Cases included in this study were children and adults with sarcoma diagnosed between January 1, 2000 and December 31, 2013, and living in one of the administrative areas covered by a population-based cancer registry of the French Network (details in online supplementary material). The French sarcoma pathological reference network (RRePS) and the French reference Network for bone sarcoma and rare bone tumors (RESOS) propose a systematic second histologic review and confirmation for all diagnoses of sarcomas across France .
Data collection and classification
The following data were collected for each case: general demographic characteristics of the patients (age, sex, and residence area), the date of diagnosis, the anatomical site, and the histology of the tumor according to the International Classification of Diseases for Oncology, third edition (ICD-O-3) (12).
This study included intermediate (only with a “/3” behavior) and malignant sarcomas presenting morphologic criteria described in the 2013 WHO Classification of Tumors of Soft Tissue and Bone (fourth edition), regardless of the anatomic site . This recent classification includes histologic updates not defined in ICD-O-3 and new terms, synonyms, morphology and behavior codes. For this reason, and whenever possible, cases were reclassified according to the updated version. The alignments from ICD-O-3 to the 2013 WHO standard classification of tumors have been validated by a panel of sarcoma specialists (clinical and pathological experts) from sarcoma Networks (NP, JMC and IRC).
Certain alignments could not be performed: ten morphological terms not described in this updated classification (e.g. sarcoma NOS, periosteal fibrosarcoma, fascial fibrosarcoma…) have been maintained for analyses. Conversely, well differentiated liposarcoma and chondroblastoma have been changed from malignant to borderline diseases. In the same way, behaviors for dermatofibrosarcoma protuberans and pigmented dermatofibrosarcoma protuberans have been also changed from malignant to borderline with henceforth, only fibrosarcomatous dermatofibrosarcoma protuberans which is coded as malignant behavior. In our analyses, we have made the choice to keep all dermatofibrosarcomas. Indeed, we do not have the possibility to differentiate if this is a dermatofibrosarcoma borderline or malignant. Besides, endometrial stromal sarcoma NOS (89303), low grade endometrial stromal sarcoma (89313) and stromal sarcoma (89353) not described in the WHO 2013 have been also included. Additional details on the list and choice of classification systems are provided in the online supporting material (see Additional File 1).
This classification also provides new genetic and molecular data for each histologic entity allowing a better characterization of sarcomas. The same group of experts were consulted with the aim of proposing the optimal classification system for sarcomas based on the genetic profile. Two main distinct genetic groups were defined: (i) sarcomas defined with simple genetics based on recurrent translocations (e.g. Ewing sarcoma, myxoïd liposarcoma), activating or inactivating mutations (e.g epithelioid sarcoma, gastrointestinal stromal tumor), MDM2 amplification (e.g. dedifferentiated liposarcoma, low-grade central osteosarcoma); and (ii) sarcomas with complex genomic profiles (e.g. angiosarcoma, leiomyosarcoma). Another group was defined for miscellaneous and undefined alterations. The list of histology codes according to their genetic groups is presented in the supplementary material.
This study is based on data from cancer registries gathered in the French network of cancer registries and a representative of each registry was involved in the study and approved the use of its data All French registries received an authorization to collect patient data from the data protection authority (Commission Nationale de l’Informatique et des Libertés). Ethics approval and consent to participate were not required for this study which is an observational research without direct contact with patient.
Two datasets were used: i) the first one was used to estimate the incidence of patients diagnosed during the 2010-13 period and that included data from 19 registries; and ii) the second one was used to examine trends in the incidence from 2000 to 2013 in only 11 registries for which data were available over the entire studied period. Incidence rates were presented per 100 000 person-years.
The incidence of sarcomas was described according to 1) the anatomic group (i.e. soft-tissue, bone, gastro-intestinal, skin, female genital organs, other viscera and other sites), and to 2) histologic and 3) genetic groups based on guidelines developed by sarcoma specialists (see Additional File 1).
Age-standardized incidence rates (ASR) were estimated using direct standardization and were calculated using the population data for each age group and year supplied by the National Institute of Statistics and Economic Studies (www.insee.fr) and the European (ASR-E), Segi World (ASR-W), and the US (ASR-US) standard populations. The analyses presented here describe the overall ASR and the ASR by sex. Age-specific incidence rates are provided by age groups (0-14; 15-24; 25-39; 40-64; 65-74 and 75 and more) and by sex and presented in figures.
Time trends were calculated using Joinpoint Trend Analysis Software setting a maximum of a single Joinpoint (details in online supplementary material). The annual percent change (APC) with the 95% confidence interval (CI) was estimated according to topographic and histologic groups.