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Lung cancer

Affiliations.

1 Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia.
2 Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
3 Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. Electronic address: [email protected].
PMID: 34273294
DOI: 10.1016/S0140-6736(21)00312-3

Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide with an estimated 2 million new cases and 1·76 million deaths per year. Substantial improvements in our understanding of disease biology, application of predictive biomarkers, and refinements in treatment have led to remarkable progress in the past two decades and transformed outcomes for many patients. This seminar provides an overview of advances in the screening, diagnosis, and treatment of non-small-cell lung cancer and small-cell lung cancer, with a particular focus on targeted therapies and immune checkpoint inhibitors.

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Conflict of interest statement

Declaration of interests BJS reports personal fees from Pfizer, Novartis, Roche/Genentech, AstraZeneca, Merck, Bristol Myers Squibb, Amgen, and Loxo Oncology outside the submitted work. JFG has served as a consultant or received honoraria from Bristol-Myers Squibb, Genentech, Ariad/Takeda, Loxo/Lilly, Blueprint, Oncorus, Regeneron, Gilead, Helsinn, EMD Serono, AstraZeneca, Pfizer, Incyte, Novartis, Merck, Agios, Amgen, and Array; has had research support from Novartis, Genentech/Roche, Ariad/Takeda, Bristol-Myers Squibb, Tesaro, Moderna, Blueprint, Jounce, Array Biopharma, Merck, Adaptimmune, and Alexo; and has an immediate family member who is an employee of Ironwood Pharmaceuticals. LVS reports grants and personal fees from AstraZeneca; grants from Novartis and Boehringer Ingelheim; grants and consulting fees from Genentech Blueprint and Merrimack Pharmaceuticals; and consulting fees from Janssen and grants from LOXO, all outside the submitted work. LVS has a patent about treatment of EGFR-mutant cancer pending. RSH reports honoraria from Novartis, Merck KGaA, Daichii Sankyo, Pfizer, Roche, Apollomics, Tarveda, and Boehringer Ingelheim; and grants from Novartis, Genentech Roche, Corvus, Incyte, Exelixis, Abbvie, Daichii Sankyo, Agios, Mirati, Turning Point, and Lilly when writing this Seminar. AAT declares no competing interests.

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Published: 15 September 2011

Cancer research: past, present and future

Ronald A. DePinho 2 ,
Matthias Ernst 3 &
Karen Vousden 4

Nature Reviews Cancer volume 11 , pages 749–754 ( 2011 ) Cite this article

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Therapeutics

Research into cancer over the past 10 years has diverged enormously, partly based on the large number of new technologies that are now at our finger tips. With areas of cancer research so disparate, it is not always easy to identify where the next new findings and therapies might come from. With this in mind, we asked four leading cancer researchers from around the world what, in their opinion, we have learnt over the past 10 years and how we should progress in the next 10 years.

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Acknowledgements

M.E. is a research fellow of the National Health and Medical Research Council Australia. Y.C. thanks Z. Dong and A.M. Bode, The Hormel Institute, University of Minnesota, USA.

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Ya Cao is at the Cancer Research Institute of Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China.,

Ronald A. DePinho is at the University of Texas MD Anderson Cancer Center 1400 Pressler, Unit 1491 Houston, Texas 77030, USA.,

Ronald A. DePinho

Matthias Ernst is at the Melbourne-Parkville branch of the Ludwig Institute for Cancer Research, 6th floor, Centre for Medical Research, Royal Melbourne Hospital, Royal Parade, Parkville, Victoria VIC 3050, Australia.,

Matthias Ernst

Karen Vousden is at the Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.,

Karen Vousden

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Correspondence to Ya Cao , Ronald A. DePinho , Matthias Ernst or Karen Vousden .

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Cao, Y., DePinho, R., Ernst, M. et al. Cancer research: past, present and future. Nat Rev Cancer 11 , 749–754 (2011). https://doi.org/10.1038/nrc3138

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Vidya Vedham, Ph.D., Center For Global Mental Health Research, National Institute of Mental Health

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“Among the community, cancer survivors are perceived as ‘walking dead,’ disabled, and weak.” ( Global Cancer Stigma Research Workshop, 2022 )

“The woman [with cancer] becomes a victim of stigma by her family, relatives, colleagues and is judged by her physical appearance. At worst, she is abandoned, most often by her husband, fired from her job, driven into debt to support herself, denied medical insurance, salary increases, and loses her responsibilities, promotion, and benefits when she returns to work.” (Johnson & Samson, 2024 )

“People with cancer…the employers find out that they have cancer then they must definitely stop working. Because the disease makes them unable to work, for example, so they cannot do hard work, for example, or cannot meet the assigned quota or target. They are fired.” ( Eschliman et al., 2024 )

Cancer Stigma: Scope and Impact on Cancer Control

As poignantly illustrated by the quotes above – collected from cancer patients, survivors, advocates, and community members around the world – stigma is a complex and powerful social process that involves labeling certain human characteristics as socially undesirable, often associating them with negative stereotypes. This process often leads to a loss of status and discrimination, among other negative consequences, against those who are labeled (4) . Unfortunately, individuals at-risk of cancer, cancer patients and survivors, caregivers, and family members encounter varying levels of stigma throughout their care journey (5) . This stigma can arise from various factors, including public and healthcare provider misconceptions, cultural and religious beliefs, and media portrayals that further reinforce negative stereotypes.

Cancer stigma continues to be a major challenge for cancer prevention and control efforts, exerting profound effects on cancer incidence, morbidity, and mortality worldwide (5) . It can impede preventive health-seeking behaviors, screening, treatment adherence, and care engagement. Individuals affected by cancer stigma often experience guilt, social isolation, and avoidance, which can worsen health outcomes and reduce their quality of life. We believe addressing cancer stigma is critical for improving the health and wellbeing of individuals affected by cancer as well as for enhancing cancer prevention and control efforts broadly.

The U.S. National Cancer Institute Efforts

Despite its significant impact, cancer stigma remains under-researched, with minimal attention given to the topic, insufficient measurement instruments, and a shortage of evidence-based mitigation interventions. In response, over the past several years, the National Cancer Institute (NCI) has implemented an international workshop, a special issue of a leading cancer journal, and a series of funding opportunities, all aimed at supporting researchers and practitioners in advancing the global field of cancer stigma research.

NCI’s Global Cancer Stigma Research Workshop

The first of these efforts took place in September 2022 when NCI's Center for Global Health (CGH) and the Division of Cancer Control and Population Sciences (DCCPS) hosted NCI’s Global Cancer Stigma Research Workshop . For this two-day virtual event, we brought together over 100 participants from five continents, including researchers, cancer survivors, advocates, clinicians, and representatives from non-governmental and governmental organizations. Through the workshop, focused on the intersection of cancer and stigma, we aimed to emphasize the impact of stigma on global cancer control; foster the exchange of ideas within the cancer stigma research community; and highlight domestic and global cancer stigma research to identify potential research gaps for stigma measurement and the development of context-specific stigma reduction interventions.

As shown in the figure below, key areas of focus included cancer stigma manifestations and types, drivers and contributors, impacts and consequences, measurement, interventions, and resilience. In addition, workshop participants identified research gaps and priority areas resulting in several calls to action for the cancer stigma research community, including the need to further conceptualize cancer stigma in global contexts; develop and implement inclusive research approaches; expand research methodologies; and promote collaboration among stakeholders.

JNCI Monographs: Global Cancer Stigma: Research, Practice, and Priorities

Building on the momentum from the workshop, we sought to develop a research monograph to further highlight the diverse efforts in cancer stigma research and to allow academic partners, health providers, trainees, advocates, and community members to engage with these ideas. Released in June 2024, a special issue of JNCI Monographs titled Global Cancer Stigma: Research, Practice, and Priorities is a collection of peer-reviewed articles showcasing efforts to understand, measure, and address cancer stigma across global communities – including Vietnam, Nigeria, and Kenya – as well as to consider identified research gaps and opportunities including:

Issue cover for JNCI Monograph "Global Cancer Stigma: Research, Practice, and Priorities"

Conceptualizing Cancer Stigma in Global Contexts : Eschliman et al. report on findings from in-depth interviews in Vietnam and the application of the “What Matters Most” framework, recognizing that achieving and maintaining cultural capabilities, such as staying employed, can alleviate some of the negative effects of stigma.

Measuring Cancer Stigma : Studts et al. focus on the operationalization and measurement of stigma and conclude that mitigating stigma toward individuals with a history of smoking may be critical to ensuring unbiased care and fostering broader health system improvement

Mitigation Strategies : Banerjee et al. report on an adaptation of an empathic communication skills training intervention and the implementation of a pilot feasibility study among oncology clinicians in Nigeria.

Broader Implications and Recommendations : Representatives of the Union for International Cancer Control highlight the need for policy and country-level changes to reduce cancer stigma.

The efforts highlighted in this special issue illustrate the complexity of studying cancer stigma and the necessity of a multifaceted approach. It is our hope that these articles spark innovative ideas for future research efforts and practice improvements.

Funding Opportunities

In addition to hosting an international meeting and publishing a special issue, we continue to prioritize related funding opportunities for the extramural research community. Historical efforts include participating in the Fogarty International Center’s funding opportunity (R21, R01) on “Interventions for Stigma Reduction to Improve HIV/AIDS Prevention, Treatment and Care in Low- and Middle- Income Countries” (LMICs) (2017-present). In fiscal years 2021 and 2023, CGH published a series of administrative supplements ( “NOSI: Administrative Supplement Opportunity to Support Global Cancer Stigma Research” ) to support one-year exploratory research studies to expand the current understanding of cancer stigma, assess its impact on cancer prevention and control, and develop stigma-reduction interventions to improve cancer outcomes in LMICs. Notable among our upcoming efforts is the release of two funding opportunities ( R01 , R21 ) focused on the confluence of HIV stigma and cancer stigma among individuals with a dual diagnosis of HIV and cancer. These cancer stigma-related funding opportunities contribute to our broader goal of cultivating innovative research in global cancer prevention and control.

Addressing cancer stigma in global communities requires a comprehensive and inclusive approach that encompasses diverse perspectives and strategies. By advancing the understanding, measurement, and mitigation of cancer stigma, the cancer research community can work toward reducing the global cancer burden and promoting health equity, ultimately improving quality of life and survival rates worldwide. We are committed to actively engaging with key stakeholders to drive research and practice in this critical area, ensuring that these efforts are impactful and responsive to the needs of the global communities they serve.

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CANCER SURVIVORSHIP

In recent years. more cancers are being detected but treatments and outcomes are also improving. megaflopp/iStockphoto/Getty Images hide caption

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Four years after their diagnosis, Monje, now 29, is teaching part time, and grateful for stability and the potential of many years left to live.

“I feel like my quality of life is pretty good…considering I thought I was going to die,” Monje says.

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Jane Figueiredo, a researcher at Cedars Sinai in Los Angeles and one of the co-authors of the report, says treatments and better detection methods have made even highly lethal cancers like lung or melanoma much more survivable. The report notes that from July 1, 2023, to June 30, 2024, the Food and Drug Administration approved 15 new anticancer treatments.

“New therapies, including immunotherapies, had been very successful across a number of different cancers,” she says.

Similarly, tools like artificial intelligence are able to scan patient databases, to identify common features of cancers, for example, making it easier to identify existing medicines that might target a person’s specific disease.

In other words, says Figueiredo, never before has cancer science moved so swiftly toward finding new treatments.

But, at the same time, increased rates of obesity and alcohol consumption and environmental factors, for example, are likely driving up cancer rates substantially among young people under the age of 50.

In the U.S., 40% of all cancers are associated with modifiable risk factors, according to the report, including excess alcohol use.

Cancers like colorectal cancer are becoming more common and more lethal among the young.

“It’s very concerning; these are individuals that are in the prime of their life,” Figueiredo says.

Cancer can no longer be thought of as a disease for older people. “These are individuals that are trying to advance their careers. They may be caring for children or family members, trying to save money, and they often don't recognize some of their symptoms.”

All these trends also mean there are more Americans living with, and surviving cancer. Three decades ago, survivorship was relatively rare; cancer survivors made up 1.4% of the population three decades ago, but now make up 5%. That’s the equivalent of 18 million Americans living with a cancer diagnosis in their past.

colorectal cancer
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Oracle Introduces New Research Service for Analyzing Global Trends in Cancer Treatment

Cloud service enables pharmaceutical and biotech companies to explore historical oncology treatment trends to guide development and commercialization strategies

Oracle today announced CancerMPact® Treatment Architecture Trends. The new cloud-based service enables pharmaceutical companies to analyze historical and global cancer treatment patterns to determine the impact of market events, such as new drug approvals, and the uptake of drugs and drug classes.

Treatment Architecture Trends is the latest module in CancerMPact, a comprehensive oncology decision support resource. It can be utilized for market sizing and analysis, strategic planning, and identification of commercial opportunities in the U.S., Europe, Japan, and China. The CancerMPact resource also includes the cloud-based integrated Future Trends and Insights, CancerLandscape, and Treatment Architecture modules.

“Understanding the opportunities and trends that exist within cancer treatments and standards of care is critical when designing pivotal development strategies for new therapies for cancer,” said Seema Verma, executive vice president and general manager, Oracle Health and Life Sciences. “Through our evolving CancerMPact platform, Oracle continues to help uncover new insights that drive critical decisions—as we have done for the largest pharmaceutical companies in the world for more than two decades.”

Treatment Architecture Trends assesses the current and historical trends in the clinical management of patients by site and stage for all cancer treatment modalities—including surgical, radiologic, and systemic agents, as well as untreated patient populations for up to 31 tumor types in the G8 markets. It provides users the ability to explore a rich data set of annual drug treatment (by stage, patient segment, and line of therapy), duration of therapy, modality use, and outcomes data that can help guide commercialization and treatment strategies.

Offered as an add-on to the existing Treatment Architecture module, the trends-focused service provides access to, and analysis of, more than seven years of cancer data (2017 to present) across four global geographies including the U.S., Japan, China, and the EU5 (Germany, Spain, France, Italy, and the United Kingdom). Oracle plans to continue to be expand the solution with new data being added in future years. The drug data can be queried and filtered by technology, target, and regimen within an interactive, cloud-based dashboard. The analysis can also be further segmented by physician specialty and treatment practice setting.

Additionally, drug approval events are provided for each geography to provide contextual understanding of impactful market events. As with all of the CancerMPact modules, users will also gain direct access to Oracle’s CancerMPact team for further support in exploring these rich longitudinal datasets derived from our physician survey-based Treatment Architecture reports.

Treatment Architecture and TA-Trends are based on Oracle’s proprietary online market research with direct responses from more than 7,500 oncology healthcare providers annually across the globe, representing more than 450,000 treated patients monthly. It offers added confidence due to the benefit of global consistency in our research methods, providing a more reliable comparison of treatment trends among the G8 countries, and curated standardization of historical data allows for appropriate year-over-year comparisons and analyses.

To learn more about CancerMPact, please visit: https://www.oracle.com/a/ocom/docs/industries/life-sciences/factsheet-cancermpact-improving-business-outcomes.pdf

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Judi palmer, about oracle.

Oracle offers integrated suites of applications plus secure, autonomous infrastructure in the Oracle Cloud. For more information about Oracle (NYSE: ORCL), please visit us at www.oracle.com .

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Oracle Life Sciences is a leader in cloud technology, pharmaceutical research, and consulting, trusted globally by professionals in both large and emerging companies engaged in clinical research and pharmacovigilance, throughout the therapeutic development lifecycle, including pre- and post-drug launch activities. With more than 20 years of experience, Oracle Life Sciences is committed to supporting clinical development and leveraging real-world evidence to deliver innovation and accelerate advancements—empowering the Life Sciences industry to improve patient outcomes. Learn more at www.oracle.com/lifesciences

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Cancer screening and early detection in the 21 st century

Jennifer loud.

Clinical Genetics Branch, DCEG, NCI, NIH 9609 Medical Center Drive Rockville, Maryland 20850-9772

Jeanne Murphy

Breast and Gynecologic Cancer Research Group, DCP, NCI, NIH 9609 Medical Center Drive Rockville, Maryland 20892-9712

To review the trends in and principles of cancer screening and early detection.

Data Sources

Journal articles, United States Preventive Services Task Force (U SPSTF) publications, professional organization position statements, evidence-based summaries

Cancer screening has contributed to decreasing the morbidity and mortality of cancer. Efforts to improve the selection of candidates for cancer screening, to understand the biological basis of carcinogenesis, and the development of new technologies for cancer screening will allow for improvements in the cancer screening over time.

Implications for Nursing Practice

Nurses are well-positioned to lead the implementation of cancer screening recommendations in the 21 st Century through their practice, research, educational efforts and advocacy.

The goal of cancer screening and early detection is to cure cancer by detecting the malignancy, or its precursor lesion, at an early stage prior to the onset of symptoms, when treatment of cancer is most effective. Indeed, overall cancer mortality has decreased by 25% from 1990 to 2015 for the United States U.S.), with even greater declines in the mortality rates for colorectal cancer (47% among men and 44% among women) and, breast cancer (39% among women). A portion of this decrease can be attributed to the introduction of high-quality cancer screening for colorectal and breast cancer. 1 The most successful cancer screening programs lead to the identification of precursor lesions (e.g., cervical intra-epithelial neoplasia (CIN) with cervical cancer screening and colonic polyps with colorectal cancer screening) where the treatment of the precursor lesion leads to a decrease in the incidence of invasive cancer over time. The guiding principles of screening for disease were proposed in 1968 by Wilson and Jungner 2 of the World Health Organization ( Table 1 ). Not all cancer screening recommendations meet each of these guiding principles; historically there has been a balance between the identification of early or precursor lesions and the avoidance of overdiagnosis which may lead to overtreatment ( Table 2 ).

Wilson and Jungner Criteria for disease screening 2

Potential negative outcomes of cancer screening.

When tumors are detected that would never become symptomatic or lead to death

When tumors are detected that would never become symptomatic or to death but are treated none-the-less

Application of Cancer Screening Principles

U.S. population screening for cervical cancer serves as an exemplar of a successfully designed and implemented screening program that has been modified as the biological mechanism of the carcinogenesis of cervical cancer is more clearly elucidated and methods for primary prevention (i.e., HPV vaccination) are developed. Cervical cancer screening programs in particular adhere to several of Wilson and Junger’s principles, most importantly, that the natural history of the disease be understood and that it be an important health problem. Chronic human papilloma virus (HPV) infection is the underlying etiologic agent of the carcinogenesis of cervical cancer. Chronic HPV leads to a precancerous lesion (i.e., cervical intra-epithelial neoplasia) which can be visualized, after the detection of a positive cytology (through Pap testing), with colposcopy. The removal of the precancerous lesion using colposcopy successfully led to an overall decrease in the incidence of cervical cancers, even though there was over treatment of some early lesions. Cervical cancer screening represents an example of the use of an accurate screening test (i.e., PAP, colposcopy and now HPV testing) with adequate sensitive, specificity and positive and negative predictive value (PPV and PNV) leading to the identification of a high risk population, a pre-cancer or a cancer ( Tables 3 and and4). 4 ). Population screening for colon cancer also conformed to many of Wilson and Jungner’s principles and led to improvements in overall survival of individuals who adopted screening recommendations. 1 A key feature of both cervical and colon cancer screening is the ability to directly access the tissue of interest and apply an adequate screening test. Population screening for cervical cancer reduced the incidence and mortality rates from cervical cancer and led to enthusiasm that screening programs for other cancers, or pre-cancers, would be equally successful. However, screening, detection and removal of pre-cancer or early cancer in other cancer types has not always been as successful.

Characteristics of an accurate screening test.

→ delivers same result each time, each instrument, each rater

→ delivers the correct result each time:

= correctly classify cases (pre=cancer or cancer)

Sensitivity=Cases found/all cases

= correctly classify non-cases (things that are not cancer)

Specificity= Non-cases identified/all non-cases

Performance characteristics of a screening test

The chance that a person with a positive test (e.g., an abnormal pap test) has cancer or pre-cancer

The chance that a person with a negative test (e.g., a normal pap test) does not have cancer or pre-cancer

A major assumption about the natural history of carcinogenesis is based on the models of carcinogenesis of colorectal cancer proposed by Vogelstein et.al. 3 The model predicted a slow-growing, linear progression from a pre-cancer to a localized cancer that would occur at a rate of time that was amendable to cancer screening, similar to the pattern of carcinogenesis observed in cervical cancer. It also assumed that there was similarity within cancer types, such that all prostate or breast cancers behaved similarly. Based on that assumption, population-based screening programs for other solid tumors were developed including breast and prostate cancer screening. However, outcomes from multiple screening programs between 1980–2010 demonstrated that breast and prostate cancers are a heterogeneous group of diseases that do not necessarily conform to the pattern of carcinogenesis as initially proposed in the Vogelstein model. 4 After population screening was introduced for breast and prostate cancer and outcomes documented overtime, lessons learned ( Table 5 ) included that

Lessons learned from population screening for breast, prostate and colon cancer

Breast and prostate cancers were not uniform in their biology (they are heterogeneous)
Not all early lesions (i.e., ductal carcinoma insitu or indolent prostate cancer) lead to invasive cancer
Early detection does not always lead to improvements in overall survival, and
There is risk to individuals when introducing screening interventions in otherwise healthy populations, including overdiagnosis and overtreatment ( Table 2 )

In addition, other cancer screening techniques rely on indirect methods to screen for cancer such as radiographic imaging (e.g., mammography) or measuring a biomarker associated with cancer (e.g., CA-125 or PSA), rather than direct visualization and access to the target organ as in colorectal and cervical cancer screening. These indirect methods of cancer screening led to compromised screening efficacy due a decrease in performance characteristics of the screening technique [(including false positives and false negatives ( Table 6 )] and an increase in overdiagnosis and overtreatment. 4 As more evidence of screening efficacy accumulates, changes in cancer screening recommendations and practice continue to occur. Prostate cancer screening guidelines changed to include shared decision-making as it became evident that the risk-to-benefit ratio of routine prostate cancer screening in men over the age of 50 was unfavorable; routine prostate cancer screening led to overdiagnosis of indolent cancer without a survival benefit while placing men at greater risk of injury related to the treatment of indolent prostate cancer. 5

Possible test outcomes of cancer screening

Correctly indicates there is cancer

: Incorrectly indicates there is cancer

Correctly indicates that no cancer is present

: Incorrectly indicates that

Improving the Precision of Candidates for Cancer Screening

Ideally, cancer screening is undertaken when the risk of cancer is high enough to justify the risk of overdiagnosis and overtreatment in an otherwise healthy population. 6 Cancer screening in healthy populations balances patient tolerance of risk, personal attitudes and the choice of a screening program most likely to have net benefit to the individual. In low-to-average risk populations, the recommended age to begin routine cancer screening is the age at which the risk of cancer begins to rise (e.g., 50 years for colorectal cancer screening) and when the tumor develops slowly. Slow tumor progression allows for the identification of a malignancy (or pre-malignancy) at an early stage which reduces the incidence of late stage cancer. For instance, the optimal screening interval for colorectal cancer screening with colonoscopy in the general population is 10 years, which allows for the removal of the pre-cancerous lesion, the adenomatous polyp, thereby reducing colon cancer. Cancer screening does not work as effectively for rapidly growing tumors or those that disseminate early, as they tend to occur between screening intervals and present with symptoms.

Integrating exposure history is commonly used to improve the identification of individuals at higher risk of cancer than the general population. 4 Targeting smokers with a 30 pack-year for low-dose chest tomography (CT) to screen for early lung cancer and identifying women with HPV infection to define a high risk population at risk of cervical cancer demonstrate efforts to use risk stratification in order to offer screening to individuals most likely to benefit and reduce screening in low risk individuals.

Risk-prediction models attempt to identify individuals at higher risk of cancer than the general population. The Breast Cancer Risk Assessment Tool 7 was one of the first tools aimed at identifying women who could benefit from breast cancer chemoprevention trials and accounts for clinical risk factors (i.e., family history, personal history, breast biopsy) as well as hormonal exposures (i.e., age of menarche). More recent risk-prediction models incorporate exposures (i.e., radiation exposure), breast density as well as biomarkers (i.e., single nucleotide polymorphisms) in an effort to improve risk-stratification. 8

The contribution of genetics and genomics to risk-stratification has steadily progressed since the identification of the germline p53 mutation in Li Fraumeni Syndrome. 9 , 10 The ability to identify individuals who carry a germline mutation associated with a hereditary cancer syndrome greatly improves risk-stratification and helps identify those individuals who may benefit from more frequent cancer screening and other preventive procedures. For example, individuals at high risk of cancer due to inherited cancer susceptibility (such as carrier of a BRCA1 or BRCA2 mutation) undergo aggressive cancer screening for the tumors associated with the syndrome and may also consider prophylactic surgery to reduce their risk of cancer. Within a family with a known BRCA1 mutation, those family members who did not inherit the mutation do not need to undergo intensive screening nor do they need to consider prophylactic surgery to prevent cancer. As the expense of genetic sequencing decrease, there is an increase in the use of genetic testing panels and other genomic technologies for risk stratification. However, important clinical challenges exist with these technologies regarding the classification of the identified genetic variants, reporting of the variants or unknown significance and how to handle incidental findings. 11 Multiple organizations have developed standards and guidelines for interpreting sequence variants and conclude that clinical genetic tests should be performed in Clinical Laboratory Improvement Amendments (CLIA)-approved labs and the results should be interpreted by a board certified clinical molecular geneticist, a molecular genetic pathologist or the equivalent. 12

When it is not so Simple to Screen: ovarian cancer

Ovarian cancer is rare, with incidence of 11.9 per 100,000, and a 5-year survival rate of only 46%. 13 It is also the most lethal of all cancers of the female reproductive system. 14 Recent evidence suggests that high-grade serous ovarian cancer, the most common and dangerous type, actually arises from malignant cells in the fimbriated end of the fallopian tube. 15 Much of this lethality is due to the difficulty of diagnosis because ovarian cancer’s vague symptoms include bloating, abdominal fullness and pain, and fatigue. 16 This leads to delayed detection, with 60% of cases diagnosed at a late stage with distant metastasis. 13 The median age at ovarian cancer diagnosis is 63, and is more common among women with a family history. Since 1975, 5-year survival has increased from 33.7% in 1975 to 46% in 2008. 13

Given its lethality, it is essential to develop effective screening strategies for ovarian cancer in order to intervene earlier in the process of disease. The challenge of ovarian cancer screening lies with the site. Unlike the uterine cervix, whose cells can be sampled directly through cervical cytology or by testing for human papillomavirus, 17 the ovaries and fallopian tubes lie deep in the pelvis, making them inaccessible to routine evaluation. This is especially problematic for asymptomatic women with germline mutations in BRCA1 or BRCA2 that place them at much higher risk of ovarian cancer (lifetime risk of 10%–25% for BRCA1 or BRCA2 vs 1.7% for the general population), but it is also problematic for the general population. 16 Ovarian cancer risk in a high-risk population can be determined through taking a careful family history, and this is a reasonable and inexpensive “Precision Public Health” intervention. 18 Population-based genetic testing for hereditary breast and ovarian cancer, called for by Mary Claire King in an opinion piece published as she accepted the 2014 Lasker Award from the National Institutes of Health 19 may identify more women who can benefit from targeted ovarian cancer screening strategies, though there is no consensus for this recommendation to date.

For asymptomatic, low risk women, strategies for ovarian cancer screening have included direct examination through bimanual examination during pelvic examination, and visualization through transvaginal (TV) ultrasonography and Doppler studies. 20 , 21 Both approaches attempt to evaluate the ovaries for abnormal, possibly cancerous, masses. Despite its recommended use, bimanual examination suffers from low sensitivity for both adnexal masses in general 22 and for ovarian cancer specifically, 23 and is associated with harms from false positive results resulting in unnecessary surgical biopsies. 24 Currently some have begun to question the inclusion of the bimanual examination in primary care guidelines as a screening test for ovarian masses. 25 Similarly, a one-time transvaginal ultrasound of asymptomatic women did not result in reduction in ovarian cancer mortality in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKTOCS) and is not recommended as a stand-alone screening test for ovarian cancer. 26

Serum biomarkers such as CA-125 and others have been tested for efficacy in screening for ovarian cancer. CA-125, also known as MUC16, is a large glycoprotein membrane marker from the MUC family found on ovarian cancer cells, but it is not specific to them. 27 , 28 Serum levels of CA-125 are elevated in ovarian cancer and many non-cancerous conditions such as ovarian cysts and liver cirrhosis, and also in non-ovarian malignancies. 29 CA-125 as a standalone screening test is relatively insensitive for ovarian cancer, finding only about 60% of women with ovarian cancer. 30 Other serum biomarkers such as human epididymis protein (HE4) and human chorionic gonadotropin (HCG) have been tested in combination with CA-125 to improve performance characteristics of serum biomarker screening for ovarian cancer as standalone serum screening tests, 29 , 31 though evidence suggests that CA-125 is the most robust biomarker of the group. 32

The most promising approach for ovarian cancer screening is a strategy combining serum CA-125, with or without other biomarkers, and TV ultrasound. The UKTOCS in the UK 26 and the Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) trial in the US 33 tested similar strategies. Despite its promise, this co-testing strategy has not resulted in overall reduction in mortality due to ovarian cancer. 26 , 33 The UK trial tested a proprietary algorithm named ROCA ® that adjusted the biomarker level cut-off for normal results based on women’s clinical characteristics and the TV ultrasound result. 31 The promotion of ROCA ® (Abcodia, Cambridgeshire, UK) serum testing with TV ultrasound ran afoul of the Food and Drug Administration (FDA) for the claim that the ROCA ® test detects ovarian cancer early and reduced mortality. In late 2016 FDA issued a warning against using commercial screening tests for ovarian cancer, saying that, especially for women at high risk for hereditary ovarian cancer, “women and their doctors may not take appropriate actions to reduce their future risk if they rely on a result that shows no cancer currently present.” 34 FDA further stipulated that they did not recommend the use of ovarian cancer screening tests in the general population. 34

The history of ovarian cancer screening is a cautionary tale for nurses in considering the use of screening tests in low risk populations. It also highlights the importance of understanding the potential for harm with using what may prove, with more evidence, to be effective screening strategies that save lives.

Improving the Infrastructure for Cancer Screening

Continued progress to reduce death rates from cancer in the United States will only be achieved if there is broad commitment to understanding the determinants of cancer, including access to care, affordability, and social and environmental factors associated with cancer risk. 1 National cancer registries, linked to cancer screening programs, can support detailed cohort studies to improve outcomes research leading to quality improvements in cancer screening programs. Indeed, the Breast Cancer Screening Consortium 4 has linked data from regional mammography registries to increase the diversity of their sample populations and the American College of Radiology’s national lung cancer screening aims to develop outcomes-based research in support of quality improvements. Such efforts support evidence-based practices and will allow for continuous process improvement in outcomes of cancer screening and research methodologies.

The selection of ideal candidates to screen or not screen is an understudied area ripe for future research. As individuals age and acquire co-morbidities (competing risks), the balance between risk and benefit of screening may shift in favor of increased risk with limited- to no-benefit. One risk prediction model, e-Prognosis ( http:eprognosis.ucsf.edu/ ) uses age and specific health measures to predict overall survival at different ages. Future research will address the utility of these tools across all cancer screening recommendations to identify those who will benefit most from screening and those most likely to be harmed. 35

The translation of cancer screening research into effective public health policy requires nurses to be cognizant of the multiple levels of policy complexity. 36 As evidence of screening efficacy is demonstrated through research, healthcare legislation requires insurance coverage for screening recommendations developed by the United States Preventive Services Task Force (USPSTF). Changes in screening recommendations by the USPSTF can ignite professional, public and political controversy as evidenced by the debate surrounding the revised 2009 Task Force recommendation for breast cancer screening. 37 All healthcare providers should plan to effectively communicate the scientific underpinnings of new research and the potential for cultural, political and policy implications. A well-developed communication plan incorporates a review of the research, the basis of the recommendation and the implications of the research for all stakeholders (including the public, politicians and policymakers). Nurses play an essential role in the dissemination of research and the evaluation and implementation of new cancer screening programs to the public and other stakeholders.

Cancer screening practice in the 21 st century will integrate genomics, risk prediction, patient preferences and improvements in health care delivery systems into patient care services. Essential nursing functions will continue to be in high demand as the aging population of the United States increases and more individuals have access to care ( Table 7 ). Nurses will lead the transformation of cancer care in all healthcare settings and work to ensure that all patients receive high quality cancer care. 38 Cancer screening recommendations have been shown to significantly decrease the mortality from certain cancers (i.e., cervical and colorectal), while more modestly decreasing mortality of others. At every point of care, and every level of practice, nurses will improve cancer screening through their interactions with patients and families to increase understanding of the rationale for and importance of adherence to cancer screening recommendations. As always, nurses will continue to follow the evidence for practice to maintain nursing practice at the state-of-the-art of cancer screening and advocate in support of public policies that expand access to care.

Nursing actions in support of cancer screening

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Contributor Information

Jennifer Loud, Clinical Genetics Branch, DCEG, NCI, NIH 9609 Medical Center Drive Rockville, Maryland 20850-9772.

Jeanne Murphy, Breast and Gynecologic Cancer Research Group, DCP, NCI, NIH 9609 Medical Center Drive Rockville, Maryland 20892-9712.

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More Cancer Cases in Areas Where Incarceration Rates Are High: Study

Key Takeaways

Cancer death rates rise in U.S. states and counties with relatively high rates of incarceration

Social, insurance and other barriers may keep incarcerated people from speedy diagnosis and care

The trend was especially strong for cancers of the lung and liver

TUESDAY, Sept. 17, 2024 (HealthDay News) -- Counties and states where jails and prisons are packed are more likely to have higher rates of cancer, new research shows.

“These results aren’t surprising. Incarceration in the U.S. is recognized as a key element of social determinants of health and is linked to a wide range of adverse health outcomes,” said study lead author Dr. Jingxuan Zhao , She's a senior scientist for health services research at the American Cancer Society (ACS).

The study can't prove that being in prison raises a person's odds for cancer, but the two conditions might be linked in many ways, Zhao's team believes.

The team published its findings Sept. 17 in the Journal of the National Cancer Institute.

According to Zhao, he and his team wanted "to better understand the associations of incarceration and cancer mortality at the community level."

To do so, they looked at national data on incarceration rates for 1995 through 2018, broken down for all states and counties. They rated those on four levels, from lowest to highest.

Compared to counties that ranked in the lowest quartile of incarcerations, those in the highest fourth had a cancer death rate that was 3.9% higher, on average, the team found. Local cancer death rates rose along with the rate of people kept in prisons and jails.

Similar results were observed at the state level: States ranking highest for incarcerations also had a 3.9% higher cancer death rate, compared to states in the lowest quartile.

Differences were largest when it came to lung and liver cancers, the team added.

These associations didn't vary by race or gender, Zhao's group added.

“Our findings from this study suggest that programs to address adverse health effects of mass incarceration are warranted, particularly for populations that suffer from inequities in cancer care and outcomes and are disproportionately incarcerated in the U.S.,” Zhao said in an ACS news release.

Why might deadly cancers be more likely in an area with a high prison population?

“Populations in areas with high incarceration rates may have limited access to cancer prevention, early detection and treatment," Zhao theorized.

Insurance could also be an issue, according to Lisa Lacasse , president of the ACS' Cancer Action Network.

"Having comprehensive health insurance is a critical factor for survivorship against cancer,” she said. “Medicaid is an important source of health insurance for people who would not otherwise have access to care, including those who are transitioning back to their communities following incarceration. We urge lawmakers in the 10 states that have not expanded Medicaid to do so to improve health outcomes and reduce the burden of cancer."

More information

Find out more about the health toll of incarceration at the American Academy of Family Physicians .

SOURCE: American Cancer Society, news release, Sept. 17, 2024

What This Means For You

Levels of cancer death tend to rise in U.S. states and counties with high rates of incarceration.

Research Impact: School of Medicine researcher reduces disparities for liver cancer patients

Research Impact is a series that pulls back the curtain of IU Research, showcasing the faculty creating, innovating and advancing knowledge that improves communities and changes lives.

Since she was a little girl, Dr. Lauren Nephew knew she wanted to help people. That desire, coupled with a passion for talking to others and an inquisitive nature, led her to a career as a physician scientist.

Now, Nephew is an assistant professor of medicine in the Division of Gastroenterology and Hepatology and assistant vice chair of health equity at the Indiana University School of Medicine . Her research focuses on understanding the barriers patients face in getting treatment for liver disease and liver cancer, and she is developing tools to remove those barriers.

Question: What is the goal of your research?

Answer: I am a health equity researcher and a liver doctor. I am focused on developing interventions that alleviate health care disparities, particularly for patients with liver cancer and end-stage liver disease, including liver transplant patients.

Beyond just describing the various health disparities between different populations, I am at the point of my research where I am developing interventions to help patients. Indiana University Health is the only liver transplant center in the state, so my main goal is to develop tools that help patients get treatment, and transplant is one of the main treatments for liver cancer.

We have the potential to make a real difference for patients here in Indiana, but lessons we learn here can also be applied across the country.

Q: What tools are your team developing to improve patient outcomes?

A: In talking to patients with liver cancer, we have learned that they feel overwhelmed by the amount of information they receive about their diagnosis and how they receive that information. We have discovered they want to talk to others who have their condition and to feel supported in a way beyond just talking to their physician. We have also learned that they need help navigating the various steps it takes to get from a diagnosis to treatment.

My team has a multi-step approach that includes a social support group for people with liver cancer to engage with each other, education tools that make the information more clear and break it up into modules so it doesn’t come to the patient all at once, and a binder with navigation tools and maps to help patients understand upfront the various steps they’ll need to take to get to a cure. Used together, we hope to help patients with liver cancer achieve better outcomes and reduce disparities.

Q: How is your research helping to address health disparities?

A: In the United States, there are disparities and outcomes in patients based on race, gender, ethnicity, socioeconomic status and geography. There are diseases like liver cancer and end-stage liver disease where certain populations may not do as well as majority populations do. We call that a disparity.

My work is around understanding those disparities – how large it is, who is experiencing this disparity, and, most importantly, what are the determinants? We want to know whether they exist at the neighborhood level, the health system level, the provider level or the patient level. But more than likely, there is a combination of all those reasons for why the disparities are happening. When we can understand the determinants of those disparities, then we can develop solutions to address them.

I have a three-step process of identifying the disparity a group is experiencing, trying to understand the determinants of that disparity and then developing a solution that will lower, and if we’re lucky, completely alleviate that disparity.

Additionally, even though I am a liver doctor, I’m also the associate vice chair for health equity in the Department of Medicine. Our goal is to understand the disparities in care beyond just liver disease, at a population-health level within our health system. I’ve enjoyed looking at some of the problems that exist upstream of liver disease, such as high blood pressure.

Q: What interested you in pursuing research in this field?

A: I became interested in liver disease and liver transplantation when I was in medical school. I had attended a transplant committee meeting where patient information is reviewed and decisions are made about who gets listed for transplant. I looked around at the people making these decisions and the conversations being had, and I realized it was important to have somebody like me in the room.

It is important to have diversity in voice, perspective and lived experience in that kind of setting, and it just wasn’t there. I felt somebody needed to represent the interests of marginalized groups from a place of understanding. That’s how I first became interested in this concept of scarce resource allocation and transplant.

Q: What do you wish people knew about liver disease and liver cancer?

A: I wish people knew that alcohol and viruses are not the only cause of liver disease. Having fat in the liver can cause cirrhosis, permanent scarring of the liver, and people with cirrhosis are at a higher risk of developing liver cancer.

Obesity, diabetes and other risk factors for putting fat in the liver can put someone at an increased risk of liver disease and liver cancer. I don’t think many people realize that.

Q: What do you enjoy most about your work?

A: I really enjoy talking to patients, hearing their solutions and what they think the barriers and needs are. For a long time, people who have developed interventions have come up with solutions on their own. But we are bringing patients into focus groups, telling them about the problems and asking them how they would solve the problems from their perspectives. If we can understand that better, we have a better chance at being effective and improving outcomes.

Kelsey Cook

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Revolutionizing education: Democracy Quest VR will take students on historic journey

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£9m research centre targets cancer, dementia and heart disease treatment in the north

The molecular imaging facility will focus on research and treatment for cancer, dementia and heart disease

13:57, 16 SEP 2024

Prof Nick Stafford, founder and chair of the Daisy Appeal, with Prof Pat Price (left), chair of Radiotherapy UK, and Sallyann Wright, head of the molecular imaging research centre (MIRC)

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A new £9m research centre in East Yorkshire is set to target cancer, dementia and heart disease treatment in the north. The long-awaited handover of the molecular imaging facility at Castle Hill Hospital has been made official in a ceremony to mark the occasion.

Professor Pat Price, an internationally renowned expert in cancer research, said the significance of the new molecular imaging research centre (MIRC) is underlined by data which shows more must be done to develop a much-needed national cancer recovery plan for the UK.

Prof Price has also commented: “What is happening in Hull with the new MIRC and the Jack Brignall Centre is fantastic but now we need this push in terms of fundraising to show people what we can do. We need more capacity in diagnostic imaging otherwise cancer patients in the area are just going to have to wait longer. This will save lives.”

Prof Nick Stafford, founder and chair of the Daisy Appeal, said: “We currently carry out 4,500 scans every year in the Jack Brignall Centre but the scanner is at capacity. We are looking to upgrade it to a digital device capable of getting through 7,500 scans per year, but new technology does not come cheap.”

This new research centre complements the existing PET CT scanning centre which has been operating for the last nine years. There are ongoing plans for further development to improve medical services in Hull and the charity is looking to secure new funding for the digital scanner at a cost of approximately £2.8m within the next year.

Dr Rebecca Hargreaves, deputy production manager, working on the hot cells

Prof Stafford, a former professor of head and neck surgery, founded the Daisy Appeal in 2000. He remains chair of the charity which created a partnership between the Hull University Teaching Hospitals NHS Trust and the University of Hull . Milestones include the opening of the £8m Daisy Appeal Medical Research Centre in 2008 and the £4.5m Jack Brignall PET-CT Scanning Centre in 2014.To date £23m has been raised by the charity.

Equipped with its own cyclotron, the MIRC will make its own radiotracers which in the past have had to be bought in from manufacturers elsewhere – a journey of an hour or more for products which have a short half-life. When the new facility is up and running the radiotracers will be produced on-site and delivered directly to the Jack Brignall Centre for immediate use in scans to detect cancers, dementia and heart disease.

Work on the MIRC commenced in 2018 with completion due in 2021 but construction, complications and equipment delays caused by the impact of Covid have pushed the project back. Having taken delivery of the facility, Prof Stafford said work will now begin on the commissioning and licensing procedures, with radiotracer production on course to start in the next two months and the cyclotron operational in about six months.

He said: “We will be able to manufacture a variety of clinically relevant radiotracers not currently available to patients in the north of England and, as the only facility of its kind between Cambridge and Edinburgh, we aim to become a referral centre for specialised PET imaging.

“Clinical scanning activity in the UK is predicted to rise 12 per cent year on year for the next decade and the industry partners we work with are gearing up to meet that. GE, who supplied our cyclotron have predicted an increase in sales for radiotracers and radiotherapeutics in the United States from $1.17bn in 2020 to $24.9bn by 2031. I’d like our facility to have a share of the UK element of this market.”

Annual running costs for the MIRC are £700,000 and the charity will continue to pursue other revenue opportunities from grants, corporate and personal donations and fundraising activities in the community.

The NHS review commissioned by the new government and published this week by Lord Darzi, reported that the UK has appreciably higher cancer mortality rates than other countries, with no progress whatsoever made in diagnosing cancer at stage one and two between 2013 and 2021.

Prof Price, chair of Radiotherapy UK, Professor at Imperial College London and a clinical oncology consultant for 35 years, said: “The importance of the new facility is about dealing with the increased incidence of cancer. There will be a 30 per cent increase in the incidence of cancer by 2040, one in two people will get it and there is a big delay in terms of diagnostics.

“We need chemical science centres like this one that can develop the methodology for PET studies. Not many places in the UK can do that and Hull would not normally be up for this level of infrastructure but we have known Nick for a long time, he came to us with his vision for Hull and he did something really tough and really important.

“It’s complex clinical science, it’s ambitious and they have attracted some very good people who can go to the next level now in terms of international support. To really make the most of this they need to get some pilot data which will help them secure bigger grants and become a jewel in the crown for the UK.”

Castle Hill Hospital
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