Histotype or molecular driven treatment of sarcomas? Prof.ssa Maria - - PowerPoint PPT Presentation

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Histotype or molecular driven treatment of sarcomas? Prof.ssa Maria - - PowerPoint PPT Presentation

Feb 20, 2024 154 likes •523 views

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

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Prof.ssa Maria A Pantaleo Dipartimento Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna “GistStudyGroup” “Sarcomastudygroup” Bologna

Histotype or molecular driven treatment of sarcomas?

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Classification of Sarcoma

soft-tissue sarcomas bone sarcomas WHO 2013 Classification

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The soft-tissue sarcomas are a group of rare but anatomically and histologically diverse neoplasms with diverse outcome and treatment

Classification of Soft tissue Sarcoma

Approximatevely 50 recognized histologic subtypes of soft-tissue sarcomas

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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

2000

  • All sarcomas

– Doxorubicin – Ifosfamide – DTIC

Treatment of Soft tissue Sarcoma

Histotype or Molecular driven treatment ?

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Histotype or Molecular driven treatment?

Histotype driven treatment Molecular driven treatment

Doxorubicin Ifosfamide Dacarbazin Gemcitabin Taxotere Trabectedin Eribulin Aldoxorubicin CHEMOTHERAPY TARGET THERAPY Pazopanib Imatinib Sunitinib Regorafenib mTOR inhibitors Crizotinib

> Trabectedin in traslocated myxoid liposarcoma > Pazopanib non in liposarcoma

BOTH indications!

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Molecular driven treatment

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First line recommendations

Histotype driven treatment Molecular driven treatment

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Histotype driven treatment First line treatment:

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First line treatment: Histotype driven treatment in L – sarcoma

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Histotype driven treatment First line treatment:

in angiosarcoma in leiomyosarcoma in solitary fibrous tumor

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First line treatment: Histotype driven treatment in angiosarcoma

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First line treatment: Histotype driven treatment in leiomyosarcoma

Dacarbazine in favor to Ifosfamide

+

Doxorubicn

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First line treatment: Histotype driven treatment in solitary fibrous tumor

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Moelcular driven treatment First line treatment:

in dermatofibrosarcoma protuberans (DFSP) Gstrointestinal stromal tumors (GIST) KIT mutant Gstrointestinal stromal tumors (GIST) BRAF or SDH mutant

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Molecular driven treatment in DFPS First line treatment:

Tumor with COL1A1-PDGFB gene fusion

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Gastrointestinal stromal tumors Imatinib first line therapy

Joensuu H, New Engl J MED 2001 Demetri G, New Engl J Med 2002

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BRAF inhibitor in BRAF mutant GIST

Falchook GS, Oncotarget 2013

Regorafenib in SDH mutant GIST

First line treatment (prospective) :

ClinicalTrials.gov Identifier:NCT02638766: Single Agent Regorafenib in First-line for Metastatic/Unresectable KIT/PDGFR Wild Type GIST (REGISTRI)

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Second line recommendations

Targeted therapy in selected histotype Chemotherapy in all and selceted histotype

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Second and more line treatment

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Second and more line treatment

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Second and more line treatment

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Second and more line treatment Gem and DTC

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Second and more line treatment:

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Second and more line treatment

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Second line

Targeted therapy in selected histotype Chemotherapy in all and selceted histotype

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Second and more line treatment

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Second and more line treatment

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Ricerca

Second and more line treatment

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Ricerca

Second and more line treatment

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Second and more line treatment

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Second and more line treatment

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> 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 Other considerations ……..

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New concepts of clinical research

SStudy Designs 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

Project Title: RF-2016-02361851 Pantaleo Maria Abbondanza Phase II Basket trial on rare tumors: precision treatments based on genome profiling evaluated with next-generation sequencing approach

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Thank you

maria.pantaleo@unibo.it www.giststudygroup.it www.sarcomastudygroup.it UERACAN member

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