Onkologisk behandling af lokaliseret og
lokalavanceret esophagus og
gastroesophageal cancer
Marianne Nordsmark
overlæge, phd, lektor
Onkologisk afdeling
Aarhus Universitetshospital
Historically, this has been a source of
intensive debate
between smart oncologists and even
smarter surgeons worldwide
Marianne Nordsmark
Overlæge afd D
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
Metaanalyse esophagus cancer
Sjokvist et al Lancet oncol 2011
Metaanalyse esophagus cancer
Sjokvist et al Lancet oncol 2011
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
MAGIC trial
Design
n=253
Surgery < 6 wks
n=240
R
n=250
3x ECF
n=237
86%
Surgery 3-6 wks
3x ECF 6-12 weeks
n=137
n=104
n=219
55%
42%
Cunningham et al NEJM 2006
MN 04/11/2012
MAGIC trial
5 yr OS
36%
23%
Cunningham et al NEJM 2006
MN 04/11/2012
Is CROSSing over so hard to do?
Blum & Ajani Nat. Rev. Clin. Oncol. 9, 493–494 (2012)
Metaanalyse esophagus cancer
Sjokvist et al Lancet oncol 2011
Van der Gaast
Hagen et al NEJM 2012
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 N0 1
• 18 75 years
• WHO PS 0 2
• Weight loss 10% or less of body weight
Hagen et al NEJM 2012
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
Study enrollment 2004 to 2008
Hagen et al NEJM 2012
Hagen et al NEJM 2012
Hagen et al NEJM 2012
Hagen et al NEJM 2012
5 year overall survival estimates
HR 0.657
95% CI 0.495 to 0.871
Hagen et al NEJM 2012
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.
Hagen et al NEJM 2012
Subgroup analyses
Hagen et al NEJM 2012
CROSSing over may take a while some
places….
Blum & Ajani Nat. Rev. Clin. Oncol. 9, 493–494 (2012)
Hvad gør du, når patienten selv vil
bestemme?
Data fra patienter, der fravælger operation efter
afsluttet præoperativ CHRT
Taketa et al Oncology 2012
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
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
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
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
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
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.