Cancer control opportunities in low- and middle-income countries

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With rising global burdens of cancer case numbers, deaths, incidence and mortality, medical science, humanitarian and medical diplomatic agendas and efforts to address these need to be pragmatic and realistic.

Metronomics and low/middle income countries, especially in breast cancer

In this communication, we propose to practitioners addressing this rising global burdens problem as one of public health oncology or population-affecting cancer medicine, and then consider the major functional variables, models of international development efforts and specific areas of interventions likely to combat these mortality and case burdens successfully. Globally, cancer is now the second leading cause of death [ 1 ]. While greater attention to poor outcomes from cancer is needed across all countries, numerically the major burdens are falling on Asian countries.

Thus, the focus of our communication is on countries in this part of the world. In broad frameworks, in the United States in particular, we have usually seen cancers as isolated events to individuals and have framed the challenges and issues in private sector business terms. This dominant framework is limiting in that the focus is mostly on cancer biology in humans and less on the ecological circumstances so critical in the causation, development and management cycles in our complex societies [ 3 ].

Here focusing on human ecology—the relationships between human beings and their natural, social and constructed environments. One cancer-related area in which broad societal approaches have been effective has been smoking. In fact, markets at the bottom of our global population pyramid have been ignored [ 4 ]. With respect to cancer, perhaps in the intervening time things have become even worse. Paralysis and neglect best characterize cancer medicine for most citizens in LMCs, where cost issues scare government officials, big business and major pharmaceutical companies control what care is given for everyone, and the majority of any funds for cancer is spent on individual systemic treatments of marginal value.

In summary, for these reasons we propose here that a paradigm of public health oncology-population cancer medicine perspectives may be useful in addressing global cancer burdens more effectively. In the remainder of this communication, we spell out what such perspectives show us and indicate for specific actions interested practitioners can consider.

The dominant high-income country framework for better cancer care applied globally repeatedly leads to calls for workforce development or capacity building , national cancer control plans and guidelines, drug pricing system creation, innovative financing and infusions of large volumes of capital [ 7 , 8 ].

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It is hard to not compare these approaches with those advocated for economic development generally for the last half century, and found by many to have been so wanting [ 9 , 10 ]. We believe that in fact, the major issues are broader than these, and that in any event, these current dominant framework foci can hardly be successfully addressed without attention to bigger ecological issues and themes such as:. Such transient communities or communities in development present particular challenges to struggling health systems. One cannot work in the most populous Asian countries without being repeatedly challenged by cultures of corruption and poor governance [ 14 ].

The critical importance of human rights issues in health has received far less attention than these deserve. The strongest and most rigorous statement has been made by Farmer in his book Pathologies of Power [ 13 ]. Increasingly, responsibility for social development and problem solving in LMCs, particularly in South Asia, has fallen on non-governmental organizations. In the development field, there has been a shift in focus, toward local community and small-scale enterprise e. This reflects a gradual year trend to community empowerment and an increasingly active citizenship, with local ownership of developmental processes.

There is a growing understanding that the active involvement of communities, within which members promote self-reliance, is critical to the long-term sustainability of development activities [ 19 , 20 ]. While there appears to be no consensus on an ideal model for international development, this new emphasis on community assets—of individuals, associations and institutions—and of local successes, is an essential starting point [ 19 ].

Cancer control in low and middle income countries: New solutions to evolving challenges

Applied to public health oncology, these ideas emphasize the major and important roles of local communities in successfully addressing health issues like cancer. Under such approaches, ecological considerations and cultural anthropological realities play important roles in defining actions. This common approach de facto often leads to outsider-defined, unsustainable solutions, making citizens dependent consumers of services and products drugs , all with unintended consequences [ 19 , 20 ].

Indeed as summarized in the case studies from Bangladesh, community involvement is critically necessary to scaling up apparently successful health interventions, a continuing challenge overall anyway [ 20 ]. There are considerable data that should encourage much greater efforts to prevent cancer in populations: activities directed at limiting tobacco use, immunization against or treatment for oncogenic infectious agents—hepatitis B virus HBV , human papilloma virus HPV , Helicobacter pylori and reducing exposure to indoor smoke [ 21—23 ].

These efforts however are all ones directed at populations and ones for which, in specific countries optimal implementation strategies have yet to be defined. Additionally, nutritional change is strongly suggested to be beneficial, but exactly what nutritional change and how any change is to be achieved in populations are research matters for gastric, esophageal, colorectal and for aflatoxin-induced liver malignancies [ 24 , 25 ].

There has been only limited attention to the severe limitations of early detection strategies for populations with low incidences of disease. As a general observation in LMCs, cancers are diagnosed in advanced stages. A critical distinction here must be made between diagnosed and detected; most cancers are detected or suspected by patients themselves, but not acted upon because of complex human rights issues which give victims in LMCs no viable choices to act.

This reality is not going to change significantly without interventions directed at or changes in the major human rights situations. For breast cancer, a recent analysis lays out the numerical considerations in detail [ 12 ]. In sum, as a general premise, we suggest that there are no specific rigorous scientific grounds as yet for major demonstration or other efforts in early detection of cancers in LMC.

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Investigation of specific strategies in individual countries is appropriate, and in particular, ongoing research into cost effective strategies for detection of uterine cervical and oral cancers in LMCs deserve strong and substantial international support. What then should be done?

It would seem that the central issues involve identifying men and women with serious problems likely to be cancer case finding, not screening at local levels and facilitating their entry into and through available tertiary care systems. All countries need much more attention to centralization and coordination of efficient, guideline-based cancer treatment and the roles of innovation—particularly with information technology IT —and horizontal health system strengthening, dominantly for outpatient systems [ 13 , 26 ].

These are collectively individual practitioner, but really public health oncology issues. As has been noted above, in high-income countries, we behave as though we have much better evidence and interventions than we in fact have in truth, we are prisoners of half-way technologies. For systemic therapies, which account for large fractions of the expenditures for cancer care in high-income countries, for one comprehensive and leading set of guidelines, a recent review found limited high-quality evidence [ 27 ].

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Unnecessary or not-used and nongeneric drugs especially growth factors and sequential therapies in incurable patients. Here, a complex of health system, corruption and unethical behavioral issues demand greater attention [ 16 , 26 ]. There is a significant need to demonstrate for cancer, bundled-care packages which give good value for expenditure [ 26 ]. Further in cancer, as in health generally in LMCs, we need to demonstrate IT sustainable efficiency tools: for example Telemedicine Case Conferences, reinforcing locally defined guidelines from testing to treatment; use of cell-phone platforms and electronic medical records by all health care workers and electronic web-based test reporting.

Finally in treatment, we all need coordinated palliative care to provide everyone in need greater comfort at lower costs [ 26 ]. Again, IT solutions need development and testing. We need far more attention to assessing the value of interventions and to the absolute necessity of using such information: the benefits, harms and costs, including the downstream costs; and the incremental cost-effectiveness ratios [ 26 , 28 ]. The most obvious opportunities for such attention are in international scientific meetings where LMC health professionals are present, and when high-income country health professional participate in LMC in-country meetings, and can learn first-hand about local circumstances.

We believe that considerable attention in LMCs to these health system issues is desperately needed before, in fact, tight insurance systems or government payments for cancer care can be compellingly argued for. Practitioners in high-income countries or settings are very aware of the marginal efficacies of their systemic interventions for solid tumors, and of the expensive infrastructure necessary to provide likely benefit for systemic or radiotherapeutic interventions.

Such credible practitioners need to lead in calling attention to and pursuing the mandates for progress listed in this table. In another communication, we have stressed policy priorities in cancer, which appear appropriate for governments in LMC, and the need for more broad-spectrum research in cancer [ 21 ]. LMCs governments are significantly resourced-challenged at present however, and the major need for better data and on-site, country-specific solutions bring us again to the critical roles of local communities in public health oncology [ 19 , 20 ].

As we have suggested above, responding to such a mandate for efforts in cancer with local exploratory projects makes sense to us. The more common roles of universities and cancer-specific foundations, in our view, should be to partner sustainably with local LMC communities to define rigorous potentially scalable community grown cancer control solutions, which can also inform national and international policies [ 20 ]. There is a need for a sustainable effort that can only come about if this work is valued as a bona fide part of physicians' careers.

Population and Cancer Incidence

There are many well-intentioned and generous efforts to improve cancer outcomes in LMCs. Recent increased concern in addressing the challenges with cancer in LMCs is laudable and a positive sign.

Cancer control in low and middle income countries: New solutions to evolving challenges

We have argued that efforts for better cancer control in LMCs would benefit from horizontal public health oncology perspectives. Practitioners should champion efforts addressing the broad challenges of defining better health systems, addressing governance, corruption and human rights and defining cost-effective practical interventions. Bottom-up activities with local communities are the time-tested most successful framework. While treatment interventions are what high-income country practitioners do, they more than any other professionals realize the limitations of current approaches, and can therefore most credibly lead in encouraging public health-mandated efforts.

In MC, cancer cells die with premature or inappropriate entry of cells into mitosis and aberrant chromosome segregation due to severe DNA damage by RT. DNA damage often induces MC in cancers which have defective cell cycle checkpoints and resistant to apoptosis [ 32 ]. In necrosis, damaged cells swell with the subsequent breakdown of the cell membrane and disintegration of cellular organelles.

Although necrosis has been long considered as an accidental cell death, recent studies suggest that there are several genetically regulated form of necrosis. Autophagy is an important catabolic process in which the cell digests itself via degradation of intracellular components such as proteins and organelles. Although autophagy mainly contributes to cell survival, it can lead to Type II programmed cell death depending on the cell context. Several reports suggest that RT induces autophagy in cancers, and in certain conditions, autophagy-inducing agents can act as radiosensitizers [ 33 ].

Cancer cells that receive severe or irreparable DNA damage by RT undergo permanent cell cycle arrest called cellular senescence rather than cell death depending on the cell context. Senescent cells are still alive but not able to duplicate, therefore, it acts as an anti-cancer mechanism [ 34 ]. In ICD, instead of undergoing conventional forms of apoptosis, damaged cancer cells by RT emit a specific combination of signals that induce a cytotoxic T lymphocyte CTL response leading to cancer cell killing and also the killing of unirradiated tumor cells systemically [ 35 ].