A global challenge: Treating children with cancer in developing countries
Western institutions continue to join the fight, and small investments have led to major improvements in survival.
The Union for International Cancer Control estimates that 175,000 children are diagnosed with cancer every year and 90,000 will die of their disease.
Most childhood cancers are curable, but money plays a huge role. Roughly 80% of children in resource-rich areas will survive while 80% of children in resource-poor settings will die, according to the International Society of Paediatric Oncology and the International Confederation of Childhood Cancer Parent Organizations.
World Health Statistics 2011 — the World Health Organization’s annual compilation of health-related data for its 193 member states — paints a bleak picture. Upper middle- and high-income countries have 10 to 14 times as many physicians per 10,000 residents. High-income countries have 59 hospital beds per 10,000 residents vs. 36 in upper middle-income nations, 22 in lower middle-income countries and 13 in low-income nations.
Photo courtesy of Indiana University Health reprinted with permission.
As a percentage of gross domestic product, high-income countries spent 11.1% on health care in 2008, the most recent statistics available. In comparison, low-income nations spent 5.4%.
Survival rates reflect that disparity. Only 5% of childhood cancers diagnosed in Africa are cured vs. 80% in the rest of the world, according to AfrOx, a nonprofit organization that helps African countries implement cancer prevention and control programs.
Seventy-five percent of patients in Africa have advanced cancer at diagnosis, David J. Kerr, MD, PhD, Rhodes professor of clinical pharmacology and cancer therapeutics at the University of Oxford, United Kingdom, and past-president of the European Society for Medical Oncology (ESMO), said during a presentation at the 2011 ASCO Annual Meeting.
“The problem I have when I go into the clinic is that we see advanced disease,” Kerr said. “I’m seeing medieval-type cancers that I haven’t seen in a 30-year career as a medical oncologist.”
Although Western institutions cannot erase the lack of resources in the developing world, several are experimenting with ways to fill in the gap. Some provide funding. Others are going a step further by relocating their own physicians to countries such as Nigeria or Egypt to ensure some of the world’s poorest people receive the cancer care they desperately need.
Treating a chronic condition such as cancer is far different from addressing infections, broken bones or other acute concerns, which can be handled during relatively short stints in a rural village. Rather, experts told HemOnc Today that it will require collaboration between medical institutions, government and nongovernmental organizations, and entities such as ASCO and ESMO to make progress in the fight against cancer in low-income countries.
A case study
Sara Stulac, MD, MPH, director of pediatrics for Partners In Health, has spent the last few years developing a “twinning” program in which PIH and Dana-Farber Cancer Institute — under the direction of Larry Shulman, MD, senior oncology adviser for PIH — provide oncologic expertise for cancer patients in a country where there are no physicians trained in cancer care.
The program has since grown to include one hospital in rural Rwanda, with another expected to launch soon. Each patient is treated by a team comprised of a Rwandan generalist, a Rwandan nurse coordinator focused on oncology patients, a Rwanda-based pediatrician or internist trained in the United States, and a US-based pediatric oncologist.
Biopsies and radiologic staging studies are performed in Rwanda, but all pathologic diagnoses are made at Brigham and Women’s Hospital. Physicians from the United States are in-country for 6 months, and, along with local physicians, are in regular contact with supervisors at Dana-Farber, including Stulac and Leslie Lehmann, MD, clinical director of the pediatric stem cell transplant program at Dana-Farber/Children’s Hospital Cancer Center in Boston. There are weekly conference calls to review all patients, and outcomes are carefully tracked.
Lehmann — who said there are no trained oncologists in Rwanda, a nation of roughly 11 million — presented results of a small study at the 2011 American Society of Hematology Annual Meeting and Scientific Exposition evaluating outcomes among 10 patients aged 3 to 15 years who were diagnosed with lymphoma. Those patients were treated at Rwinkwavu, a Partners In Health-supported government district hospital in rural Rwanda.
At a median follow-up of 14 months, five patients had completed therapy, showed no evidence of recurrence and were considered cured. Two patients were still undergoing treatment and were in remission. Two patients died due to treatment complications; one patient with Hodgkin’s lymphoma died of cardiomyopathy, and one patient with Burkitt’s lymphoma died of transverse myelopathy. One patient with Burkitt’s lymphoma died of progressive disease while receiving chemotherapy. One patient with stage I lymphocyte-predominant Hodgkin’s disease underwent complete surgical excision and is not receiving chemotherapy.
A 50% cure rate — or 70% if the two patients undergoing treatment remain in remission — is lower than the 80% cure rate found in the developed world, and it is nearly impossible to draw definitive conclusions from such a small cohort. Considering the paucity of resources in a country such as Rwanda, however, these results represent a tremendous success, Lehmann said.
“We prioritize what we treat. We’re not treating cancers unlikely to be curable or cancers with complex and/or costly treatment regimens,” Lehmann said. “But for a constrained number of cancers, you can potentially cure a large number of people with a relatively small investment of resources. Treating cancer is different from treating other chronic conditions, both in terms of infrastructure required and the knowledge that, without treatment, virtually all patients would die. In addition, most patients who are cured can look forward to a return to a healthy life. Because we backed into this practice, we decided to focus on cancers that are relatively easy to treat with a higher likelihood of cure.”
‘Fertile ground for growth’
Jodi Skiles, MD, a third-year pediatric oncology fellow at Riley Hospital for Children at Indiana University Health in Indianapolis, has been traveling to Kenya as part an exchange program with Moi University School of Medicine in Eldoret, Kenya, for the past 7 years. She recently returned from a 6-month stint there.
Skiles said she caught the “international bug” while working at Moi as a medical student. An Indiana native, she still remembers the culture shock she experienced during her first visit to Africa.
“The first 2 weeks I was there as a medical student, I remember thinking, ‘I’ve made the biggest mistake of my life.’ It took me about a month to get past feeling overwhelmed so I could recognize the amazing opportunity before me,” she said. “By the end of the second month, I didn’t want to go home. It’s so rewarding to know you’re making a difference on a grander scale. In that setting, there are many clinical scenarios that you know would have a different outcome had you not been there. To know that your presence makes such a difference is incredibly rewarding and inspires me to continue to advocate for change.”
The partnership between the two schools started just before the HIV/AIDS epidemic in sub-Saharan Africa took hold in the early 1990s. As care for HIV/AIDS patients in Kenya improved over the years, many patients are now thriving with HIV. While the HIV patients are now living longer, it has also resulted in a sharp increase in HIV-related cancers such as lymphoma and Kaposi’s sarcoma.
In response, physicians at Moi and Indiana universities began to focus on adult cancers about 3 years ago, and a pediatric program grew out of that. Skiles, a specialist in pediatric oncology, served as interim director of the adult and pediatric cancer programs for 6 months.
“One of the things I love most about international work is that a little bit of education and a little bit of resources can result in drastic change,” she said. “In this day and age in Western medicine, there’s not a lot of low-hanging fruit in terms of intervening in a way that makes a huge impact in clinical care. It’s increasingly more difficult to make small changes that have a big benefit. In international work, there is fertile ground for so much growth. It’s so exciting to be part of something where a relatively small amount of education and resources in the right hands can accomplish a lot.”
The power of one
St. Jude Children’s Research Hospital developed its International Outreach Program in 1993, largely through the efforts of one woman. Her son was referred to the hospital in Memphis, Tenn., because he needed cancer treatment that he could not get in their native El Salvador.
“She was very impressed with the model we had here of a very specific place dedicated to pediatric oncology with full-time nurses, full-time doctors and a fundraising organization that allowed all kids to be treated regardless of ability to pay,” said Raul C. Ribeiro, MD, director of the International Outreach Program at St. Jude. “When she went back, she tried to emulate this program locally. She built a foundation, she persuaded the pediatric hospital there to dedicate an area to oncology and to send a pediatrician to Mexico to be trained in pediatric oncology.”
Then Saint Jude officials approved a one-time request to help develop a program with El Salvador, and doctors decided to address acute lymphoblastic leukemia because it is a common, easily curable disease.
“After 3 years, we measured outcomes and noted that we had serviced 155 kids with ALL, and 55 of them were alive,” Ribeiro said. “The 3-year investment was what we would have spent in 1 year treating three children at St. Jude.”
St. Jude officials were so impressed, they decided to make that model — an ongoing relationship with a local public hospital dedicated exclusively to pediatric oncology — a permanent part of its mission. The program now operates at 19 hospitals in 14 countries. The program’s reach extends to China, the Middle East, Africa, Central America and South America.
Since St. Jude began working in El Salvador, the cure rate for ALL improved from 5% to 75%, Ribeiro said. The 5-year survival rate for ALL in the United States is 89%, according to NCI.
“In many countries, cancer is like a death sentence,” Ribeiro said. “When we started this program, as many as 40% of families in some countries abandoned treatment. In talking to other people in the community whose children had been successfully treated, little by little, that perspective changed.”
Small investments, big rewards
Results of a survey of the status of pediatric cancer care in 10 low- and middle-income countries published by The Lancet in 2008 showed annual government health care expenditure per capita was the strongest independent predictor of survival (P=.0001), but only for countries with the lowest annual expenditure.
“About 25% to 30% of patients are not successfully treated, even with optimum treatment. Therefore, once access to early diagnosis and adequate care (with the requisite hospital infrastructure) are available, additional investment of public health resources has a smaller beneficial effect on survival,” Ribeiro and colleagues wrote. “Because childhood cancer has a low overall incidence and most patients can be managed without complex infrastructure or procedures, a relatively small investment by governments or private sectors in conjunction with local organizations might make a large difference in survival in low-income and mid-income countries.”
Skiles said all of the chemotherapy offered to her patients is deeply discounted. Patients pay about $5 per treatment cycle. However, not every patient can afford to pay even that, so there is constant concern about keeping the program financially viable.
“Kenya is in the process of developing a health care system that will be able to support these patients. We are hopeful that the government will soon help subsidize the costs so that the program won’t be entirely responsible for the cost of chemotherapy,” Skiles said. “In addition to clinical care, we’re also doing research. Moving forward, as we open clinical therapy trials, some of the cost of treatment will be built into the research funding, which should help relieve some of the financial burden for care, as well.”
As evidenced by Dana-Farber Cancer Institute’s experience in Rwanda and St. Jude’s experience in El Salvador, it is not difficult to make major improvements in survival with relatively minimal investments in these countries.
“Every time we build a structure to treat ALL, we can treat most pediatric cancers,” Ribeiro said. “The treatment of pediatric cancer does not depend on new drugs or expensive treatments, like in adult cancer. All the effective drugs for pediatric oncology were produced in the 1990s. With the current armamentarium, we can effectively treat 70% to 75% of kids.”
Challenges beyond cancer
Cancer still may not represent the best use of health care money in developing countries.
Although adult deaths caused by infectious disease are declining, WHO said in 2008 that infectious disease represented 64% of deaths in children aged younger than 5 years and that roughly 75% of all child deaths were caused by preventable causes such as neonatal conditions, pneumonia, diarrhea, malaria and measles.
The 2010 Levels & Trends in Child Mortality report from the UN Inter-agency Group for Child Mortality Estimation found that the biggest killers of young children were pneumonia (18%) and diarrheal diseases (15%). Malnutrition plays a role in one-third of deaths for children aged 5 years and younger in sub-Saharan Africa and Southern Asia.
Six countries — China, Democratic Republic of the Congo, Ethiopia, India, Nigeria and Pakistan — represent 50% of deaths in this age group.
WHO’s 2011 World Health Statistics estimated that the number of underweight children aged younger than 5 years in Africa increased from 24 million in 1990 to 30 million in 2010, and the report estimated that 71 million children in Asia are underweight. Approximately 178 million children globally are too short for their age group, a key indicator of chronic malnutrition.
Considering those grim statistics, Lehmann said there may be times when cancer care must take a back seat. Still, it is a complicated issue with no good answers.
“Should you be giving cancer care in a country that doesn’t have electricity for every inhabitant?” she said. “I don’t know. It sounds a little ruthless, but I wasn’t asked whether or not cancer care should be delivered in Rwanda. I came into a system that already existed, and I’m trying to make it better.” – by Jason Harris
Is there value in conducting a short-term intervention in low-resource areas?
What works, works.
Every twinning program is going to be unique to the site. There isn’t one best approach. In the end, a program that ultimately leads to a country becoming self-sufficient in this area is great. If a developed country makes a commitment to have people on the ground without the feeling that they are going to withdraw at any moment, and there is a long-term commitment, that’s fantastic and enriches both sides.
The world should get smaller and smaller with our ability to travel and the communications technology we have available. Also, getting on a plane and traveling to almost anywhere can be done in less than a day.
The only ideal way to conduct one of these programs is the one that works in a given setting. Everyone will say their way of doing it is the best, but clearly there are a diverse number of successful strategies. We must do whatever it takes to get the job done, and there are many, many roads to get there.
It would be really nice if there was a special international effort in this area, something that would be completely cross-cultural. I’ve spoken on this and I don’t think it’s impossible to have a global comprehensive children’s cancer center. If one could get people to work together toward that end, it would go a long way toward improving care in other regions of the world, as well as help to eliminate the still-present gaps in outcome for children with cancer.
The value is limited, unless conducted in the context of a long-term program.
Short-term programs may be extremely effective for surgeons, dentists and others who can provide a life-changing service during a short visit, but for cancer care a long-term approach is mandatory. Therefore, any short-term interventions must be conducted in the context of a long-term program, in which they help promote, develop, sustain, advertise and advocate the long-term program. Otherwise, going for 2 weeks or 3 months may be almost the worst thing one can do (except for the visiting individual, who may experience life-changing growth).
Two types of short-term help may be particularly risky. The first is a short visit to treat oncology patients who have little chance of cure absent development of a long-term cancer care program. The second is a short-term grant-funded project in which infrastructure is developed, and people are hired and trained, but when the term of the grant expires, everything collapses and leaves behind cynical and demoralized health care professionals.
One example of short-term aid placed in the context of long-term commitment and support is provided by Texas Children’s Hospital, which funds a full-time pediatric oncologist in Botswana, and also supports the on-site clinician with visits by other faculty to assist with teaching or cover during vacation.
The hospital rotates this person every 1 or 2 years, but with the understanding that the individual will care for patients and also train local professionals and eventually develop a self-sustaining oncology program. A similar program is being implemented in Ethiopia, with the goal to develop an independent program in a few years. Once the local programs are up and running, this is only the beginning. The supporting institutions and individuals can stay involved as twinning partners to facilitate continued improvement in services and outcomes. The ongoing involvement may involve exchange visits, but increasingly online case discussion plays a role in day-to-day oncology collaboration. For example, www.Cure4Kids.org hosts about 100 meetings per month of oncology professionals worldwide at no cost to participants. Weekly online contact plus occasional visits to support a long-term twinning program seems to be the recipe for long-term success, and adding in the energy and new ideas of short-term visitors makes such programs even more rewarding.
At St. Jude, we used to talk about “knowledge transfer” but now speak exclusively of “knowledge sharing” — not transfer of knowledge, but learning from each other. Interaction with colleagues on other continents paves the way for all of us to become better doctors and human beings — not short-term aid, but long-term partnership. Only then can we effectively and sustainably help cancer patients worldwide.
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- St. Jude Childrens Research Hospital. International Outreach Program: Guide to Establishing a Pediatric Oncology Twinning Program. Available at: www.stjude.org/SJFile/IOP_Twinning_Manual_082908.pdf.
- Stulac S. #4222. Presented at: the 2011 ASH Annual Meeting and Scientific Exposition; Dec. 10-13, 2011; San Diego.
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- WHO. Levels & Trends in Child Mortality Report 2010. Estimates Developed by the UN Inter-agency Group for Child Mortality Estimation. Available at: www.who.int/pmnch/activities/jointactionplan/201009_unicef_childmortaliy.pdf.
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For more information:
- Robert J. Arceci, MD, PhD, is the King Fahd Professor of Pediatric Oncology at Johns Hopkins University.
- Scott C. Howard, MD, MS, is director of clinical trials for the International Outreach Program at St. Jude Children’s Research Hospital in Memphis, Tenn.
- Drs. Arceci, Howard, Kerr, Lehmann, Ribeiro and Skiles report no relevant financial disclosures.