Validation of a novel risk score to predict early and late recurrence in solitary fibrous tumour.

BACKGROUND: Current risk models in solitary fibrous tumour (SFT) were developed using cohorts with short follow-up and cannot reliably identify low-risk patients. We recently developed a novel risk model (G-score) to account for both early and late recurrences. Here, we aimed to validate the G-score in a large international cohort with long-term follow-up. METHODS: Data were collected from nine sarcoma referral centres worldwide. Recurrence-free interval (RFi) was the primary endpoint. RESULTS: The cohort comprised 318 patients with localised extrameningeal SFTs. Disease recurrence occurred in 96 patients (33%). The estimated 5-year RFi rate was 72%, and the 10-year RFi rate was 52%. G-score precisely predicted recurrence risk with estimated 10-year RFi rate of 84% in low risk, 54% in intermediate risk and 36% in high risk (p < 0.001; C-index 0.691). The mDemicco (p < 0.001; C-index 0.749) and SalasOS (p < 0.001; C-index 0.674) models also predicted RFi but identified low-risk patients less accurate with 10-year RFi rates of 72% and 70%, respectively. CONCLUSIONS: G-score is a highly significant predictor of early and late recurrence in SFT and is superior to other models to predict patients at low risk of relapse. A less intensive follow-up schedule could be considered for patients at low recurrence risk according to G-score.

Retrospective Analysis of the Clinical Presentation, Treatment and Outcome of Angiosarcoma in a Sarcoma Referral Center.

INTRODUCTION: Angiosarcoma (AS) is a rare subtype of soft tissue sarcoma. We performed a retrospective analysis of patient characteristics, treatments and prognostic factors in patients treated in a single sarcoma center. METHODS: We reviewed records of patients treated between 1987 and 2018, categorized in 7 different subtypes according to tissue of origin and underlying risk factors. The Kaplan-Meier method was used to estimate overall survival (OS); the Cox proportional hazards model was used to study prognostic variables. RESULTS: Among 134 patients, 30% had radiation-induced, 31% primary soft tissue, 24% cutaneous, 5% breast, 4% bone, 2% lymphedema-associated and 4% unknown primary AS. Key patient/disease characteristics varied between subgroups. The median OS was 22.0 months for the entire cohort, with 28.9% with a 5-year survival. Metastasis at diagnosis was seen in 23% of patients; 38% developed metachronous metastasis. Sixty-six (49%) patients received systemic therapy; common first-line treatments were doxorubicin (48%) and paclitaxel (39%), without a significant difference in OS between agents. Younger age, breast/radiation-induced AS, primary surgery and palliative chemotherapy were associated with better OS. Synchronous metastasis, soft tissue/unknown primary location correlated with poor survival. CONCLUSION: AS is a very heterogeneous sarcoma subtype, with substantial variability in clinical presentation and survival among patient subsets. Prognosis is poor, and there is no difference in outcome comparing the 2 most frequently used chemotherapy agents in the first line, paclitaxel and doxorubicin.

Management of Synovial Sarcoma in a Tertiary Referral Center: A Retrospective Analysis of 134 Patients.

BACKGROUND: Synovial sarcomas (SS) are malignant mesenchymal neoplasms that account for about 10% of all sarcomas. Complete surgical excision is the mainstay of primary treatment for localized disease, but SS have a high tendency for local relapse and metastases. Metastatic disease is commonly treated with systemic chemotherapy. METHODS: We designed a retrospective analysis to describe the clinical presentation, course of treatment, outcome, and prognosis of patients with SS. Univariate and multivariate analyses were performed for potential prognostic factors. RESULTS: We identified 134 patients treated between 1987 and 2018, with a cutoff date of December 2018. Demographics, disease characteristics, treatment, and survival rates were collected and analyzed. The median overall survival (mOS) from the date of diagnosis was 96.7 months. The median progression-free survival was 6.37 months. Disease-free survival was 26 months. Age over 65 years was found to be a prognostic factor with statistically significant value in the univariate analysis regarding mOS (p = 0.015) and mOS after local relapse (p = 0.0228). CONCLUSIONS: Even though our study is limited by the retrospective nature of the analysis, it adds an important amount of clinical data regarding the treatment and outcome of SS.

Establishment of an Academic Tissue Microarray Platform as a Tool for Soft Tissue Sarcoma Research.

Soft tissue sarcoma (STS) is a heterogeneous family of rare mesenchymal tumors, characterized by histopathological and molecular diversity. Tissue microarray (TMA) is a tool that allows performing research in orphan diseases in a more efficient and cost-effective way. TMAs are paraffin blocks consisting of multiple small representative tissue cores from biological samples, for example, from multiple donors, diverse sites of disease, or multiple different diseases. In 2015, we began constructing TMAs using archival tumor material from STS patients. Specimens were well annotated in terms of histopathological diagnosis, treatment, and clinical follow-up of the tissue donors. Each TMA block contains duplicate or triplicate 1.0-1.5 mm tissue cores from representative tumor areas selected by sarcoma pathologists. The construction of TMAs was performed with TMA Grand Master (3DHistech). So far, we have established disease-specific TMAs from 7 STS subtypes: gastrointestinal stromal tumor (72 cases included in the array), alveolar soft part sarcoma (n = 12 + 47), clear cell sarcoma (n = 22 + 32), leiomyosarcoma (n = 55), liposarcoma (n = 42), inflammatory myofibroblastic tumor (n = 12 + 21), and alveolar rhabdomyosarcoma (n = 24). We also constructed a multisarcoma TMA covering a representative number of important histopathological subtypes on arrays for screening purposes, namely, angiosarcoma, dedifferentiated liposarcoma, pleomorphic liposarcoma, and myxoid liposarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, myxofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma, with 7-11 individual cases per subtype. We are currently expanding the list of TMAs with additional sarcoma entities, considering the heterogeneity of this family of tumors. Our extensive STS TMA platform is suitable for rapid and cost-effective morphological, immunohistochemical, and molecular characterization of the tumor as well as for the identification of potential novel diagnostic markers and drug targets. It is readily available for collaborative projects with research partners.

Characterization of the adipokinetic hormone receptor of the anautogenous flesh fly, Sarcophaga crassipalpis.

Adipokinetic hormone (AKH) is an insect neuropeptide mainly involved in fat body energy mobilization. In flies (Phormia regina, Sarcophaga crassipalpis), bugs (Pyrrhocoris apterus) and cockroaches (Periplaneta americana) AKH was also demonstrated to be involved in the regulation of digestion. This makes AKH an important peptide for anautogenous female flies that need to feed on a supplementary protein meal to initiate vitellogenesis, the large scale synthesis of yolk proteins and their uptake by the developing oocytes. Flesh fly AKH, originally identified as Phormia terraenovae hypertrehalosemic hormone (PhoteHrTH), functions through activation of the AKH receptor (AKHR). This is a G protein-coupled receptor that is the orthologue of the human gonadotropin-releasing hormone receptor. Pharmacological characterization indicated that the receptor can be activated by two related dipteran AKH ligands with an EC50 value in the low nanomolar range, whereas micromolar concentrations of the Tribolium castaneum AKH were needed. Consistent with the energy mobilizing function of AKH, the receptor transcript levels were most abundant in the fat body tissue. Nonetheless, Sarcophaga crassipalpis AKHR transcript levels were also high in the brain, the foregut and the hindgut. Interestingly, the receptor transcript numbers were reduced in almost all measured tissues after protein feeding. These changes may enforce the use of ingested energy carrying molecules prior to stored energy mobilization.