UPDATE ON PODC ACTIVITIES

In the last week of August, Tom Vôute, Honorary Founding Member and president of SIOP from 1990-1992, suddenly past away. He acted as Consultant of the PODC Committee, was a strong promoter of SIOP’s globalisation and was highly respected as a teacher and researcher.

When Tom Vôute became president, SIOP had 256 European, 64 North-American and 35 members from other continents, the latter accounting for approximately 10%. In 2008 the respective numbers are 700, 182, 597 and 40%.
If Russia, Belarus, the Baltic states, the Ukraine, Bulgaria and Romania, Latin America, Africa and Asia except Japan, South Korea, Taiwan and Singapur are considered as developing, the percentage of SIOP members from developing countries rose from 6% in 1990 to 33% in 2008: 2% in Africa, 2,1% in Eastern Europe, 6,8% in Latin America and 16,4% in Asia.
In 2008 SIOP had, per 100 million people, 7 members in Africa, 9 in Asia, 35 in North America, 38 in Latin America, 99 in Europe and 247 in Australia and Oceania (total world population 6'256 million).
Of the PODC’s Committee yearly budget of approximately 45-50'000.-€ , 30'000.- were used for scholarships in Mumbai and the rest for SIOP’s nurses project in Malawi and for P.Hesseling’s development of treatment guidelines for endemic Burkitt’s Lymphoma (BL).
Recently P.Hesseling reviewed the charts of the first 34 patients treated under the auspices of P.Mc Cormick and his team from April to August 2008 according to the new Cameroon 2008 BL treatment guidelines.The latter had been presented at the Burkitt’s Lymphoma Symposium held in Mutengene, Cameroon, on December 7-9 2007. The guidelines are based on experiences made by P.Hesseling and coworkers with low cost, not too toxic, cyclophosphamide-based treatments of over 600 children with endemic BL. These guidelines provide a risk-adapted initial treatment, and, if necessary, directions for the treatment of relapses.
Preliminary results indicate that these guidelines will fulfill the goal set at the 1996
Workshop in London on the role of PODC in the developing world, i.e. to cure at least half of the children with endemic BL. If up to two thirds of all children with endemic BL can be cured, these guidelines will represent an important tool in sub-saharan PODC.
In SIOP NEWS 36 (January 2008),p 9-17 a report on PODC MUMBAI was published, in particular the presentations and discussions on Childhood Cancer Registration (Session I), Palliative Care (Session II) and the Establishment of Cooperative Trial Groups (Session III).
For SIOP BERLIN 52 PODC abstracts were graded, assistance was provided for the selection of scholarship recipients and the PODC BERLIN program was developed.
The PODC Committee was represented by the chairman at the Lymphoma Symposium in Mutengene, Cameroon; at the 5th SIOP-Asia Conference in Muscat, Oman (February 26-28, 2008); and at the 8th Continental SIOP-Africa Meeting in Tunis (May 14-17, 2008).

Minutes of the SIOP PODC Committee Business Meeting
Friday, October 3, 2008, 08.30-09.00, Estrel Convention Center, Berlin

Agenda:
1) Opening and apologies
2) Minutes of the last business meeting (SIOP NEWS 36 (January 2008) p 10/11)
3) PODC Committee Annual Report 2007/2008
4) News from the President and the Board
5) News from the Continental Presidents
6) Proposals for PODC activities at the 41st SIOP International Congress in Sao Paulo 2009 and the XXII Latin American Congress of Pediatric Oncology
7) PODC in SIOP and SIOP in PODC: Changes in the provenance of SIOP members:
possible onsequences for SIOP
8) Work on Tools for PODC
9) Any other business

Apologies: P Hesseling, J Lemerle, L Molyneux, CK.Li, W Newton Jr., A Schouten-van Meeteren, N Usmani
Present: E Abdel Khalek, A Alzaben, I Ayan, F Azici, S Bakhsi, O Björk, E Boldrini, H Caron, J Challinor, M Chintagumpala, I Christosova, S Cutland, S Day, J de Kraker, U Dirksen, Z Dreyer, S Emir, D Epelman, A Erbey, L Faulkner, J Finlay, M Greenberg, E Güler, S Howard, L Hsu, T Israels, R Kebudi, D Konstantinov, R Kortmann, M Krischke, P Kurkure, T Kutkuk, S Lie, T Linden, S Luna-Fineman, G Macfarlane, E Makimbetov, C Mambetova, J Margolin, K Mattey, P McCormick, R Melaragno, G Mitchell, C Moell, T Mosby, B Mueller, T Nyenget, O Oberlin, A Oguz, F Oubich, C Patte, A Pedrosa, F Pedrosa, J Poole, Y Quintana, M Quintero de Chary, S Qureshi, N Rainusso,Y Ravindranath, L Renner, R Ribeiro, H Rifi, D Schrey, B Sevinir, A Shad, J Skeen, C Stefe, N Tacyicdiz, G Tokue,A Trabzi, M Trame, A Trehan, A Veerman, S Vural, HP Wagner, B Yalcin, G Yavuz

Minutes:
Ad 1) Opening by the chairman.
Ad 2) The minutes of the last business meeting were accepted;
Ad 3) There was no comment on The Annual Report 2007/2008
Ad 4) T.Eden, past president of SIOP, reported on World Childhood Cancer Foundation (WCCF), „My child Matters“ and Afrox (see below at the end of Symposium III).
Ad 5) None
Ad 6) Both Congresses will overlap. A PODC SAO PAULO program is in preparation.
Special activities will include: The writing of a scientific report; Twinning between
Portuguese speaking African countries and South America; Neuro-oncology.
Ad 7) As summarized in the Annual Report the structure of the SIOP Membership is
changing. The significance and consequences of these changes were briefly discussed.
As 8) Some of the „tools“ used for PODC, e.g. certain recommendations, need to be adjusted (see Symposium II, below).

New PODC Projects/Progress Reports.
Chairman: HP Wagner
C. Patte was replacing J. Lemerle who could not attend. She gave a brief overview on the  actual structure and activities of GFAOP. Of particular interest were the new results on the treatment of children with Burkitt’s lymphoma in sub-saharan Africa (Dhakar, Bamako, Abidjan, Ouagadougou, Yayunde and Antananarivo: see also Abstract AO.005, p.17, SIOP Abstract Book 2008). Children were first treated according to the Malawi guidelines and, if they were not in CR after 3 chemo-cycles, they received 2 COMP and 2 CYM courses for rescue. Of 176 patients evaluated (an additional 79 were excluded) 50% were in CR after 3 chemo-cycles. Of 83 not in CR, 59 received rescue and of these 18 (31%) had maintained CR, while all of the 24 who did not receive rescue died. Based on these observations one can estimate that the overall survival (basic treatment for all stages plus rescue for high risk patients ) is around 60%.
P. McCormick reviewed experiences made with the Malawi protocols for BL in 3 Baptist hospitals in Western Cameroon. While the 1 yr EFS was approximately 55% with i.v. or oral cyclophosphamide monotherapy, an 80% survival was observed, if ultrasound revealed a regression of the largested abdominal tumor to 30 ml or less before chemo 4. In the 2008 BL study, patients are stratified by ultrasound after chemo 3, and then receive 1-3 intensification cycles, based on cyclo (60mg/kg) alone or cyclo, vincristine and a single dose of MTX (1g/m2). With this regimen an overall 1 year survival between 60-65% can be achieved Two hospitals register now their patients with the St. Jude’s Pond4kids program.
S MacFarlane reported on the New Zealand’s Pacific Project (SIOP NEWS 37 (July 2008), p10/11). Three Pacific nations (Fiji, Samoa and Tonga) have worked with the Pediatric Oncology Steering Group from New Zealand to agree treatment protocols adjusted in intensity to match supportive care capability. In tandem, palliative care protocols have been agreed to provide for those patients for whomcurative therapy will not be undertaken. The future goal is to achieve a sound pediatric oncology service in Fiji twinned with Christchurch and robust shared care arrangements between Tonga and Samoa twinned with Auckland.
C. Moell reported on the Lund Vietnam Childhood Cancer Programme. The Lund University Hospital in Sweden and the National hospital for Pediatrics in Hanoi, NHP, have started cooperation with the aim to improve the treatment of childhood cancer in northern Vietnam. The programme, which started January 2008, will run for six years and is financed by IKEA. During this first year doctors and nurses from Sweden have made repeated visits to Hanoi, and doctors from Vietnam have visited Lund. There have been discussions on all aspects of treatment of childhood cancer and several changes in the work routines have been implemented. A registry for children with cancer at NHP was started in January 2008. During the first six months 132 patients were registered. In July 2008 less than 50% of them were on treatment for their disease, the rest had abandoned therapy for various reasons.The current priorities include optimizing the treatment of ALL and Wilms tumor. Multidiciplinary teamwork was initiated and laboratories and other departments in the hospital important for PO will be supported. There will be annual national conferences for doctors and nurses to stimulate the development of PO in all of Vietnam. Particular efforts will be made to identify reasons for the abandonment of treatment. The whole programme is based on the assumption that improvements made will be sustained through improved support by the government of Vietnam.
J. Finlay, chairman of the International Outreach Committee(IOC) of the Society of Neuro-Oncology (SNO) stated, that after societal causes (accidents, suicides and homocides) brain cancer is the major cause of death in children 1-15 years of age in affluent countries. In North America the overall 5-year survival approaches 75% but does not mean cure. In developing countries, where children <15 account for 30-50% of the population, propgress in the management of childhood brain cancer has lagged far behind the progress achieved in lymphomas, leukemias and certain solid tumors. Both, survival and quality of survival, are poor, due to limited access to quality care, or even any care. In the abscence of adequate imaging (CT and MRI), neurosurgical and radiotherapeutic skills, pediatric oncologists can do little for most children with a brain tumor. However, since the socioeconomic and/or the regional or local situation may vary enormously in developing countries, SNO has established geographically based outreach subcommittees to promote clinical and research activities in neuro-oncology adjusted to the regional or even local needs. To initiate progress neuro-oncologic and neuro-surgical training, provision of adequate neuro-imaging tools, of neuro-anesthesia and of neuro-surgical equipment are essential for the establishment of national centers of excellence providing centralized management of pediatric brain tumors. The immediate goals of the SNO IOC reached are i) the provision of educational materials via the SNO website; ii) the availability of the SNO journal „Neuro-oncology“ for only US$ 75 to hospitals and individuals in developing countries; and iii) the establishment of scholarships to bring young specialists working in developing countries to the Annual Meeting of SNO. Short term goals planned are i) the organization and promotion of CME activities on brain tumors in the developing world; ii) to facilitate the placement of clinical and research trainees from developing countries in leading centers of the developed world; and iii) to integrate SNO’s International Outreach efforts with other societies dedicated to the development of neuro-oncology world-wide.
W.A.Newton Jr. could not attend but sent a 2008 report from CURE Childhood Cancer in China.By 2009 three staff members of the Beijing Children’s Research Hospital (BCRH) with primary roles in the diagnosis and treatment of childhood cancer will have received advanced training in leading US childhood cancer centers. Similar staff training is scheduled for Shanghai Children’s Hospital and the Children’s Hospital of Fudan University and will be funded primarily by the Soong Ching Ling Foundation in Shanghai. The next step in the development of a model care system for childhood cancers in China is the development of local pediatric oncology networks. After training staff of hospitals in the area of Centers of Excellence, these hospitals will provide up-to-date diagnostic evaluation and will refer patients requiring more intensive treatment to their Center of Excellence, while all other patients will be treated locally.

Summary of Symposia I - III
Syposium I : Progress of Pediatric Oncology in Eastern Countries.
Chairpersons: R.Kebudi, J.Stary
As J.Stary stated, about 60 million children <15 years live in Eastern Europe and about 8'000 new cases of childhood cancer are observed each year. Since the end of the communist era, PO gradually improved (Lancet 2004;364:2097). Thus SIOPE standards for training and postgraduate education have been accepted, comprehensive pediatric cancer units have been established and the participation in prospective clinical trials has improved. Despite this progress there remain marked differences between East and West: of the papers published in MPO/PBC 1991-2007 only 3% are from Eastern as compared to 38% from Western Europe.
At the SIOP meetings 2004-2007 4-7% of the oral presentations came from Eastern, 50% from Western Europe. Of the 700 European SIOP members, only 17% are from Eastern Europe.
E.Makimbetov reviewed the actual status of PO in the 5 Central Asian countries: Kazakhstan in the North (2,7 million km2, 15,3 million people, 22% <15yrs, infant mortality 27/1000), Uzbekistan (447'000 km2, 28,3 million: 32% <15yrs, 68/1000) and Turkmenistan (488'100 km2, 5,2 million : 34% <15yrs, 32/1000) in the South-West, and Kyrgyzstan (198'000 km2, 5,4 million: 30% <15yrs,, 32/1000) and Tajikistan (143'000 km2, 7,2 million: 35% <15yrs, 42/1000) in the South-East. There are over 100 different ethnic groups, Usbeks being the largest. In Kazakhstan there are 30% Russians, in Kyrgyzstan13%.The per capitum income (2007) is around 10'000 US$ in Kazakhstan and Turkmenistan, and around 2000 in the other countries (data from CIA, The World-Fact Book: www.cia.gov),The total health expenditure is highest in Turkmenistan (3,5%).Assuming 120 new childhood cancers/1 million children
<15yrs/year about 2200 new cancers arise in the 5 countries: about 1100 in Usbekistan, 400 in Kazakhstan, 300 in Tajikistan, 200 in Turkmenistan and 200 in Kyrgyzstan.
In Kyrgyzstan the incidence of childhood cancer is highest in Bishek (112/million/yr).There are 30 beds for PO at the National Center of Oncology in Bishek where 2'322 new cases were registered since 1985 to assess crude, age-standardized rates in urban (35%) and rural areas (65%). The majority (72%) were diagnosed in the specialized center. Histological and cytological verification was obtained in 75% of all cases. While Kyrgyzs and Usbeks had higher rates of ocular and testicular tumors, the tumor spectrum of Russian children was as in Western countries. Within 2 decades, the overall 5 yr. survival of patients treated increased
from 29 to 47%, but 60% of the children with cancer (mainly in the South of the country) have no access to care. The only pediatric cancer unit in Bishek has only 2 pediatric oncologists and only 4 PO nurses. Autologous stem cell reinfusion is available since 2007 due to a Turkish grant. There is also a rehabilitation center at 3'200 m altitude,120 km South of Bishek,, open for 3 months/year, helping many survivors to recover completely.
In Kazakhstan there is one 30 bed pediatric cancer unit for solid tumors at the Kazakh Institute of Oncology and Radiology and additional beds in the Hematology Institute in Almaty. In Uzbekistan there are specialized PO units at the Republican Oncology Center in Tashkent (54 beds), in Samarkand and Andijan, the latter comprising 40 beds together.
Practically no actual information on PO is available from Turkmenistan and Tajikistan.
R.-D. Kortmann underscored the fact that radiotherapy could play an important role in the treatment of childhood cancers in countries with limited resources. In order to optimize the use of infrastructures avaiable and access to radiotherapy, the multi-disciplinary disease management has to be modified considering low absconding rate and low costs as well as supportive care. This requires specially tailered quality standards including educational programmes for radiooncologists, physicists, technicians and nurses.
T.Kutluk addressed the question of how to improve survival of children with cancer if PO has no priority for the national health authorities..He focused on activities of the Union of National Pediatric Societies of Turkish Speaking Countries (UNPSTSC), the Turkish International Cooperation and Development Agency (TIKA) and the International Children’s Center (ICC), such as joint meetings; scholarships; scientists exchange programs; and site visits to assess needs, develop model services and educational programs providing training for physicians and nurses in Turkey. A hematology training program, a bone marrow transplantation and a thalassemia program were established in Azerbeijan and Kyrgyzstan. In 2002 a
project was developed to support the Ataturk Children’s Hospital in Kabul.
In the general discussion the role of radiotherapy in PODC, in particular indications for the irradiation of brain tumors, was debated. It was also acknowledged the the republics in Central Asia had received no attention from SIOP ASIA so far, and that this had to change.

Symposium II : Bases for PODC of to-morrow.
Chairpersons: A.Shad, S.Lie, A. Veerman.
After a brief review of the SIOP Recommendations issued in 1991 for „The Organization of Pediatric Cancer Units (PCUs)“ and „Requirements for Training of Pediatric Hematologists/Oncologists“ by A. Shad, there were 3 brief presentations on the Organization of PCU’s and Training of Pediatric Oncologists in 3 developing countries.
Organization of PCU’s:
F. Madanat reviewed the progress made at the King Hussein Cancer Center (KHCC) in Jordan, S. Epelman did the same for his unit in Sao Paulo, Brazil. A. Naqvi from Pakistan covered the services available at three related centers in Karachi, Pakistan. In the first two presentations there was general consensus, that the centers in Jordan and Brazil, had more than met the 1991 guidelines, and in fact in many respects, the level of support and practice of PO was at levels similar to those in developed countries. A. Naqvi noted the significant differences in resources, capability and level of services available in PCUs in public, private, and academic centers in Karachi. He enumerated the difficulties encountered in treating patients who originate outside the larger cities in Pakistan (Karachi, Lahore, and Islamabad), which are the only locations of advanced PO-care in Pakistan.
Using these presentations as a basis for discussion, several consensus points were reached:

• The 1991 guidelines are good, but may represent a standard that is still difficult to achieve in many developing countries, particularily in Africa and some parts of Asia.
• On the other hand, significant progress has been made in PO in other parts of the world, e.g. India, Brazil and several countries in the Middle East, necessitating the addition of other elements for a „State-of-the-art“ PCU.
• The guidelines, therefore, need revision.
• The inability to reach the Standards of Care recommended in the 1991 guidelines should not discourage pediatric oncologists in developing countries from developing PCUs. Treatment and relief of suffering from pediatric cancers can begin in units that do not yet meet the ideal/recommended standards.
• There was general consensus at the PODC meeting, that there should be several levels of PCU’s and that they should be clearly defined. Hence any country could have several PCUs depending on the facilities available.
• Participants felt strongly that funding was critical for the development of medical infrastructure (a PCU or improvement of a PCU) in any institution. Different sources of funding that could be solicited to help develop PCU’s (governments, hospitals, parent groups, local and international businesses) were discussed. Actually proposals for general guidelines for all PCU levels and for defining basic, intermediate and advanced PCUs are being elaborated.

B.Mueller summarized the discussion on Training in Pediatric Hematology/Oncology:
Brazil, Jordan and Pakistan have taken different approaches to training in pediatric
hematology/oncology, but all of them emphasized the value of relatively short in-country or abroad training opportuities (up to 4 months). In several countries, the emphasis is more on oncology training, although the physicians clearly also need experience in hematology.
There are some important aspects to consider:

• Any training program has to avoid contributing to the „brain drain“, thus, a shorter training period markedly decreases the chances that the „trainee“ will stay in the host country instead of returning
• One consideration is to train not just pediatric hematologists/oncologists, but to extend training opportunities to adult oncologists, radiotherapists, pediatricians, etc., since in many countries one person has to be able to perform many different functions.
• Training should not just be limited to medical training, but could also include management training, leadership training, training in fund raising, introductions to academic research and publications, etc.. Many „trainees“ will become leaders in their countries and will play important social roles apart from their medical role. A combined training with a School of Public Health might be beneficial as well, since many countries need to buil an infrastructure, such as cancer registries, etc..
• SIOP, and especially its Euopean and American partners should serve as hosts for trainees from developing countries.

Comments voiced during the discussion:

• Certain countries may have too few patients to qualify as „training site“ as specified in the initial guidelines.
• The Amsterdam oncology course received several positive comments.

Symposium III : PODC in SIOP, SIOP in PODC
Chairpersons: J. Poole, G.P. Hadley
G.P. Hadley (Future role of PODC in SIOP) pointed out that all undeveloped nations except Haiti were in Africa, and that in many African countries „poverty is absolute, both at an individual and governmental level. PO is not seen as a priority when malnutrition, malaria, diarrhoea, measles, pneumonia, HIV/AIDS and parasites.are the main killers of children <5.
Only a few countries in Africa have even the basic infrastructure required to start twinning programs, and if they do, the obstacles to improve treatment and reduce the rate of treatment abandonment are bigger than on other continents. In this resource constraint environment PODC has set itself high goals, e.g. defining the geography of malignancy in childhood, promoting public and professional education, setting standards of training and care etc..If the basis for all PODC’s ambitions is data collection and interpretation, the data management surrounding the HIV/AIDS pandemic suggests, that data might generate a funding response from the government. In this respect the Pond4kids program of the St. Jude International
Outreach Program should be tested in sub-saharan Africa and complemented by GFAOP or SIOP funded pragmatic studies within Africa, taking into account, that internet and more traditional communication media are either expensive or not available. At this stage, data managers might well become more important than oncologists!
J. Poole (SIOP in Africa-What is the way forward?) confronted SIOP’s new vision that „No child should die of Cancer“ with the reality in Africa. Besides the problems already alluded to by G.P.Hadley civil wars and political instability produce countless refugees and disrupted families. Although there are some areas with well established facilities and units and others that have at least some PO, the majority of sub-saharan countries have practically nothing. In addition where there are some facilities poor salaries in the public sector force doctores and nurses to spend more of their in private practice. From the biannual SIOP Africa meetings since 1994, certain projects and initiatives have been created such as SMHOP in Morocco, FAPOG with Burkitts and Wilms protocols and the Malawi Burkitts project that extended to the Cameroon and Ghana. The reality is, however, that the majority of children with cancer do not get treatment or are even diagnosed. The initial way forward is to identify and make
contact with those who are treating children with cancer and to start dialogue so that lines of communication may be established. Hopefully the SIOP Africa meeting in Ghana in March 2010 will act as a forum for this.
T. Israels (Nephroblastoma and more) reported on activities and treatment results of the 17 bed pediatric cancer unit at the Queen Elizabeth II Hospital in Blantyre, Malawi, under the direction of Liz Molyneux. About 160 new children with cancer are seen each year, more than half of them with Burkitt’s lymphoma (BL), around 20 with AIDS related Kaposi’s sarcoma, 10 with other lymphoma and 10-15 with Wilms’ tumor. More than half of the patients are acutely malnourished at admission and receive chiponde, a therapeutic peanut butter-based food. Simple treatment guidelines with limited toxicity (one per disease irrespective of risk factors, except for BL and Wilms) are used. A pediatric palliative care team does rounds daily and social support is provided for the family. Several clinical research projects, have been carried out. Under the guidance of P.Hesseling a local protocol for BL has been developed, which is short, cheap and of limited toxicity and which cures approximately half of the children with BL.This pediatric cancer unit is a good model for PCUs in poor countries.
T. Eden (WCCF,AFROX),past president of SIOP, brought news from the Board to the PODC meeting, demonstrating that PODC continues to be one of the most important topics for SIOP and characterizing some aspects of SIOP’s role in PODC.
The International Confederation of Childhood Parents’ Organization (ICCCPO) created the World Childhood Cancer Foundation (WCCF) which was joined by SIOP to provide sustained funding for twinning projects. So far WCCF could raise enough money to support two projects, one in Malawi and one in Colombia, each with about 30’000€ per year for 5 years. The „My Child Matters“ programme, funded by the Sanofi Humanitarian Fund, actually finances 26 projects in 16 countries for two years. It is not known, what will happen afterwards. AFROX, set up in 2007 by the Institute of Cancer Medicine in Oxford University, England, attempts to coordinate the delivery of comprehensive cancer control in Africa. It works with governmental and non-governmental organisations, but is also working closely
with African health ministers. In May 2007 the London declaration listing 6 essential steps (registration,prevention,early diagnosis, curing, palliation and training) was accepted. The concept will first be propagated by politicians and media and by the creation of an African Journal of Oncology. Second the planing of cancer control will be tested and implemented in a few countries, and finally cancer control will be promoted by twinning, lobbying for reduced costs, e.g. of cytostatics, other anticancer drugs, vaccines etc.. AFROX has limited resources. Governmental funds are being sought.

Hans Peter Wagner, PODC Committee