gcig updates portec-3 and portec-4a oct dgog slides portec 3 & … · m o l ec u a r (p a i ndp...
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GCIG updates – PORTEC-3 and PORTEC-4a
Lisbon, October 2016
Carien CreutzbergLeiden University Medical Centre, The Netherlands
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The PORTEC-3 trial
R
Pelvic RT (48.6 Gy)
• uniform schedule
• upfront pathology review
• quality of life analysis
PORTEC - 3
Pelvic RT plus 2x cisplatin-> 4x carboplatin/paclitaxel
High risk Endometrial Cancer
686
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PORTEC-3 trial – toxicity and quality of life
De Boer et al, Lancet Oncology 2016
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PORTEC-3 – progress and analysis
• Radiotherapy QA to be completed this year
• Ongoing data checks, queries, FU information and QOL
• ANZGOG: TROG benchmarking study published*
Patient preferences study accepted to BJC
• Analysis of pathology review completed (NL-UK)
• TransPORTEC consortium for translational research
• Final analysis of PORTEC-3 expected 2017
depending on timely follow-up information and prompt
reporting of events!
* Jameson et al, Journal of Medical Imaging and Radiation Oncology 60 (2016) 554–559
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Molecular characteristics of endometrial cancer
TGCA, Kandoth et al, Nature 2013
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Molecular analysis PORTEC-1 and 2 cohort (N=834)
Stelloo et al, Clinical Cancer Research 2016
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The 4 TCGA subgroups by surrogate markers
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Distant metastasis Overall survival
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Consistent in independent studies
Talhouk et al, Br J Cancer 2015
A clinically applicable molecular-based classification for endometrial cancers• 152 -> 143 patients evaluable• 17% serous/mixed• 39% low risk, 16% intermediate risk, 45% high risk
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L1-CAM
Zeimet, JNCI 2013; Bosse, EJC 2014; Van der Putten for ENITEC, Br J Cancer 2016
L1-CAM strong negative prognostic factor• About 7-10% overall L1CAM+• More often L1CAM+ in grade 3, p53+, NEEC• Confirmed in large ENITEC series (n=1200)
Zeimet et al 2013 Bosse et al 2014
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Stelloo et al, Clinical Cancer Research 2016
Molecular integrated risk profile PORTEC-1/2 cohort
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Molecular integrated risk profile PORTEC-1/2 cohort
Stelloo et al, Clinical Cancer Research 2016
Molecular integrated risk profile is a stronger risk stratification model with
improved risk prediction
Decrease overtreatment and undertreatment
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New PORTEC-4a trial design
Molecular integrated vs standard indications for adjuvant treatment:
Endometrial carcinoma
Surgery and pathology diagnosis
FIGO 2009 – high intermediate risk Stage IA (with invasion), any age and grade 3 (with or without LVSI)Stage IB, grade 1-2 and age > 60Stage IB, grade 1-2 and LVSI+Stage IB, grade 3 without LVSIStage II (microscopic), grade 1
Randomisation
Utrecht
Ijsselmeer
Groningen
DrentheNoord
Holland
Gelderland
Limburg
Flevoland
Zuid Holland
Noord Brabant
Zeeland
Overijssel
Friesland
Waddenzee
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New PORTEC-4a trial design
Molecular integrated vs standard indications for adjuvant treatment:
Individual treatment recommendation based on
molecular pathology analysis
2 1 Standard treatment recommendation based on clinicopathological factors
Vaginal brachytherapy
Vaginal brachytherapy (~40%)
Observation (~55%)
External beam radiation therapy (~5%)
Follow-up and Quality of Life
Randomisation
Favourable
Intermediate
Unfavourable
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PORTEC-4a – pilot phase started
• Pilot phase: N = 50 (Netherlands)
• Endpoints: logistics, patient acceptance
• Ongoing site activations; first 7 patients randomised
• Proceed into full trial (international)
• Endpoints: vaginal recurrence, recurrence-free survival, AE and
QOL, health costs
• Validation of molecular profile procedure in pathology centers
• NCRI UK and ANZGOG planning to participate
Trial specific meeting Friday 28 Oct, 12:30 pm, Augusta I room
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PORTEC - 3International Intergroup Trial
Thanks to all ---