© 2017 Ion Beam Applications SA. All rights reserved.

RadKor 2017 - Ankara

Latest development in Proton Therapy

Gregory Saive, MEng, MBA

ProteusONE Global Product Manager

Disclaimer

PROPRIETARY INFORMATION

THE INFORMATION CONTAINED IN THIS DOCUMENT IS CONFIDENTIAL AND IS THE EXCLUSIVE PROPERTY OF IBA S.A. BELGIUM. THIS

INFORMATION IS SHARED FOR INFORMATION PURPOSES ONLY. THE REPRODUCTION, TRANSMISSION OR USE OF THIS INFORMATION IS

FORBIDDEN, UNLESS PRIOR WRITTEN PERMISSION OF IBA IS PROVIDED.

This document may contain express or implied forward-looking statements, opinions, expectations or analysis (the “Statements”). The Statements are

subject to a variety of risks and uncertainties, many of which are beyond IBA’s control, and some of which could cause actual results that differ materially from those contemplated in the Statements. IBA assumes no obligation nor makes

any warranty or commitment with respect to the Statements.

2

The starting point

3

IBA CONFIDENTIAL

Head & Neck example with unilateral radiation

Study conditions:

Unilateral irradiation

Similar target dose, schedule and constraints

4

Characteristic IMRT (N=23) Median PBT (N=18) Median P value

Target volume parotid only 129.5 cc 78.3 cc 0.934

Target volume parotid and ipsilateral neck 373.0 cc 314.3 cc 0.442

PTV max dose to 0.15 cc 72.0 Gy 71.5 CGE 0.554

Photons Protons

Courtesy of Dr Nancy Lee, MSKCC

Study conditions:

Unilateral irradiation

Similar target dose, schedule and constraints

IBA CONFIDENTIAL

Example with unilateral radiation - analysis and outcomes

5

Courtesy of Dr Nancy Lee, MSKCC

Brain stem DVH

Dose (cGy)

Dose (cGy)

Spinal cord DVH

Vo

lum

e (

%)

Vo

lum

e (

%)

Brain stem DVH

Spinal cord DVH

Dysgeusia Mucositis Nausea

20%

40%

60%IMRT

IMRT

IMRT

PBT

PBT

PBT

Dosimetric advantage of protons

translated into lower rates of acute

treatment-related toxicities

Dutch Model : 4 Categories Of Indications – 11.7% Of RT Patients

Standard : 0.4% of RT Improved Local Control : 2% of RT

Reduced Side Effects : 8% of RT Reduced 2nd Cancers : 1.3% of RT

- Eye

- Pediatrics

- Base of Skull

- Brain

- Intracranial

- Head & Neck

- Urologic (prostate & bladder)

- Lung (NSCLC)

- Sarcoma

- Reirradiation

- Breast

- Lymphoma

- Testis

- Intracranial

- H&N

- Urologic

- Lung

- Breast

- Gynecological

- GI (Esophagus, gastric,

rectal, pancreas)

- Lymphoma

- Sarcoma

« Model Based »

7

Update of NCCN guidelines in the US

The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 27 leading cancer centers devoted to patient care, research, and education

7

Update in March 2017

5 new indications where proton therapy is appropriate or may be appropriate in specific situations

Central Nervous System CancersIt is reasonable to consider proton beam for craniospinal irradiation where available as it is associated with less toxicity.

Head and Neck CancersIMRT or other conformal techniques (3-D conformal, helical tomotherapy, VMAT, and proton beam therapy [PBT]) may be used as appropriate depending on the stage, tumor location, physician training/experience, and available physics support.

Non-Small Cell Lung CancerMore advanced technologies are appropriate when needed to deliver curative RT safely. These technologies include (but are not limited to) 4D-CT and/or PET/CT simulation, IMRT/VMAT, IGRT, motion management, and proton therapy.

Hepatocellular CarcinomaProton beam therapy (PBT) may be appropriate in specific situations.

Eosophagial and Esophagogastric Junction CancersIntensity-modulated radiation therapy (IMRT) or proton beam therapy is appropriate in clinical settings where reduction in dose to organs at risk (eg. Heart, lungs) is required that cannot be achieved by 3-D techniques.

Update of ASTRO model policies for PT

Updated in June 2017

Recommendations for medical insurance coverage regarding the use of proton therapy to treat cancer

8

Based on new evidence published since the original

policy was issued in 2014, the updated model policy

outlines two categories of appropriate clinical indications,

or diagnoses, for proton beam therapy.

Group 1 Group 2

lists disease sites that frequently support

the use of Proton Beam Therapy

include all other indications for Coverage

with Evidence Development (CED)

Group 1 - May 2014 Ocular tumors, including intraocular melanomas

Tumors that approach or are located at the base of skull,

including but not limited to ;

Chordoma

Chondrosarcoma

Primary or metastatic tumor of the spine where the spinal cord

tolerance may be exceeded with conventional treatment or where

the spinal cord has previously been irradiated

Primary hepatocellular cancer treated in a hypofractionated

regimen

Primary or benign solid tumor in children treated with curative

intent and occasional palliative treatment of childhood when at

least one of the four criteria of the poly apply

Patient with genetic syndromes making total volume of irradiation

minimization crucial such as but not limited to NF-1 patients and

retinoblastoma patients

Group 1 - June 2017 Ocular tumors, including intraocular melanomas

Tumors that approach or are located at the base of skull,

including but not limited to ;

Chordoma

Chondrosarcoma

Primary or metastatic tumor of the spine where the spinal cord

tolerance may be exceeded with conventional treatment or where

the spinal cord has previously been irradiated

Primary hepatocellular cancer treated in a hypofractionated

regimen

Primary or benign solid tumor in children treated with curative

intent and occasional palliative treatment of childhood when at

least one of the four criteria of the poly apply

Patient with genetic syndromes making total volume of irradiation

minimization crucial such as but not limited to NF-1 patients and

retinoblastoma patients

Malignant and benign primary CNS tumors

Advanced (eg T4) and/or unresectable head and neck cancers

Cancers of the paranasal sinuses and other accessory sinuses

Non-metastatic retroperitoneal sarcomas

Re-iradiation cases (where cumulative critical structure dose

exceed tolerance dose)

Group 2 - May 2014 Head and neck malignancies

Thoracic malignancies

Abdominal malignancies

Pelvic malignancies, including genitourinary, gynecologic and

gastrointestinal carcinomas

Update of ASTRO model policies for PT

9

Group 2 - June 2017 Non T4 and resectable Head and neck malignancies

Thoracic malignancies, including non-metastatic primary lung

and esophageal cancers, and mediastinal lymphomas

Abdominal malignancies, including non-metastatic primary

pancreas, biliary and adrenal cancers

Pelvic malignancies, including genitourinary, gynecologic and

gastrointestinal carcinomas non-metastatic rectal anal, bladder

and cervical cancers

Non-metastatic prostate cancer

Breast cancer

IBA CONFIDENTIAL

Proton Therapy is growing

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2020: 41

2015: 21

2010: 10

2005: 4

2000: 3

2020: 44

2015: 20

2010: 13

2005: 11

2000: 10

2020: 35

2015: 15

2010: 7

2005: 5

2000: 1

* PTCOG 2017 Data including centers with eye treatments only

Centers treating from 2000 to 2020 per region*

IBA CONFIDENTIAL

IBA – a global leader in proton therapy

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Share of installed base - rooms

Total accumulated: 250 rooms

Including commercial PT rooms at end 2016

IBA market share is 56% in US, 54% in APAC

ex. Japan and 56% in EUR & ROW

IBA CONFIDENTIAL12

At the end of 2016 almost 60 000patients* treated on IBA equipment. More than all competitors combined

* Source: PTCOG 2015

61% of patients treated on IBA equipment

Number of patients treated

On commercial PT systems at end 2016

EMEA Market Status

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2000

2005

2010

2015

2020

What about Turkey ?

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163500 cancer patients in 2014

Source : Turkish MOH

Dutch report applied to Turkey

PT : 11,600 patients annually

Needs : 32 rooms today

Top 5 cases : Lung (32 %)

Breast (20%)

Colorectum (14%)

Prostate (8%)

Pediatrics (5%)

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3%4%

20%

1%

14%

1%1%

5%2%

32%

0%1% 2%

2%

1% 8%1%

0%

PT Patients Mix

Bladder

Brain, nervous system

Breast

Cervix uteri

Colorectum

Corpus uteri

Hodgkin lymphoma

Pediatrics

Lip, oral cavity

Lung

Nasopharynx

Non-Hodgkin lymphoma

Oesophagus

Other (Reirradiation)

Pancreas

Prostate

Stomach

Testis

0

10

20

30

40

50

60

0

50000

100000

150000

200000

250000

2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021

Cancer incidence PT rooms

Globocan

data

Turkish MOH

data

10% yearly increase

extrapolation

Needed Room in 2020 : 45

What are the barriers to acceptance?

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Affordability Technology Clinical evidences

How to improve affordability?

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Proteus®ONE*

Significant cost reduction

thanks to compactness

Less than

15 min

including CBCT for a 2 fields pelvic

treatment

Gantry and PPS22%

Imaging19%

Irradiation7%

Setup beam52%

Treatment beam48%

Setup beam52%

Efficient workflow similar to

linear accelerator

How to improve affordability?

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20%more efficient

Ambient

Experience

Solution

Open

environment

Wireless

Hand

Pendant

Shallow

tumor

optimization

Fixed oblique

flat panelsFast Delivery

Fast Room

Availability

~ +1500*extra fractions can be delivered per year in your

institution!

* 350 patients

What are the barriers to acceptance?

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Affordability Technology Clinical evidences

Pencil Beam Scanning: Smallest spot size

Best in class for cancers where lateral penumbra is critical Conformality improved

Treatment planning improved

Dosimetric advantage of IMPT

IBA

3 mm

Competitor 1

4 mm

Competitor 2

5 mm

Spot size comparison (σ)

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Image-Guided Proton Therapy

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Medium Field View CBCT Fully Integrated In-Room CT Large Field View CBCT

34cm x

34cm

50cm x

34cm

Complete toolset for motion management

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Fast and various

repainting strategyGating interfaceHigh speed irradiation for

breath-hold techniques

15seconds to irrediate

a 5x5x5 volume

Shallow tumor optimized treatment

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Small airgap improves critical organ sparing

Lateral penumbra typically decreased by 50%

Challenges in PT

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Conformality

Monitor &

Adapt

Motion

management

IBA CONFIDENTIAL25

LFOV

CBCT

Fast irradiation

Repainting

15s

Gating

Interplay

simulator

Treating moving targets

Ambient

Experience

RPD

Multiframe

imaging

Imaging

Beam

Integration

Workflow

What does already exist?

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motion

management?

patient-

specific

motion

mitigation

Planning phase Treatment phase

Verification

if planning

hypotheses

remain

validApply motion

mitigations as

planned

no

yes

Repainting

strategy ?

Repainting

strategy?

Available solutions:

Breath hold

Gating

Abdominal compression

Layer repainting

Volumetric repainting

4D planning and 4D robust optimisation

What is still missing : checking planning hypotheses before treatment

Verify treatment planning hypothesis: free breathing

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image orthogonal to beam axis

Multi frame: number of images in respiration cycle to reduce dose

Just before irradiation/during beam pauses

Low dose

Verify treatment planning hypotheses: 4D-CBCT

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MOTION

ANALYSIS

Visualisation small tumours

More rigourous motion pattern analysis

Currently available in

IBA CONFIDENTIAL29

Treating the H&N region

LFOV

CBCT

In-

Room

CT

Snouts

Airgap

tuner

TPS

Coaches

and immobilization

devices

Ambient

Experience

RPD

Wireless

hand

pendant

Imaging

Beam

Integration

Workflow

IBA CONFIDENTIAL

Online Clinical Indicators

IBA CONFIDENTIAL

Online Clinical Indicators

What are the barriers to acceptance?

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Affordability Technology Clinical evidences

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Organs at Risk Photon IMRT (70 Gy) Proton IMPT (70 Gy) Difference map

V5

V10

V15

V20

V25

V30

V35

V40

V45

V50

V55

V60

V65

V70

V5

V10

V15

V20

V25

V30

V35

V40

V45

V50

V55

V60

V65

V70

V5

V10

V15

V20

V25

V30

V35

V40

V45

V50

V55

V60

V65

V70

Esophagus inlet100 100 100 100 100 100 46 2 0 0 0 0 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0 0 93 100 100 100 100 100 46 2 0 0 0 0 0 0

Brain stem74 72 90 80 70 60 50 30 5 0 0 0 0 0 90 70 50 30 2 0 0 0 0 0 0 0 0 0 -16 2 40 50 68 60 50 30 5 0 0 0 0 0

Spinal cord74 72 71 69 67 66 64 44 14 0 0 0 0 0 45 38 37 35 21 6 0 0 0 0 0 0 0 0 29 33 34 34 46 60 64 44 14 0 0 0 0 0

Parotid gland right100 90 69 62 58 54 50 45 38 28 1 0 0 0 68 58 52 47 42 37 32 28 22 17 3 0 0 0 32 31 17 15 16 17 17 17 16 12 -1 0 0 0

Cricopharyngeus100 100 100 100 100 100 80 50 31 15 0 0 0 0 52 34 24 17 12 9 6 4 2 0 0 0 0 0 48 66 76 83 88 91 74 46 28 15 0 0 0 0

Submandibular gland R100 100 100 100 100 100 100 100 100 100 53 0 0 0 100 100 100 100 100 100 100 100 100 100 56 0 0 0 0 0 0 0 0 0 0 0 0 0 -3 0 0 0

Carotid artery100 100 98 97 90 80 77 67 56 56 50 40 20 0 100 100 100 90 70 56 41 40 34 20 10 0 0 0 0 0 -2 7 20 24 36 27 22 36 40 40 20 0

Glottis100 100 100 100 100 100 100 99 87 69 45 28 14 3 100 96 91 85 78 69 58 47 39 32 25 17 10 5 0 4 9 15 22 31 42 52 48 38 20 11 4 -2

Thyroid gland100 100 100 100 100 98 96 95 80 59 47 30 11 3 100 100 100 100 100 100 85 72 40 6 0 0 0 0 0 0 0 0 0 -2 11 23 40 53 47 30 11 3

Middle PCM100 100 100 100 100 100 100 100 100 100 74 67 61 4 100 100 100 100 100 99 97 95 92 85 64 62 59 49 0 0 0 0 0 1 3 5 8 15 10 5 1 -45

Inferior PCM100 100 100 100 100 100 100 99 81 57 41 36 28 8 99 94 88 82 75 69 64 58 52 43 32 26 22 16 1 6 12 18 25 31 36 41 29 14 9 10 6 -9

Supraglottis100 100 100 100 100 100 100 100 100 100 98 87 74 8 100 100 100 100 100 99 98 96 93 91 86 80 71 50 0 0 0 0 0 1 2 4 7 9 12 8 3 -42

Parotid gland left100 100 100 95 76 66 58 52 46 40 34 29 23 8 92 74 64 58 53 49 45 42 38 34 30 25 20 11 8 26 36 37 22 17 13 10 8 6 4 3 3 -2

Superior PCM100 100 100 100 100 100 100 100 100 98 95 84 71 35 100 100 100 100 100 99 97 95 92 85 64 62 50 34 0 0 0 0 0 1 3 5 8 13 31 22 21 1

Submandibular gland L100 100 100 100 100 100 100 100 100 100 100 98 88 43 100 100 100 100 100 100 100 100 100 50 12 0 0 0 0 0 0 0 0 0 0 0 0 50 88 98 88 43

Body volume (scan)45 40 39 30 23 20 18 15 13 10 6 4 3 1 25 22 18 16 14 12 11 10 9 8 5 4 3 2 20 18 21 14 9 8 7 5 3 2 1 0 0 -1

∆NTCP Model-Based

Courtesy Prof. Langendijk

Propose alternative evidences

Conclusion

Proton therapy market is growing

45 rooms should be built in Turkey by 2020

Barriers still exist but IBA develops adequate solutions

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Proteus®CLASS, world-class innovative proton therapy solutions

36

Secure the future of your patients

©2017 Ion Beam Applications SA. All rights reserved. Reproduction of any of the material contained

herein in any format or media without the prior and express written permission of Ion Beam Applications SA is prohibited.

Thank you

37

Gregory Saive, MEng, MBA