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:
Childhood Solid Tumours
Published in 1968, maintenance dactinomycin following surgery was found to be superior (continued remission rate of 86%) compared to when no maintenance was given (continued remission rate of 48%) - Single versus multiple dose dactinomycin therapy of Wilms's tumor. A controlled co-operative study conducted by the Children's Cancer Study Group A (formerly Acute Leukemia Co-operative Chemotherapy Group A)
Colleagues in Europe investigated the role of radiotherapy and actinomycin d (dactinomycin) in Wilms tumour - Preoperative versus postoperative radiotherapy, single versus multiple courses of actinomycin d, in the treatment of Wilms' tumor. Preliminary results of a controlled clinical trial conducted by the international society of paediatric oncology (S.I.O.P.). This was the first SIOP study and also the first international randomized trial in Europe. Pre-op radiotherapy reduced the tumour rupture rate at surgery. Also there was no added benefit of post-op radiotherapy after receiving pre-op radiotherapy.
Childhood CNS Tumours
Tait et al from SIOP examined adjuvant vincristine and CCNU in medulloblastoma - Adjuvant chemotherapy for medulloblastoma: The first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I). Their results were that although there was no overall statistical difference between the two arms of the trial, a benefit for chemotherapy was seen in a number of sub-groups; partial or sub-total surgery, brainstem involvement , and stage T3 and T4 disease.