Onkologisk behandling af lokaliseret og lokalavanceret esophagus og gastroesophageal cancer

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1 Onkologisk behandling af lokaliseret og lokalavanceret esophagus og gastroesophageal cancer Marianne Nordsmark overlæge, phd, lektor Onkologisk afdeling Aarhus Universitetshospital

2 Historically, this has been a source of intensive debate

3 between smart oncologists and even smarter surgeons worldwide Marianne Nordsmark Overlæge afd D

4 Nationale Retningslinier i DK Standardbehandlinger Neoadjuverende kemoradioterapi efterfulgt af operation til planocellulaer esophagus cancer Perioperativ kemoterapi til adenocarcinomer i disdale esophagus GEJ og ventrikel cancer Definitiv kemo/strålebehandling til ikke resektabel eller medicinsk inoperable lokaliseret eller lokalavanceret esophagus og GEJ cancer Adeno og planocellulaere karcinomer

5 Metaanalyse esophagus cancer Sjokvist et al Lancet oncol 2011

6

7 Metaanalyse esophagus cancer Sjokvist et al Lancet oncol 2011

8 Nationale Retningslinier Standardbehandlinger Neoadjuverende kemoradioterapi efterfulgt af operation til planocellulaer esophagus cancer Perioperativ kemoterapi til adenocarcinomer i disdale esophagus GEJ og ventrikel cancer Definitiv kemo/strålebehandling til ikke resektabel eller medicinsk inoperable lokaliseret eller lokalavanceret esophagus og GEJ cancer Adeno og planocellulaere karcinomer

9 MAGIC trial Design n=253 Surgery < 6 wks n=240 R n=250 3x ECF n=237 Surgery 3-6 wks 3x ECF 6-12 weeks n=219 n=137 n=104 86% 55% 42% Cunningham et al NEJM 2006 MN 04/11/2012

10 MAGIC trial 5 yr OS 36% 23% Cunningham et al NEJM 2006 MN 04/11/2012

11 Is CROSSing over so hard to do? Blum & Ajani Nat. Rev. Clin. Oncol. 9, (2012)

12 Metaanalyse esophagus cancer Sjokvist et al Lancet oncol 2011 Van der Gaast

13 Hagen et al NEJM 2012

14 Eligibility criteria most of them listed here Esophagus or GEJ upper border of tumor at least 3 cm below upper esophageal sphincter. Histological confirmed, potentially curable andenoand squamous cell or large cell undifferentiated carcinomas. Tumor length max 8 cm and with max 5 cm T1N1 or T2 3 N years WHO PS 0 2 Weight loss 10% or less of body weight Hagen et al NEJM 2012

15 Study design Chemotherapy with carboplatin and paclitaxel day 1, 8, 15, 22 and 29 Radiotherapy 41.4 Gy in 23 fractions, 1.8 Gy per fx Surgery as soon as possible after randomisation or after CHRT Within 4 to 6 weeks Follow up every 3 months first year, every 6 moths second year and then once every year untill 5 years after treatment. Hagen et al NEJM 2012

16 Study enrollment 2004 to 2008 Hagen et al NEJM 2012

17 Hagen et al NEJM 2012

18 Hagen et al NEJM 2012

19 Hagen et al NEJM 2012

20 5 year overall survival estimates HR % CI to Hagen et al NEJM 2012

21 Pathological response Among 161 neoadjuvant treated and resected patients 29% had complete pathological response. Complete tumor resection within 1 mm margin was 92% in CHRT arm vs 69% in surgery alone arm.

22 Hagen et al NEJM 2012

23 Subgroup analyses Hagen et al NEJM 2012

24 CROSSing over may take a while some places. Blum & Ajani Nat. Rev. Clin. Oncol. 9, (2012)

25 Hvad gør du, når patienten selv vil bestemme?

26 Data fra patienter, der fravælger operation efter afsluttet præoperativ CHRT Taketa et al Oncology 2012

27 Eligible patients 61 among 622 pts with histological verified carcinoma treated in Houston between 2002 and 2011 declined surgery after preop CHRT. Diagnostic work up with CT, PET, esophagodoudenogastroscopy, Endoscopic ultrasound Triple modality (CH+RT+Surgery) eligible if Technical resectable Physiologic ability to withstand surgery Taketa et al Oncology 2012

28 Trimodal Treatment Pre operative chemoradiotherapy 5FU, Cisplatin or a Taxane Radiotherapy 50.4 Gy 1.8 Gy per fx Evaluation 5 to 6 weeks after end of CHRT with Gastroscopy and PET CT Complete Clinical Response versus Less than Complete Clinical Response Surgery Salvage surgery performed for locoregional recurrence more than 3 months after completed chemoradiation. Taketa et al Oncology 2012

29 Overall survival in 61 patients with complete response after preop CHRT who declined surgery. Estimated 5 yr OS rate 58% Taketa et al Oncology 2012

30 Relapse Free Survival in patients with complete response after preop CHRT who declined surgery. Estimated 5 yr RFS rate 35% 33 recurrences 13 local 20 distant mets Median follow up 50 months Taketa et al Oncology 2012

31 Konklusioner fra Taketa et al Studiets svagheder Retrospektiv analyse Faa patienter Manglende valideret eller struktureret tilgang til beslutningsalgoritme om behandling Resultatet behaeftet med selektionsbias Studiets styrker Det foerste studie, der viser data hos pt, der afslaar planlagt operation efter praeop kemort 12 pt fik salvage kirurgi Taketa et al Oncology 2012

32 Behandling af lokaliseret og lokal avanceret esophagus og GEJ cancer Standardiseret algoritme ved udvaelgelse af pt. til præ op kemo eller kemort. Præop kemort - CROSS studiet NEJM 2012 Randomiseret fase III med overlevelsesgevinst hos planoog adenocarcinomer. Skal onkologisk behandling tilpasses CROSS studiet? Timing af operation efter kemo eller komort? Evaluering efter kemo eller kemort og før operation. Hvornår skal pt evalueres? Hvilke modaliteter skal anvendes? CT? Endoskopi? Andre? Salvage kirurgi Hvilke pt skal tilbydes det? Ingen tumorrest ved CT follow up 4-6 uger efter definitiv kemort. Hvad så? Operation eller kontrol.