Use of DNA image cytometry in conducting oral cancer screening in rural India.

OBJECTIVES: Oral cancer screening can assist in the early detection of oral potentially malignant lesions (OPMLs) and prevention of oral cancers. It can be challenging for clinicians to differentiate OPMLs from benign conditions. Adjunct screening tools such as fluorescence visualisation (FV) and DNA image cytometry (DNA-ICM) have shown success in identifying OPMLs in high-risk clinics. For the first time we aimed to assess these technologies in Indian rural settings and evaluate if these tools helped clinicians identify high-risk lesions during screening. METHODS: Dental students and residents screened participants in five screening camps held in villages outside of Hyderabad, India, using extraoral, intraoral, and FV examinations. Lesion and normal tissue brushings were collected for DNA-ICM analysis and cytology. RESULTS: Of the 1116 participants screened, 184 lesions were observed in 152 participants. Based on white light examination (WLE), 45 lesions were recommended for biopsy. Thirty-five were completed on site; 25 (71%) were diagnosed with low-grade dysplasias (17 mild, 8 moderate) and the remaining 10 showed no signs of dysplasia. FV loss was noted in all but one dysplastic lesion and showed a sensitivity of 96% and specificity of 17%. Cytology combined with DNA-ICM had a sensitivity of 64% and specificity of 86% in detecting dysplasia. CONCLUSION: DNA-ICM combined with cytology identified the majority of dysplastic lesions and identified additional lesions, which were not considered high-risk during WLE and biopsy on site. Efforts to follow-up with these participants are ongoing. FV identified most high-risk lesions but added limited value over WLE.

Transforming Canada's role in global cancer control.

Cancer has not been an explicit priority of Canada's international health and development agenda, but it is key to realising the country's Sustainable Development Goal commitments. Multiple converging political, health, and social forces could now drive support for a more integrated Canadian approach to global cancer control. Success will depend on the extent to which Canadian leaders and institutions can build consensus as a community and agree to work together. Collaboration should include agreement on the framing and prioritisation of the core issues, building a broad coalition base, aligning with priorities of international partners, and on a governance structure that reflects the principles of equity, diversity, and inclusion. This Series paper will discuss global cancer control within Canada's global health agenda, how Canada can address its history of colonisation and present-day disparities in its global work, and the challenges and opportunities of creating a Canadian global cancer control network.

Comparing Perspectives of Canadian Men Diagnosed With Prostate Cancer and Health Care Professionals About Active Surveillance.

Active surveillance (AS) has gained acceptance as a primary management approach for patients diagnosed with low-risk prostate cancer (PC). In this qualitative study, we compared perspectives between patients and health care professionals (HCP) to identify what may contribute to patient-provider discordance, influence patient decision-making, and interfere with the uptake of AS. We performed a systematic comparison of perspectives about AS reported from focus groups with men eligible for AS (7 groups, N = 52) and HCP (5 groups, N = 48) who engaged in conversations about AS with patient. We used conventional content analysis to scrutinize separately focus group transcripts and reached a consensus on similar or divergent viewpoints between them. Patients and clinicians agreed that AS was appropriate for low grade PC and understood the low-risk nature of the disease. They shared the perspective that disease status was a critical factor to pursue or discontinue AS. However, men expressed a greater emphasis on quality of life in their decisions related to AS. Patients and clinicians differed in their perspectives on the clarity, availability, and volume of information needed and offered; clinicians acknowledged variations between HCP when presenting AS, while patients were often compelled to seek additional information beyond what was provided by physicians and experienced difficulty in finding or interpreting information applicable to their situation. A greater understanding of discordant perspectives about AS between patients and HCP can help improve patient engagement and education, inform development of knowledge-based tools or aids for decision-making, and identify areas that require standardization across the clinical practice.

Novel Microbial-Based Immunotherapy Approach for Crohn's Disease.

Background: Current Crohn's disease (CD) therapies focus on suppressing immune function and come with consequent risk, such as infection and cancer. Notwithstanding, most CD patients still experience disease progression. There is a need for new CD treatment strategies that offer better health outcomes for patients. Aims: To assess safety, efficacy, and tolerability of a novel microbial-derived immunotherapy, QBECO, that aims to restore rather than suppress immune function in CD. Methods: A randomized, double-blind, placebo-controlled trial was conducted in 68 patients with moderate-to-severe CD. Primary endpoints: safety and Week 8 clinical improvement. Secondary endpoints: Week 8 clinical response and remission. Week 8 responders continued blinded treatment through Week 16; non-responders received open-label QBECO from Weeks 9-16. Exploratory analyses included immune biomarker and genotype assessments. Results: QBECO was well-tolerated. Mean reduction in Crohn's Disease Activity Index (CDAI) score was -68 for QBECO vs. -31 for placebo at Week 8. Improvement with QBECO continued through Week 16 (-130 CDAI reduction). Week 8 QBECO clinical response, improvement and remission rates were 41.2%, 32.4%, 29.4% vs. 26.5%, 23.5%, 23.5% for placebo. TNFα inhibitor-naïve subjects achieved higher response rates at Week 8 with QBECO (64%) vs. placebo (26%). Specific immune biomarkers were identified that linked to QBECO response. Conclusion: This proof-of-concept study supports further investigation for the use of QBECO as a novel immunotherapy approach for CD. Biomarker analyses suggests it may be feasible to personalize CD treatment with QBECO. Larger trials are now needed to confirm clinical improvement and the unique biological findings. Clinical Trial Number: NCT01809275 (https://clinicaltrials.gov/ct2/show/NCT01809275).

Immune Stimulation Using a Gut Microbe-Based Immunotherapy Reduces Disease Pathology and Improves Barrier Function in Ulcerative Colitis.

Background: Current ulcerative colitis (UC) treatments are focused on symptom management primarily via immune suppression. Despite the current arsenal of immunosuppressant treatments, the majority of patients with UC still experience disease progression. Importantly, aggressive long-term inhibition of immune function comes with consequent risk, such as serious infections and malignancy. There is thus a recognized need for new, safe and effective treatment strategies for people living with UC that work upstream of managing the symptoms of the disease. The objective of this study was to evaluate a microbial-based treatment, QBECO, that functions to productively activate rather than suppress mucosal immune function as a novel approach to treat UC. Methods: Two established models of experimental colitis, namely chemically-induced DSS colitis and the spontaneous colitis that develops in Muc2 deficient mice, were used to assess whether QBECO treatment could ameliorate gastrointestinal disease. A small exploratory 16-week QBECO open-label trial was subsequently conducted to test the safety and tolerability of this approach and also to determine whether similar improvements in clinical disease and histopathology could be demonstrated in patients with moderate-to-severe UC. Results: QBECO treatment successfully reduced inflammation and promoted mucosal and histological healing in both experimental models and in UC patients. The preclinical models of colitis showed that QBECO ameliorated mucosal pathology, in part by reducing inflammatory cell infiltration, primarily that induced by neutrophils and inflammatory T cells. The most rapid and noticeable change observed in QBECO treated UC patients was a marked reduction in rectal bleeding. Conclusion: Collectively, this work demonstrates for the first time that strategically activating immune function rather than suppressing it, not only does not worsen colitis induced-damage, but may lead to an objective reduction in UC disease pathology.

Describing perspectives of health care professionals on active surveillance for the management of prostate cancer.

BACKGROUND: Over the last decade, active surveillance has proven to be a safe approach for patients with low-risk prostate cancer. Although active surveillance presents several advantages for both patients and the health care system, all eligible patients do not adopt this approach. Our goal was to evaluate the factors that influence physicians to recommend active surveillance and the barriers that impact adherence to this approach. METHODS: Focus groups (n = 5) were held with physicians who provided care for men with low-risk prostate cancer and had engaged in conversations with men and their families about active surveillance. The experience of health care professionals (HCPs) was captured to understand their decisions in proposing active surveillance and to reveal the barriers and facilitators that affect the adherence to this approach. A content analysis was performed on the verbatim transcripts from the sessions. RESULTS: Although physicians agreed that active surveillance is a suitable approach for low-risk prostate cancer patients, they were concerned about the rapidly evolving and non-standardized guidelines for patient follow-up. They pointed out the need for additional tools to appropriately identify proper patients for whom active surveillance is the best option. Urologists and radiation-oncologists were keen to collaborate with each other, but the role of general practitioner remained controversial once patients were referred to a specialist. CONCLUSIONS: Integration of more reliable tools and/or markers in addition to more specific guidelines for patient follow-up would increase the confidence of both patients and physicians in the choice of active surveillance.

Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy.

Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity. Rather, QBKPN induced anti-tumor innate immunity that required NK cells and NKG2D engagement. QBKPN increased NK cells and macrophages in the lungs, altered macrophage polarization, and augmented the production of cytotoxic molecules. An exploratory trial in patients with non-small cell lung cancer demonstrated QBKPN was well tolerated, safe, and induced peripheral immune changes suggestive of macrophage polarization and reduction of PD-1 and PD-L1 expression on leukocytes. These data demonstrate preclinical efficacy, and clinical safety and tolerability, for this cancer immunotherapy strategy that exploits innate anti-tumor immune mechanisms.

Planning for cancer control programs: Leadership considerations.

Cancer is a significant challenge globally. Reducing the impact of cancer requires a program and plans that address the main aspects of cancer from prevention through to end-of-life care. This article summarizes the requirements of a robust cancer control program and outlines the contextual and leadership considerations that are required to ensure that the planning and implementation of a control program can achieve improved cancer outcomes.

The implementation of the Plan Esperanza and response to the imPACT Review.

Following the implementation of the National Cancer Prevention and Control Results-based Budget Programme (PpR Cancer-024) in 2011, the Peruvian Government approved the Plan Esperanza-a population-based national cancer control plan-in 2012. Legislation that ensured full government-supported funding for people who were otherwise unable to access or afford care and treatment accompanied the Plan. In 2013, the Ministry of Health requested an integrated mission of the Programme of Action for Cancer Therapy (imPACT) report to strengthen cancer control in Peru. The imPACT Review, which was executed in 2014, assessed Peru's achievements in cancer control, and areas for improvement, including cancer control planning, further development of population-based cancer registration, increased prevention, early diagnosis, treatment and palliative care, and the engagement and participation of civil society in the health-care system. This Series paper gives a brief history of the development of the Plan Esperanza, describes the innovative funding model that supports it, and summarises how funds are disseminated on the basis of disease, geography, and demographics. An overview of the imPACT Review, and the government's response in the context of the Plan Esperanza, is provided. The development and execution of the Plan Esperanza and the execution of and response to the imPACT Review demonstrates the Peruvian Government's commitment to fighting cancer across the country, including in remote and urban areas.

Canadian Men's perspectives about active surveillance in prostate cancer: need for guidance and resources.

BACKGROUND: In prostate cancer, men diagnosed with low risk disease may be monitored through an active surveillance. This research explored the perspectives of men with prostate cancer regarding their decision-making process for active surveillance to identify factors that influence their decision and assist health professionals in having conversations about this option. METHODS: Focus group interviews (n = 7) were held in several Canadian cities with men (N = 52) diagnosed with prostate cancer and eligible for active surveillance. The men's viewpoints were captured regarding their understanding of active surveillance, the factors that influenced their decision, and their experience with the approach. A content and theme analysis was performed on the verbatim transcripts from the sessions. RESULTS: Patients described their concerns of living with their disease without intervention, but were reassured by the close monitoring under AS while avoiding harmful side effects associated with treatments. Conversations with their doctor and how AS was described were cited as key influences in their decision, in addition to availability of information on treatment options, distrust in the health system, personality, experiences and opinions of others, and personal perspectives on quality of life. CONCLUSIONS: Men require a thorough explanation on AS as a safe and valid option, as well as guidance towards supportive resources in their decision-making.

Site-Specific Immunomodulator: A Novel Treatment for Crohn's Disease.

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn's disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously every second day, for a minimum of 2.5 months and a maximum of 11 months. All 10 patients reported improvement of symptoms while on the SSI QBECO treatment. Seven patients reported full resolution of clinical symptoms during a course of SSI QBECO of at least three months. Three patients have experienced ongoing sustained clinical remission after discontinuing all medications, including SSI treatment. The longest case of clinical remission is still ongoing (>4 years). No serious severe adverse clinical events were reported. Collectively, we conclude that treatment with the immunoactive SSI QBECO was well tolerated and effective for treatment of Crohn's disease in this case series.

Impact and evaluation of International Cancer Control Congresses.

International meetings on various aspects of cancer- its etiology, its diagnosis, its treatment, its palliation, and its prevention and control are held frequently. Many have similar themes, and many seek and receive the same speakers and audiences. A fundamental question arises: what difference does any individual meeting/congress/ conference make or add to our understanding of the relevant issues? While many meetings conduct evaluations at the end of the Congress, few use evaluation as a tool to guide design, implementation, and evaluation of both short and long term impacts, and address the question of "what difference did the Congress make". The International Cancer Control Congresses, which are held biennially in different regions of the world, took the opportunity to use evaluation in this way, and ask the relevant questions. This paper describes that evaluation session of the ICCC4, held in Seoul, Korea in November 2011, which was part of the larger evaluation issue.

Prevention of cancer and non-communicable diseases.

Cancer is a leading cause of death worldwide, accounting for approximately 7.6 million deaths (13% of all deaths) in 2008. Cancer mortality is projected to increase to 11 million deaths in 2030, with the majority occurring in regions of the world with the least capacity to respond. However, cancer is not only a personal, societal and economic burden but also a potential societal opportunity in the context of functional life - the years gained through effective prevention and treatment, and strategies to enhance survivorship. The United Nations General Assembly Special Session in 2011 has served to focus attention on key aspects of cancer prevention and control. Firstly, cancer is largely preventable, by feasible means. Secondly, cancer is one of a number of chronic, non- communicable diseases that share common risk factors whose prevention and control would benefit a majority of the world's population. Thirdly, a proportion of cancers can be attributed to infectious, communicable causal factors (e.g., HPV, HBV, H.pylori, parasites, flukes) and that strategies to control the burden of infectious diseases have relevance to the control of cancer. Fourthly, that the natural history of non-communicable diseases, including cancer, from primary prevention through diagnosis, treatment and care, is underwritten by the impact of social, economic and environmental determinants of health (e.g., poverty, illiteracy, gender inequality, social isolation, stigma, socio-economic status). Session 1 of the 4th International Cancer Control Congress (ICCC-4) focused on the social, economic and environmental, as well as biological and behavioural, modifiers of the risk of cancer through one plenary presentation and four interactive workshop discussions. The workshop sessions concerned 1) the Global Adult Tobacco Survey and social determinants of tobacco use in high burden low- and middle-income countries; 2) the role of diet, including alcohol, and physical activity in modifying the risk of cancer and other non-communicable diseases; 3) the role of infections in modifying the risk of cancer; and 4) the public policies and actions that can be implemented to effectively reduce the risk of cancer at population levels. Workshop discussions highlighted the need for high quality data on the prevalence of modifiable factors in different settings, as well as the social, economic and environmental drivers of these factors, in order to inform prevention and control programs. For some factors, further work needs to be done to develop simple and valid measurement tools. Given that many of these factors are common to both cancer and other non-communicable diseases, cancer prevention should be viewed within the broader perspective of the prevention of non-communicable diseases and should engage all relevant actors, including the general public, health and other professionals, workplaces and institutions, the media, civil society, schools, governments, industry, and multinational bodies. Many policies and plans have been implemented in various settings to control the drivers of modifiable factors and promote health and well-being. Mapping, analysis, and contextualization of those policies that are relevant would be helpful to promote action around cancer prevention in different settings.

Managing population health to prevent and detect cancer and non-communicable diseases.

The goals of cancer control strategies are generally uniform across all constituencies and are to reduce cancer incidence, reduce cancer mortality, and improve quality of life for those affected by cancer. A well-constructed strategy will ensure that all of its elements can ultimately be connected to one of these goals. When a cancer control strategy is being implemented, it is essential to map progress towards these goals; without mapping progress, it is impossible to assess which components of the strategy require more attention or resources and which are not having the desired effect and need to be re-evaluated. In order to monitor and evaluate these strategies, systems need to be put in place to collect data and the appropriate indicators of performance need to be identified. Session 2 of the 4th International Cancer Control Congress (ICCC-4) focused on how to manage population health to prevent and detect cancers and non-communicable diseases through two plenary presentations and four interactive workshop discussions: 1) registries, measurement, and management in cancer control; 2) use of information for planning and evaluating screening and early detection programs; 3) alternative models for promoting community health, integrated care and illness management; and 4) control of non-communicable diseases. Workshop discussions highlighted that population based cancer registries are fundamental to understanding the cancer burden within a country. However, many countries in Africa, Asia, and South/ Central America do not have them in place. A new global initiative is underway, which brings together several international agencies, and aims to establish six IARC regional registration resource centres over the next five years. These will provide training, support, infrastructure and advocacy to local networks of cancer registries, and, it is hoped, improve the host countries' ability to assess and act on cancer issues within their jurisdictions. Multiple methods of programme evaluation were presented across workshops, but all were attuned to both the resource base and the specific questions to be addressed. Where innovative strategies were being tested, customized evaluation strategies should be undertaken. Where programmes are well-developed and data is being collected for evaluation, there is the opportunity for sophisticated analytical methods to be used to pinpoint specific areas or delivery sites for future quality improvement. Finally, unique opportunities now exist to integrate the strategies developed in cancer control and evaluation with those under development for other non-communicable diseases. This area will likely be one for future development.

Coordinating care and treatment for cancer patients.

Survival following a diagnosis of cancer is contingent upon an interplay of factors, some non-modifiable (e.g., age, sex, genetics) and some modifiable (e.g., volitional choices) but the majority determined by circumstance (personal, social, health system context and capacity, and health policy). Accordingly, mortality and survival rates vary considerably as a function of geography, opportunity, wealth and development. Quality of life is impacted similarly, such that aspects of care related to coordination and integration of care across primary, community and specialist environments; symptom control, palliative and end-of-life care for those who will die of cancer; and survivorship challenges for those who will survive cancer, differs greatly across low, middle and high-income resource settings. Session 3 of the 4th International Cancer Control Congress (ICCC-4) focused on cancer care and treatment through three plenary presentations and five interactive workshop discussions: 1) establishing, implementing, operating and sustaining the capacity for quality cancer care; 2) the role of primary, community, and specialist care in cancer care and treatment; 3) the economics of affordable and sustainable cancer care; 4) issues around symptom control, support, and palliative/end-of-life care; and 5) issues around survivorship. A number of recommendations were proposed relating to capacity-building (standards and guidelines, protocols, new technologies and training and deployment) for safe, appropriate evidence-informed care; mapping and analysis of variations in primary, community and specialist care across countries with identification of models for effective, integrated clinical practice; the importance of considering the introduction, or expansion, of evidence-supported clinical practices from the perspectives of health economic impact, the value for health resources expended, and sustainability; capacity-building for palliative, end-of-life care and symptom control and integration of these services into national cancer control plans; the need for public education to reduce the fear and stigma associated with cancer so that patients are better able to make informed decisions regarding follow-up care and treatment; and the need to recognize the challenges and needs of survivors, their increasing number, the necessity to integrate survivorship into cancer control plans and the economic and societal value of functional survival after cancer. Discussions highlighted that coordinated care and treatment for cancer patients is both a ' systems'challenge and solution, requiring the consideration of patient and family circumstances, societal values and priorities, the functioning of the health system (access, capacity, resources, etc.) and the importance assigned to health and illness management within public policy.

Knowledge exchange--translating research into practice and policy.

Substantial differences in population-based cancer control outcomes exist within and between nations. Optimal outcomes derive from 'what we know', 'what we apply in practice', and 'how complete and compliant is the population uptake of public health and clinical practice change'. This continuum of research (scientific discovery) to practice (application and uptake) to policy impacts the speed and completeness of practice change and is greatly influenced by the ability, opportunity and readiness of countries to implement evidence informed practices and policies through innovative change. Session 4 of the 4th International Cancer Control Congress focused on knowledge exchange through three plenary presentations and five interactive workshop discussions: 1) the role of epidemiological data as a basis for policy formulation; 2) existing global frameworks for cancer control; 3) knowledge exchange as it relates to public health practice and policy; 4) knowledge exchange in relation to primary, community, and specialist cancer care; and 5) the role of public engagement and advocacy in influencing cancer control policy. Common themes emerging from workshop discussions included the recognition of the importance of knowledge exchange processes, constituents and forums as key aspects of preparedness, awareness and readiness to implement public health and clinical practice change. The importance of cultural and contextual differences between nations was identified as a challenge requiring development of tools for generating relevant population/societal data (e.g., projection methodologies applied to population demographics, outcomes and resources, both societal, human and fiscal) and capacity building for facilitating knowledge transfer and exchange between the constituencies engaged in population-based public health practice and clinically based primary care and disease specialty practice exchange (researchers, health practitioners, health administrators, politicians, patients and families, and the private and public sectors). Understanding patient and public engagement advocacy and its role in influencing health and public policy investment priorities emerged as a critical and fundamental aspect of successful implementation of evidence-informed cancer control change.

A review of Canadian health care and cancer care systems.

Canada is a westernized, market-economy nation with a publicly funded health care and cancer control system and has health indices reflective of a high-resource economy. Provision of health services is in accord with the Canada Health Act and is implemented through federal, provincial, and territorial relations wherein federal funding partly provides support for the provincial/territorial delivery of health services. Cancer services are provided within the acute health care system with dedicated entities existing in parallel in most provinces to provide services specific to the diagnosis, treatment, and support of cancer patients. Interprovincial and territorial collaboration to enhance and facilitate optimal cancer system performance is enabled through the Canadian Partnership Against Cancer (the Canadian national cancer control initiative). Adolescent and young adult (AYA) cancer patients use both the pediatric and adult cancer systems. There is recognition, however, that although AYA patients are numerically a small portion of all cancer patients, the negative personal, societal, and socioeconomic impacts of potential years of life lost are substantial and can be lessened through attention to awareness, education, redesign of care and care pathways, quality of life, developmental aspects related to adolescent-teen-adult transitions, continuity of care, and surveillance across pediatric and adult settings. Appropriate solutions need to be established within the framework of the Canadian Health Service by innovative rethinking and realignment of system capacity and performance to the special needs of AYA cancer patients.

Awareness and advocacy for adolescents and young adults with cancer.

Increasing the awareness of the clinical and psychosocial needs that are particular to adolescents and young adults (AYA) was a top priority, as was strengthening advocacy efforts to empower and support this group. To date, AYA advocates had some success in generating public awareness and building a solid clinical justification for increased focus on this population. It had been established that the economic burden of their mortality was significant, their cancers were unusual, their medical care was often inadequate, and their outcomes for many cancers had not improved in the past 3 decades. As the awareness and advocacy campaign continued to grow and evolve across the globe, it was an important goal to integrate the efforts of all stakeholders to ensure that it progressed with a single, consensual, focused message identifying a common priority for action. By coordinating the efforts of the scientific, medical, and advocacy communities, it was possible to amplify their separate efforts and activities and more efficiently achieve large-scale change in the world of AYA oncology.