Transcript Mesothelioma PDT talk

The Ultimate Healing Beam:
The 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 Children’s Oncology Group
Children’s Memorial Hospital
Vice Chair of the Midwest Children’s Brain Tumor Clinic
Road Map
 Background
 History – When and Where
 Proton Mechanics – How to
 Applications/Prostate Cancer – What for
 Conclusion
High End Image Guided
Glorified Tanning Booths
Modality and Delivery Must Work
Together
Techniques to Improve
Radiation Delivery
Radiation Modality
OPTIMAL
RADIATION
THERAPY
Protons through the Ages
Bragg Peak
Named after the British physicist
William Henry Bragg (1862 - 1942)
Protons: “Ancient” History 101
Hydrogen Atom
R.R. Wilson, Radiology 1946; 47:487-491
Scientists have been perfecting proton therapy as a
treatment for cancer for 65 years
 Robert R. Wilson, PhD
 "Radiological Use of Fast
Protons" (Radiology
1946:47:487-91)
 Berkeley and Harvard
 Fermilab
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
Protons: “Modern” History 101
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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
10
Proton therapy found its first clinical home in California
 Loma Linda
 First patient 1990
 First facility designed as patient
treatment center
The CDH Proton Center, A Procure Center, Warrenville, Ill.
We are dedicated to
providing exceptional
care in a healing
environment to patients
with cancer
Mechanism of Action
Protons have Fewer Side Effects than Photons
There is no reason to irradiate healthy tissue
Photons deposit only 20% of their energy in the tumor
Photons deposit only 20% of their energy in the tumor
Protons deposit more than 80% of their energy in the tumor
Higher
20%
Radiation Dose
Radiation Dose
Higher
Prescribed Dose
to Kill Tumor
80%
0%
Prescribed Dose
to Kill Tumor
Lower
Lower
70%
20%
Depth in Tissue
 In order for photons to reach a
prescribed dose at the tumor depth,
healthy tissue gets four times the
radiation as the tumor
10%
Depth in Tissue
 Protons put 80% of their energy into the
tumor and only 20% into healthy tissue
The Physics of Protons
Depth Dose Curves for Different Treatment Types
High Energy X-Rays
Spread Out Bragg Peak (SOBP)
Relative Dose
100
80
60
40
200 MeV Protons
20
Tumor
Healthy Tissue
Healthy Tissue
0
0
5
10
15
20
Depth in Tissue (cm)
25
30
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
16
(1) Jay Loeffler, Massachusetts General Hospital, “Proton Therapy 2009”
Evidence of Distal Range Stopping
Before treatment
Treatment plan
After treatment
Why would we chose Protons?
Production of Clinically-Useful Proton Beams
Proton Accelerators
Cyclotron (spiral path)
Constant magnetic field
Variable Radius
Continuous Beam
Treatment Delivery
Production of Clinically-Useful Proton Beams
Proton Accelerators - CYCLOTRON
Production of Clinically-Useful Proton Beams
Beam Line
Energy Selection System (230 MeV  70 MeV)
Beam Transport and Switching System
Gantry 1 NPTC- Harvard
Nozzle
Snout (with aperture &
compensator)
6-axis patient positioner
Robotic Table
Protons are delivered to patients in specialized treatment
rooms
Fixed Beam Room
Gantry Room
Clinical Indications
 Current
 Pediatrics
 Paraspinal Ewing’s
 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
Prostate Cancer
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)
Definitive
Therapy
Surgery
Open
Brachytherapy
Laparoscopic
(Da Vinci)
Low-Dose Rate
High-Dose
Rate
External-Beam
Radiation
X-Ray
(IMRT &
SBRT)
Proton Beam
Definitive
Therapy
Invasive
Surgery
Open
Laparoscopic
(Da Vinci)
Brachytherapy
Low-Dose Rate
High-Dose
Rate
External-Beam
Non-Invasive
Radiation
X-Ray
(IMRT &
SBRT)
But, don’t forget about active surveillance!
Proton Beam
Misconceptions About
Proton Therapy
“Just because someone keeps saying it doesn’t make it true.”
 The typical quote: “The DVH of IMRT is better than the DVH
of protons in the high dose region, and that’s 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
Misconceptions About
Proton Therapy
“Just because someone keeps saying it doesn’t 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.
Protons have Fewer Side Effects than Photons
There is no reason to irradiate healthy tissue
Photons deposit only 20% of their energy in the tumor
Photons deposit only 20% of their energy in the tumor
Protons deposit more than 80% of their energy in the tumor
Higher
20%
Radiation Dose
Radiation Dose
Higher
Prescribed Dose
to Kill Tumor
80%
0%
Prescribed Dose
to Kill Tumor
Lower
Lower
70%
20%
Depth in Tissue
 In order for photons to reach a
prescribed dose at the tumor depth,
healthy tissue gets four times the
radiation as the tumor
10%
Depth in Tissue
 Protons put 80% of their energy into the
tumor and only 20% into healthy tissue
“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 –
Higher dose bath to healthy tissue with IMRT:
Pelvis, rectum and bladder
(1)
95%
Tumor
Less healthy tissue exposed to radiation
compared to IMRT
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.
36
Prostate Cancer Treatment Plans
Protons
IMRT
IMRT- Protons:
Excess dose for IMRT
Protons for
rectum and
bladder-dose
is much
lower
Dose -% of dose
IMRT immerses more healthy tissue with low to intermediate dose bath
The Data: Photons vs Protons
Prostate Cancer
Proton Therapy vs. Conventional Radiation (by dose) in
Locally Advanced Prostate Cancer
Modality
Dose
Recurrence
Complication
Conventional Radiation
<60 GY
38%
22%
Conventional Radiation
60 – 65 GY
36%
35%
Conventional Radiation
70 GY
28%
45%
Conventional Radiation
>75 GY
20%
60%
Protons
75 GY
15%
12%
Source: Presentation by Dr. N. Mendenhall, University of Florida, IBA
Rectum
Rectum
100
90
80
Volume
The limit of the
photon modality
IMRT - MSK
70
3D CRT - MSK
60
IMRT - MGH
50
IMRT - UFPTI
40
Proton - MGH
30
20
Proton - UFPTI
10
0
10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
Dose
Adapted from Zelefsky 2000, Trofimov 2007 and Vargas 2008
Rectal dose comparison
IMRT plans
Rectum V70
MSKCC
14%
MGH
14.5%
MDACC
15.5%
UF
14%
Protons UF
8%
Zelefsky et al Radiotherapy and Oncology 2000; 55:241-249
Trofimov et al IJROBP 2007; 69:pp. 444–453,
Zhang et al IJROBP 2007; 67: 620–629
Vargas et al IJROBP 2008; 70: pp. 744–751
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
Rectal Volume Receiving Radiation (%)
90%
80%
IMRT
70%

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

60%
50%
Why this is important
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

20%
Relative and absolute mean rectal dose savings of 59.2%
and 20.1%, respectively, with proton therapy
Proton
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
10%
0%
0
(1)
(2)
(3)
10
20
30
40
50
60
70
Radiation Dose (CGE/Gy)
80
90
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.
GI (Rectal) Side Effects and Complications
The probability of damage to the GI tract is much higher
with x-rays than protons
Chronic Radiation Proctitis in the
GI tract
Inflammation caused
by radiation
43
Necrosis and ulcer
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
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%
trial1-4
GI toxicity
The best outcome for control AND toxicity was achieved
using protons
(1)
(2)
(3)
(4)
(5)
(6)
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)
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.
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.
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.
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 2004;60: 1056–1065. (Note: no 5-year
control rates given)
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 1;74(5):1405-18.
Reviewing the Data
Parameter
PROG 9509
MSK
Collection
Prospective
Retrospective
Institutions
Multi-instituion
Single-instituion
Follow-up
>10 year
8 years
Photon RT
3D CRT
IMRT
Image Guidance?
No
Yes
The Only Difference – Proton Boost
i.e., this wasn’t even all protons – this was protons tacked onto what would be
considered, by today’s standards, inferior radiation therapy
Protons are Safer and More Effective
A 2008 MGH study determined that protons
decreases the risk of patients developing a
secondary cancer by 50%(1)
“According to the study, 6.4 percent of patients who
underwent proton therapy developed a secondary
cancer while 12.8 percent of patients who had photon
treatment [x-rays] developed another type of cancer.”
Protons significantly decrease the risk of secondary
malignancies in prostate cancer treatment over 5
year period
Modality
Baseline risk2
4%
Conventional3
10%
IMRT4
Protons5
(1)
(2)
(3)
(4)
(5)
Risk of Induced Tumor
11-15%
6%
“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)
SEER data
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
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
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
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
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 @ CDH/Procure
FULL Spectrum of Radiation Treatment options
HDR Brachytherapy
SBRT/SRS
IMRT/3D CRT/IGRT
Proton Beam Therapy
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
Tumors we are and will be able to treat:
Head / Neck
•
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Eye
Sinus/nasal
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Throat
•
Ear
Pediatric
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Brain
•
Spinal Cord
•
Bone
Neurologic
Other Solid Tumors
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Brain
•
Breast Cancer (2011)
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Spinal Cord
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Lung Cancer (2011)
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Colorectal Cancer
•
Prostate
Questions