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Trabectedin is used for the treatment of advanced soft tissue sarcomas (STSs). In this study, we evaluated if trabectedin could enhance the efficacy of irradiation (IR) by increasing the intrinsic cell radiosensitivity and modulating tumor micro-environment in fibrosarcoma (HS 93.T), leiomyosarcoma (HS5.T), liposarcoma (SW872), and rhabdomyosarcoma (RD) cell lines. A significant reduction in cell surviving fraction (SF) following trabectedin + IR compared to IR alone was observed in liposarcoma and leiomyosarcoma (enhancement ratio at 50%, ER50: 1.45 and 2.35, respectively), whereas an additive effect was shown in rhabdomyosarcoma and fibrosarcoma. Invasive cells' fraction significantly decreased following trabectedin ± IR compared to IR alone. Differences in cell cycle distribution were observed in leiomyosarcoma and rhabdomyosarcoma treated with trabectedin + IR. In all STS lines, trabectedin + IR resulted in a significantly higher number of γ-H2AX (histone H2AX) foci 30 min compared to the control, trabectedin, or IR alone. Expression of ATM, RAD50, Ang-2, VEGF, and PD-L1 was not significantly altered following trabectedin + IR. In conclusion, trabectedin radiosensitizes STS cells by affecting SF (particularly in leiomyosarcoma and liposarcoma), invasiveness, cell cycle distribution, and γ-H2AX foci formation. Conversely, no synergistic effect was observed on DNA damage repair, neoangiogenesis, and immune system.

Background and Objectives: Liposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma., Methods: We retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6-257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed., Results: The statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS)., Conclusion: Marginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objectives. The authors reported a retrospective study on myxoid liposarcomas (MLs), evaluating factors that may influence overall survival (OS), local recurrence-free survival (LRFS), metastasis-free survival (MFS), and analyzing the metastatic pattern. Methods. 148 MLs were analyzed. The sites of metastases were investigated. Results. Margins (p = 0.002), grading (p = 0,0479), and metastasis (p < 0,0001) were significant risk factors affecting overall survival (OS). Type of presentation (p = 0.0243), grading (p = 0,0055), margin (p = 0.0001), and local recurrence (0.0437) were risk factors on metastasis-free survival (MFS). Authors did not observe statistically significant risk factors for local recurrence-free survival (LRFS) and reported 55% extrapulmonary metastases and 45% pulmonary metastases. Conclusion. Margins, grading, presentation, local recurrence, and metastasis were prognostic factors. Extrapulmonary metastases were more frequent in myxoid liposarcoma. [ABSTRACT FROM AUTHOR]