Inter-observer variability in hippocampus delineation on MRI scans for Hippocampal Avoidance - PCI trial

(1)

Inter-observer variability in

hippocampus delineation on MRI scans

for Hippocampal Avoidance - PCI trial

C.Chen, M.de Ruiter, F.Bartel, M.Kwint, J.Belderbos F.Vandaele, S.Sunaert, K.De Jaeger, N.Dollekamp,

E.Dieleman, R.Achten, D.de Ruysscher, S.Schagen,

(2)

N

SCLC: M

09

PCI-PCI

SCLC:

M

12

PHA-PCI

• N

SCLC: PCI versus geen PCI

• Indien PCI: HA-PCI = 2vs + leaves

• SCLC: Standaard PCI (=2vs) en HA-PCI

• Indien standaard PCI: 2vs standaard

ZONDER leaves

• Indien HA-PCI: VMAT met planning

(3)

N

SCLC- tumoren:

M09PCI

HA-PCI + Leaves 30Gy/12 fracties/4x pw

(4)

• Standaard PCI: 2vs

• Hippocampus Avoiding Prophylactic Cranial

Irradiation(HA-PCI): VMAT

Extensive disease: 20 Gy / 5 fracties / 5x pw Limited disease: 25 Gy / 10 fracties / 4x pw

(5)

The localization of the hippocampus (braun) in the brain

http://www.visiblebody.com.

Phase III trial randomizing PCI

with or without hippocampal

avoidance NCT01780675

(6)

Overview

• Motivation of the study

• Study preparation

• Results

• Discussion

• Future work

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Motivation

• Sources of variations in the

Hippocampus Avoiding Prophylactic Cranial Irradiation

(HA-PCI) trial:

– Image registration (CT and MRI)

– Inter- and intra- observer delineation

– Dose planning – During treatment

• Motivation:

– The inter-observer variability in the HA-PCI trial

– The influence of delineation variability on dose planning

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NCT01780675 objectives and endpoints

Primary objective:

• to reduce memory function loss with hippocampal

avoidance PCI (HA-PCI) compared to standard whole brain PCI in SCLC patients

Secondary objectives:

• to assess early and late neurotoxicity and quality of life • to assess structural and functional brain abnormalities on

MRI

• to assess the incidence and location of brain metastases PFS and OS

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PCI

H

ippocampus

A

voidance

SCLC (LD and ED)

PCI

full PCI _HA-PCI

•Monitoring cognitive sequelae :

•Neuro-cognitive tests 6 times:

•Baseline and 4/8/12/18/24

• Repeat MRI

•Does HA-PCI increase QoL? R

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Interobserver variability study preparation

• 5 randomly selected trial patients (10 structures)

– A high resolution T1 weighted MRI scan was registered to the planning CT scan (1mm)

• 7 participating institutions

• According to the RTOG atlas

on axial slices of the MRI

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Results - volume

Volume per structure

Delineation structure per observer mean volume (cm3) SD volume (cm3) Mean difficulty score 1-L* 2.53 0.30 1.7 2-L* 2.35 0.33 1.8 3-L* 2.19 0.31 2.0 4-L* 2.25 0.48 2.3 5-L* 2.61 0.41 2.5 1-R* 2.72 0.29 1.7 2-R* 2.35 0.14 1.8 3-R* 2.35 0.22 2.0 4-R* 2.53 0.41 2.3 5-R* 2.75 0.47 2.5

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Results - volume

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Results - volume

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Results - volume

Delineation structure mean volume (cm3) SD volume (cm3) Mean difficulty score 1-L 2.53 0.30 1.7 2-L 2.35 0.33 1.8 3-L 2.19 0.31 2.0 4-L 2.25 0.48 2.3 5-L 2.61 0.41 2.5 1-R 2.72 0.29 1.7 2-R 2.35 0.14 1.8 3-R 2.35 0.22 2.0 4-R 2.53 0.41 2.3 5-R 2.75 0.47 2.5

Patient 4 and 5 are more difficult to delineate  larger variations in

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Results – hippocampus volume

• SD delineated volume varied from 0.14-0.48 cm3

• The overall inter-observer variability of the volume:

• Intraclass correlation coefficient: ICC=0.19

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Results –overall delineation variability

Delineation structure per observer Overall delineation variability (mm) 1-L* 0.7 2-L* 1.0 3-L* 0.7 4-L* 0.9 5-L* 0.8 1-R* 0.8 2-R* 0.9 3-R* 0.6 4-R* 0.9 5-R* 1.0 Ranges from 0.6-1.0 mm

root-mean-square of the local SD per sampled points on the median surface

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Results - volume

Volume per observer _{lower volume}

than other observers

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Problematic regions

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Problematic regions

Uncus area

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Problematic regions

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Problematic regions

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Future work

• Comparison to the golden standard

• Improving delineations

– Adherence to RTOG guidelines

Web-based workshop on delineation – Case studies of difficult patients

• The influence of delineation variability on dose planning • Is the 5 mm margin in dose planning sufficient or too

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Discussion – axial sequences

• Why do we choose to delineate on axial sequences (more difficult)?

Because it’s easy for dose planning.

• Do all institutions follow the RTOG atlas? No

• When the hippocampus is rotated (or asymmetrical), it becomes more difficult to delineate in axial sequences. • Always validate the delineations in sagittal view!

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Thanks for the teamwork

Sanne Schagen Michiel de Ruiter Marianne Kuenen Willem Boogerd Pietje Muller Chun Chen Eugene Damen Harm van Tinteren Anne Lisa Wolf Margriet Kwint Emmy Lamers Casper Carbaat Katrien de Jaeger Friederike Koppe Marjan van de Pol Joachim Widder Edith Dielemans

Dirk de Ruysscher Sabine Deprez Stefan Sunaert

Frank van den Heuvel Johan Vansteenkiste Yolande Lievens Katrien Vandecasteele Rik Achten Paul Meijders Chirs Goor Paul Parizel Matthew Holt

(26)

• NSCLC hippocampal sparing study is closed

– Results not yet available

• This also used a simpler sparing technique, with 2

lateral fields and 2 blocks.

• HVLT Hopkins Verbal Learning Test is used for

cognitive changes. End point is if patient loses 4

points on a test following HPPCI then the HP

sparing will have failed.

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Pros and Cons

VMAT Practical (Pacman) technique

96.4% Coverage 85.7% Coverage

7.4Gy mean dose (α/β=2) Hippocampus 3.9Gy mean dose (α/β=2) Hippocampus

BeamModulator, 4mm leaf MLC 1cm leaf MLC

Complex plan / dosimetry Simple plan

Fairly long irradiation time Short irradiation time

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Techniek

• Beams

– Kies A2 en 10 MV.

– 2 Dual Arcs loodrecht op elkaar.

• Gantry 340º -180º CW; tafel 90º; collimator 110º • Gantry 178º -182º collimator 20º

– Beam on Time 4x100sec ~ 7 minuten

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Objectives

Start ( = Stap 1)

BRAIN4-HC10 Min Dose 2375 100

BRAIN4-HC10 Uniform dose 2500 70

HIPPPOCAMPUS_R/L Max Dose 800 1

LENS_R/L Max Dose 800 10

Stap 2

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Objectives

Stap 3

Stap 4 BRAIN4-HC10 Min Dose 2375 100

(32)

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Objectives

Evt Stap 5 zelf toevoegen

HIPPPOCAMPUS_R/L Max Dose 600 10

EYE_R/L Max DVH 1500 30 20

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Criteria

• PTV:

- V23.75Gy > 95%

- V28.75Gy < 10% ± 8%

(bij voorkeur D1% <115%)

• Hippocampi:

- Dmean < 8.5 Gy ± 0.5Gy

- D1 < 10 Gy ± 1 Gy

• Lenzen:

- Dmax < 10 Gy