Histotype or molecular driven treatment of sarcomas?

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1 Histotype or molecular driven treatment of sarcomas? Prof.ssa Maria A Pantaleo Dipartimento Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna GistStudyGroup Sarcomastudygroup Bologna

2 Classification of Sarcoma soft-tissue sarcomas bone sarcomas WHO 2013 Classification

3 Classification of Soft tissue Sarcoma The soft-tissue sarcomas are a group of rare but anatomically and histologically diverse neoplasms with diverse outcome and treatment Approximatevely 50 recognized histologic subtypes of soft-tissue sarcomas

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5 Treatment of Soft tissue Sarcoma 2000 All sarcomas Doxorubicin Ifosfamide DTIC 2010 GIST: Imatinib, sunitinib, regorafenib LPS: Dox + Ifo, Trabectedin LMS: Dox + DTC, Trabectedin, Gem, Gem/T All but LPS: VEGFR TKI Angiosarcoma: Dox + Ifo, Gem/T, Paclitaxel DFSP: imatinib PVNS: imatinib Desmoid tumors: imatinib, sorafenib PECOMAs: m TOR inhibitors AlveolarSoft Sarcoma: sunitinib Myofibroblastic Inflammatory Sarcoma: crizotinib Histotype or Molecular driven treatment?

6 Histotype or Molecular driven treatment? Histotype driven treatment Molecular driven treatment CHEMOTHERAPY Doxorubicin Ifosfamide Dacarbazin Gemcitabin Taxotere Trabectedin Eribulin Aldoxorubicin TARGET THERAPY Pazopanib Imatinib Sunitinib Regorafenib mtor inhibitors Crizotinib BOTH indications! > Trabectedin in traslocated myxoid liposarcoma > Pazopanib non in liposarcoma

7 Molecular driven treatment

8 First line recommendations Histotype driven treatment Molecular driven treatment

9 Histotype driven treatment First line treatment:

10 First line treatment: Histotype driven treatment in L sarcoma

11 First line treatment: Histotype driven treatment in leiomyosarcoma in angiosarcoma in solitary fibrous tumor

12 First line treatment: Histotype driven treatment in angiosarcoma

13 First line treatment: Histotype driven treatment in leiomyosarcoma Dacarbazine in favor to Ifosfamide + Doxorubicn

14 First line treatment: Histotype driven treatment in solitary fibrous tumor

15 First line treatment: Moelcular driven treatment in dermatofibrosarcoma protuberans (DFSP) Gstrointestinal stromal tumors (GIST) BRAF or SDH mutant Gstrointestinal stromal tumors (GIST) KIT mutant

16 First line treatment: Molecular driven treatment in DFPS Tumor with COL1A1-PDGFB gene fusion

17 Gastrointestinal stromal tumors Imatinib first line therapy Joensuu H, New Engl J MED 2001 Demetri G, New Engl J Med 2002

18 First line treatment (prospective) : Falchook GS, Oncotarget 2013 BRAF inhibitor in BRAF mutant GIST Regorafenib in SDH mutant GIST ClinicalTrials.gov Identifier:NCT : Single Agent Regorafenib in First-line for Metastatic/Unresectable KIT/PDGFR Wild Type GIST (REGISTRI)

19 Second line recommendations Chemotherapy in all and selceted histotype Targeted therapy in selected histotype

20 Second and more line treatment

21 Second and more line treatment

22 Second and more line treatment

23 Second and more line treatment Gem and DTC

24 Second and more line treatment:

25 Second and more line treatment

26 Second line Chemotherapy in all and selceted histotype Targeted therapy in selected histotype

27 Second and more line treatment

28 Second and more line treatment

29 Ricerca Second and more line treatment

30 Ricerca Second and more line treatment

31 Second and more line treatment

32 Second and more line treatment

33 Other considerations.. > Retroperitoneal surgery as histotype driven treatment > Neoadjuvant therapy in the sarcoma of the extremities > Immunotherapy in sarcoma (Pembrosarc study) > Next generation genome studies as the basis for basket trials

34 Project Title: RF Pantaleo Maria Abbondanza Phase II Basket trial on rare tumors: precision treatments based on genome profiling evaluated with next-generation sequencing approach SStudy Designs New concepts of clinical research Phase I Phase II Phase III Studi osservazionali Casistiche retrospettive Case report Biomarkers Nuovi approcci statistici Basket trial basati sulla ipotesi Bayesana Drug 1 Drug 1 Drug 1

35 Thank you UERACAN member

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