteria. Only the German HTA agency mandated that surrogate endpoints be validated in therapeutic impact assessment. All countries except Germany included formal cost-effectiveness analyses within HTA reports. England and Japan were the only countries that specified a cost-effectiveness threshold. Of the 34 medicine-indication pairs corresponding to US top-selling cancer medicines, Germany reimbursed the maximum (34 [100%]), followed by Italy (32 [94%] recommended for reimbursement), Japan (28 [82%] reimbursed), Australia, Canada, England, and France (27 [79%] recommended for reimbursement), and New Zealand (12 [35%] recommended for reimbursement). Of the 18 cancer medicine-indication pairs with marginal clinical benefit, Germany reimbursed 15 (83%) and Japan reimbursed 12 (67%). France recommended nine (50%) for reimbursement, followed by Italy (seven [39%]), Canada (five [28%]), and Australia and England (three [17%] each). New Zealand did not recommend any medicine-indications with marginal clinical benefit for reimbursement. Considering the overall cumulative proportion across the eight countries, 58 (21%) of 272 indications for the US top-selling medicines and 90 (63%) of 144 marginally beneficial medicine-indications were not recommended for reimbursement or reimbursed., Interpretation: Our findings indicate discordance in public reimbursement decisions across economically similar countries, despite overlapping HTA decision criteria. This suggests a need for improved transparency around the nuances of the criteria to ensure improved access to high-value cancer medicines, and deprioritisation of low-value cancer medicines. Health systems have opportunities to improve their HTA decision-making processes by learning from the systems in other countries., Funding: None., Competing Interests: Declaration of interests KJ is supported by a Canadian Institutes of Health Research foreign doctoral scholarship (award number 181603). AJNR reports serving as a member of the pan-Canadian Oncology Drug Review Expert Review Committee with the Canadian Agency for Drugs and Technologies in Health, and reports a postdoctoral fellowship with the Program on Regulation, Therapeutics, and Law, which is supported by a grant from Arnold Ventures. BG has received salary support from the Ontario Institute for Cancer Research, funded by the Government of Ontario, and declares consulting fees from Vivio Health unrelated to the manuscript. AB reports consulting fees from Sanofi and honoraria from Roche, unrelated to the manuscript. DK reports honoraria from Amgen and Merck, unrelated to the manuscript. KH reports grant support from Pfizer, unrelated to the manuscript. All other authors declare no competing interests. The views expressed in the publication are the views of the authors and do not reflect those of governments, commercial entities, or health technology assessment agencies., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: DAG has received institutional research funding from Merck, Bristol Myers Squibb, and Janssen, and received consulting fees and has stock ownership from Vivio Health. BG has received consulting fees from Vivio Health. TM reports receiving personal fees from Purple Biotech, outside the submitted work. IFT declares no competing interests.

Background: Non-communicable diseases in humanitarian settings are generally under-researched, particularly in Africa and have been called a neglected crisis. Little is known about factors affecting access to and (dis)continuity of care for chronic conditions, such as hypertension (HTN) and type 2 diabetes among forcibly displaced persons (FDPs) in Uganda., Aim: To investigate factors affecting access to and (dis)continuity of HTN and/or type 2 diabetes care among FDPs in the Bidibidi refugee settlement, Uganda., Methods: A sequential explanatory mixed-methods design incorporating methodological and investigator triangulation will be conducted. The study aims to employ a community-based participatory research approach to equitably engage community members, researchers, and other stakeholders in the research process, recognising and maximising their diverse contributions. In phase 1, the quantitative arm of the study, 960 FDPs with HTN and/or type 2 diabetes will be interviewed about their sociodemographic characteristics, health status, migration experiences, social capital, and awareness, treatment, and control of these diseases. Participants will be purposively recruited from phase 1 as well as village health teams, healthcare providers, and policymakers to participate in phase 2, the qualitative study, in order to gain more insight into how mobility and social factors affect (dis)continuity of care among FDPs with HTN and/or type 2 diabetes., Discussion: The findings from phase 1 and phase 2 of the study will be integrated through a triangulation process to provide a more holistic and comprehensive insight into the factors affecting access to and (dis)continuity for HTN and/or type 2 diabetes care among FDPs. Understanding these factors is expected to pave the way for conceptualizing health-enabling environments and strengthening health systems for FDPs with chronic conditions. It is anticipated that the study will generate baseline evidence that might be beneficial in developing and implementing HTN and diabetes care models for FDPs in the region., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Many countries face a significant shortage of medical oncologists. To mitigate this problem, some countries, including Canada, have established training programs for general practitioners in oncology (GPOs), which train family physicians (FPs) in the fundamentals of cancer care. This type of GPO training model may be useful in other countries facing similar challenges. Therefore, Canadian GPOs were surveyed to learn from their experiences and inform the development of similar programs in other countries., Methods: A survey was designed and administered to Canadian GPOs to understand the methods and outcomes of GPO training and practice in the Canadian context. The survey was active from July 2021 to April 2022. Participants were recruited through personal and provincial networks and an email list provided by the Canadian GPO network., Results: The survey received 37 responses for an estimated response rate of 18%. Although only 38% of respondents indicated that family medicine training sufficiently prepared them to care for patients with cancer, 90% indicated that GPO training did. Clinics with oncologists were found to be the most effective mode of learning, followed by small group learning and online education. Critical knowledge domains and skills most relevant for GPO training were identified as the treatment of side effects, symptom management, palliative care, and breaking bad news., Conclusion: Participants in this survey felt that a dedicated GPO training program offered value beyond family medicine residency in preparing providers to adequately care for patients with cancer. GPO training can be done effectively through virtual and hybrid content delivery. Critical knowledge domains and skills identified as the most important in this survey may be valuable for other groups and nations implementing similar training programs to increase their oncology workforce.

Despite the importance of health literacy for health promotion, Nepalese undergraduate students are largely unaware of its importance. The present study assessed the health literacy levels of undergraduate health sciences students and explored various sociodemographic, clinical and health information-related factors associated with health literacy at Pokhara University in the Kaski district of western Nepal. A cross-sectional web-based observational study was conducted among 406 undergraduate students university students from five faculties at the School of Health and Allied Sciences affiliated with Pokhara University. Data on sociodemographic information, clinical characteristics and sources of health information were collected. Health literacy was assessed using the 44-item measure that captures the concept of health literacy across nine distinct domains. Associated factors were examined using a one-way analysis of variance followed by stepwise backward multiple linear regression analysis at the level of significance of 0.05. The mean score for the health literacy questionnaire was 3.13 ± 0.26. Outcomes of multivariable analyses demonstrated various factors associated with health literacy scores, including age (β = 0.10; p = 0.001), physical exercise (β = -0.13; p < 0.001), monthly household income (β = 0.05; p = 0.029) and routine health checkup (β = -0.14; p < 0.001). The study showed that there is a need to understand and address sociodemographic factors and clinical factors, including age, physical exercise, monthly household income and routine health checkups to improve health literacy levels among undergraduate students in western Nepal. More research, including longitudinal studies, is needed to better understand factors that influence health literacy among undergraduate students in Nepal., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Breast cancer places a substantial burden on patient physical and mental wellbeing, and the delivery of high-quality supportive care is essential at all stages of the disease. Given the increased uptake of technology in recent years, eHealth interventions may be a convenient and accessible method for supportive care. Within this context, we conducted a systematic review to describe and quantify the use of eHealth for breast cancer supportive care. We searched MEDLINE, EMBASE, and CINAHL databases for primary research studies published from 2016 to 2021 (present) that assessed the effects of eHealth interventions on adult patients with breast cancer. We explored the effects of the interventions on patient symptoms, lifestyle, satisfaction, and barriers, as well as factors related to feasibility and implementation. The risk of bias of each study was also assessed. Findings were presented according to stage of cancer care. We identified 43 relevant studies capturing n = 6,285 patients (30 randomized controlled trials and 13 non-randomized interventional studies); 5 evaluated patients who were newly diagnosed, 16 evaluated patients undergoing active treatment, and 22 evaluated patients in post-treatment follow-up. A total of 19 studies used mobile apps, 18 used online patient portals, 5 used text messaging, and 1 used both a patient portal and text messaging. We found that patients were broadly satisfied with the eHealth interventions; however, findings were less consistent for symptom and lifestyle-related outcomes. Eight studies were judged as high risk of bias. There was substantial between-study heterogeneity, which made it challenging to discern consistent trends. Overall, future research should continue to explore the use of eHealth for breast cancer supportive care, with a focus on improving patient symptoms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: BG has received consulting fees from Vivio Health, unrelated to the submitted work.

Cancer medicines comprise the largest proportion of expensive drugs for rare diseases (EDRDs). The US Orphan Drug Act (ODA) (Office of Inspector General, Department of Health and Human Services 2001) encourages pharmaceutical manufacturers to develop medicines for rare diseases through a range of financial incentives, which has shifted the development of cancer medicines to rare cancer subtypes. Although certain medicines approved through the ODA have revolutionized cancer treatment, only half demonstrate added therapeutic benefit compared to existing alternatives. Canadian regulators should ensure that cancer medicines that receive fast-track approval through the Health Canada Notice of Compliance with conditions offer benefit to Canadian patients. Furthermore, payers might engage in methods for reassessment and renegotiations over the medicines' lifespan., (Copyright © 2023 Longwoods Publishing.)

Competing Interests: Dr. Gyawali declares receiving consulting fees from Vivio Health unrelated to the manuscript. Dr. Knopf declares receiving consulting fees from Vivio Health and having stock options at Cadex Genomics, both unrelated to the manuscript. No other conflicts of interest to disclose.

Objective: To assess the prevalence, magnitude, and disclosure status of industry funding in editorial boards of surgery journals., Summary of Background Data: Financial COI can bias research. Although authors seeking to publish in peer-reviewed surgery journals are required to provide COI disclosures, editorial board members' COI disclosures are generally not disclosed to readers., Methods: We present a cross-sectional analysis of industry funding to editorial board members of high-impact surgery journals. We reviewed top US-based surgery journals by impact factor to determine the presence of financial COI in members of each journal's editorial board. The prevalence and magnitude of COI was determined using 2018 industry reported payments found in the Centers for Medicare and Medicaid Services Open Payments database. Journal websites were also reviewed looking for the presence of editorial board disclosure statements., Results: A total of 1002 names of editorial board members from the top 10 high-impact American surgery journals were identified. Of 688 individual physicians based in the USA, 452 (65.7%) were found to have received industry payments in 2018, totaling $21,916,503 with a median funding amount per physician of $1253 (interquartile range $156-$10,769). Funding levels varied by surgical specialty and journal. Editorial board disclosure information was found in only 3.3% of physicians., Conclusions: Industry funding to editorial board members of high impact surgery journals is prevalent and underreported. Mechanisms of disclosure for COI are needed at the editorial board level to provide readers full transparency. This would acknowledge this COI of editorial board members, and thereby attempt to potentially further reduce the risk of bias in editorial decisions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The selection of cancer medicines for national procurement requires deliberate evaluation of population benefit, budget impact, sustainability, and health system capacity. However, this process is complicated by numerous challenges, including the large volume and rapid pace of newly developed therapies offering marginal gains at prohibitively high prices. The WHO Model List of Essential Medicines (EML) and Model List of Essential Medicines for Children (EMLc) have undergone a series of evidence-based updates to ensure recommended cancer medicines offer meaningful clinical benefit. This Health Policy paper describes how cancer medicines are listed on the EML and EMLc, including two updated WHO processes: (1) the formation of the Cancer Medicines Working Group, and (2) additional selection principles for recommending cancer medicines, including a minimum overall survival benefit of 4-6 months with improvement to quality of life compared with standard treatment. These updates, along with proposals to include formal price considerations, additional selection criteria, and multisectoral collaboration (eg, voluntary licensing) promote procurement of high-value essential cancer medicines on national formularies in the context of supporting sustainable health systems to achieve universal health coverage., Competing Interests: Declaration of interests BG declares consulting fees from Vivio Health in matters unrelated to this manuscript. EGEdV declares research support from Amgen, Genentech, Roche, CytomX, G1 Therapeutics, Bayer, Synthon, Servier, Regeneron, Crescendo Biologics, GE Healthcare, and AstraZeneca; and consulting fees from National Surgical Adjuvant Breast and Bowel Project, Daiichi Sankyo, and Crescendo Biologics, in matters unrelated to this manuscript. All other authors declare no competing interests., (Copyright © 2022 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

The e cancer Kathmandu 2022 workshop on the 24th-25th September 2022 was the first e cancer conference organised in Nepal, a Southeast Asian nation sandwiched between India and China. It was focused on critical appraisal skills for evidence-based practice and was organised in partnership with the Karnali Academy of Health Sciences and the Civil Service Hospital from Nepal, and the Queen's Global Oncology Program from Canada. The workshop emphasised the need for critical thinking in understanding clinical research, and also motivated the delegates to undertake meaningful clinical research relevant to the local setting. The sessions highlighted the features of a good clinical research, identify pitfalls in the reporting of clinical trials, implementation of the research into locally relevant practice and development of local clinical guidelines. Furthermore, the faculty also discussed how to write a good scientific paper, the do's and don'ts of a systematic review and meta-analysis, the role of peer-review and how to do one properly and what do editors look for in evaluating papers submitted for publication. The audience learned the importance of finding a good mentor and fostering local and international collaboration. The local faculty also highlighted their own personal journeys and how mentorship and global collaboration played an important role in their own academic career. The enthusiastic panel discussion was a highlight of the programme where the delegates learned about several important topics from the faculties, such as work-life balance, the role of mentorship in building careers and building networks., Competing Interests: None., (© the authors; licensee ecancermedicalscience.)

Background: Spontaneous regression of advanced solid tumors is infrequent but may occur. Quantifying response rates from placebo in cancer drug trials may provide important information for physicians, patients, and regulators. We aimed to provide a pooled placebo response rate from drug trials in advanced solid tumors., Methods: We pooled the overall response rate (ORR), complete response rate (CR) and partial response rates (PR) in the placebo arm of placebo-controlled randomized controlled trials (RCTs) of cancer drugs for advanced solid tumors published during 2015-2021 using random-effects model., Findings: 45 phase 3 RCTs including 5684 patients on placebo met our inclusion criteria and formed the study cohort. The pooled overall ORR, CR and PR rates in the placebo arm were 1% (95% CI, 0%-2%), 0% (95% CI, 0%-0%), and 1% (95% CI, 0%-2%) respectively. Higher placebo responses were observed in prostate cancer and sarcoma trials., Interpretation: Overall, 1% patients with advanced solid tumors can expect to achieve some response even in absence of treatment. However, complete regression without treatment is extremely rare, almost zero percent. This information will be helpful to patients in their decisions, as well as regulators in evaluating cancer drugs' efficacy based on response rates alone., Funding: None., Competing Interests: Dr. Gyawali declares receiving consulting fees from Vivio Health unrelated to the manuscript. Other authors have no conflicts of interest to disclose., (© 2022 The Author(s).)

The 'Choosing Wisely 2022' conference, organised by the ecancer foundation, was held at the Tata Memorial Hospital, Mumbai, India, on 17 and 18 September. It was a successful event with 159 delegates attending it in person and around 328 delegates attending online. Thirty oncology experts from across the world shared their thoughts during this meeting. The theme of the conference was to focus on cancer care, in low- and middle-income countries (LMICs). The emphasis of discussion was on ways to select more cost-effective and high value treatments and interventions and minimise financial toxicity. In addition, cancer research from LMICs needs to be improved substantially. Collaboration and networking amongst cancer institutions in LMICs is essential., Competing Interests: None., (© the authors; licensee ecancermedicalscience.)

Kaplan's lesion is a rare complex metacarpophalangeal joint dislocation. A 7-year-old female child presented with pain, swelling and inability to move her right index finger. Her mother gave a history of sustaining a fall injury on the same hand around 3 weeks back. Radiographs showed a complex dorsal metacarpophalangeal joint dislocation. As the injury was already 3 weeks old at presentation, a few attempts at closed reduction were tried, under anaesthesia, which was unsuccessful. So, the patient underwent open reduction through a dorsal approach. At a 1-year follow-up, the patient was pain-free and had regained full range of motion of the index finger metacarpophalangeal joint. The differential diagnosis of Kaplan's lesion should be considered when a child presents with finger dislocation., Keywords: joint dislocations; metacarpophalangeal joint; open reduction.

Background: The field of oncology is at the forefront of advances in artificial intelligence (AI) in health care, providing an opportunity to examine the early integration of these technologies in clinical research and patient care. Hope that AI will revolutionize health care delivery and improve clinical outcomes has been accompanied by concerns about the impact of these technologies on health equity., Objective: We aimed to conduct a scoping review of the literature to address the question, "What are the current and potential impacts of AI technologies on health equity in oncology?", Methods: Following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines for scoping reviews, we systematically searched MEDLINE and Embase electronic databases from January 2000 to August 2021 for records engaging with key concepts of AI, health equity, and oncology. We included all English-language articles that engaged with the 3 key concepts. Articles were analyzed qualitatively for themes pertaining to the influence of AI on health equity in oncology., Results: Of the 14,011 records, 133 (0.95%) identified from our review were included. We identified 3 general themes in the literature: the use of AI to reduce health care disparities (58/133, 43.6%), concerns surrounding AI technologies and bias (16/133, 12.1%), and the use of AI to examine biological and social determinants of health (55/133, 41.4%). A total of 3% (4/133) of articles focused on many of these themes., Conclusions: Our scoping review revealed 3 main themes on the impact of AI on health equity in oncology, which relate to AI's ability to help address health disparities, its potential to mitigate or exacerbate bias, and its capability to help elucidate determinants of health. Gaps in the literature included a lack of discussion of ethical challenges with the application of AI technologies in low- and middle-income countries, lack of discussion of problems of bias in AI algorithms, and a lack of justification for the use of AI technologies over traditional statistical methods to address specific research questions in oncology. Our review highlights a need to address these gaps to ensure a more equitable integration of AI in cancer research and clinical practice. The limitations of our study include its exploratory nature, its focus on oncology as opposed to all health care sectors, and its analysis of solely English-language articles., (©Paul Istasy, Wen Shen Lee, Alla Iansavichene, Ross Upshur, Bishal Gyawali, Jacquelyn Burkell, Bekim Sadikovic, Alejandro Lazo-Langner, Benjamin Chin-Yee. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 01.11.2022.)

This study aimed to assess the effect of Female Community Health Volunteer (FCHV)-delivered intervention to increase cervical cancer screening uptake among Nepalese women. A community-based, open-label, 2-group, cluster randomized controlled trial (CRCT) was conducted in a semi-urban setting in Western Nepal. Fourteen clusters (1:1) were randomly assigned to the intervention group, which received a 12-month intervention delivered by FCHVs or the control group (usual care). Between April and June 2019, 690 women aged 30-60 years were recruited for CRCT during the baseline survey. A follow-up assessment was conducted after the completion of the 12 months intervention. The primary outcome was the change in cervical cancer screening from baseline to 12-month follow-up. Of 690 women, 646 women completed the trial. 254 women in the intervention group and 385 women in the control group were included in the primary outcome analysis. There was a significant increase in cervical cancer screening uptake in the intervention group [relative risk (RR), 1.48; 95 % confidence interval (CI) 1.32, 1.66; P  < 0.01)], compared to the control group. The secondary outcome was the change in median knowledge score among women that increased from 2 [interquartile range (IQR) 1-4] (baseline) to 6 [IQR 3-9] (follow-up) in the intervention group. However, the median knowledge score remained almost the same among women in the control group 2 [IQR 1-5] to 3 [IQR 2-5]. Our study findings reported that an FCHV-delivered intervention significantly increased cervical cancer screening uptake among women living in a semi-urban setting in Nepal. Trial registration: ClinicalTrials.gov NCT03808064., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)

Importance: Many randomized clinical trials (RCTs) led by high-income countries (HICs) now enroll patients from lower middle-income countries (LMICs) and upper middle-income countries (UMICs). Although enrolling diverse populations promotes research collaborations, there are issues regarding which countries participate in RCTs and how this participation may contribute to global research., Objective: To describe which UMICs and LMICs participate in RCTs led by HICs., Design, Setting, and Participants: A cross-sectional study of all oncology RCTs published globally during January 1, 2014, to December 31, 2017, was conducted. The study cohort was restricted to RCTs led by HICs that enrolled participants from LMICs and UMICs. Study analyses were conducted in November 1, 2021, to May 31, 2022., Main Outcomes and Measures: A bibliometric approach (Web of Science 2007-2017) was used to explore whether RCT participation was proportional to other measures of cancer research activity. Participation in RCTs (ie, percentage of RCTs in the cohort in which each LMIC and UMIC participated) was compared with country-level cancer research bibliometric output (ie, percentage of total cancer research bibliometric output from the same group of countries that came from a specific LMIC and UMIC)., Results: Among the 636 HIC-led RCTs, 186 trials (29%) enrolled patients in LMICs (n = 84 trials involving 11 LMICs) and/or UMICs (n = 181 trials involving 26 UMICs). The most common participating LMICs were India (42 [50%]), Ukraine (39 [46%]), Philippines (23 [27%]), and Egypt (12 [14%]). The most common participating UMICs were Russia (115 [64%]), Brazil (94 [52%]), Romania (62 [34%]), China (56 [31%]), Mexico (56 [31%]), and South Africa (54 [30%]). Several LMICs are overrepresented in the cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (27% RCTs, 1% output), and Georgia (8% RCTs, 0.2% output). Overrepresented UMICs include Russia (64% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output), and South Africa (30% RCTs, 1% output)., Conclusions and Relevance: In this cross-sectional study, a substantial proportion of RCTs led by HICs enrolled patients in LMICs and UMICs. The LMICs and UMICs that participated in these trials did not match overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity-strengthening activities require further study.

Purpose: We carried out a meta-analytic synthesis to evaluate the association between diabetes mellitus (DM) and related clinical outcomes, co-morbidities, their risk factors and resource utilization in patients with COVID-19., Methods: The MEDLINE and Web of Science databases were reviewed for identification of eligible studies. Meta-analysis was carried out using Review Manager 5.3. The random- effects model was used to compute the pooled estimates of odds ratio (OR)/mean difference and 95% confidence interval (CI)., Results: A total of 14 studies including 3,644 individuals without DM and 1,428 with DM were included in the meta-analysis. Cardiovascular diseases (CVDs) [OR 2.91, 95% CI 2.34, 3.63], hypertension [OR 2.19, 95% CI 1.39, 3.46], acute kidney injury (AKI) [OR 3.59, 95% CI 1.46, 8.84], cerebrovascular disease [OR 2.09, 95% CI 1.22, 3.61], and acute respiratory distress syndrome (ARDS) [OR 3.40, 95% CI 2.09, 5.55] were significantly associated with DM in COVID-19 patients compared with non-DM patients (p < 0.05 for all instances). Mortality was significantly higher among COVID-19 patients with DM [OR 2.46, 95% CI 1.68, 3.58]. Intensive Care Unit (ICU) admission and use of mechanical ventilation were significantly associated with COVID-19 patients with DM [OR 2.79, 95% CI 1.79, 4.34], and [OR 3.33, 95% CI 2.05, 5.42], respectively. No significant difference was observed in the length of stay (LOS) and hospitalization., Conclusions: This meta-analysis shows that CVDs, hypertension, AKI, cerebrovascular disease, and ARDS are significantly higher among DM patients with COVID-19 compared with non-DM patients. Mortality, ICU admission and the use of mechanical ventilation were significantly associated with COVID-19 patients with DM. Further long-term, multinational and large sample size clinical studies are warranted to justify the current findings., Competing Interests: Conflict of interestThe authors declare no conflict of interests associated with this publication., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2022.)

Groundwater resources in the Kingdom of Saudi Arabia (KSA) have high levels of natural radioactivity. Within the northwestern KSA, gross alpha (α) and gross beta (β) levels exceed national and international drinking-water limits. In this study, we developed and used an automated machine learning (AML) approach to quantify relationships between gross α and gross β activities and different geological, hydrogeological, and geochemical conditions. Two AML model groups (group I for gross α; group II for gross β) were constructed, using water samples collected from 360 irrigation and water supply wells, to define a robust model that explains the spatial variability in gross α and gross β activities, as well as variables that control the gross activities. Each group contained four model families: deep neural network (DNN), gradient boosting machine (GBM), generalized linear model (GLM), and distributed random forest (DRF). Model inputs include chemical compositions as well as geological and hydrogeological conditions. Three performance metrics were used to evaluate the models during training and testing: normalized root mean square error (NRMSE), Pearson's correlation coefficient (r), and Nash-Sutcliff efficiency (NSE) coefficient. Results indicate that (1) the GBM model outperformed (training: NRMSE: 0.37 ± 0.10; r: 0.92 ± 0.05; NSE: 0.85 ± 0.09; testing: NRMSE: 0.71 ± 0.08; r: 0.72 ± 0.08; NSE: 0.49 ± 0.12) the DNN, DRF, and GLM models when modelling gross α activities; (2) gross α activities are controlled by pH, stream density, nitrate, manganese, and vegetation index; (3) the DRF model outperformed (training: NRMSE: 0.41 ± 0.05; r: 0.92 ± 0.02; NSE: 0.83 ± 0.04; testing: NRMSE: 0.67 ± 0.09; r: 0.77 ± 0.07; NSE: 0.54 ± 0.12) the GBM, DNN, and GLM models when modelling gross β activities; (4) input variables that affect the gross β actives are pH, temperature, stream density, lithology, and nitrate; and (5) no single model could be used to model both gross α and gross β activities-instead, a combination of AML models should be used. Our computationally efficient approach provides a framework and insights for using AML techniques in water quality investigations and promotes more and improved use of different geological, hydrogeological, and geochemical datasets by the scientific community and decision makers to develop guidelines for mitigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the efficacy and safety profiles in cancer umbrella trials testing targeted drugs or a combination of targeted therapy with chemotherapy., Methods: Our study was prospectively registered in PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella trials testing targeted agents or a combination of targeted therapies with chemotherapy. We included solid tumor studies published between 1 January 2006 and 7 October 2019. We measured the risk using drug-related grade 3 or higher adverse events (AEs), and the benefit by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). When possible, data were meta-analyzed., Results: Of the 6207 records identified, we included 31 sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 17.7% (95% confidence interval [CI] 9.5-25.9). The ORR for targeted therapies in the experimental arms was significantly lower than the ORR for a combination of targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median PFS was 2.4 months (95% CI 1.9-2.9), and the median OS was 7.1 months (95% CI 6.1-8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 0.8% (95% CI 0.3-1.4), and the average drug-related grade 3/4 AE rate per person was 0.45 (95% CI 0.40-0.50)., Conclusions: Our findings suggest that, on average, one in five cancer patients in umbrella trials published between 1 January 2006 and 7 October 2019 responded to a given therapy, while one in 125 died due to drug toxicity. Our findings do not support the expectation of increased patient benefit in cancer umbrella trials. Further studies should investigate whether umbrella trial design and the precision oncology approach improve patient outcomes., (© 2022. The Author(s).)

Purpose: Randomized controlled trials (RCTs) are the cornerstone of delivering sustained improvements in cancer outcome. To inform radiation therapy research policy and prioritization, we analyze the radiation therapy RCT landscape including comparison with trials of systemic therapies over the same period, with a specific focus on funding and disparities across income settings., Methods and Materials: This retrospective cohort study identified all phase 3 RCTs evaluating anticancer therapies published from 2014 to 2017. RCTs were classified according to anticancer modality and country of origin. Descriptive statistics were used to compare key characteristics of radiation therapy RCT studies according to study design characteristics, tumor types evaluated, types of intervention appraised, treatment intent and main funding sources., Results: The study cohort included 694 RCTs of which 64 were radiation therapy RCTs (9%) compared with 601 systemic therapy RCTs (87%). Among all radiation therapy RCTs, 47% of them focused on 2 areas of evaluation: (1) combining radiation therapy with systemic agents (25%) and (2) changes in dose fractionation (22%). The most common cancers studied were head and neck (22%), lung (22%), and breast (14%), with cervical cancer trials representing only 3% of the cohort. Among the radiation therapy RCTs, 33% of them met their primary endpoint, and 62% assessed interventions in the curative setting compared with 31% in systemic therapy RCTs. For their country locations, 77% of radiation therapy RCTs took place in high-income countries, 13% in low-and-middle-income countries, and 11% in both high-income and low-and-middle-income countries. For funding, 17% of radiation therapy RCTs received funding from industry compared with 79% of systemic therapy RCTs., Conclusions: This study highlights the need for greater investment in radiation therapy RCTs and the need to look at the disparities in conducting RCTs globally. The study emphases the urgent need for more capacity building for cancer clinical trials in low-and-middle-income countries and more sustainable funding sources., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Many oncologists have relationships with industry. Previous work has shown that these payments are usually modest; however, there exist a subset of medical oncologists who receive more than $100,000 US dollars (USD) annually. Here, we describe the characteristics of these physicians., Methods: This retrospective cohort study used the Open Payments data set to identify all US-based medical oncologists/hematologists who received $100,000+ USD in general payments linked to cancer medications in 2018. Open Payments and a web-based search were used to identify physician characteristics, demographics, research profile, and leadership positions., Results: One hundred thirty-nine medical oncologists received > $100,000 USD in general payments. The median payment was $154,613 USD, and the total payment was $24.2 million USD. These high-payment physicians represent 1% of all US medical oncologists (N = 10,620) yet account for 37% of all industry payments in 2018. Sixty percent (84 of 139) and 21% (29 of 139) of these high-payment physicians hold hospital and specialty association leadership roles, respectively. One quarter (24%, 33 of 139) serve on journal editorial boards, and 10% (14 of 139) have authored clinical practice guidelines; 72% (100 of 139) hold faculty appointments., Conclusion: A small number of medical oncologists receive very high payments from the pharmaceutical industry. These physicians hold major leadership roles within oncology. Further work is needed to understand the extent to which these conflicts of interest may shape clinical practice and policy.

Purpose: The WHO essential medicines list (EML) guides selection of drugs for national formularies. Here, we evaluate which medicines are considered highest priority by Indian oncologists and the extent to which they are available in routine practice., Methods: This is a secondary analysis of an electronic survey developed by the WHO EML Cancer Medicine Working Group. The survey was distributed globally using a hierarchical snowball method to physicians who prescribe systemic anticancer therapy. The survey captured the 10 medicines oncologists considered highest priority for population health and their availability in routine practice., Results: The global study cohort included 948 respondents from 82 countries; 98 were from India and 67 were from other low- and middle-income countries. Compared with other low- and middle-income countries, the Indian cohort was more likely to be medical oncologist (70% v 31%, P < .001) and work exclusively in the private health system (52% v 17%, P < .001). 14/20 most commonly selected medicines were conventional cytotoxic drugs. Universal access to these medicines was reported by a minority of oncologists; risks of significant out-of-pocket expenditures for each medicine were reported by 19%-58% of oncologists. Risk of catastrophic expenditure was reported by 58%-67% of oncologists for rituximab and trastuzumab. Risks of financial toxicity were substantially higher within the private health system compared with the public system., Conclusion: Most high-priority cancer medicines identified by Indian oncologists are generic chemotherapy agents that provide substantial improvements in survival and are already included in WHO EML. Access to these treatments remains limited by major financial burdens experienced by patients. This is particularly acute within the private health system. Strategies are urgently needed to ensure that high-quality cancer care is affordable and accessible to all patients in India.

Importance: Although quality of life (QOL) is an important clinical end point, cancer drugs are often approved based on overall survival (OS) or putative surrogate end points such as progression-free survival (PFS) without QOL data., Objective: To ascertain whether cancer drug trials that show improvement in OS or PFS also improve global QOL of patients with cancer compared with the control treatment, as well as to assess how unchanged or detrimental QOL outcomes are reported in trial publications., Design, Setting, and Participants: This retrospective cohort study included all patients with cancer in the advanced setting who were enrolled into phase 3 randomized clinical trials (RCTs) of cancer drugs reporting QOL data and published in English language in a PubMed-indexed journal in the calendar year 2019. The systematic search of PubMed was conducted in July 2020., Main Outcomes and Measures: Association of QOL outcomes with OS and PFS, framing of unchanged QOL outcomes in trial publications, and the association of favorable framing with industry funding of the trials., Results: A total of 45 phase 3 RCTs enrolling 24 806 participants (13 368 in the experimental arm and 11 438 in the control arm) met the inclusion criteria and were included in the study analyses. Improvement in global QOL with the experimental agent was reported in 11 (24%) RCTs. The RCTs with improved QOL were more likely to also show improved OS vs trials with unimproved QOL (7 of 11 [64%] trials vs 10 of 34 [29%] trials; χ2 = 4.13; P = .04); there was no such association observed for PFS (6 of 11 [55%] trials vs 17 of 34 [50%] trials, χ2 = 0.03; P = .87). Six trials reported worsening QOL, of which 3 (50%) were trials of targeted drugs, and 11 trials reported improvement in QOL, of which 6 (55%) were trials of immunotherapy drugs. Of the 34 trials in which QOL was not improved compared with controls, 16 (47%) reported these results in a positive frame, an observation statistically significantly associated with industry funding (χ2 = 6.35; P = .01)., Conclusions and Relevance: In this cohort study, a small proportion of RCTs of cancer drugs showed benefit in global QOL with the experimental agent. These results showed an association between QOL benefit and OS benefit but no such association with PFS benefit. Trials that failed to show improved QOL often reported their QOL outcomes more favorably. Non-immunotherapy-targeted drugs led to worse QOL more often than did cytotoxic agents.

Purpose: Access to essential cancer medicines is a major determinant of childhood cancer outcomes globally. The degree to which pediatric oncologists deem medicines listed on WHO's Model List of Essential Medicines for Children (EMLc) essential is unknown, as is the extent to which such medicines are accessible on the front lines of clinical care., Methods: An electronic survey developed was distributed through the International Society of Pediatric Oncology mailing list to members from 87 countries. Respondents were asked to select 10 cancer medicines that would provide the greatest benefit to patients in their context; subsequent questions explored medicine availability and cost. Descriptive and bivariate statistics compared access to medicines between low- and lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs)., Results: Among 159 respondents from 44 countries, 43 (27%) were from LMICs, 79 (50%) from UMICs, and 37 (23%) from HICs. The top five medicines were methotrexate (75%), vincristine (74%), doxorubicin (74%), cyclophosphamide (69%), and cytarabine (65%). Of the priority medicines identified, 87% (27 of 31) are represented on the 2021 EMLc and 77% (24 of 31) were common to the lists generated by LMIC, UMIC, and HIC respondents. The proportion of respondents indicating universal availability for each of the top medicines ranged from 9% to 46% for LMIC, 25% to 89% for UMIC, and 67% to 100% for HIC. Risk of catastrophic expenditure was more common in LMIC (8%-20%), compared with UMIC (0%-28%) and HIC (0%)., Conclusion: Most medicines that oncologists deem essential for childhood cancer treatment are currently included on the EMLc. Barriers remain in access to these medicines, characterized by gaps in availability and risks of catastrophic expenditure for families that are most pronounced in low-income settings but evident across all income contexts., Competing Interests: Scott C. HowardConsulting or Advisory Role: Sanofi, BTG, ServierSpeakers' Bureau: Sanofi, Jazz Pharmaceuticals Dorothy LombeThis author is a member of the Journal of Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript. Bishal GyawaliThis author is a member of the Journal of Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Vivio Health Felipe RoitbergHonoraria: Boehringer Ingelheim, AstraZeneca, Oncologia BrasilConsulting or Advisory Role: MSD OncologyResearch Funding: Roche (Inst), Boehringer Ingelheim (Inst), MSD (Inst), Bayer (Inst), AstraZeneca (Inst), Takeda (Inst) Elisabeth G. E. De VriesConsulting or Advisory Role: Daiichi Sankyo (Inst), NSABP Foundation (Inst), Crescendo Biologics (Inst)Research Funding: Amgen (Inst), Synthon (Inst), CytomX Therapeutics (Inst), Regeneron (Inst), G1 Therapeutics (Inst), Bayer (Inst), Roche (Inst), Genentech (Inst), Servier (Inst), Crescendo Biologics (Inst)Uncompensated Relationships: ESMO (Inst)Uncompensated Relationships: World Health Organization (Inst)Uncompensated Relationships: RECIST (Inst) Richard SullivanThis author is a member of the Journal of Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Honoraria: PfizerConsulting or Advisory Role: Pfizer (Inst)No other potential conflicts of interest were reported.

Importance: Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators., Objective: To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines., Design, Setting, and Participants: This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022., Main Outcomes and Measures: Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results., Results: In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA., Conclusion and Relevance: In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

Competing Interests: Simon Van WambekeConsulting or Advisory Role: JanssenTravel, Accommodations, Expenses: Roche, Janssen-Cilag, Ipsen Francisco Emilio Vera-BadilloConsulting or Advisory Role: Bayer, AstraZeneca, Janssen OncologyResearch Funding: AstraZeneca/MedImmune (Inst) Bishal GyawaliConsulting or Advisory Role: Vivio HealthNo other potential conflicts of interest were reported.

Background: As the landscape of haematological malignancies dramatically changes due to diagnostic and therapeutic advances, it is important to evaluate trends in clinical trial designs. The objective of our study was to describe the design of clinical trials for five common haematological malignancies with respect to randomisation and end-points. We also aimed to assess trends over time and examine the relationships of funding source and country of origin to proportions of randomisation and utilisation of clinical end-points., Methods: This systematic review identified haematological malignancy clinical trials starting in 2015-2020 registered at ClinicalTrials.gov as of 20th February 2021. Trial-related variables including randomisation status, type of primary end-point, and both projected and actual enrolment numbers were captured. Clinical end-points were defined as overall survival and quality of life, while surrogate end-points included all other end-points., Results: Of 2609 relevant trials included in this analysis, only one-fifth were randomised (538, 21%), with a significant decrease in the proportion of randomised clinical trials from 26% of trials in 2015 to 19% in 2020 (p < 0.00001). Between the years 2015 and 2020, the proportion of randomised trials for all haematological malignancies using primary surrogate end-points remained relatively consistent, ranging from 84% in 2015 to 78% in 2020 (p = 0.352). Overall, only 15% of trials utilised primary end-points of overall survival or quality of life in a randomised design., Conclusions: This systematic review of haematological malignancy trials found that the majority of trials are non-randomised and that there has been an increase in the ratio of non-randomised to randomised studies over time. The vast majority of randomised haematological malignancy trials use surrogate primary end-points., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests, although the study did not recieve any funding from these sources: Vinay Prasad reports royalties from Johns Hopkins Press, Medscape, MedPage, consulting for UnitedHealthcare, and speaking fees for Evicore. Vinay Prasad has a plenary session podcast that has Patreon backers. Vinay Prasad is funded to study low value drugs through a grant from Arnold Ventures. The funder had no role in the design of this study. Aaron Goodman reports consulting for Seattle Genetics and EUSA Pharma. Douglas Sborov reports consulting for Janssen, SkylinDx, GlaxoSmithKline, Legend Biotech, Amgen and Celgene. None of the authors have any other conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Colorectal cancer (CRC) ranks among the top five incident cancers in Sri Lanka (SL). Here, we describe disease characteristics and treatment patterns of patients with CRC in SL., Methods: All adult patients (age > 18 years) diagnosed with CRC during 2016-2020 were identified from the National Cancer Institute SL cancer registry. Cancer stage at diagnosis was defined according to the seventh edition of the TNM staging system. Concordance between recommendations for adjuvant therapy and actual rates of delivery was also analyzed. Descriptive statistics were used to describe the study cohort and treatment patterns., Results: A total of 1,578 patients were diagnosed with CRC during the study period, 53% (n = 830) with colon cancer and 47% (n = 748) with rectal cancer. Mean age was 61 (range, 18-91) years. Stage distribution was 13%, 28%, 46%, and 12% for stage I, II, III, and IV cancers, respectively. Adjuvant chemotherapy was delivered to 82% of patients with stage III colon cancer. There was a lack of concordance with delivery of neoadjuvant chemoradiotherapy, which was only delivered to 50% of patients with stage III rectal cancer for whom this treatment was indicated., Conclusion: Aging population and advanced stage of CRC at diagnosis will continue to challenge the provision of high-quality CRC care in SL. Further quantitative and qualitative research may help better understand the nonconcordance with treatment guidelines. Such information would help ease the burden of advanced-stage CRC in SL., Competing Interests: Scott BerryConsulting or Advisory Role: Merck, MD Briefcase, Apo Biologix, Amgen Bishal GyawaliThis author is a member of the JCO Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Vivio HealthNo other potential conflicts of interest were reported.

Purpose: Nepal lacks enough cancer care providers to address the growing burden of cancer in the country. One way of addressing this issue is to train general practitioners (GPs) in oncology (GPOs) so that they can task-share and task-shift oncology care. However, limited information is available regarding the current level of oncology expertise of Nepali GPs and whether they perceive a need for, and have an interest in, such a GPO training program if available in Nepal., Methods: A survey was distributed to GPs in Nepal to collect data on current oncology training and clinical practice and evaluate levels of interest and need for a GPO training program. The survey was distributed electronically from February to July 2021., Results: The survey obtained 71 individual responses from GPs in Nepal. The majority of respondents were male (87%), and most worked as consultants or senior consultants (63%). Only 6% of respondents had a mandatory oncology rotation during their GP training, and only 15% indicated that their GP training had adequately prepared them to care for patients with cancer. Ninety-six percent of respondents perceived a need for a GPO training program in Nepal, with 94% indicating an interest in enrolling in such a program and 71% indicating that they were very interested., Conclusion: The findings indicate an urgent need for and an encouraging interest in establishing a GPO training program in Nepal. These findings will be used to guide the development and implementation of this type of program., Competing Interests: Bishal GyawaliThis author is a member of the JCO Global Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Vivio Health Colleen SavageResearch Funding: Pfizer Scott BerryConsulting or Advisory Role: Merck, MD Briefcase, Apobiologix, AmgenNo other potential conflicts of interest were reported.

Background: In this study, we compared and contrasted design characteristics, results, and publications of randomized controlled trials (RCTs) in gastrointestinal (GI), lung, and breast cancer. Methods: A PUBMED search identified phase III RCTs of anticancer therapy in GI, lung, and breast cancer published globally during the period 2014−2017. Descriptive statistics, chi-square tests, and the Kruskal−Wallis test were used to compare RCT design, results, and output across the cancer sites. Results: A total of 352 RCTs were conducted on GI (36%), lung (29%), and breast (35%) cancer. Surrogate endpoints were used in 55% of trials; this was most common in breast trials (72%) compared to GI (47%) and lung trials (43%, p < 0.001). Breast trials more often met their primary endpoint (54%) than GI (41%) and lung trials (41%) (p = 0.024). When graded with the ESMO-MCBS, lung cancer trials (50%, 15/30) were more likely to meet the threshold for substantial benefit. GI trials were published in journals with a substantially lower impact factor (IF; median IF 13) than lung (median IF 21) and breast cancer trials (median IF 21) (p = 0.038). Conclusions: Important differences in RCT design and output exist between the three major cancer sites. Use of surrogate endpoints and the magnitude of benefit associated with new treatments vary substantially across cancer sites.

Importance: Hormone receptor-positive, ERBB2 (formerly HER2/neu)-negative metastatic breast cancer (HR-positive, ERBB2-negative MBC) is treated with targeted therapy, endocrine therapy, chemotherapy, or combinations of these modalities; however, evaluating the increasing number of treatment options is challenging because few regimens have been directly compared in randomized clinical trials (RCTs), and evidence has evolved over decades. Information theoretic network meta-analysis (IT-NMA) is a graph theory-based approach for regimen ranking that takes effect sizes and temporality of evidence into account., Objective: To examine the performance of an IT-NMA approach to rank HR-positive, ERBB2-negative MBC treatment regimens., Data Sources: HemOnc.org, a freely available medical online resource of interventions, regimens, and general information relevant to the fields of hematology and oncology, was used to identify relevant RCTs., Study Selection: All primary and subsequent reports of RCTs of first-line systemic treatments for HR-positive, ERBB2-negative MBC that were referenced on HemOnc.org and published between 1974 and 2019 were included. Additional RCTs that were evaluated by a prior traditional network meta-analysis on HR-positive, ERBB2-negative MBC were also included., Data Extraction and Synthesis: RCTs were independently extracted from HemOnc.org and a traditional NMA by separate observers. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for NMA with several exceptions: the risk of bias within individual studies and inconsistency in the treatment network were not assessed., Main Outcomes and Measures: Regimen rankings generated by IT-NMA based on clinical trial variables, including primary end point, enrollment number per trial arm, P value, effect size, years of enrollment, and year of publication., Results: A total of 203 RCTs with 63 629 patients encompassing 252 distinct regimens were compared by IT-NMA, which resulted in 151 rankings as of 2019. Combinations of targeted and endocrine therapy were highly ranked, especially the combination of endocrine therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. For example, letrozole plus palbociclib was ranked first and letrozole plus ribociclib, third. Older monotherapies that continue to be used in RCTs in comparator groups, such as anastrozole (251 of 252) and letrozole (252), fell to the bottom of the rankings. Many regimens gravitated toward indeterminacy by 2019., Conclusions and Relevance: In this network meta-analysis study, combination therapies appeared to be associated with better outcomes than monotherapies in the treatment of HR-positive, ERBB2-negative MBC. These findings suggest that IT-NMA is a promising method for longitudinal ranking of anticancer regimens from RCTs with different end points, sparse interconnectivity, and decades-long timeframes.

Cancer Groundshot is a philosophy that calls for prioritization of strategies in global cancer control. The underlying principle of Cancer Groundshot is that one must ensure access to interventions that are already proven to work before focusing on the development of new interventions. In this article, we discuss the philosophy of Cancer Groundshot as it pertains to priorities in cancer care and research in low- and middle-income countries and the utility of technology in addressing global cancer disparities; we also address disparities seen in high-income countries. The oncology community needs to realign our priorities and focus on improving access to high-value cancer control strategies, rather than allocating resources primarily to the development of technologies that provide only marginal gains at a high cost. There are several "low-hanging fruit" actions that will improve access to quality cancer care in low- and middle-income countries and in high-income countries. Worldwide, cancer morbidity and mortality can be averted by implementing highly effective, low-cost interventions that are already known to work, rather than investing in the development of resource-intensive interventions to which most patients will not have access (i.e., we can use Cancer Groundshot to first save more lives before we focus on the "moonshots").

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in Nepal. Female community health volunteers (FCHVs) have proven effective in the delivery of reproductive, maternal, and child health services in Nepal and recently in the prevention and management of hypertension and type 2 diabetes. Evidence on their roles in COPD management is not yet available. The aim of this study was to develop, implement, and evaluate a training program for FCHVs regarding COPD prevention and management. The training program was part of a cluster-randomized trial of a 12-month intervention to improve COPD outcomes in a semi-urban area of Western Nepal. A six-day workshop consisting of thirty hours of training was developed for FCHVs. Training materials incorporated introduction to COPD, risk factors and symptoms, COPD status assessment guide for FCHVs, guidance on breathing techniques, and exercises for people living with COPD. Pre- and post-test questionnaires were administered to assess the change in knowledge of FCHVs, post training skills assessment followed by semi-structured interviews assessed FCHVs' satisfaction with the training program. The findings of the pre- and post- test assessments showed a significant improvement in FCHVs' COPD-related knowledge from a median (interquartile range) score of 12 (3-16) before to 21 (21-22) (p<0.001) after the training program. The qualitative assessment revealed the feasibility of FCHVs' training on COPD and their acceptability to deliver the intervention package within the community. It also indicated that implementing future training with an extended period and a few days break in-between could enhance the effectiveness. Training of FCHVs in COPD management is feasible and leads to improvement in knowledge. The motivation shown by FCHVs to deliver the intervention could inform and guide community programs and policies for COPD prevention and management in Nepal and similar settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Adhikari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)