bims-myxlip Biomed News
on Myxoid liposarcoma
Issue of 2022‒10‒30
three papers selected by
Laura Mannarino
Humanitas Research

  1. Oncology. 2022 Oct 25.
      INTRODUCTION: Soft tissue sarcomas (STS) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available after the conventional first line regimen. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS. This led to a FDA approval in 2015, but real-world evidence are still required, complementary to the pivotal phase II and III trials.METHODS: One hundred twenty-six patients with STS, treated by trabectedin between 2002 and 2019 were analysed in this retrospective study, in two French centers. The effects of trabectedin on survival, response, and toxicity, were described. All patients were tested for toxicities, and efficacy was assessed in patients exposed to at least 2 cycles of trabectedin.
    RESULTS: Three median cycles were administered per patient (1-79). Among the 113 patients analysed for efficacy, the median progression free survival was 3.0 months [CI95%: 2.3 - 4.8], with an overall survival of 12.3 months [CI95%: 10.2 - 16.9]. The rate of disease control was 46% at the end of treatment. Myxoid liposarcoma (n = 11) was the histology subtype that benefited most from this chemotherapy with median progression free survival and overall survival of 13.3 months [CI95%: 2.3 - 18.7] and 27.8 months [CI95%: 3.2 - 64.7], respectively. Adverse events were manageable.
    DISCUSSION AND CONCLUSION: Efficacy of trabectedin is confirmed in terms of clinical benefit and low toxicity, especially for myxoid liposarcoma. Combinatory regimen are under clinical trials to optimize the place of this chemotherapy.
  2. Subcell Biochem. 2022 ;100 115-141
      The accurate repair of genomic damage mediated by ionizing radiation (IR), chemo- or radiomimetic drugs, or other exogenous agents, is necessary for maintenance of genome integrity, preservation of cellular viability and prevention of oncogenic transformation. Eukaryotes have conserved mechanisms designed to perceive and repair the damaged DNA quite efficiently. Among the different types of DNA damage, double strand breaks (DSB) are the most detrimental. The cellular DNA DSB response is a hierarchical signaling network that integrates damage sensing and repair with chromatin structural changes that involve a range of pre-existing and induced covalent modifications. Recent studies have revealed that pre-existing histone modifications are important contributors within this signaling/repair network. This chapter discusses the role of a critical histone acetyl transferase (HAT) known as MOF (males absent on the first) and the histone deacetylases (HDACs) Sirtuins on histone H4K16 acetylation (H4K16ac) and DNA damage repair. We also discuss the role of this important histone modification in light of metabolic rewiring and its role in regulating human pathophysiologic states.
    Keywords:  Chromatin; DNA damage response; Histone H4K16ac; MOF
  3. Oncology. 2022 Oct 21.
      INTRODUCTION: Soft tissue sarcomas (STS) are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic Liposarcoma (LPS) patients, who have failed first line chemotherapy and has been approved for the use in patients with LPS in the United States and Europe due to its efficacy in this histological subtype in a phase III trial. We have evaluated efficacy and tolerability of eribulin in LPS and Leiomyosarcoma (LMS) patients in the routine clinical setting at our department.METHODS: In this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in advanced LPS and LMS patients at the Division of Oncology, Medical University of Vienna.
    RESULTS: A total of 32 adult patients treated with eribulin were identified and included in this analysis. Overall response rate (ORR) was 9.4% for all patients, with one patient with LPS and two patients with leiomyosarcoma (LMS) showing a partial response (PR). Disease control rate (PR plus stable disease -SD) for all patients was 50% (LPS: 47.1%; LMS 53.3%). No statistically significant difference in median progression free survival (PFS) and overall survival (OS) was detected between patients with LPS and LMS (p=0.807 and p=0.519), respectively. Patients with LMS (n=2) had received fewer previous therapy lines than patients with LPS (n=14) (≤ previous treatment lines, p < 0.001). Toxicity was generally manageable, and grade 3+4 events were rare.
    CONCLUSION: The activity and tolerability of eribulin in LPS as well in LMS patients in the routine clinical setting is comparable to outcomes reported in published phase III trials.