SYDNEY MEDICAL SCHOOL

John Kipritidis, CINSW Early Career Fellow

Radiation Physics Laboratory

UNIVERSITY OF SYDNEY

Innovations in Cancer Treatment and Care Conference

October 17th 2014

Can we use Ventilation Imaging to measure, predict and reduce

pulmonary function loss in lung cancer radiotherapy?

Acknowledgements

Peter MacCallum Cancer Centre

Prof. Michael Hofman.

Dr Shankar Siva

Jason Callahan

Prof. Rodney Hicks

DisclosureSupported by a Cancer Institute NSW Early Career Fellowship, NHMRC Australia Fellowship,

NHMRC project grant 1034060 and NIH/NCI P01CA116602.

University of Sydney

Prof Paul Keall

Dr John Kipritidis

Dr Enid Eslick

Andy Shieh

Virginia Commonwealth Univ.

Jeffrey Williamson, Ph.D.

Geoffrey Hugo, Ph.D.

Elisabeth Weiss, Ph.D.

Contributing authors:

Special thanks:

Nepean Cancer Care Centre

Dr Fiona Hegi-Johnson

Dr Roland Yeghiaian-Alvandi

Jeffrey Barber

Dr Chuong Bui

Katrina West

Kylie Unicomb

University of Sydney

Dr Ricky O’Brien

Benjamin Cooper

Royal North Shore Hospital

Dr Dale Bailey

Dr Jeremy Booth

› 10-30% of lung cancer radiotherapy patients experience radiation-induced lung toxicity (RILT)

› Functionally weighted dose-volume metrics can outperform standard dose-volume metrics as

a predictor of RILT;

c.f. Hoover et al. 2014. J Med Imaging Radiat Oncol 58 (2)

› Functional image-guided treatment planning requires functional imaging! `Gold standard' is

SPECT ventilation / perfusion.

4

(i) Why is ventilation imaging important in lung

cancer radiotherapy?

Peter MacCallum Cancer Centre

Technegas SPECT Galligas PET

Nepean Cancer Care Centre

› “CT-ventilation imaging” models regional air volume change in terms of regional lung volume

(or intensity) changes during the breathing cycle.

c.f. Guerrero et al. (IJROBP 2005)

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(ii) Innovative ventilation imaging using 4D-CT

4DCT data courtesy of

Nepean Cancer Care Centre

(i) Acquire 4D-CT (ii) Deformable image registration (iii) Quantify volume/intensity

change

high

low

Ventilation

Main advantages:

High accessibility

High resolution (same as CT)

No-extra cost in scan time / imaging dose (just image processing!)

› CT-ventilation will allow greater access to functional image guided radiotherapy treatment planning, with

the potential to reduce functionally-weighted mean lung dose by 2-5 Gy.

(iii) How could CT-ventilation be practice-changing?

Yamamoto et al. 2011

IJROBP 79 (1)

› In-room 4D cone beam CT could maximise sparing of functional

lung by enabling adaptive functional image guidance:

Modalities 4D-CT 4D-CBCT SPECT V/Q 4D-PET V/Q PFTs

4D-CT VCU VCU NCCCPMCC

RNSH

RNSH

NCCC

BH-CT RNSH RNSH RNSH

4D-CBCT VCU VCU NCCC NCCC

• NCCC = Nepean Cancer Care Centre (Ongoing QA study)

• RNSH = Royal North Shore Hospital (Ongoing prospective trial)

• PMCC = Peter MacCallum Cancer Centre (Ongoing prospective trial)

• VCU = Virginia Commonwealth University (Existing database from earlier study)

We are aiming to validate CT-ventilation imaging across multiple modalities:

LEGEND Under-wayHappening

soon

Not

yet

(iv) How is CT-ventilation being validated?

8

high

low

Ventilation

Patient 7 (Best case)

4D-CT ventilation:

PET ventilation: VPET

Std

rVHU

MC

(iv) How is CT-ventilation being validated?

› 12-patient comparison* using baseline Galligas 4D-PET/CT scans.

› Strongest voxel-wise correlation with nuclear medicine ventilation imaging (so far!)

*Kipritidis et al. Med Phys 2014 41(1)

Data courtesy of Peter MacCallum Cancer Centre

(Melbourne, VIC Australia)

12 patients:

9

Data courtesy of Nepean Cancer Care Centre

(Penrith, NSW Australia)

(iv) How is CT-ventilation being validated?

high

low

Ventilation

4D-CBCT ventilation:

SPECT perfusion:

› Comparing daily 4D-CBCT ventilation images to baseline Q-SPECT in lung SBRT patients:

› Ongoing QA study; comparison of functional changes underway.

5 patients:

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• Comparing CT ventilation to Technegas V-SPECT:

Technegas V-SPECTCT ventilation

(HU based)

Data courtesy of Nepean Cancer Care Centre

(Penrith, NSW Australia)

(iv) How is CT-ventilation being validated?

Author Reference

modality

Subjects Dice similarity Voxel-wise

correlation

Fuld et al.

(J Apply Physiol 2008)

Xe-CT 4 sheep ~ 0.81

(Small ROIs)

Reinhardt / Ding et al.

(Med. Image Anal.

2008)

Xe-CT 5 sheep ~ 0.85

(Small ROIs)

Yamamoto et al.

(IWPIA 2010)

SPECT V/Q 1 patient ~ 0.18/0.48

(Whole lung)

Castillo et al.

(PMB 2010)

SPECT V 7 patients 0.30-0.35

(low function)

~

Castillo et al.

(PMB 2012)

SPECT Q 10 patients 0.78

(low function)

~

Mathew et al.

(Med. Phys. 2012)

3He-MRI 11 patients 0.86-0.88

(good function)

~

Kipritidis, Siva et al. Ga 4D PET/CT 12 patients 0.38-0.68

(low function)

0.22-0.76

(Whole lung)

Hegi-Johnson et al. SPECT V/Q 30 patients

(goal)

TBA TBA

Eslick et al. Ga PET/CT 30 patients

(goal)

TBA TBA

(iv) How is CT-ventilation being validated?

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4D-CBCT patient study:

o 19 locally advanced NSCLC patients received daily 4D-CBCTs over 4-6 weeks

o We generated 56 interfraction pairs (Week 1 vs. Weeks 2, 4 and 6).

o Main question: How does ventilation change during radiotherapy treatment?

(v) New technologies, new questions

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First day

Week 2

Week 4

Week 6

First day

Week 2

Week 4

Week 6

Sca

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Ventilation increase

Transient change

Stable

Ventilation decrease

Highly variable

• 4D-CBCT ventilation images can exhibit a wide range of changes

(both positive and negative!) during treatment.

• Adaptive functional image guidance is important as poor-functioning

lung can re-ventilate.

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• Patients breathe differently from day-to-day (and breath-to-breath!)

4D-CBCTs courtesy Virginia Commonwealth Univ.

(Richmond, VA USA)

(v) New technologies, new questions

• Intrafraction changes can sometimes exceed interfraction changes.

• Careful normalisation of serial images is required.

› CT-ventilation imaging: a potentially practice-changing technology enabling (adaptive)

functional image guidance in radiotherapy treatment planning.

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Take home messages

› In-room ventilation imaging: innovative technology driving new questions.

› Australian researchers are driving world-first validation studies across multiple imaging

modalities.

SYDNEY MEDICAL SCHOOL

Thanks for listening!

Radiation Physics Laboratory

UNIVERSITY OF SYDNEY

John Kipritidis, CINSW Early Career Fellow

john.kipritidis@sydney.edu.au