Advances in Adaptive Image Guided Brachytherapy for Cervical Cancer Richard Pötter MD Department of Radiation Oncology Comprehensive Cancer Center General Hospital and Medical University of Vienna The Mr. and Mrs. H M Lui Memorial Lecture 18 December, 2015 P. Breughel The Elder: The Tower of Babel 1563 KHM Vienna
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Advances in Adaptive Image Guided Brachytherapy for ... · Advances in Adaptive Image Guided Brachytherapy for Cervical Cancer Richard Pötter MD Department of Radiation Oncology
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GTVHR CTVJastaniyah N, Yoshida K et al; fellows at MUW/AKH Vienna, ASTRO 2014
N=68
Mean GTV45.2 cm3
Mean HR CTV24.6 cm3
Volumetric tumour regression: FIGO stage IIB cervical cancer, large tumor at diagnosis subgroup from EMBRACE data base, N=183/345
• Assessment of initial GTV and residual GTV + pathologic residual tissue based on repetitive MRI (CT/US) + clinical exam. at diagnosis and at time of Brachytherapy (40-45 Gy)
• Introduction of an initial and adaptive target concept related to the GTV: High Risk CTV-T and Intermediate Risk CTV-T
The language challenge I Risk orientated (“High Risk”)
Nodal CTV-E based on Risk Group Residual GTV-T, Adaptive HR CTV-T, IR CTV-T
High Risk
Intermediate Risk
Low Risk
CTV-E
Initial HR CTV-T
EMBRACE IIStart 1/2016
General aims for EMBRACE II
• To systematically apply advanced image guided EBRT and adaptive
BT (IC/IS) in a prospective multicentre setting
• To systematically implement a dose prescription protocol with
specific dose constraints for target volumes (GTV, CTVHR and OARs
(high, intermediate and low dose volumes) applied in ≤50 days
• To apply for EBRT individualised risk adapted target concepts and
lymph node boosting
• To systematically administer simultaneous chemotherapy to EBRT,
in particular in high risk patients
• To benchmark an outstanding high level of local, nodal, systemic
control and survival as well as a low incidence of intermediate and
major morbidity and QOL
pp
Target concepts EMBRACE II, EBRT
CTV-E based on risk of spread
CTV-T LR (CT/MRI), ITV-T LR, CTV-E, PTV 45 (T+E)
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Motivation for reduced margins : reduction of morbidity“orange and the peel…50% vs. 50% volume”, no evidence for nodal recurrence at margins (except cranial)
CTV-E
CTV-E + 5mm
CTV-E + 10mm
CTV-ECTV-E +
5mmCTV-E + 10mm
~1000 cc ~1500 cc ~2000 cc
43Gy vol -> ~1700 cc ~2200 cc
Diarrhoe (EMBRACE)
D90
CTVHR
EQD210
D98
CTVHR
EQD210
D98
GTV
EQD210
D98
CTVIR
EQD210
D
Point A
EQD210
Planning
Aims
> 90 Gy
< 95 Gy
> 75 Gy >95 Gy > 60 Gy > 65 Gy
Limits for
Prescribed
Dose
> 85 Gy - >90 Gy - -
Planning aims and Dose prescription (I) CTV-T EMBRACE II protocol (EBRT+BT) (1/2016)
Bladder
D2cm³
EQD23
Rectum
D2cm³ EQD23
Recto-
vaginal
point
EQD23
Sigmoid/
Bowel D2cm³
EQD23
Planning
Aims
< 80 Gy < 65 Gy < 65 Gy < 70 Gy
Limits for
Prescribed
Dose
< 90 Gy < 75 Gy < 75 Gy < 75 Gy
Planning aims and Dose prescription (II)OAR EMBRACE II protocol (EBRT+BT) (1/2016)
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EMBRACE II Planning AIMS and Limits for Prescription
OTT < 50 Days
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In EMBRACE II, the improved therapeutic window (through increased application of IC/IS) will be exploited for tumour dose-escalation 715
and/or OAR dose de-escalation (figure 4.1). In tumours with large residual CTVHR volumes at time of brachytherapy, dose-escalation has 716
the potential to improve local control significantly. In limited size CTVHR volumes dose-de-escalation will be performed since dose de-717
escalation has minor impact on local control while it has potential to reduce morbidity. The strategy of EMBRACE II is to aim for an 718
application of the IC/IS technique in at least 20% of the patients in each institution. The threshold of 20% is relevant for a classical stage 719
distribution of ~20% IB, ~50% IIB, ~20% IIIB and ~10% others. If a given patient population includes significantly higher proportions of 720
limited or extensive disease, the threshold of 20% IC/IS applications must be adapted. 721
Figure 4.1 Principles for dose de-escalation and dose escalation in EMBRACE II. The figure shows the current distribution of CTVHR dose 722
and volume in the EMBRACE study (each point represents one patient). A number of 6 dose and volume groups are defined according 723
to cut-points of 85Gy and 95Gy for CTVHR dose and of 30cm3 for CTVHR volume. For each dose-volume group the expected actuarial local 724
control at 3 years is indicated (according to dose effect data from the retroEMBRACE study (Tanderup K. et al. 2014, RetroEMBRACE 725
work in progress). 726
4.1.2 REDUCTION OF VAGINAL SOURCE LOADING 727
A multicenter investigation in 50 EMBRACE patients from 3 institutions (Mohamed SM. et al, in submission 2015) shows that reduced 728
loading in ring/ovoids and increased loading in tandem (and needles when available) can be applied without compromising CTVHR and 729
GTVres dose. Decrease of relative vaginal loading from a mean of 50% to 33% had potential to reduce ICRU recto-vaginal dose by a mean 730
of 4±4Gy, and furthermore, bladder and rectum doses could be reduced by 2-3Gy with the same re-arrangement of loading. Similar 731
evidence is available from a study on simulation of different intracavitary standard loading patterns in EMBRACE patients, where it was 732
shown that limited size tumours could often be covered by tandem loading alone (Nkiwane KS. et al. 2013). 733
4.1.3 SYSTEMATIC UTILISATION OF IMRT 734
Many institutions deliver 3D conformal radiotherapy (3D CRT) based on a four-field box technique although IMRT has been available for 735
a number of years. The practice in EMBRACE has been utilisation of IMRT and 3D CRT in 27% and 73% of the patients, respectively. 736
However, EMBRACE morbidity data as well as data published by Mundt et al (Mundt AJ. et al. 2003) indicate that IMRT significantly 737
reduces the incidence of bowel morbidity, and therefore IMRT is considered as instrumental for reducing the incidence of bowel 738
morbidity and with a potential also to be beneficial for urinary morbidity. 739
740
General endpoints
for EMBRACE II (www.embracestudy.dk)
Improvement by prescription protocol for IGRT EBRT and IGABT
- reduced local failures in patients with adaptive CTV-T HR > 30cm2
- improved nodal control in high risk patients (Stage III, IV or N1)
- improved systemic control
+ Reduction of morbidity: prescribed dose constraints
by dose de-escalation in low risk patients (Stage I, II and N0)
by margin reduction for CTV-E (5 mm) in all patients (IMRT, IGRT)