I sarcomi dei tessuti molli
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1 Novità e sequenze terapeutiche nelle neoplasie ginecologiche, melanoma e tumori rari: I sarcomi dei tessuti molli Giacomo G. Baldi Oncologia Medica Sandro Pitigliani Nuovo Ospedale S.Stefano Azienda USL Toscana centro Prato
2 Adipocytic tumours Well deifferentiated / dedifferentiated liposarcoma Myxoid / round cell liposarcoma Pleomorphic liposarcoma Fibroblastic / myofibroblastic tumours Fibromatosis (desmoid) DFSP Solitary fibrous tumour / haemangiopericytoma IMT Low grade myofibroblastic sarcoma Infantile fibrosarcoma Adult fibrosarcoma Mixofibrosarcoma SEF LGFMS Smooth muscle tumours Leiomyosarcoma Skeletal muscle tumours Embryonal rhabdomyosarcoma Alveolar rhabdomyosarcoma Pleomorphic rhabdomyosarcoma Vascular tumours Epithelioid haemangioendothelioma Angiosarcoma of soft tissue GIST Nerve sheath tumors MPNST Malignant GCT Chondro-osseous tumours Mesenchymal chondrosarcoma Extraskeletal osteosarcoma Tumours of uncertain differentiation Synovial sarcoma Epithelioid sarcoma Alveolar soft part sarcoma Clear cell sarcoma of soft tissue Extraskeletal myxoid chondrosarcoma Extraskeletal Ewing sarcoma Desmoplastic small round cell tumour Extra-renal rhabdoid tumour Malignant mesenchymoma Malignant PEComa Intimal sarcoma Fletcher CDM et al, WHO Classification 2013
3 Soft tissue sarcoma Courtesy A.P. Dei Tos
4 Soft tissue sarcoma # 1463 pts Full 56% Partial 35% Zero 8% Ray-Coquard I et al, Ann Oncol 2012
5 Soft tissue sarcoma: localised disease Soft tissue sarcoma-high risk-primary and localised disease completely resected/resectable standard: surgery +/- RT (neo) adjuvant systemic treatment to increase the chance of cure
6 Soft tissue sarcoma: localised disease 5-10% absolute improvement in OS Pervaiz et al, Cancer 2008
7 Soft tissue sarcoma: localised disease # 351 pts Median FUP 8 yrs Adm 75 mg/sqm + Ifo 5 g/sqm G2 and G3 (46%) Any histology (90 pts other histo) Woll et al, Lancet Oncol 2012
8 Soft tissue sarcoma: localised disease epiadm 120 mg/sqm + IFX 9 g/sqm q 21 days Frustaci et al, J Clin Oncol 2001 Gronchi et al, J Clin Oncol 2012
9 Soft tissue sarcoma: localised disease Gronchi et al, Lancet Oncol 2017
10 Soft tissue sarcoma: localised disease Median FUP 12.6 months Gronchi et al, Lancet Oncol 2017
11 Soft tissue sarcoma: localised disease Weaknesses One-sided significance test No control arm Short median follow-up (12.6 months) Actions taken Amendment to two-sided significance test Final analysis awaited Strengths Significance both in DFS and OS Size of the effect Persistent difference in DFS in 2 indipendent sets of observations Effect on DM free survival Gronchi et al, Lancet Oncol 2017
12 Soft tissue sarcoma: localised disease Longer FU is needed but the shape of the curve of the standard arm is superimposable to the previous study
13 Soft tissue sarcoma: localised disease (Neo) adjuvant chemotherapy not standard High risk Waiting for the final analysis of the STS-ISG study
14 Soft tissue sarcoma: advanced disease Tap et al, Lancet 2016
15 Soft tissue sarcoma: advanced disease Tap et al, Lancet 2016
16 Soft tissue sarcoma: advanced disease Tap et al, Lancet 2016
17 Soft tissue sarcoma: advanced disease Weaknesses Unknown mechanisms of actions Discrepancy between PFS and OS improvement Limited number of patients Actions taken Phase 1b study ongoing in potentially resectable patients Phase 1 study ongoing olara plus doxorubicin and ifosfamide vs doxorubicin and ifosfamide Phase 3 study completed, results awaited Strengths First study showing a improvement in OS Magnitude of improvement Tap et al, Lancet 2016
18 Soft tissue sarcoma: advanced disease Novel standard? Patient selection (need for tumor shrinkage, histology) Doxorubicin: 8 cycles? (75 mg/smq = 600 mg/smq) Cardioxane administration (off label) Tap et al, Lancet 2016
19 Soft tissue sarcoma: advanced disease further line Schöffski et al, Lancet 2016
20 Soft tissue sarcoma: advanced disease further line Schöffski et al, Lancet 2016
21 Soft tissue sarcoma: advanced disease further line Schöffski et al, Lancet 2016
22 Soft tissue sarcoma: advanced disease further line Schöffski et al, Lancet 2016 X Demetri et al, J Clin Oncol 2017
23 Soft tissue sarcoma: advanced disease further line Demetri et al, J Clin Oncol 2017
24 Soft tissue sarcoma: advanced disease further line Progressive WD/DD retroperitoneal LPS 4 th line Eribulin X 3
25 Soft tissue sarcoma: what future? Frezza et al, BMC Med 2017
26 Soft tissue sarcoma: what future? Phase I-II trial of sunitinib plus nivolumab after standard treatment in advanced soft tissue and bone sarcomas Main inclusion criteria Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangiosarcoma, solitary fibrous tumor and epithelioid sarcomas) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing sarcoma or dedifferentiated chondrosarcoma) Pathology specimens available for centralized review ECOG PS <=2 Patients have previously received at least anthracyclines Main exclusion criteria Three or more previous lines of chemotherapy for the advanced disease
27 Soft tissue sarcoma: conclusions Sarcomas are heterogeneous Accurate diagnosis is a challenge Referral to expert rare cancer pathologist Multidisciplinar approach in referral institutions
28 Networks are the best tool for proper referral
29
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