The 21st century has see the emergence of multi-centre collaborative research from low and middle income countries with reports from Central America, Africa, China and India. This is a very welcome development and I will briefly describe some of these initiatives below. But I would like to start with Brazil where cooperative groups for childhood cancer started in the 1980s.
The Cooperative Groups Initiative in Brazil started in 1980, allowing exchange of expertise and proposals of better care. There are seven well-established cooperative groups with ongoing protocols including the participation in international studies. Among their earliest works which was published in 1991 was the randomised controlled study on Single‐dose versus fractionated‐dose dactinomycin in the treatment of wilms' tumor with no significant difference in overall or relapse‐free survival. Shortly afterwards, they published the Treatment results of three consecutive Brazilian cooperative childhood ALL protocols: GBTLI-80, GBTLI-82 and -85 and were able to examine the role and dose of cranial radiation as well as treatment intensification.
For further reading - Brazilian Society of Pediatric Oncology - SOBOPE: 30 years of history, a lot in the present, full of the future and Pediatric hematology oncology in Brazil
This project is implementing a SIOP PODC adapted treatment guideline for Wilms tumour in several centres in sub-Saharan Africa. This is done as a multi centre prospective clinical trial with uniform outcome evaluation. The project started in 2014. More than 300 patients have been included and treated. End of treatment survival without evidence of disease increased from 52% to 68%. Death during treatment decreased from 21% to 13% and abandonment of treatment from 23% to 13% - Improved outcome at end of treatment in the collaborative Wilms tumour Africa project
There are several other regional and national initiatives in pediatric oncology collaborative research in LMIC which have blossomed in recent years e.g. the Turkish Pediatric Oncology Group, The Pediatric Oncology East and Mediterranean (POEM) network and others. We look forward to seeing their work in the future. I would like to now focus on China and India, which together would constitute nearly a third of the childhood cancer burden. And so both of these countries have to strengthen their collaborative research so that they individually and the world collectively can aspire to reach the WHO Global Initiative for Childhood Cancer target of at least 60% survival by 2030.
For further reading - Treatment of childhood cancer in China: Current status and future direction
The earliest report of collaboration in the field of pediatric oncology in India was that between Cancer Institute, Chennai and the National Cancer Institute, USA in the early 1980s. Adopting a more intense protocol (MCP841) than that being used at the time, led to an improvement in the event free survival of acute lymphoblastic leukemia from 20% to 40%. This treatment strategy was then adopted by Tata Memorial Hospital, Mumbai in 1986 and All India Institute of Medical Sciences, New Delhi in 1992. With this common protocol, event free survival rates of 40-60% were achieved - Treatment of acute lymphoblastic leukaemia in countries with limited resources; lessons from use of a single protocol in India over a twenty year period.
The need to establish a national cooperative group in order to develop prospective multi-centre clinical trials in India became increasingly apparent. Such a strategy was critical to understand the biological differences in the disease, to assess responses to treatment and ultimately to improve childhood cancer survival in India. Active since 2015, the mission of InPOG is to improve the outcomes of children with cancer in India by collaborative research. At present here are 26 disease and discipline subcommittees with a portfolio of 31 studies.
The InPOG-HL-15-01 was amongst the first studies to start recruitment and standardised therapy of children with Hodgkin disease on an ABVD backbone – InPOG-HL-15-01 - Challenges and lessons learnt in setting up the first collaborative multicentre prospective clinical trial in childhood cancer in India. Initial results are expected to be published next year.
For further reading - Indian Pediatric Oncology Group (InPOG) - Collaborative research in India comes of age
The future looks very exciting. May this momentum gather an even greater speed!
September is Childhood Cancer Awareness Month and it is a good time to reflect on the progress we have made in curing childhood cancer and how we got here. An important part has been the ability of all stakeholders to get together and enroll children with cancer on to clinical trails, specially multicentre collaborative research. In this first part I look at some of the earliest works done in North America and Europe and highlight a few studies.
This all started in 1948 when Sidney Farber attempted to use a folate antagonist, Aminopterin to block the function of folic acid in patients with acute leukemia in hopes of achieving remission - Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. Of 16 children, 10 demonstrated clinical, hematological and pathological evidence of improvement for three months. At that time this observation was met with disbelief and also it was felt to be unethical to "experiment" with the life of a child with leukemia when cure was not possible.
Thankfully, he and others like him continued in their efforts. The relative rarity of the disease and the need for shared expertise in management led to the creation of the first pediatric oncology co-perative groups (Cancer and Leukemia Group B Cooperative Group as well as the Acute leukemia Chemotherapy Cooperative Study Group A) in the US in 1955 which were the forerunners of the now well established and respected Children's Oncology Group. For the last 65 years, COG in North America and SIOP in Europe have increased our knowledge and understanding of childhood cancers and conducted studies which have improved outcomes. Here are some of the earliest studies:
