6.O.02 PEDIATRIC SOFT TISSUE SARCOMA (STS) AS A MODEL FOR RARE TUMORS: HOW TO INTEGRATE CLINICAL RESEARCH INTO CLINICAL PRACTICE.

Abstract

While STS as a group represent a significant portion of all solid tumors in childhood, individual histologic entities are rare due to their extreme heterogeneity. This represents the principal obstacle to clinical trials. A compromise between clinical vs. statistical precision has been necessary in the majority of clinical trials on STS resulting in contradictory conclusions. Clinical trials have to reduce uncertainty but trials, which overlook clinical heterogeneity can even contribute to it. An example is many clinical trials, which have been carried out in the recent decades to answer the question of the role of adjuvant chemotherapy in “Non-RMS-STS”. Majority of these trials have overlooked clinically relevant subgroups. The result is that we still do not have certainty whether and which adjuvant chemotherapy is beneficial.

In addition, most clinical trials of treatments for STS rely on the endpoints of survival or event-free survival, so results have taken years to accrue and even longer to report. However, in STS with well defined genetic abnormalities and strong preclinical rationale for activity of a molecular targeted therapy the demonstration of clinical activity in only a few cases might be sufficient. In dermatofibrosarcoma protuberans, a very rare entity, the demonstration of clinical activity of the molecular targeted therapy was very convincing and led to approval of the drug, although the number of cases was very low.

International collaboration is necessary to obtain a sufficient number of patients but participation of many different centers with different expertise for a given rare tumor may compromise the quality of patient’s care. It is also difficult for many pediatric departments to open and maintain large numbers of trials with low accrual rates.

In conclusion, new methods for clinical research in the field of STS especially surrogate outcome variables and novel technique for early assessment of response are urgently needed.