35 Years of Research in Soft Tissue Sarcoma


   Ewa Koscielniak & Thomas Klingebiel

The CWS group was launched in 1981 under the umbrella of the German Society of Paediatric Oncology GPO (later called Society of Paediatric Oncology and Haematology GPOH). It was the third soft tissue sarcoma group in Europe, after SIOP which started the first trial in 1975 followed by the Italian Cooperative Group ICG RMS-79. Jörn Treuner was the first designated Chair of the study and retained this function until his retirement in 2005. Subsequently Ewa Koscielniak and Thomas Klingebiel, who had been involved with the CWS study since 1984, have taken over the leadership. figure1From the very beginning the leaders of the European groups, Jörn Treuner, Francoise Flamant, Modesto Carli and Michael Stevens started a very close cooperation and a continuous exchange of information, which led to the realization of the first common projects and trials. Since 1991 Austria, Switzerland, Sweden, and Poland have joined the CWS group and, most recently, Finland in 2015. The national chairs Ruth Ladenstein, Felix Niggli, Ildiko Marky, Gustaf Ljungman and Bernarda Kazanowska have contributed to the smooth functioning of the CWS Group, as a result of their enthusiasm and continuous commitment. The first pan-European trial on metastatic rhabdomyosarcoma was initiated by CWS, MMT and ICG in 1989 (MMT-89 and -91) (Figure 1) and provided important new insights into the therapy of patients with metastatic RMS (in a paper published by Modesto Carli). The six drugs therapy CEVAIE became a standard induction treatment for metastatic tumours in Europe. The next important joint initiative was the first Pan-European randomized trial examining the role of chemotherapy intensification (6 drugs CEVAIA vs. 4 drugs VAIA vs. 3 drugs IVA) for prognosis of children with localized high-risk rhabdomyosarcoma. It was a great success for all three European groups and their leaders, since this large international project was realized prior to the EU directive facilitating the conducting of international trials. Many other important successes have been achieved, for example the consensus on standards for staging, definitions of primary sites, risk groups and trial end points, which facilitate the comparisons of study results and make international cooperation successful. figure-2The high degree of personal commitment, enthusiasm and friendship of the group leaders Jörn Treuner, Francoise Flamant, Modesto Carli, Michel Stevens and Ildiko Marky was a very important factor in the close cooperation within Europe. They laid the foundations for the sustained international cooperation in the field of soft tissue sarcoma, which was not limited to Europe but extended over the Atlantic to the Intergroup Rhabdomyosarcoma Study, with its former leader Harold Mauerer. Two big international conferences were organized in Stuttgart: the Soft Tissue Sarcoma in Children and Adolescents in 1997 (Figure 2) and the SMS Sarcoma Meeting in 2005, where the whole “sarcoma community” from both sites of the Atlantic met. There was an active exchange of information and discussion which resulted in future therapeutic plans being made. This network of “old connections,” new contacts and friends subsequently contributed to the common struggle to improve the cure rate for childhood sarcoma. The dream was to merge the efforts and create one strong STS group in Europe. We met in Padua in 2001 (Figures 3 and 4) and the European Paediatric Soft Tissue Sarcoma Group was officially created on the 22nd June 2001 in Chiesa delle Zitelle, according to the files of Gianni Bisogno. A common protocol for localized RMS was agreed upon. The circumstances were however not very supportive for the “new born child”. In 2001, the Directive 2001/20/EC of the European Parliament and of the Council was approved at the EU level. It brought a big change in conducting clinical trials in Europe, and was not implemented in all countries in the same way. Therefore, the CWS group decided to retain its structure but develop further protocols based on the common agreements, continuing to cooperate with the EpSSG. The EpSSG was re-born in 2005 by the International Society of Paediatric Oncology – Malignant Mesenchymal Tumour Committee (SIOP-MMT) and the Italian Paediatric Oncology Association (Associazione Italiana Ematologia Oncologia Paediatrica, AIEOP) – Soft Tissue Sarcoma Committee figure3Since 1981 the CWS group has steadily evolved. It is now a consortium conducting a registry for all patients under 21 years-old with soft tissue sarcoma in the participating countries, phase II-III trials, tumour banking and participates in many translational and late effects projects. It acts as a consultation centre for more than 125 centres in 7 countries, promoting the adherence to therapy standards. The CWS team together with our reference radiologist, surgeons and radiation oncologists handles more than 300 requests per year. More than 200 publications in peer review journals have been published based on the results of the CWS studies.figure4 All this would not have been possible without the financial support of our sponsors: the Bundesministerium für Bildung und Forschung (CWS-81 and CWS-86), Deutsche Krebshilfe (CWS-91, -96 and 2002P) and finally the Deutsche Kinderkrebstiftung which has supported the CWS since 2009. These are the “big supporters”, but without the continuous financial support of the Parent Initiative Stuttgart (Förderkreis Krebskranke Kinder e.V. Stuttgart) which has helped the CWS group to “survive” in the times “between funding periods”, the group probably would not be celebrating this anniversary. We will celebrate our 35th anniversary in Stuttgart on December 16th 2016, with many sarcoma experts from Europe and the USA, and we sincerely hope that the new generation of enthusiastic sarcoma researchers will continue the work which began 35 years ago.