Download Proton Therapy and the Risks of Irrational Exuberance

Proton Therapy and the Risks of
Irrational Exuberance
David Shepard
AAMD Annual Meeting - Seattle
June 1, 2014
Acknowledgments
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Thomas Bortfeld
Martijn Engelsman
Alexei Trofimov
Lei Dong
Daniel Ollendorf
Daniel Lessler
4/22/14
Questions
• Is this rapid growth based on
good fundamentals or
irrational exuberance?
• What does the future hold
for proton therapy?
• Is the proton bubble about to
burst?
“I’m fascinated and horrified by
the way it’s developing. This is
the dark side of American
medicine.”
Anthony Zietman – Endowed professor of
radiation oncology @ Harvard, Editor of the
Red Journal, Chair and Past President of
ASTRO
NYT – 12/26/07
“Proton-beam therapy is like the
death star of American medical
technology; nothing so big and
complicated has ever been
confronted by the system. It’s a
metaphor for all the problems that
we have in American medicine.”
Amitabh Chandra – Health Economist – John F.
Kennedy School of Government @ Harvard
Business Week 3/26/12
Key Questions
1. Are protons better dosimetrically?
2. Are protons better clinically?
3. What are the financial implications?
Key Questions
1. Are protons better dosimetrically?
2. Are protons better clinically?
3. What are the financial implications?
GoodThe
News
is that
good
newsprotons
is that stop.
protons stop.
The bad news is that we often do not know
exactly where they will stop.
Proton dose distributions are highly sensitive to changes in anatomy or
tissue densities such as bowel filling or a clogged up sinus.
Courtesy of Martijn Engelsman
Proton Uncertainties
Proton beams are much more sensitive to
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Anatomy changes in the beam path
Organ Motion
CT number accuracy
Treatment devices in the beam path
Issues 1: Range uncertainties due to setup
Jan 08
Chen, Rosenthal, et al., IJROBP 48(3):339, 2000
Courtesy of Thomas Bortfeld
Issues 1: Range uncertainties due to setup
Jan 11
Chen, Rosenthal, et al., IJROBP 48(3):339, 2000
Courtesy of Thomas Bortfeld
Distal Variations Due to Femur Rotation
Alexei Trofimov and Lei Dong
Photon IMRT
Protons
“To minimize the effects of the range uncertainties, prostate
patients are typically irradiated using opposed lateral proton beams
which generally forces at least a portion of the dose limiting
anterior rectal wall into the high dose region.”
Alexei Trofimov
Issues 2: Range effects of breathing, 4D CT
exhale
inhale
95%
95%
Engelsman et al., IJROBP 64(5):1589-1595, 2006
Courtesy of Thomas Bortfeld
Tumor Shrinkage
Initial Planning CT
GTV 115 cc
5 weeks later
GTV 39 cc
S. Mori, G. Chen
Courtesy of Thomas Bortfeld
Tumor shrinkage results in proton overshoot
Planning CT (T40%)
Beam stops at distal edge
CT after 5 weeks (T40%)
Beam overshoot
S. Mori, G. Chen
Courtesy of Thomas Bortfeld
Spherical tumor in lung
The “static dose cloud” approximation
Paralell opposed photons
Single field photons
Single field protons
Displayed isodose levels: 50%, 80%, 95% and 100%
Courtesy of Thomas Bortfeld
Spherical tumor in lung
The “static dose cloud” approximation
Paralell opposed photons
Single field photons
Single field protons
Displayed isodose levels: 50%, 80%, 95% and 100%
Courtesy of Thomas Bortfeld
Spherical tumor in lung
The “static dose cloud” approximation
Paralell opposed photons
Single field photons
Single field protons
Displayed isodose levels: 50%, 80%, 95% and 100%
Courtesy of Thomas Bortfeld
CT artifacts
High-density streak artifacts
 Density override
Contrast / Onyx glue
 Multiple CT-scans
 Density override
Proton Reality Check
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Protons plans are kept simple using 1, 2, or 3 fields.
Patient alignment with proton therapy is typically
achieved using orthogonal 2D images rather than IGRT
despite the fact that proton treatments are much more
sensitive to organ motion.
While there is great interest in pencil beam scanning, the
actual utilization of pencil beam scanning and IMPT is
quite low.
Are protons better dosimetrically?
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In many cases, the answer is NO.
Because proton plans are highly sensitive to organ
motion, changes in anatomy, and errors in CT number
accuracy, the quality of the delivered dose distribution
can be seriously compromised.
Using photons makes it possible to use tighter margins
and take advantage of techniques such as intensity
modulation, VMAT, and IGRT.
Key Questions
1. Are protons better dosimetrically?
2. Are protons better clinically?
3. What are the financial implications?
History of Proton Therapy
• Proton treatments were first delivered in the 1950s.
• First hospital based program in the U.S. was built in
1990 in Loma Linda, CA.
• Despite the fact that over 100,000 patients have
been treated with proton therapy, there is very little
clinical evidence to support their use.
“The evidence that proton therapy has
helped any cancer patient either live
longer or with a better quality of life, in
comparison with 3D-CRT, is almost nonexistent. Furthermore, there is
substantial risk that the outcome may
be worse after proton therapy.”
Bhadrasain Vikram, MD - Chief of the Clinical
Radiation Oncology Branch at the NCI
Perils of Proton Therapy - 2009
“There is no solid clinical evidence to
date that protons are better. If you
are going to spend a lot more money,
you want to make sure the patient
can detect an improvement, not just
a theoretical improvement.”
Dr. Theodore Lawrence – Chairman of Radiation
Oncology @ University of Michigan, ASTRO Gold
Medal Winner, and ASTRO past president
NYT – 12/26/07
“Statements about their superiority
are just unjustified. They are
unsupportable. The bottom line is
that it hasn’t been proven to be
better.”
W. Robert Lee – Professor of Radiation Oncology
@ Duke University Medical School, Editor of
Practical Radiation Oncology (PRO)
Business Week – 3/26/12
Proton Beam Therapy
An Assessment of
Comparative Clinical Effectiveness
& Comparative Value
Presented to the Washington State Health Care Authority by
Daniel A. Ollendorf, MPH
May 16, 2014
Condition
Cancer
Bone
Brain/spinal
Breast
Esophageal
GI
Gynecologic
Head/neck
Liver
Lung
Lymphomas
Ocular
Pediatric
Prostate
Sarcomas
Seminoma
Thymoma
Noncancerous
AVMs
Hemangiomas
Other
Incidence
(per 100,000)
Net Health
Benefit vs.
Comparators
Type of Net
Health Benefit
Strength of
Evidence
Guideline
Recommendations
Coverage
Policies
1.3
9.6
97.7
7.5
100.6
38.2
17.2
12.8
95.0
32.9
1.2
9.1
99.4
4.8
4.0
0.2
Insufficient
Incremental
Insufficient
Insufficient
Insufficient
Insufficient
Insufficient
Comparable
Comparable
Insufficient
Superior
Incremental
Comparable
Insufficient
Insufficient
Insufficient
--B: = H: ↓
----------B: = H: =
B: = H: =
--B: ↑ H: ↓
B: = H: ↓
B: = H: =
-------
+
+
o
o
o
o
+
+
++
o
++
o*
++
o
o
o
M
U
NM
NM
NM
NM
NM
NM
M
NR/NC
U
U
M
NM
NM
NM
M
U
NR/NC
NR/NC
NR/NC
NR/NC
M
M
M
NR/NC
U
U
M
M
NM
NM
1.0
2.0
2.0
Insufficient
Comparable
Insufficient
--B: = H: =
---
o
+
o
NM
NM
NM
M
NM
M
*Rating based on widespread acceptance rather than evidence base
B: Benefits; H: Harms
Strength of Evidence: Low=+; Moderate=++; High=+++; No evidence=o
Legend: U=Universally recommended or covered; M=Mixed recommendations or coverage
policies; NM=Not mentioned in guidelines or coverage policies; NR/NC=Not recommended or
not covered
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Summary & Conclusions
Comparative evidence generated to date for PBT is sparse and of
generally lower quality:
> Moderate evidence of superior net health benefit only available for ocular
cancers
> Judgment of incremental benefit for brain and spinal tumors, but with low
strength of evidence
> Acceptance of PBT for pediatric cancers based on assumption of benefit from
dosimetry and simulation, not clinical study
> Even situations with evidence suggesting “comparable” performance to
alternatives (liver, lung, and prostate cancer, hemangiomas), strength of
evidence was low or moderate
Ongoing RCTs and registries will provide opportunity to revisit
evidence base as it emerges
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Key Questions
1. Is it better dosimetrically?
2. Is it better clinically?
3. What are the financial implications?
Costs of a Proton Center
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Mayo Clinic - $370 million for 2 (MN & AZ)
Scripps Health - $220 million (San Diego)
MSKCC - $250 million (NYC)
Hampton University - $225 million (Virginia)
Univ. Maryland - $200 million (Baltimore)
The operational costs of a proton therapy are also very high due to the
substantial number of clinical and technical staff needed as well as
the specialized staff for maintaining the particle accelerator.
Who is paying for all of
these new proton
centers?
Forbes Magazine: “Most of the $1.5 billion that has
been sunk into or committed to building proton
therapy centers has come from investors hoping to
make a profit.”
Forbes – 3/25/09
Forbes Magazine article featuring ProCure CEO
Hadley Ford:
“A fully operational proton center with four treatment rooms
running 6 days a week, 16 hours a day - a typical usage - can
dispense 40,000 treatments a year, generating $50 million in
revenue and $18 million in pretax profits, says Ford. Ford aims
to deliver a 15% to 20% annual return for his equity investors,
more or less what they could get on a leveraged buyout pool, if
not for the recession.”
Forbes – 3/25/09
“One hazard of procuring third party investors, however, is
that the business plans and pro form analyses generated by
these parties may appear highly attractive at first glance
but create outsized expectations. Institutions attempting to
fulfill these expectations may struggle with balancing the
need to generate revenue with the imperative to use proton
therapy only when clinicians deem it appropriate”
The Advisory Board
The Path to Economic Viability
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High patient volumes (> 100 per day).
High patient throughput.
High reimbursement rates.
Economics of Proton Therapy
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The per fraction reimbursement for protons is currently
60% higher than the reimbursement for IMRT.
The cost per vault, however, is approximately a factor of
10 higher for the big-box solutions.
Typically, profitability requires extended treatment days
and high work loads on each gantry.
Journal of the American College of Radiology, August 2012
• Financial analysis showed that a 4 room proton therapy clinic
focusing on complex and pediatric cases would not have
enough time slots to cover even 60% of their debt service.
• “Debt service for a modern proton center requires a
considerable number of simple or prostate cancer cases…
centers without considerable workload devoted to these
patients should not be expected to survive.”
“Radiation oncologists have gotten
themselves into a trap. They’ve built
very expensive centers, and the only
way they can recoup the costs is to
treat lots of prostate cancers. A lot of
men are going to be channeled into
proton therapy, not necessarily to their
advantage at a very great cost.”
Anthony Zietman – Endowed professor of
radiation oncology @ Harvard, Editor of the
Red Journal, Chair and Past President of ASTRO
Business Week – 3/26/12
“There is definitely pressure from a few of
the investors to treat only prostate cancer.”
Dr. Jim Cox – Division Head, Dept. of Radiation
Oncology MD Anderson, Former Editor of the Red
Journal
“I’ve got people breathing down my neck
who want to make money on this place.
Dr. Allan Thorton – Medical Director @ the Midwest
Proton Radiotherapy Institute
US News – 4/16/08
Proton
Center
Reality Check
• Many proton therapy centers
are struggling to meet their
projected patient volumes.
• As more centers come on line
fewer patients are taking a
“radiation vacation”.
Crain’s Chicago Business – 7/11/13
Proton Therapy Reimbursement
• Proton reimbursement has a very uncertain future.
• In many cases insurers are putting in place very
significant restrictions on what cases they will
reimburse.
LA Times – 8/29/13
“Washington State and other payers face an unenviable choice:
pay for an expensive therapy that has not been shown to be better
than less expensive alternatives for prevalent malignancies or
restrict coverage to rare tumors in which clinical benefit appears
compelling. We propose a better way forward: reference pricing
with evidence development.”
“Reference pricing establishes a common level of payment for
different therapies with similar outcomes. Under reference
pricing, payers pay a set price for whichever therapy is selected
from various alternatives. For proton therapy, the reference
price should be set at the rate currently paid for IMRT. Patients
should have no additional out-of-pocket expenses, and providers
should be paid the same irrespective of treatment type.”
Proton therapy centers are
choosing this:
In order to avoid this:
Financial Concerns & Risks (1)
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Budgets are highly sensitive to patient volumes.
Many proton therapy centers have fallen well short
of their projected patient volumes.
This is due in part to poorer than expected
throughput and difficulty in attracting patients
regionally and nationally.
Financial Concerns & Risks (2)
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Institutions risk cannibalizing their existing their
existing radiation therapy business
Changes in reimbursement are highly likely:

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CMS and private insurers may limit payment to only
those indications where proton therapy has
demonstrated superiority
Capitation vs. fee-for-service
Summary
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Current clinical evidence does not justify the
conclusion that proton therapy will supplant photon
radiation therapy and current enthusiasm for proton
therapy is well ahead of the research.
We need to reign in our irrational exuberance and
take a more measured approach to the use of
protons in radiation therapy.
Photo credit goes here. ©2014 Photographer Name
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