New therapeutic advances of bone sarcomas

Introduction

Sarcomas are a group of heterogeneous mesenchymal malignancies, with over 155 histological subtypes in the most recent WHO classification, not taking into account molecular classification which includes genomic rearrangements (translocations, mutations, amplification, tumor suppressor gene loss, etc.) [ ]. Sarcomas are rare diseases with an overall incidence of 9/100 000/year in adults [ ], representing 2% of all human cancers in adults, but over 10% in children. The recently reported nationwide series of sarcomas and connective tissue tumors reported by the Netsarc network enables to identify groups of sarcomas with an incidence >1/10e5/year, from 1/10e5/year to 1/10e6 per year, those with an incidence from 1/10e6/year and 1/10e7/year, and ultrarare sarcomas with an incidence <1/10e7 per year [ ].

Bone sarcomas are rarer than soft tissue and visceral sarcomas, gathering 10%–15% of all sarcomas and tumors of intermediate malignancy [ ], with over 30 different subtypes, for a global incidence close to 12/10e6 per year [ ]. The incidence of individual bone sarcoma subtypes (e.g., osteosarcomas, Ewing's sarcoma, chondrosarcomas, undifferentiated sarcomas, etc.) is consistently <10e5/year.

Bone sarcomas are a highly fragmented group of diseases. As for other sarcomas, molecular classification guides nosological classification leading to specific treatment strategies (Ewing's sarcoma, vs. other small round cell tumors, vs. small cell osteosarcomas, etc.), as well as specific medical treatment selection for a growing number of sarcoma subtypes [ ]. Characterization of genetic alterations has been proven effective to refine nosological classification but less frequently than for soft-tissue and visceral sarcomas resulted in a guidance medical treatment. Targeted therapies used for bone sarcomas are not directed against mutated activated oncogenes, as now frequently observed in soft-tissue and visceral sarcomas [ , ], but more often against general processes such as angiogenesis, or osteoclast activation as observed in giant cell–rich tumors of the bones [ ].

Nevertheless, important progresses were made in the past year for the development of targeted treatments in sarcomas, and refinement in the application of classical cytotoxic treatments was also demonstrated. In this chapter, we describe the novel results achieved with medical treatments reported in the recent years which impact on the management of bone sarcomas.

Management in reference centers

Guidelines consistently recommend that sarcomas should be managed in reference centers [ ]. Several national series have now established that the compliance to clinical practice guidelines, the relapse-free survival, and survival of patients with sarcomas, including bone sarcomas, is superior in patients whose management was handled by an expert multidisciplinary board [ , ], and having surgery in reference centers [ ]. The magnitude of superiority for overall survival (OS) observed for patients managed in reference centers is superior to that of any medical treatment. Figure 52.1 shows the progression-free survival (PFS) and OS of the subgroup of patients with bone sarcomas managed or not in reference centers.