Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.

The population-based incidence of sarcoma and its histological subtypes in Germany is unknown. Up-to-date information on a disease with an incidence comparable to other cancer entities is of high public health relevance. The aim of this study was to determine this incidence and to detect significant changes in incidence trends using data from German epidemiological cancer registries. Pooled data from the German Centre for Cancer Registry Data with a primary diagnosis occurring in 2013 were used. To date, this is the latest data on cancer incidence available for Germany. All German cancer registries with sufficient completeness were included (10 out of 11), covering a population of 70.0 million people, representing 87% of the German population. All malignant sarcomas according to the RARECARE Project and the WHO classification 2002 were considered for analysis and, above all, gastrointestinal stromal tumours (GIST) of uncertain behaviour. Sensitivity analysis was performed excluding certain histologies. The analysis included 3404 cases in men and 3442 cases in women diagnosed in 2013. The age adjusted sarcoma incidence (European standard) was 7.4 (men) and 6.6 (women) per 100,000 inhabitants. About 70% of sarcomas were soft tissue sarcomas, about 22% GIST, and about 9% bone sarcomas. The most common histological subtypes besides GIST were fibrosarcomas (14%) and liposarcomas (12%) in men and complex mixed and stromal neoplasms (22%), non-uterine leiomysarcomas (10%) and fibrosarcomas (9%) in women. Considering the trend for the years of diagnosis 2004 to 2013, there was a significant increase in incidence for GIST while the incidence of soft tissue sarcomas (only men) as well as of bone sarcoma stayed constant over time. As to soft tissue sarcoma in women, the incidence stayed constant up to the year 2009 and significantly decreased afterwards. This study is the first detailed analysis of a German-wide population-based sarcoma incidence showing results comparable to the incidence detected in the RARECARE Project.

Sarcomas are rare cancers with high heterogeneity in terms of type, location, and treatment. The health-related quality of life (HRQoL) of sarcoma patients has rarely been investigated and is the subject of this analysis. Adult sarcoma patients and survivors were assessed between September 2017 and February 2019 in 39 study centers in Germany using standardized, validated questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)). Associated factors were analyzed exploratively using multivariable linear regressions. Among 1113 patients, clinically important limitations and symptoms were most pronounced in emotional (63%, 95% CI 60–66%), physical (60%, 95% CI 57–62%), role functioning (51%, 95% CI 48–54%), and pain (56%, 95% CI 53–59%) and fatigue (51%, 95% CI 48–54%). HRQoL differed between tumor locations with lower extremities performing the worst and sarcoma types with bone sarcoma types being most affected. Additionally, female gender, higher age, lower socioeconomic status, recurrent disease, not being in retirement, comorbidities, and being in treatment were associated with lower HRQoL. Sarcoma patients are severely restricted in their HRQoL, especially in functioning scales. The heterogeneity of sarcomas with regard to type and location is reflected in HRQoL outcomes. During treatment and follow-up, close attention has to be paid to the reintegration of the patients into daily life as well as to their physical abilities and emotional distress.

Purpose: Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib. Patients and Methods: The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses. Results: During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15–0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31–0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib. Conclusions: Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.