Com cal fer la primera maniobre terapèutica en els sarcomes d extremitats. Tractament sistèmic.

Transcription

1 Com cal fer la primera maniobre terapèutica en els sarcomes d extremitats. Tractament sistèmic. Dr. Javier Martín Broto Oncología Médica. HU Son Espases. Palma

2 DIAGNOSTIC PROCEDURE: CRUCIAL ISSUE J F Abellán et al, Sarcoma 2009

3 GP Referral delayed GS Positive Margins MO Overtreated P RAD FIS Loss of function OS Blindtreated RT

4 GP MO OS RT FIS P RAD

5 RISK ASSESSMENT J Clin Oncol :

6 TREATMENT CHOICES: Localized disease, limbs SURGERY ALONE SURGERY RADIOTHERAPY SURGERY CHEMOTHERAPY RADIOTHERAPY CHEMO RTP SURGERY ILP +/ SURGERY

7 Enneking Classification of Surgical Margins SURGERY: THE THERAPEUTIC MAINSTAY

8 Adjuvant RT allowed to limit margins width

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12 Resectable Unresectable 80% 5% 15%

13 biology governs early tumor related mortality microscopic resection margins influence late outcome.

14 Tools to improve resectability Technical Plastic reconstructive surgery Vascular surgery Nerve repair Bone resection Preop Tx CT and or RT ILP

15 A preop Tx Unlikely converts to resectability 5% of primary STS of extremities Improves quality of margins in borderline resectable tumors

16 ROLE OF CHEMOTHERAPY IN PERIOPERATIVE TREATMENT STS OF LIMBS AND TRUNK WALL DRUG SELECTION PATIENT/TUMOR SELECTION

17 SELECTING DRUG Ensayos incluidos en meta analisis: 14 Datos de pacientes individualizados analizados: 1568 Fiabilidad: evaluados 98% de pacientes incluidos ADM dosis total: mg/m 2 ADM/ciclo: mg/m 2 en monoquimio o en poliquimio

18 Sarcoma Meta analysis Collaboration (Lancet, 350: , 1997) SURVIVAL EE (n= 886) ABSOLUTE BENEFIT P value OS 7% SURV 10 Y OUTCOME ABSOL P Value TREATM CONTROL BENEF DFS 55% 45% 10% SURV 10 Y OUTCOME ABSOL P Value TREATM CONTROL BENEF OS 54% 50% 4% 0.12

19 VC,Dac,C A ADIC VADIC CYVADIC IF - CRITICS: Heterogeneity grades & stages Heterogeneity in treatments (with low dose-intensity) Ifosfamide just in 5% A C VC A C ADIC C D MAID A I CYVADIC I C A ADIC ECOG GOG SWOG DFCI EORTC EORTC ECOG

20 GROUP DOSE PERIOD D.I. (mg/m2/s) NCI 92 ADR 70 IFOS 4 EORTC ADR 75 IFOS 5 RTOG 9514 ADR 20 D1 3 IFOS 2,5 D1 3 DTIC 225 D1 3 4 SEM X 5 ADR 17.5 IFOS SEM X 5 ADR 25 IFOS SEM X2 +4 ADR 20 IFOS 2500 DTIC 225 ITALIA EPI 60 D1 2 IFOS 1,8 D1 5 3SEM X 5 EPI 40 IFOS 3000

21 Median follow-up: 89.4m Treatment Control Treat F.U. N pts Cens Events m. OS n.r p= Intent to treat analyses Overall Survival Percent surviving Treatment p = Control time (months) Treated or not analyses Treat F.U. N pts Cens Events m.surv n.r p=0.038

22 LOCALIZED, HIGH RISK SOFT TISSUE SARCOMAS (STS) OF THE EXTREMITIES AND TRUNK WALL IN ADULTS: THREE VS FIVE CYCLES OF FULL DOSE ANTHRACYCLINE AND IFOSFAMIDE ADJUVANT CHEMOTHERAPY: A PHASE III RANDOMIZED TRIAL FROM THE ITALIAN SARCOMA GROUP AND SPANISH SARCOMA GROUP Alessandro Gronchi, Sergio Frustaci, Mario Mercuri, Javier Martin, Antonio Lopez Pousa, Lidia Mariani, Paolo Verderio, Vittorio Quagliuolo, Paolo G. Casali and Piero Picci.

23 1.0 probability months

24 RELATIVE RISK WITH 95% CI FOR LC, DR, GR, OS LOCAL RECURRENCE DISTAL RECURRENCE TOTAL RECURRENCE OVERALL SURVIVAL RR 95%IC RR 95%IC RR 95%IC RR 95%IC DOXO DOXO+IFOS TODOS % NNT 25 10% NNT 10 10% NNT 10 6% NNT 17 Cancer, 113:

25 SELECTING PATIENTS HAZARD RATIO CON 95% DE IC PARA SG GRADO 2 (N=625) HR (95% IC) P GRADO 3 (N=627) HR (95% IC) P EDAD > 51 años 2.1 ( ) < ( ) TUMOR > 5 cm 1.8 ( ) ( ) Local superficial NS 0.6 ( ) 0.02 Invasión 1.9 ( ) ( ) neurovascular QTP adyuvante 0.8 ( ) ( ) A. Italiano et al. Ann Oncol, 2010

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28 ASCO ISG GEIS 0101

29 ASCO ISG GEIS 0101

30 Strata 1: istofin_four=leiomyosarcoma Strata 2: istofin_four=mfh/ups+spindle CELL SARCOMA NOS Strata 3: istofin_four=other Strata 4: istofin_four=synovial SARCOMA

31 G3T2BN0M0 OR G2 with necrosis 50% MRI G2 3T1BN0M0 OTHER ST G1 3 UNRESECTABLE OR G1 3 WITH M1 NO OPERABLE CHEM+RADIOT OR SURGERY SURGERY CHEM (3) +/ ILP SURGERY RTP RTP

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