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> Treating breast cancer while sparing the heart (https://www.elsevier.com/connect/treating-breast-cancer-while-spari…

Treating breast cancer while sparing the heart

The difference between conventional X-ray therapy and proton therapy – and why
we are re-examining the way we treat left-side breast cancer
By Brian H. Chon, MD
    Posted on 25 November 2014

The gantry rotates 360 degrees around the patient to deliver treatment from different angles, allowing physicians to precisely target the
tumor site. It is typically used to treat complex cases, such as those found in pediatric patients and hard-to-reach tumors in adult
patients. (Photo courtesy of ProCure Proton Therapy Center)

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The majority of breast cancer patients today are able to preserve their breasts as they undergo a


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lumpectomy followed by post-operative radiation. However, research shows that left-side breast cancer
patients treated with radiation have an increased risk of radiation-induced heart problems.

Here, Dr. Brian Chon writes about the connection between X-ray therapy and heart disease and how proton
therapy is being used as a cardiac-sparing cancer therapy.

The great success story in breast cancer today is that the vast majority of patients will be able to preserve
their breasts as they undergo a lumpectomy followed by post-operative radiation. As patients are cured of
their breast cancer and live a normal lifespan, some of them, especially those with left side breast cancer,
are developing heart disease from their breast radiation.

We now know that radiation exposure from the treatments to the heart and the coronary vessel plays a role.

Last year, researchers in Sweden and Norway established a direct link between major cardiac events in
women who received radiation therapy for breast cancer.

The study, published in The New England Journal

of Medicine Dr. Brian Chon
(https://www.nejm.org/doi/full/10.1056/NEJMoa120 (https://www.procure.c
9825) , followed more than 2,000 breast cancer om/New-Jersey-Meet)
patients for over 20 years. The researchers is a radiation
reported that a typical left breast-side cancer oncologist at ProCure
patient received about 5-6 gray (Gy), unit of Proton Therapy Center
radiation, to the heart and also to the coronary (https://www.procure.c
arteries. om/New-Jersey-
Brian H. Chon, MD
Explore) in Somerset,
This didn't surprise us too much because we have New Jersey, one of 14
always known that modest doses of radiation centers in the United States that offer proton
were delivered to the heart for left breast cancer therapy. He received his medical degree from
patients, but we thought these doses were Robert Wood Johnson Medical School at Rutgers
relatively low and would have little clinical University (https://rwjms.rutgers.edu) in New
consequence. Jersey. Dr. Chon was chief resident in radiation
oncology at Massachusetts General Hospital
However, this landmark study showed that over (https://www.massgeneral.org) (MGH) and
time, 1 Gy delivered to the heart increased the Harvard Medical School
relative risk for an adverse coronary event by 7.4 (https://hms.harvard.edu) . He also completed a
percent. This means that if an average breast sub-fellowship in basic science research on
cancer patient's heart receives 5 Gy, the relative breast cancer genetics at Harvard Medical
risk increased to 35 percent to 42. This is not a School.
trivial risk.
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As a practicing radiation oncologist who has been
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using proton therapy to treat breast cancer
patients for the past two years, I didn't need this
study to convince me that it is the most
sophisticated tool we have today to spare healthy
surrounding tissue while treating the tumor.
Even when internal mammary lymph nodes (near
the sternum or breast bone) need to be treated,
protons can essentially eliminate the dose to the
heart. This is nearly impossible to accomplish
with conventional X-ray therapy.
He has extensive proton therapy experience
from both the Harvard Cyclotron and Francis H.
Burr Proton Therapy Center at MGH, and has a
special expertise in cranial and extracranial
stereotactic radiation therapy as well as high
dose rate brachytherapy for the treatment of
gynecologic and breast cancer. He is a member
of the American Medical Association and the
American Society for Radiation Oncology.

Conventional X-ray therapy acts like a bullet. The X-ray radiation enters the body with great velocity,
eventually hits the tumor and destroys it, but it also leaves a trail of collateral damage as it goes straight
through the body.

Protons, on the other hand, can come into the body and stop at a desired distance. Once protons hit their
target in the body, they detonate and release all of their energy in the tumor and then come to a complete
stop — with no exit dose. Protons spare up to 60 percent to 80 percent of the radiation delivered to healthy
surrounding tissues compared to X-ray therapy.

Each patient receives an individualized treatment

typically delivered daily in less than 30 minutes
How does proton therapy work?
over five to six weeks. Daily treatments are non-
invasive and pain-free. Watch a video

The short-term side effects are similar to what a

patient can expect with conventional X-ray,
including skin irritation overlying the breast. This
side effect is temporary and well tolerated.

I first learned about proton therapy during my

training at Harvard Medical School. Protons were
used here first to treat breast patients in hopes of
minimizing heart and coronary artery damage. (https://www.proton-therapy.org/howit.htm)
My mentors Alphonse Taghian
(https://www.massgeneral.org/radiationoncology/ Source: National Association for Proton Therapy
doctors/doctor.aspx?id=16842) , MD, who is (https://www.proton-therapy.org) and ProCure
Professor of Radiation Oncology at Harvard Proton Therapy Center
Medical School and Chief of Breast Radiation (https://www.procure.com/New-Jersey-Explore)
Oncology at Massachusetts General Hospital, and
Simon N. Powell
(https://www.mskcc.org/research/lab/simon-
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powell) , MD,Chair of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center


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(https://www.mskcc.org/doctor/department/department-radiation-oncology) , continue to push the field
forward with their pioneering work with protons.

Since my time at Harvard, radiation oncology has continued to evolve, especially as advancements in
imaging, such as PET/CT scans and MRIs, allow more targeted radiation treatments. The better we can
localize tumor cells through these sophisticated imaging modalities, the more precisely we can leverage
proton's precision.

Today we use proton therapy for pediatric cancers, prostate cancers, lung cancers, head and neck cancers,
esophageal cancers, pancreatic cancers and breast cancers. Protons have long been used for brain tumors,
especially skull-based tumors abutting critical organs like the brainstem and optic nerves.

Proton therapy remains difficult to access because there are only 14 centers in the United States. Proton
centers are very difficult to build, finance and operate. As the prices for proton therapy centers come down
with more compact proton units on the horizon, we expect patients to have better access.

ProCure's inclined beam technology can treat 80% of tumors using the industry standard gantry, but in a space half the size. The innovation
of inclined-beam technology is that the proton beam is

In some cases, collaborations with multiple hospitals systems are occurring to expand access. In New York
City, for example, Memorial Sloan-Kettering Cancer Center, Montefiore Medical Center, Mount Sinai
Search by keyword, title, subject area
Medical Center and NYU Langone Medical Center have partnerships with ProCure in New Jersey.
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Not too long ago in a Harvard Health Blog (https://www.health.harvard.edu/blog/radiation-for-breast-


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cancer-can-increase-heart-risks-2-201310306820) , my old mentor Dr. Taghian, in speaking about proton
therapy as a treatment for breast cancer, predicted, "In the future, it will probably be the dominant way to
spare the heart."

Proton therapy is a very elegant and sophisticated way of radically reducing the dose of radiation to the
heart and lungs and consequently minimizing the potential long-term side effects. I, too, am a big believer
that this is the wave of the future.

Protons vs. X-rays

X-rays are electronic waves that penetrate
tissue, gradually losing energy as they move
along. To penetrate deeply enough in the body
to reach most tumors, higher doses of
radiation must be used. With X-ray therapy,
however, the highest radiation dose occurs
shortly after entering the body meaning that
much of the radiation is deposited in the
healthy tissue in front of the tumor. When the
X-ray exits the tumor, it continues to affect
healthy tissue as it leaves the body. That can
cause a variety of short- and long-term side
effects, some of which can seriously affect
quality of life and health.

Protons are particles that can be manipulated

to release their energy at a precise point. The more energy, the deeper the protons can penetrate into
the body. The amount of proton energy is calculated to release the proton radiation precisely at the
tumor site. The peak of this radiation dose (called the Bragg Peak) is designed to conform to the back
of the tumor. Immediately after that point, the radiation dose falls to zero. Less of the radiation
affects the healthy tissue in front of the tumor, and virtually none of it affects the healthy tissue
behind the tumor. That results in much less damage to healthy tissue or nearby organs and
structures. It also means that a higher dose often can be delivered, leading to more effective
treatment.

With X-ray radiation therapy (black line), the radiation dose peaks soon after entering the body and
often, long before reaching the tumor, gradually decreases. Healthy tissue surrounding the tumor
receives much of the dose. With proton therapy (blue lines), treatment conforms more closely to the
tumor, so that less radiation is deposited in the healthy tissue in front of the tumor compared to X-
ray therapy, and almost none is deposited in the healthy tissue behind the tumor.Source: ProCure
Treatment Centers Inc.
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Proton therapy: a capsule history

The 220-ton cyclotron is 18 feet in diameter and 8 feet high. (Photo courtesy of ProCure Proton Therapy Center)

The idea that protons could be used for radiation therapy was first proposed in 1946 by Dr. Robert R.
Wilson, a physicist at Harvard and designer of Harvard's cyclotron who came to be known as "the
father of proton therapy." Dr. Wilson was a member of the Manhattan Project, which developed the
atomic bomb. He went on to lead the development of the particle accelerator at the Fermi National
Accelerator Laboratory (Fermilab) (https://www.fnal.gov) near Chicago, publishing some of his
research in Elsevier journals.

Early treatments for patients were performed at nuclear physics facilities in the 1950s but had limited
applications. Advancements in imaging and computer technology made it possible to expand its
medical applications, including treating cancer. It was first used for cancer treatment in the US in
1974 at a physics research laboratory.

In 1988, proton therapy received US Food and Drug Administration (FDA) approval for the treatment
of cancer.

In 1990, the first US hospital-based proton facility at Loma Linda University Medical Center began
treating patients. Since then, more than 50,000 people in the US have received proton therapy and
more than 100,000 people have been treated worldwide.

Proton therapy was first used for breast cancer at the Proton Treatment and Research Center at Loma
Linda
Search University
by keyword, Medical
title, subjectCenter
area (https://www.protons.com/proton-therapy/index.page) in California.
In 2007, investigators there published a study in The Cancer Journal
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(https://journals.lww.com/journalppo/Abstract/2007/03000/A_Technique_of_Partial_Breast_Irradiation.8.
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 aspx) that found protons can provide substantial normal tissue protection compared with


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conventional X-rays when used for partial breast treatment. Proton therapy in breast cancer continues
to be an expanding area of research.

Sources: Cancer.net (https://www.cancer.net) , National Association for Proton Therapy

(https://www.proton-therapy.org/pr10.htm) , Particle Therapy Co-Operative Group 2013
(https://www.ptcog.ch) , MD Anderson Cancer Center (https://www.mdanderson.org/patient-and-cancer-
information/proton-therapy-center/what-is-proton-therapy/history-of-proton-therapy/index.html) , and
Elsevier

Research on proton therapy for breast cancer

Various Elsevier journals have published articles on proton beam therapy for breast cancer. Here is a
sample that has been made freely available until February … 2015:

• Ares C, Khan S, MacArtain AM, et al: "Postoperative proton radiotherapy for localized
and locoregional breast cancer: potential for clinically relevant improvements?
(https://www.sciencedirect.com/science/article/pii/S0360301609003654) " International
Journal of Radiation Oncology*Biology*Physics (March 2010)

• MacDonald S, Specht M, Isakoff S, et al: "Prospective pilot study of proton radiation

therapy for invasive carcinoma of the breast following mastectomy in patients with
unfavorable anatomy – first reported clinical experience
(https://www.sciencedirect.com/science/article/pii/S0360301612011406) ," International
Journal of Radiation Oncology*Biology*Physics (November 2012)

• David A. Bush, Sharon Do, Sharon Lum, Carlos Garberoglio, Hamid Mirshahidi, Baldev
Patyal, Roger Grove, Jerry D. Slater: "Partial Breast Radiation Therapy With Proton Beam:
5-Year Results With Cosmetic Outcomes
(https://www.sciencedirect.com/science/article/pii/S0360301614019592) ," International
Journal of Radiation Oncology*Biology*Physics, (November 2014)

• John P. Plastaras, MD, PhD, et al: "Special Cases for Proton Beam Radiotherapy:

Reirradiation, Lymphoma, and Breast Cancer
(https://www.sciencedirect.com/science/article/pii/S0093775414002449) ," Seminars in
Oncology (October 2014)

The following article is published open access:

Search by keyword, title, subject area
• Johannes A. Langendijk, et al: "Selection of patients for radiotherapy with protons
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aiming at reduction of side effects: The model-based
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(https://www.sciencedirect.com/science/article/pii/S0167814013002193)

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Oncology (June 2013)

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