ONTWIKKELINGEN IN NEOADJUVANTE CHEMORADIOTHERAPIE OESOPHAGUSCARCINOOM. 5D s, 8 februari 2018 Francine Voncken

Transcriptie

1 ONTWIKKELINGEN IN NEOADJUVANTE CHEMORADIOTHERAPIE OESOPHAGUSCARCINOOM 5D s, 8 februari 2018 Francine Voncken

2 GEEN DISCLOSURES

3 NEOADJUVANT CHEMORADIOTHERAPIE OESOPHAGUS [TEKST] [tekst] 5y OS 33% vs 47% Shapiro Lancet Oncol

4 CROSS CHEMORADIOTHERAPIE S only CRT-S 5y OS 33% vs 47% N R0 69% 92% In hospital mortality 4% 4% Median survival 24.0 months 48.6 months 2y Overall survival 50% 67% 5y Overall survival 33% 47% van Hagen NEJM 2012, Shapiro Lancet Oncol

5 ONTWIKKELING NEOADJUVANT CHEMORADIOTHERAPIE VERDERE VERBETERING NODIG van Hagen NEJM 2012, Shapiro Lancet Oncol

6 CROSS CHEMORADIOTHERAPIE 5y OS 33% vs 47% RCT fase III T1N1 of T2-3N0-1 M0 <75 years N= 366 patiënten (75% AC, 23% SCC) OK vs CRT (41.4 Gy + carbo/taxol) +OK 3D CRT van Hagen NEJM 2012, Shapiro Lancet Oncol

7 ONTWIKKELINGEN NEOADJUVANTE CRT TECHNISCHE RT ONTWIKKELING RT planning (3D-CRT, IMRT, VMAT) Setup (CBCT, fiducials) EPID MR linac Protonen NCRT + (NIEUWE) SYSTEMISCHE MIDDELEN EGFR HER2 IMMUNOTHERAPIE 7

8 TECHNISCHE RT ONTWIKKELING 2 schuine laterale velden RT PLANNING APPA, 3D-CRT, IMRT, VMAT) Perez and Brady RT target volume bepaald obv barium slikfoto 1 AP veld 2 aanvul velden caudaal 8

9 IMRT VMAT 9

10 VMAT EPID movie 10

11 TECHNISCHE RT ONTWIKKELING CBCT EPID 11

12 TECHNISCHE RT ONTWIKKELING RT SETUP CBCT, fiducials 12

13 TECHNISCHE RT ONTWIKKELING: RT SETUP: CBCT Diafragma stand Hoger Lager

14 IN VIVO EPID DOSIMETRY Planned dose EPID-measured dose -Klinisch geimplemeteerd in Alle behandelingen met curatieve intentie sinds Alle behandelingen sinds Elekta product sinds 2016 Comparison Results in vivo dose verificatie bij 6MV VMAT oesophagus delivery 14

15 TECHNISCHE RT ONTWIKKELING: MR LINAC 15

16 TECHNISCHE RT ONTWIKKELING: MR LINAC 16

17 TECHNISCHE RT ONTWIKKELING: PROTONEN 17

18 TECHNISCHE RT ONTWIKKELING: PROTONEN Prayongrat, adv in RO 2017 Tumoren bij kinderen Bij tumoren nabij n. opticus Toekomst voor oes????? 18

19 NCRT + (NIEUWE) SYSTEMISCHE MIDDELEN UITKOMSTEN VERBETEREN pcr LRR, DFS, OS Tolerantie? 19

20 NCRT + (NIEUWE) SYSTEMISCHE MIDDELEN EGFR Cetuximab (SCOPE 1 trial) Cetuximab (RTOG 0436) Panitumumab (ACOSOG Z4051) HER2 Trastuzumab (RTOG 1010: fase III) Trastuzumab (fase I/II) Trastuzumab+ Pertuzumab (TRAP studie) IMMUNOTHERAPIE Atezolizumab (PERFECT studie) Pembrolizumab + CRT (NCT ) 20

21 NCRT + EGFR: SCOPE 1 TRIAL Multicenter RCT fase 2/3 dcrt (50Gy/25fr + cisplatin & capecitabine) +/- cetuximab (geen OK) N=258 (129 elke behandelarm) Failure free bij 24 weken 66.4% vs 76.9% (CRT+cetuximab vs CRT alleen) Overall survival bij CRT+ cetuximab 22 1 months vs 25 4 months (CRT+C vs CRT) p=0 035 CRT + cetuximab non-haematological grade 3 or 4 toxicities 79% vs 63% CRT alone p= CRT+C meer dosis reducties en niet volledige kuren door toxiciteit Crosby, Lancet Onc

22 NCRT + EGFR: SCOPE 1 p= Crosby, Lancet Onc 2013

23 NCRT + EGFR: RTOG 0436 CETUXIMAB Multicenter RCT, fase III studie N=344 dcrt 50,4Gy/ 28fr (geen OK) Paclitaxel+ cisplatin +/- cetuximab Primair eindpunt: Overall survival Geen verbetering in OS 2Y survival 44% vs 44.9% (CRT vs CRT+C) ccr: 56% versus 28% (CRT vs CRT+C) Toxicity Gr 3/4/5 50%/17%/1% CRT vs 46%/23%/4% CRT+C Overall survival Local Failure Suntharalingam, JAMA Oncology nov 2017

24 NCRT + EGFR: ACOSOG Z4051 PANITUMUMAB Phase II studie N=70 adenocarcinoom ncrt +OK 50,4Gy/ 28fr + Docetaxel+ cisplatin + panitumumab Primair eindpunt pcr 35% N=70 -> 65 eligible -> 11 no surgery -> n=54 pcr=33,3%, near pcr= 20,4% Completed treatment (73% CTX, 92% RT) 48,5% graad 4 Lymfopenie 43% Operatieve mortaliteit 3,7% Conclusie: toxisch! Lockhart, Ann of Onc 2014 All patients median OS 17,8 months N=65 median OS 19,4 months CROSS studie 24 median OS 48,6 months

25 NCRT + ANTI-HER % HER2 OVEREXPRESSIE TRASTUZUMAB (RTOG 1010: FASE III) Phase III Trial SAFRAN (TRASTUZUMAB) Fase I/II studie TRAP STUDIE (TRASTUZUMAB + PERTUZUMAB) Fase I/II studie 25

26 NCRT + ANTI-HER2: RTOG 1010 TRASTUZUMAB A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of Her2-Overexpressing Esophageal Adenocarcinoma ncrt 50.4Gy + carboplatin, paclitaxel +/- trastuzumab Studie gesloten! Resultaten verwacht! 26

27 NCRT + ANTI-HER2 TRASTUZUMAB Fase I/II n=19 CRT 50,4Gy + carboplatin+paclitaxel + trastuzumab Primair eindpunt: OS Median OS= 24 maanden, 2Y survival=50% (CROSS OS= 48 maanden, 2Y survival 67%) Geen toegenomen toxiciteit Safran, IJROBP

28 NCRT + ANTI-HER2 TRAP STUDIE (TRASTUZUMAB + PERTUZUMAB) Feasibility studie Primary endpoint: Withdrawal rate from surgery Secondary endpoint pcr Toxicity Post-operative complications Resultaten verwacht komende ASCO 28

29 NCRT + IMMUNOTHERAPIE 40% UPREGULATED PD-L1 Minimale expressie op de kanker cel Response rates in palliatieve setting 22-27% in PD-L1+ tumoren Subsets van tumor type (TGCA subtype: EBV, MSI high) PERFECT STUDIE CROSS+ (ATEZOLIZUMAB) Fase IB/II CRT CROSS + Atezolizumab PD-L1 Open voor inclusie Prim Eindpunt: feasibility Sec eindpunt: toxicity, complete CRT, uitstel OK PEMBROLIZUMAB +RT (NCT ) Fase IB/II Neoadjuvant CRT (Carbo/Taxol) + concurrent Pembrolizumab Eindpunt: pcr, PFS Open voor inclusie 29

30 ONTWIKKELINGEN NEOADJUVANTE CRT TECHNISCHE RT ONTWIKKELING RT planning (3D-CRT, IMRT, VMAT) Setup (CBCT, fiducials) EPID MR linac Protonen NCRT + (NIEUWE) SYSTEMISCHE MIDDELEN EGFR HER2 IMMUNOTHERAPIE 30

31 ONTWIKKELING NEOADJUVANT CHEMORADIOTHERAPIE MEER ONDERZOEK NODIG! van Hagen NEJM 2012, Shapiro Lancet Oncol

32 DANK VOOR UW AANDACHT 32