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Leiomyosarcoma PowerPoint Presentation

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Slide 1 - Leiomyosarcoma – Undifferentited Pleomorphic Sarcoma. Dr Philippe CASSIER, MD Centre Léon Bérard Lyon, France
Slide 2 - Outline Local therapy Prognosis Molecular markers Therapeutic intervension
Slide 3 - Local therapy - Surgery ID 1403273, The effect of the setting of a positive margin on local recurrence for extremity soft tissue sarcoma. Dr O’Donnel how good a margin do we need? how can we further improve local control
Slide 4 - LRFS
Slide 5 - Negative Critical Structure Margin 72.7% (p = 0.005) Positive Critical Structure Margin 52.2% Metastasis-Free Survival, Negative vs. Positive Critical Structure Margin Depth, p=0.594 Grade, p=0.61 Size, p=0.89 Chi-square/ Fisher’s Exact for depth/grade t-test for size as it is continuous
Slide 6 - Prognosis ID 1437122 Long-term outcomes of patients with leiomyosarcoma of uterine versus extra-uterine origin. S.N. Divi et al. ID 1414211 Uterine leiomyosarcoma management, outcome and associated molecular biomarkers. K. Lusby et al ID1436107 The outcome of patients with leiomyosarcoma: a retrospective single center analysis. H. Kosela et al
Slide 7 - Prognosis uLMS vs eLMS: not really different, and overall poor= less than half of patients survive 5 years… uLMS have poor prognosis when M+ and overall, express markers similar to other LMS, molecular features of agressive disease confer poor prognosis… uLMS > eLMS > RP-LMS; large, high grade tumors fare worse….
Slide 8 - Survival of LMS patients Kosela et al. N=162 yrs 1998-2010 Lusby et al. N=349 yrs 1989-2011 Divi et al. N=640 yrs 1982-present
Slide 9 - Prognosis uLMS vs eLMS: not really different, and overall poor = less than half of patients survive 5 years… uLMS have poor prognosis when M+ and overall. Express markers similar to other LMS, molecular features of agressive disease confer poor prognosis… uLMS > eLMS > RP-LMS Large, high grade tumors fare worse….
Slide 10 - Molecular markers ID 1423580 Gene expression signature from tumor initiating population predicts clinical outcome in undifferentiated pleomorphic sarcoma. I. Han et al. ID1424007 Gene expression identifies heterogeneity of metastatic behavior among high-grade pleomorphic soft tissue sarcomas. K.M. Skubitz et al ID 1433743 Identification of a novel, recurrent MBTD1-CXorf67 fusion in low grade endometrial stromal sarcoma. B.M. Dewaele et al
Slide 11 - Gene expression signatures Nielsen TO et al. Lancet 2002 Hierarchical clustering identifies differents subtypes Great! So what?
Slide 12 - Tumor initiating cells in STS Wu et al. Cancer Res 2007 15 samples of UPS Separate TIC Gene profilling Apply to 114 STS samples Prognosis/metastasis-free survival
Slide 13 - Gene expression signatures CINSARC – Chibon et al. Nat Med 2010 PrMet – Skubitz et al Cancer 2012 Skubitz et al. CTOS
Slide 14 - t(X;17) MBTD1-CXorf67 in ESS
Slide 15 - Therapeutic intervension 1436034 Targeting hormone receptors in uterine leiomyosarcoma (U-LMS): phase II clinical study of Letrozole in women with advanced U-LMS expressing estrogen and/or progesterone receptors. S. George et al ID1417328 Systematic chemotherapy for inoperable, locally advanced, recurrent or metastatic uterine leiomyosarcoma: a systematic review. A. Gupta et al ID 1437166 Small molecule inhibitors for Polo-Like Kinase-1 (Plk-1) sensitize uterine leiomyosarcoma to Rapamycin. W. Shan et al
Slide 16 - Endocrine therapy for uLMS Median PFS = 9.1 weeks (90% CI, 6.1-12.4) George et al. CTOS 2012 N=26
Slide 17 - Endocrine therapy for uLMS N=34 Median 2.9 months O’Cearbhaill et al. Gynecol Oncol 2010
Slide 18 - Chemotherapy for uLMS Systemic chemotherapy for inoperable, locally advanced, recurrent or metastatic uterine leiomyosarcoma: a systematic review. A. Gupta et al
Slide 19 - Chemotherapy for uLMS Overall response-rate
Slide 20 - Targeted therapy for uLMS Plk1 inhibitors and rapamycin
Slide 21 - UPS and LMS: Conclusions Local therapy: not all positive margins are the same….but relapse is in most cases systemic. Overall prognosis remains poor Molecular studies should aim at identifying predictive rather than prognostic markers. Obviously we need more effective systemic therapies
 

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