Laying Foundations: The First Year

by Ian Magrath

The INCTR Annual meeting in April marked the passing of a convenient, if arbitrary, milestone in the INCTR's brief history, for it was almost exactly a year ago that our offices opened in Brussels. We have come just a short way along a road that extends into the invisible future, but even the short distance we have traveled—sometimes uphill—allows us to look back at what has been accomplished and perhaps, from a somewhat higher vantage point, to perceive more clearly the obstacles that must be overcome. In this first year, we have shaped much of the foundation on which the INCTR will be built, and already a clearer idea of the edifice itself —one that will continue to evolve over many years—is coming into view.

Figure 1

Developing the Network
The word "Network" was not casually incorporated into the INCTR's name. Its clear implication is of a "horizontal" or "matrix" organization—i.e., a mesh of interacting nodes located in cancer units, centers or laboratories, spread out across the globe and encompassing both affluent and not-so-affluent countries. Interactions between universities or cancer centers in more and less affluent countries should be mutually beneficial. A complementary and potentially exploitable mutual benefit, for example, particularly with research in mind, might arise from the generally higher numbers (proportionate to the population) of physicians and nurses in the richer countries (Figure 1) and, conversely, the greater numbers of patients and broader range of clinical manifestations in the poorer countries. Another benefit might arise from the greater variability in lifestyles and environments in developing countries, and the greater numbers of epidemiologists and cancer researchers in the affluent nations. In both cases, working together may improve infrastructure whilst providing better patient care and taking advantage of a broader range of research opportunities—to the ultimate benefit of patients with cancer. The network principle extends also to the involvement of other organizations in specific projects, leading, in some cases, to the formation of a consortium in which the sum is greater than the individual parts. With so few organizations based in wealthier countries interested in cancer in developing countries, it is important that the few organizations that are interested complement efforts, rather than stumble over each other in pursuit of priority in a certain area of endeavor (the territorial imperative!).

One of the first tasks of the INCTR was to establish and consolidate its network. Of course, long-standing collaborations already existed between INCTR staff and some major centers in the developing world, but this nucleus has been expanded considerably in the last year. One of the mechanisms that has been adopted in this expansion has been through INCTR Associate Membership (Box 1). Such membership is open to corporations, academic institutions, hospitals, and cancer centers (or departments of such bodies), as well as to other organizations anywhere in the world. Associate Members are kept informed of INCTR activities through Network and the INCTR web site, www.inctr.org, both of which were launched in the year 2000, and attend the Annual Meeting. Associate Members, predominantly located in more affluent countries, provide a source of expertise that will become a part of the INCTR's own infrastructure, enabling it to develop programs encompassing a broad range of research and educational activities. Associate Members in developing countries that take part in INCTR protocols or projects are designated as Collaborating Units. In both Associate Member institutions and Collaborating Units it is intended that some staff will eventually be supported by the INCTR, either full-time or part-time. At a recent count, 45 organizations, institutions, departments or associations had become Associate Members of the INCTR, and there were 14 Collaborating Units. These numbers are continuously increasing, and the INCTR network is shaping up rather well.

New Associate Members of INCTR
Technical University–Munich, Germany	Dokuz Eylül University, Institute of Oncology–Turkey
Al Amal Center–Jordan	Israeli Society of Pediatric Hematology/Oncology–Israel
ICEDOC–Egypt	King Faisal Sp. Hospital & Research Center–Saudi Arabia
Ibadan Multidisciplinary Tumour Group–Nigeria	Chantal Biya Foundation–Cameroun
Cancer Institute (WIA)–India	Nepal Network for Cancer Treatment and Research–Nepal
All India Institute of Medical Sciences–India	Tata Memorial Hospital–India
African Org. for Research and Training in Cancer–Canada	St Jude Children's Research Hospital–USA
Instituto Oncologico Del Oriente Boliviano–Bolivia	HI Albert Einstein–Brazil
University of Nebraska Medical Center–USA	Instituto Nacional de Pediatria–Mexico
Philippine Children's Medical Center–Philippines	Ankara University Medical School–Turkey
Ocean Road Cancer Institute–Tanzania	MAHAK Society–Iran
Hopital 20 août 1953–Morocco	Hussain Maki Juma Cancer Center–Kuwait
St George's Hospital Beirut–Lebanon	Shanghai Children's Center–China
University of Zimbabwe–Zimbabwe
Note: Some members are departments within the institutions listed
Box 1

Creation of Strategy Groups
The inaugural meeting of the INCTR, held in November 1999, was instrumental in identifying a number of initial projects and demonstrating the need for several disease-specific strategy groups that would assist the INCTR in its mission. Pediatric cancer was identified as one of the areas in which developing countries lag far behind. This, coupled to its importance in terms of potential person–years of life lost and higher frequency in developing countries (in which 30–50% of the populations are children), suggested that we might expect to make rapid progress in childhood cancer— simply through effective transfer of resources and knowledge and the development of strategies to ensure that patients reach expert care early in the course of their disease. Consequently, strategy groups for retinoblastoma, osteosarcoma, and, more recently, acute lymphoid leukemia have been created, and specific, relevant projects, focused on early detection and treatment, as well, in the case of acute lymphoblastic leukemia, on sub type profiling in different geographic regions, have been defined and developed. Other strategy groups are in the planning stages, e.g. one for cancer of the uterine cervix, and over the years we anticipate that these groups will become a driving force behind the INCTR's programs in clinical and laboratory research. Of course, it will be essential to build on existing resources in developing countries. In this regard, it is important to note that strategy groups are comprised of investigators from the larger or more experienced centers in developing countries, which are well–placed to disseminate knowledge and technology in their own regions. The strategy group members themselves select and design the projects, after which independent scientific and ethical reviews are undertaken. Experts from anywhere in the world may act as advisors and facilitators of studies selected and designed by the strategy groups. As studies mature, we expect that the more experienced centers will help to support the conduct of the same, or similar studies in smaller or less experienced centers in their own regions, including the training of health care professionals. This approach will ultimately benefit broader professional and patient constituencies and will lead to the development of a much larger foundation of information on which future studies will be built.

Establishment of Committees
While committees can be structures of little function, INCTR committees will have an active role in the development of policy and programs that are not disease–specific, or in overseeing an area of activities. Of particular importance to the efforts of the strategy groups, for example, is the Ethical Review Committee, chaired by Dr Francis Crawley. The ERC is responsible for reviewing all INCTR research protocols. The committee so far has approved one treatment protocol for osteosarcoma, and a questionnaire designed to gather information that will help to explain why patients with retinoblastoma in developing countries generally have more advanced disease at the time of the initiation of definitive treatment. Two additional protocols are scheduled for review later this year. The Ethical Review Committee may also advise on bio–ethical matters that may not be associated with a specific research study. Other new committees established include a Corporate Liaison Committee, a Tissue Banking Committee and an Education Committee.

The Corporate Liaison Committee was established, under the chairmanship of Dr Nassir Habboubi, to assist the INCTR in the development of appropriate relationships, generally through the Corporate Associate Membership program, with the corporate world. Its first meeting was held last summer. Essentially all products used for the diagnosis, treatment, and early detection of cancer are manufactured commercially, and these companies ought to be in a position to help to improve access for cancer patients and "at–risk" populations in developing countries to the products they need. Availability and cost of drugs or investigations are frequently more important factors than scientific evidence in determining which diagnostic tests will be performed and which therapies used for cancer patients in the developing world. The media have given considerable attention to such issues, as well as to intellectual property rights and the conduct of industry–sponsored research designed to lead to approval of products by regulatory bodies. The Corporate Liaison Committee will greatly assist the INCTR where its activities may impinge upon these complex and controversial areas, some of which will inevitably overlap into the territory of the Ethical Review Committee—indeed, several public statements on the ethics of medical research in developing countries have recently been made.

The Tissue Banking Committee met for the first time at the 2001 Annual Meeting in Brussels. Because of complex legal and ethical considerations pertaining to the use, for scientific purposes, of human tissues and body fluids, particularly when investigations are performed in countries other than those from which such human materials originate, it was important to assemble a panel of experts to advise the INCTR in such matters. In addition, committee members will participate in designing standard operating procedures for the collection, storage and record maintenance for tissue and body fluids collected in the course of studies in which the INCTR is involved. Dr Robert Hewitt chairs this committee.

The Education Committee, which will meet for the first time later this year, will have an important role in developing educational programs, as well as educational tools, relating to all aspects of cancer prevention and treatment. An important difference in emphasis between the INCTR's programs and those of other organizations is the attempt to conduct as much of the training and education as possible within participating developing countries. Whilst training in countries with greater resources has been of critical importance in the provision of some of the pioneers of cancer treatment and research in developing countries, many young people, not surprisingly, strive not only to receive training in more wealthy countries, but choose to spend their lives there. This represents a veritable "brain–drain" from the developing world, to the benefit of the resource–rich countries, which profit from the influx of immigrant professionals, many of whom will have a major impact upon programs in science, technology, and medicine in their adopted countries (Box 2). Enhancing existing in–country training programs through visiting experts, developing new training programs, e.g., in cancer control and clinical research and oncology nursing, amongst others, and making educational tools more widely available are some of the ways in which the INCTR can help to build knowledge and infrastructure in developing countries. The Education Committee and its specialized sub–committees will both advise and take an active role in such programs, which are in their early stages of evolution. The building of improved infrastructure in developing countries should begin to reduce the loss of the "best and brightest" to the more affluent nations, and, eventually, may even tempt some ex–patriots to return to their home country—if only as part of an INCTR Visiting Expert program!

Fostering Collaboration
In addition to developing its own long–term collaborations with hospitals and cancer centers in developing countries, the INCTR wishes to promote collaboration and concerted actions. One example of this is the Global Alliance for the Cure of Children With Cancer (GACCC), which was discussed in the last edition of Network. The GACCC had its second meeting in Brussels immediately after the Annual Meeting. There appears to be increasing interest in this concept, and we hope that the GACCC will serve as a model for other consortia of organizations and associations dedicated to different aspects of cancer research, prevention and treatment. The underlying concept governing the development of such consortia is that multiple organizations are synergistic when they work together in multifaceted projects in cancer control. Each organization would be responsible for that element of the project in which its experience and goals reside, e.g., tobacco control, cervical cancer screening, cancer registration, public education, treatment protocols, etc. The net benefits should be amplified as a result not only of what each organization is doing, but also of the synergy that comes from a multifaceted approach. This concept will be further developed in the coming year and will be expanded to adult cancer.

As well as encouraging the development of international consortia, the INCTR has assisted in the development of several cooperative groups (i.e., hospital or cancer unit–based, rather than association–based alliances) for the study and treatment of cancer. In October 2000, a group of 13 Arab countries met at a meeting sponsored jointly by the King Faisal Specialist Hospital and Research Center and the INCTR to discuss the formation of a cooperative group for childhood cancer. From this beginning, the Middle East Children's Cancer Association (MECCA) has been formed. MECCA will have its second meeting later this year. In November 2000, participants from a number of Indian cancer centers and units met in Hyderabad, India, in conjunction with INCTR, and agreed to form the Indian Group for the Study of Leukemia. The INCTR is also assisting a small group of centers in China to establish a cooperative group for the treatment of childhood leukemias and lymphomas. It is hoped that this work can be furthered through collaboration with the organization known as CURE, which is focused exclusively on pediatric cancer in China. Finally, the US Branch of the INCTR held a meeting on cancer of the uterine cervix in Latin America in February 2001, and plans to follow up with initiatives in the early detection and treatment of this disease.

Looking to the Future
The first year of INCTR operations has been eventful and productive. This was confirmed by the enthusiasm much in evidence at the Annual Meeting. But it does represent only a beginning. In the next year, while consolidating and expanding the work of the strategy groups, extending its Association Membership, and developing its education and training programs, the INCTR will also initiate a pilot project on cancer control in Nepal, in collaboration with the Nepalese Cancer Relief Society, and will examine how it can effectively work in the area of cancer control with centers in Pakistan. In both projects it is encouraging participation by other major organizations. Clearly, early detection—prevention where possible—should be important bulwarks of the INCTR's programs, and cervical cancer, head and neck cancer, and certain childhood cancers will be high priorities in this area. Earlier detection will lead to improved treatment results in cancer in general, even without any change in the resources available—a message that is worth repeating again and again. This will entail collecting information on the causes for late presentation. Although many of these are already known, their relative importance will vary greatly from one country to another, and from region to region. Early detection does not, of course, mean that treatment is not necessary—just that treatment may be simpler and more effective. Early detection programs, encompassing the appropriate mix of professional and public education coupled to effective screening programs must, of course, be associated with a coordinated treatment program.

Similarly, progress in developing the INCTR's external structure, programs and projects must be accompanied by the development, pari passu, of its internal structure. The Brussels office will evolve into several Offices and Departments, including Administration, Clinical Trials, Resource Development, and Laboratory/Translational Science. In addition, an INCTR presence in developing countries, in the form of Offices and Branches, will become increasingly important. As programs evolve, there will be a need to ensure effective coordination of national and regional projects (whether clinical, laboratory or educational) among participating Associate Members and Collaborating Units, and to develop and maintain links with governmental departments and agencies as well as with relevant private organizations. In addition to the existing US Branch, INCTR Offices are planned for the UK, India, Egypt and Brazil. Others will follow. Offices will evolve into fully–fledged Branches, and the INCTR truly will be on its way to becoming a global organization.

It is unfortunate that so much of the talent available in developing countries is either lost to them, by emigration, or is unable to reach its full potential because of socioeconomic problems. The INCTR cannot, of course, address these underlying socioeconomic problems, or even deal with cancer at a national level, but it can demonstrate, through assistance in the development of pilot and model programs, that a difference can be made. This should also lead to improved use of existing resources, to expansion of infrastructure, and to the provision or improvement of "growth centers" from which programs can be rapidly expanded as resources become available. But it must be acknowledged that most of the work must originate and must be done in the developing countries themselves. The INCTR's role, although an active and participatory one, is primarily facilitatory, supportive, and educational. Maximal gain will accrue when there is effective collaboration between those in resource–poor countries who are particularly motivated to develop relevant programs in a national or regional context, and with experts from anywhere in the world willing to devote their time and energy to helping such motivated persons. Gradually, as communications improve, people throughout the world are recognizing that their similarities outweigh their differences, that everything is to be gained by working together, and that much is lost by working against each other. If we are to forge a way forward against powerful retrogressive currents, it is essential, in the spirit of the Kenyan national motto, Harambee, that we all pull together.