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

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Britney Small
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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, Maddalena Rossi

Bartel, M.Kwint, J.Belderbos F.Vandaele, S.Sunaert, K.De Jaeger, N.

2 NSCLC: SCLC: M09PCI-PCI M12PHA-PCI NSCLC: 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 NSCLC- tumoren: M09PCI HA-PCI + Leaves 30Gy/12 fracties/4x pw

$fracties/4x pw$

4 SCLC- tumoren: M12PHA-PCI 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

$/ 5 fracties / 5x pw Limited disease: 25 Gy / 10$

5 Phase III trial randomizing PCI with or without hippocampal avoidance NCT The localization of the hippocampus (braun) in the brain

6 Overview Motivation of the study Study preparation Results Discussion Future work

7 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 Any suggestions on the current 5mm margin in dose planning?

planning During treatment Motivation: The inter-observer variability in the HA-PCI trial The

8 NCT 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

Secondary objectives: to assess early and late neurotoxicity and quality of life to assess

9 PCI Hippocampus Avoidance SCLC (LD and ED) PCI R Does HA-PCI increase QoL? full PCI HA-PCI Monitoring cognitive sequelae : Neuro-cognitive tests 6 times: Baseline and 4/8/12/18/24 Repeat MRI

10 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

scan was registered to the planning CT scan (1mm) 7 participating

11 Results - volume Delineation structure per observer mean volume (cm3) SD volume (cm3) Mean difficulty score 1-L* L* L* L* L* R* R* R* R* Volume per structure 5-R* *Observers 1-5 for both L (left) and R (right) hippocampus)

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 Volume per structure 5-R* 2.

12 Results - volume Delineation structure per observer mean volume (cm3) SD volume (cm3) Mean difficulty score 1-L* L* L* L* L* R* R* R* R* Volume per structure 5-R* *Observers 1-5 for both L (left) and R (right) hippocampus)

13 Results - volume Delineation structure per observer mean volume (cm3) SD volume (cm3) Mean difficulty score 1-L* L* L* L* L* R* R* R* R* Volume per structure 5-R* *Observers 1-5 for both L (left) and R (right) hippocampus)

14 Results - volume Delineation structure mean volume (cm3) SD volume (cm3) Mean difficulty score 1-L L L L L R R R R R Volume per structure Patient 4 and 5 are more difficult to delineate larger variations in volume

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.

15 Results hippocampus volume SD delineated volume varied from cm3 The overall inter-observer variability of the volume: Intraclass correlation coefficient: ICC=0.19 A high variability among observers Volume per structure

48 cm3 The overall inter-observer variability of the

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.

16 Results overall delineation variability Delineation structure per observer Overall delineation variability (mm) 1-L* L* L* L* L* R* R* R* R* R* 1.0 Ranges from mm root-mean-square of the local SD per sampled points on the median surface *Observers 1-5 for both L (left) and R (right) hippocampus)

9 3-R* 0.6 4-R* 0.9 5-R* 1.0 Ranges from 0.6-1.

17 Results - volume Volume per structure Volume per observer lower volume than other observers *Observers 1-5 for both L (left) and R (right) hippocampus)

19 Problematic regions Uncus area Head and tail

20 Problematic regions Head and tail Uncus area

21 Problematic regions Head and tail

22 Problematic regions Head and tail

23 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 large to cover the delineation variation?

24 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!

25 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.

27 Pros and Cons VMAT Practical (Pacman) technique 96.4% Coverage 85.7% Coverage 7.4Gy mean dose (α/β=2) Hippocampus BeamModulator, 4mm leaf MLC Complex plan / dosimetry Fairly long irradiation time Hotspots: >115% prescribed dose 3.9Gy mean dose (α/β=2) Hippocampus 1cm leaf MLC Simple plan Short irradiation time Homogeneous, no hotspots

28 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

29 Objectives Start ( = Stap 1) BRAIN4-HC10 Min Dose BRAIN4-HC10 Uniform dose HIPPPOCAMPUS_R/L Max Dose LENS_R/L Max Dose Stap 2 BRAIN4-HC10 Min Dose BRAIN4-HC10 Uniform dose HIPPPOCAMPUS_R/L Max Dose LENS_R/L Max Dose

30 Stap 1 Stap 2

31 Objectives Stap 3 BRAIN4-HC10 Min Dose BRAIN4-HC10 Uniform dose HIPPPOCAMPUS_R/L Max Dose LENS_R/L Max Dose Stap 4 BRAIN4-HC10 Min Dose BRAIN4-HC10 Uniform dose HIPPPOCAMPUS_R/L Max Dose LENS_R/L Max Dose RingAnt (1,1,3,0,0,0) Max dose

32 Stap 3 Stap 4

33 Objectives Evt Stap 5 zelf toevoegen BRAIN4-HC10 Min Dose BRAIN4-HC10 Uniform dose HIPPPOCAMPUS_R/L Max Dose LENS_R/L Max Dose EYE_R/L Max DVH RingAnt (1,1,3,0,0,0) Max DVH

34 Uiteindelijke Plan

35 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

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