[Challenges for clinical research on rare tumors in Europe]

Rare cancers are defined by an annual incidence below 6/100 000 new cases. According to this definition, 20% of malignancies in the European Union are rare cancers. These cancers are associated with considerable excess mortality, as they account for close to 30% of all cancer deaths within the E.U. This article reviews the specific management challenges pertaining to this group of neoplastic diseases, but also the research opportunities they represent for the entire field of oncology. The principal challenges are related to their low incidence: inaccurate diagnosis is frequent (up to 30% of cases), and initial management does always not follow clinical practice guidelines because of their limited diffusion in the medical community. These patients are also under-represented in clinical trials, because of the rarity of dedicated clinical trials in both the academic and industrial settings. The situation has evolved in recent years, however, because it is increasingly recognized that rare cancers offer major opportunities for clinical development. Indeed, the underlying molecular alterations are easier to identify than those responsible for frequent cancers. Other advances include the development of novel statistical methods, the unification of academic and industrial clinical research projects, the integration of patient advocacy groups in research programs, and importantly, paradigm shifts such as the development of tyrosine kinase inhibitors for GIST and other connective tissue tumors. With the increasing fragmentation of frequent tumors into subsets of rare tumors, as exemplified by lung cancer, many frequent tumors will need to be managed with approaches similar to those developed in recent years for rare cancers. In the age of routine molecular biology, the challenges of clinical research on rare tumors are thus becoming the challenges of all clinical research in oncology. This will required extensive multinational collaboration within the European Union and beyond.