Journalist(s):

Sophie Fessl

Introduction

SIOP is the multidisciplinary society devoted to paediatric and adolescent cancers. It was founded in Europe and now has branches worldwide. The society’s members include doctors, nurses, other healthcare professionals, scientists and researchers. SIOP’s mission is to improve the lives of children and adolescents with cancer through global collaboration, education, training, research and advocacy.

SIOP was established in 1969 at a time when paediatric oncology was pioneered in Europe and the US. The society’s aims have expanded to basic and clinical research and the inclusion of parents and the wider healthcare community, and to programmes for developing nations and societies.

The society has also established international consensus on treatment protocols, and advocated for training requirements for paediatric oncologists and standards for paediatric cancer units.

History of SIOP

In 1967, paediatricians, surgeons and pathologists with a shared interest in paediatric oncology met at Gustave Roussy cancer institute in Paris and formed Club d’Oncologie Pédiatrique. The club met again in 1968, and then again the next year in Madrid, where participants from several countries joined the meeting (6–8 November 1969) and decided to relaunch the club as Société Internationale d’Oncologie Pédiatrique, with a mission to advance the study and care of children with cancer. Odile Schweisguth, who in 1952 set up Europe’s first paediatric oncology unit, at Gustave Roussy, was SIOP’s first president.

In the 1970s and 1980s, SIOP had a dual role. It was a research group that conducted clinical studies, and also a professional society, as many of the growing number of members could not enter patients in SIOP studies. During the presidency of Patricia Morris Jones (1980–1981), one of the first child cancer specialists in the UK, a new constitution reflecting these roles was written.

In the 1980s, a scientific committee was created, and international consensus reached for some indications, such as on soft tissue sarcoma histopathology. Other committees were set up, such as for paediatric oncology training, and recommendations were made for organising paediatric cancer units.

In 1984, at a meeting in Barcelona, Jean Lemerle, who was the founding secretary of SIOP, promoted the challenges of paediatric oncology in the developing world, and a number of physicians from developing countries attended. Lemerle would go on to dedicate much of his time to child cancers in Francophone Africa, and in 2000 he set up Groupe Franco Africain d’Oncologie Pédiatrique (GFAOP), and after he died, an institute in Dakar, Senegal, was named in his honour.

SIOP also set up a committee in 1993, Paediatric Oncology in Developing Countries (PODC), with a key founding member being Hans-Peter Wagner. The PDOC working groups are now part of SIOP‘s Global Health Network.

In the 1990s, the society, formerly with a focus on Europe and North America, was transformed into a global association. In 1998, SIOPE was established as the European branch of SIOP (see below).

For administrative and financial reasons, a SIOP trial centre could not be established. From the 2000s onwards, and especially after the now repealed Clinical Trials Directive became law in the European Union, clinical trials had to be run by national or continental cooperative groups, which in Europe are represented in SIOPE.

In 2005, the importance of radiotherapy was recognised when a motion was carried at the annual meeting to set up the Paediatric Radiation Oncology Society (PROS), which was officially established the following year in Lyon.

Progress in research

SIOP was established after the modern era of leukaemia therapy started under the famous American paediatric pathologist, Sidney Farber, and in 1959, Odile Schweisguth, SIOP’s first president, spent time at Farber’s childhood cancer centre (see also here for an appreciation of Schweisguth and Farber as pioneers in the field). In the 1960s, combination therapies for leukaemia were being developed in the US.

In the 1970s and 1980s, SIOP provided a framework for clinical studies in Europe to gather the number of patients needed for randomised trials in rare diseases. The first such trial, the SIOP-1 nephroblastoma (Wilm’s tumour) study launched in 1971, and was the first international randomised trial in paediatric oncology in Europe.

In the US, the National Wilm’s Tumor Study (NWTS), funded by the National Cancer Institute, had already started in 1969. While the NWTS researchers in the US advocated primary surgery, the SIOP trial was inspired by a retrospective study from Sweden that indicated an impact of pre-operative radiotherapy on the survival of children with Wilm’s tumour. SIOP-1 was designed to compare pre-operative radiotherapy with primary surgery. Under the SIOP protocols, preoperative chemotherapy was given in both study arms. SIOP-1 showed that preoperative radiotherapy reduced intraoperative rupture, a finding confirmed by SIOP-2.

SIOP’s nephroblastoma studies sought to avoid radiotherapy as much as possible, so another SIOP study, SIOP-5, compared preoperative radiotherapy with preoperative chemotherapy. While decreasing the proportion of children requiring radiotherapy, researchers also aimed to decrease the dose of radiotherapy, establish histologic classification, precise staging and risk factor criteria, and reduce the dose of doxorubicin chemotherapy.

These studies were conducted in dialogue with the NWTS researchers in the US: for example, the protocol for children with pulmonary metastases avoided routine lung irradiation, which was adopted by the US study. That children in both arms of early trials received dactinomycin (AMD) and vincristine in combination was due to the US experience, and the second NWTS trial showed that survival was better when both agents were given in combination.

Close dialogue with the US was also a feature of the other early SIOP trials. For children with medulloblastoma (the most common brain tumour in children) a study in 1972 was modelled after the American trial underway at the time, but differed in the chemotherapy used. This was the first intercontinental research by SIOP. Results of the European and US studies were analysed together and separately, and indicated a beneficial effect of chemotherapy when added to radiotherapy.

The success of the Wilm’s tumour and medulloblastoma studies encouraged other cross-European trials under the patient recruitment framework. The International Childhood Liver Tumors Strategy Group (SIOPEL), initially named SIOP Epithelial Liver Tumour Study Group, was set up in 1987, and the first study, SIOPEL-1, ran from 1990 to 1994.

Again the approach diverged from primary surgery advocated in the US, with preoperative chemotherapy. SIOPEL-1 was also the first study to use the PRETEXT system for staging and risk stratification, which is used to describe tumour extent before therapy, and allows for more effective comparison among studies.

SIOP has also been instrumental in advances in soft-tissue sarcoma, a heterogenous disease in which national studies could not have addressed essential questions. The SIOP malignant mesenchymal tumours group, formed in 1975, initially involved France, Belgium and the Netherlands. The group’s objective was to reduce the risk of late functional or cosmetic sequelae of treatment, while maintaining survival.

The first trial was performed from 1975 to 1984 and tested a VAC regime (vincristine, dactinomycin and cyclophosphamide) before and after local therapy. Patients who received chemotherapy first had similar survival but less aggressive local treatment.

Later trials, which other countries including Argentina, Spain, Switzerland and the UK joined, tried to further reduce or avoid intensive local therapy.

See also: Fifty years of clinical and research studies for childhood renal tumours within the International Society of Paediatric Oncology (SIOP).**

Europe’s organisation - SIOPE

Since SIOP Europe (SIOPE) became an independent organisation with a secretariat in Brussels it has played a leading role in pan-European paediatric projects.

In 2009, it published European standards of care for children with cancer, which is now available in 22 languages.

SIOPE was awarded an EU grant for helping to establishing the European Network for Cancer research in Children and Adolescents (ENCCA), a 5 year ‘virtual institute’ that was coordinated by Ruth Ladenstein, a past SIOPE president and a paediatric oncologist in Vienna, Austria. There then followed a 3 year network pilot that paved the way for a European reference network (ERN) for paediatric oncology, named PaedCan, for which SIOPE has management responsibilities.

Other European projects include PanCareFollowUp and PanCareSurPass, for survivorship care. See this list of past and current projects.

According to SIOPE’s latest strategic plan, oncopolicy for children has been successfully embedded in Europe’s Beating Cancer Plan, the Cancer Mission, and the Pharmaceutical Strategy for Europe, which opens the potential for legislative change within the paediatric and orphan regulations to address the failure to deliver new therapies for children with cancer.

See links to European clinical trial groups that are members of SIOPE’s clinical research council.

Among them is the International BFM (I-BFM) study group, which is for children and adolescents diagnosed with leukaemia and lymphoma. BFM stands for Berlin, Frankfurt, Münster, after clinicians in these cities started a first multicentre trial in 1975 on acute lymphoblastic leukaemia (ALL). The international designation was added in 1987 as it expanded to other countries. See brief history here.

See also a brief history of the SIOPE brain tumour group and how the SIOPEN neuroblastoma group was formed.

Further reading

The SIOP story: an informal history of the International Society of Paediatric Oncology (this is a 42 page document with a multiplicity of initiatives, reflections and personnel).