The Ultimate Healing Beam: The Future is Now

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The Ultimate Healing BeamThe Future is Now

• John Han-Chih Chang, MD
• Radiation Oncologist
• CDH Proton Center, a ProCure Center
• Primary Investigator for the Radiation Therapy
  Oncology Group
• Primary Investigator for the Childrens Oncology
  Group
• Childrens Memorial Hospital
• Vice Chair of the Midwest Childrens Brain Tumor
  Clinic

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Road Map

• Background
• History When and Where
• Proton Mechanics How to
• Applications/Prostate Cancer What for
• Conclusion

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High End Image Guided Glorified Tanning Booths
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Modality and Delivery Must Work Together
OPTIMAL RADIATION THERAPY
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Protons through the Ages
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Bragg PeakNamed after the British
physicistWilliam Henry Bragg (1862 - 1942)
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Protons Ancient History 101
Hydrogen Atom
R.R. Wilson, Radiology 1946 47487-491
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Scientists have been perfecting proton therapy as
a treatment for cancer for 65 years

• Robert R. Wilson, PhD
• "Radiological Use of Fast Protons" (Radiology
  194647487-91)
• Berkeley and Harvard
• Fermilab

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Protons History 101
1946 Robert Wilson proposes using protons
clinically
1955 The first patient is treated at Berkley
1961 The Harvard Cyclotron Lab (HCL) begins
therapy
1991 Loma Linda (LL) operates the first proton
gantry
2001 HCL closes ? NPTC opens
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Protons Modern History 101

• Loma Linda Univ Medical Center Loma Linda, CA
  1990
• MGH NPTC Boston, Massachusetts 2002
• MPRI Bloomington, Indiana 2004
• MDAH Houston, Texas 2006
• FPTI Jacksonville, Florida 2006
• PPC Oklahoma City, Oklahoma 2009
• RPTC Philadelphia, Pennsylvania 2010
• HUPTI Hampton, VA 2010
• CDH Chicago, IL 2010

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Proton therapy found its first clinical home in
California

• Loma Linda
• First patient 1990

• First facility designed as patient treatment
  center

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The CDH Proton Center, A Procure Center,
Warrenville, Ill.

We are dedicated to providing exceptional care
in a healing environment to patients with cancer
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Mechanism of Action
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Protons have Fewer Side Effects than Photons
There is no reason to irradiate healthy tissue
Protons deposit more than 80 of their energy in
the tumor
Photons deposit only 20 of their energy in the
tumor

• In order for photons to reach a prescribed dose
  at the tumor depth, healthy tissue gets four
  times the radiation as the tumor

• Protons put 80 of their energy into the tumor
  and only 20 into healthy tissue

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The Physics of Protons
Depth Dose Curves for Different Treatment Types
High Energy X-Rays
Spread Out Bragg Peak (SOBP)
100
80
Relative Dose
60
40
200 MeV Protons
20
Tumor
Healthy Tissue
Healthy Tissue
0
0
5
10
15
20
25
30
Depth in Tissue (cm)
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The Value of Protons

• Protons are physically superior to X-rays
• Protons behave differently than x-rays
• Protons
• X-Rays do not
• Protons improve the therapeutic ratio
• maximizing tumor control while minimizing side
  effects
• At a given radiation dose to a tumor protons
  deliver, on average, less than half the radiation
  dose to normal tissues than do x-rays 1

(1) Jay Loeffler, Massachusetts General Hospital,
Proton Therapy 2009
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Evidence of Distal Range Stopping
Before treatment
Treatment plan
After treatment
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Expected Integral Dose Vs. Tumor Conformity
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Why would we chose Protons?
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Production of Clinically-Useful Proton
Beams Proton Accelerators

• Cyclotron (spiral path)
• Constant magnetic field
• Variable Radius
• Continuous Beam

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Treatment Delivery
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Production of Clinically-Useful Proton Beams
Proton Accelerators - CYCLOTRON
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Production of Clinically-Useful Proton Beams
Beam Line
Energy Selection System (230 MeV ? 70 MeV) Beam
Transport and Switching System
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Gantry 1 NPTC- Harvard
Snout (with aperture compensator)
Nozzle
6-axis patient positioner
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Robotic Table
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Protons are delivered to patients in specialized
treatment rooms
Fixed Beam Room
Gantry Room
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Clinical Indications

• Current
• Pediatrics
• Paraspinal Ewings
• Optic pathway glioma
• Optic nerve meningioma
• Prostate/Pelvic RMS
• Exophytic BSG
• Craniospinal irradiation
• Suprasellar NGGCT
• Prostate
• Head and Neck/Base of Skull
• Intracranial
• Meningioma
• Paraspinal/Sacrum
• Chordoma

• Planned
• Lung
• Organ motion
• Density changes
• Tumor response
• Inspiration Expiration
• GI
• Organ motion
• Density changes
• Breast - API
• Lymphoma
• Ocular

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Prostate Cancer
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Radiation Treatment Options

• Radiation therapy options include
• Brachytherapy (BT) is vastly underutilized
• Effective
• Safe (in the appropriately selected patients)
• Convenient (1 to 2 day procedure)
• External Beam Radiation Therapy (EBRT) Proton
  beam is superior to IMRT
• Higher cure rates
• Lower complication rates
• Stereotactic Body Radiotherapy (SBRT)
• Effective
• Convenient (3 to 5 day non-invasive procedure)
• Safety seems to be similar to IMRT (it is still
  X-rays)

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Invasive
Non-Invasive
But, dont forget about active surveillance!
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Misconceptions About Proton Therapy
Just because someone keeps saying it doesnt
make it true.

• The typical quote The DVH of IMRT is better
  than the DVH of protons in the high dose region,
  and thats what really counts
• FACT Protons, regardless of delivery method,
  and with equivalent PTVs, should yield superior
  DVH curves without overlap
• The typical quote There is no data showing
  protons have better control rates
• FACT Protons do have better control
• By definition, protons will never have worse
  control rates than x-rays

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Misconceptions About Proton Therapy
Just because someone keeps saying it doesnt
make it true.

• The typical quote There is no data showing
  that side effects and complications (toxicity)
  are lower with protons
• FACT At a similar treatment dose and volumes,
  the toxicity is lower with protons
• The typical quote Protons are 2x to 5x times
  more expensive than IMRT
• FACT Protons are at most 40 60 more than
  IMRT, based on Medicare, and offer a much better
  value
• The lifetime costs of protons are much less than
  IMRT

Patient access must not be based on
misconceptions. We must rely on science and
data to drive these decisions.
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Protons have Fewer Side Effects than Photons
There is no reason to irradiate healthy tissue
Protons deposit more than 80 of their energy in
the tumor
Photons deposit only 20 of their energy in the
tumor

• In order for photons to reach a prescribed dose
  at the tumor depth, healthy tissue gets four
  times the radiation as the tumor

• Protons put 80 of their energy into the tumor
  and only 20 into healthy tissue

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Direct Radiation Complications Never Occur In
Unirradiated Tissues Dr. Herman Suit1
IMRT immerses more healthy tissue with radiation
Radiation Therapy Plans for Prostate Cancer
IMRT - 7-field co-planer
Proton Therapy - 2-field DS
Blue 13 Green 51 Purple 63 Yellow
76 Red 95
Tumor
Less healthy tissue exposed to radiation compared
to IMRT
Higher dose bath to healthy tissue with
IMRTPelvis, rectum and bladder

• Herman Suit, The Grey Lecture 2001 Coming
  Technological Advances in Radiation Oncology,
  International Journal of Radiation Oncology
  Biology Physics 53 No. 4 (2002) 798-809.

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Prostate Cancer Treatment Plans
IMRT- Protons Excess dose for IMRT
Protons
IMRT
Protons for rectum and bladder-dose is much lower
Dose - of dose
IMRT immerses more healthy tissue with low to
intermediate dose bath
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The Data Photons vs Protons
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Prostate Cancer
Proton Therapy vs. Conventional Radiation (by
dose) in Locally Advanced Prostate Cancer
Modality Dose Recurrence Complication
Conventional Radiation lt60 GY 38 22
Conventional Radiation 60 65 GY 36 35
Conventional Radiation 70 GY 28 45
Conventional Radiation gt75 GY 20 60
Protons 75 GY 15 12
Source Presentation by Dr. N. Mendenhall,
University of Florida, IBA
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Rectum
The limit of the photon modality
IMRT - MSK
3D CRT - MSK
IMRT - MGH
IMRT - UFPTI
Proton - MGH
Proton - UFPTI
Adapted from Zelefsky 2000, Trofimov 2007 and
Vargas 2008
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Rectal dose comparison
IMRT plans IMRT plans
Rectum V70
MSKCC 14
MGH 14.5
MDACC 15.5
UF 14

Protons UF 8
Zelefsky et al Radiotherapy and Oncology 2000
55241-249 Trofimov et al IJROBP 2007 69pp.
444453, Zhang et al IJROBP 2007 67
620629 Vargas et al IJROBP 2008 70 pp. 744751
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University of Florida Dosimetry Data Show Protons
Reduce Dose To The Rectum By 59
IJROBP 2008 Radiation dose to the rectum proton
therapy and IMRT1

• Background on study
• First prostate patients seen at University of
  Florida Proton Therapy Institute (UFPTI)
• Both proton and IMRT plans were planned
  prospectively for each patient
• The results
• Relative and absolute mean rectal dose savings of
  59.2 and 20.1, respectively, with proton
  therapy
• Why this is important
• Entire Dose Volume Histogram (DVH) does matter,
  not just high the dose region
• Rectal wall volume irradiated at 32.4 Gy is
  biggest predictor of rectal toxicity2
• Extremely high correlation between rectal volume
  irradiation to 70 Gy and 5-year toxicity rates3

90
80
IMRT
70
60
50
Rectal Volume Receiving Radiation ()
Dose to rectum is more than 2x with IMRT vs.
protons at 32 Gy
40
30
Dose to rectum is almost 2x with IMRT vs. protons
at 70 Gy
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Proton
10
0
0
10
20
30
40
50
60
70
80
90
Radiation Dose (CGE/Gy)

• Carlos Vargas et al., Dose-Volume Comparison of
  Proton Therapy and Intensity-Modulated
  Radiotherapy for Prostate Cancer, International
  Journal of Radiation Oncology Biology Physics 70
  No.3 (2008) 744-751.
• Susan Tucker, Lei Dong, Rex Cheung, et al.,
  Comparison of Rectal Dose-Wall Histogram Versus
  Dose-Volume Histogram for Modeling the Incidence
  of Late Rectal Bleeding After Radiotherapy,
  International Journal of Radiation Oncology
  Biology Physics 60 (2004) 1589-1601.
• Mark Storey, Alan Pollack, Gunar Zagars et al.,
  Complications from Radiotherapy Dose Escalation
  in Prostate Cancer Preliminary Results of a
  Randomized Trial, International Journal of
  Radiation Oncology Biology Physics 48 (2000)
  635-642.

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GI (Rectal) Side Effects and Complications
The probability of damage to the GI tract is much
higherwith x-rays than protons
Chronic Radiation Proctitis in the GI tract
Inflammation causedby radiation
Necrosis and ulcer
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Dose Escalation Trials Support the Use of Protons
for Prostate Cancer
Protons offer better control and lower toxicity
than X-Rays
Randomized Boost Planning High 5-year GI toxicity GI toxicity
trial1-4 Modality Technique dose arm control G2 G3
MD Anderson X-rays 2-D/3-D 78.0 Gy 78 28 10
CKVO96-10 X-rays 3-D 78.0 Gy 64 32 5
MRC RT01 X-rays 3-D 74.0 Gy 71 33 10
PROG 95-09 X-rays/Protons 3-D 79.2 Gy 92 17 1
The best outcome for control AND toxicity was
achieved using protons

1. DA Kuban, SL Tucker, L Dong et al., Long-term
   results of the M.D. Anderson randomized
   dose-escalation trial for prostate cancer,
   International Journal of Radiation Oncology
   Biology Physics 70 (2008) 67-74. (Note toxicity
   updated from Viani et al, ref 6)
2. ST Peters, WD Heemsbergen, PC Koper et al.,
   Dose-response in radiotherapy for localized
   prostate cancer results of the Dutch multicenter
   randomized phase III trial comparing 68 Gy of
   radiotherapy with 78 Gy, 24 (2006) 1990-1196.
3. DP Dearnaley, MR Sydes, JD Graham et al,
   Escalated-dose versus standard-dose conformal
   radiotherapy in prostate cancer first results
   from the MRC RT101 randomized controlled trial,
   Lancet Oncology 8 (2007) 475-487.
4. Anthony L. Zietman, Correction Inaccurate
   analysis and results in a Study of Radiation
   Therapy in Adenocarcinoma of the Prostate, JAMA
   299 No. 8 (2008) 898-900. Anthony L. Zietman et
   al., Comparison of Conventional-Dose vs.
   High-Dose Conformal Radiation Therapy in
   Clinically Localized Adenocarcinoma of the
   Prostate. A Randomized Controlled Trial, JAMA
   294 No. 10 (2005) 1233-1239.
5. Beckendorf V, Guerif S, Le Prise E, et al. The
   GETUG 70 Gy vs. 80 Gy randomized trial for
   localized prostate cancer Feasibility and acute
   toxicity. Int J Radiat Oncol Biol Phys 200460
   10561065. (Note no 5-year control rates given)
6. Viani GA et al. Higher-than-conventional
   radiation doses in localized prostate cancer
   treatment a meta-analysis of randomized,
   controlled trials. Int J Radiat Oncol Biol Phys.
   2009 Aug 174(5)1405-18.

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Reviewing the Data
Parameter PROG 9509 MSK
Collection Prospective Retrospective
Institutions Multi-instituion Single-instituion
Follow-up gt10 year 8 years
Photon RT 3D CRT IMRT
Image Guidance? No Yes

The Only Difference Proton Boost The Only Difference Proton Boost The Only Difference Proton Boost
i.e., this wasnt even all protons this was protons tacked onto what would be considered, by todays standards, inferior radiation therapy i.e., this wasnt even all protons this was protons tacked onto what would be considered, by todays standards, inferior radiation therapy i.e., this wasnt even all protons this was protons tacked onto what would be considered, by todays standards, inferior radiation therapy
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Protons are Safer and More Effective
Protons significantly decrease the risk of
secondary malignancies in prostate cancer
treatment over 5 year period
A 2008 MGH study determined that protons
decreases the risk of patients developing a
secondary cancer by 50(1)
Modality Risk of Induced Tumor
Baseline risk2 4
Conventional3 10
IMRT4 11-15
Protons5 6

1. Comparative Analysis of Second Malignancy Risk
   in Patients Treated with Proton Therapy versus
   Conventional Photon Therapy, presented by Nancy
   Tarbell, M.D. at ASTRO 2008 (Chung et al. study)
2. SEER data
3. McGee et al., Comparison of Second Cancer Risk
   in Prostate Cancer Patients Treated with
   Neutron/Photon Irradiation, Photon Irradiation,
   or Prostatectomy, International Journal
   Radiation Oncology Biology Physics 66 (2006)
   S318-S319
4. Fontenot et al., Risk of secondary malignant
   neoplasms from proton therapy and
   intensity-modulated x-ray therapy for early-stage
   prostate cancer, International Journal Radiation
   Oncology Biology Physics 74 (2009) 616-622
5. Chung et al., Comparative Analysis of Second
   Malignancy Risk in Patients Treated with Proton
   Therapy versus Conventional Photon Therapy,
   International Journal Radiation Oncology Biology
   Physics 72 (2008) S8

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Prostate Cancer Summary

• Protons are AN option for prostate cancer
  treatment
• Protons are superior to IMRT
• Protons are different from surgery and
  brachytherapy
• Active surveillance is perfectly acceptable for
  many men with prostate cancer
• Discussions should be had with patients about ALL
  the options

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Parting Shots

• Take home points
• All cancers should be approached in a
  multi-specialty or multi-disciplinary fashion
• Patient care should be performed in team
  approach
• Concierge/Receptionists, Nurses, Therapists,
  Physicists/Dosimetrists, Physicians
• State of the Art Radiation Therapy _at_ CDH/Procure
• FULL Spectrum of Radiation Treatment options
• HDR Brachytherapy
• SBRT/SRS
• IMRT/3D CRT/IGRT
• Proton Beam Therapy

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Parting Shots

• Photons/Electrons will still be needed
• Brachytherapy will still be utilized
• Image guidance will remain critical for all
  modalities of radiation therapy
• Proton beam therapy can improve the side effects
  profile in many of the disease we currently treat
  with photon radiation.
• We are seeing just the tip of the iceberg

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Tumors we are and will be able to treat

• Head / Neck
• Eye
• Sinus/nasal
• Throat
• Ear

• Pediatric
• Brain
• Spinal Cord
• Bone

• Neurologic
• Brain
• Spinal Cord

• Other Solid Tumors
• Breast Cancer (2011)
• Lung Cancer (2011)
• Colorectal Cancer
• Prostate

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Questions