Proton therapy, or proton beam therapy, is a type of radiation therapy used in the treatment
of cancer. Unlike photon-based forms of external beam radiotherapy, proton therapy enables
an intense dose distribution pattern, depositing radiation in the precise dimensions of a tumor
while eliminating the exit dose and damage to adjacent normal tissue.
Because of its unique dose-deposition characteristics, proton therapy is indicated for treating
tumors near critical organs and brain tissue, and for the treatment of pediatric tumors.
Over the last 40 years, the 5-year survival rate for children diagnosed with cancer has
skyrocketed from 10% to nearly 90%. Yet, because of the radiosensitive nature of developing
tissue, approximately 60% of survivors suffer from late effects, such as growth deficiencies
and secondary cancers. Proton therapy has given pediatric oncologists a promising option in
the complicated matter of treatment planning for child patients.
Children tolerate proton therapy well because it is non-invasive and painless, and it typically
results in fewer side effects. Most importantly, proton therapy may reduce the risk of late
effects, including secondary malignancies, which is of particular concern for pediatric cancer
survivors.
The idea of using protons in the treatment of cancers has been in existence since 1946, with
the first patient being treated with protons in 1954 at the Berkeley Radiation Laboratory. A
limited number of physics laboratories offered proton therapy over the next few decades, as
advancements in imaging, accelerator, and treatment-delivery technology made proton
therapy more viable for routine medical applications. The pediatric population was not
excluded from treatment with protons during this time. In fact, the Mass General Department
of Radiation Oncology has been treating children with fractionated proton radiotherapy since
1974.
The development of pencil beam or spot-scanning technology in proton therapy has
contributed to a more widespread acceptance of proton therapy as a radiation therapy
modality, particularly in the pediatric population.
Pencil beam scanning is the most precise form of proton therapy. Using an electronically
guided scanning system and magnets, pencil beam scanning delivers proton therapy
treatment via a proton beam that is just millimeters wide. With pencil beam scanning, beam
position and depth are able to be controlled, allowing for highly precise deposition of
radiation to be delivered in all three dimensions of the tumor. The technology’s precision
reduces neutron contamination generated by proton scatter and scatter produced from
beam shaping devices required with non-scanned proton beams, thereby reducing the risk
of secondary malignancies.
Not coincidentally, the development of pencil beam scanning technology corresponds with
the rise of pediatric-specific proton therapy treatment programs.
Sparing normal tissue and improving quality of life is important for all patients. But because
of the long natural life expectancy of pediatric patients — and the particularly radiosensitive
nature of developing tissue — pediatric oncologists place heightened emphasis on late
effects.
Childhood cancer survivors often overcome one enormous battle only to encounter another,
months, years, or even decades after treatment has ended. Cosmetic, hormonal,
neurocognitive, reproductive, and other physical impairments are prevalent among survivors.
This is particularly true for pediatric patients whose disease sites occur near the brain stem,
spinal cord, and other sensitive organs.
Of utmost concern are radiation-induced secondary cancers. The relationship between
radiation therapy and secondary cancers has been clarified. For example, the Childhood
Cancer Survivor Study has assessed more than 14,000 childhood cancer survivors to
determine how different treatment plans have affected their long-term health. This data
demonstrates a correlation between radiotherapy and various secondary malignancies,
including, but not limited to:
A growing body of research suggests that proton therapy may spare pediatric patients from
developmental, cognitive, and other complications associated with photon-based forms of
external beam radiotherapy. This is especially promising for the prevention of secondary
malignancies.
The following offers an overview of the most recent research regarding the decreased risks
associated with proton therapy versus photon radiation therapy in pediatric cancer patients.
A number of studies suggest there is a decreased risk of secondary malignancies in
childhood cancer survivors when treated with proton therapy instead of photon-based forms
of radiotherapy.
● A study of 26 pediatric cancer patients by Tamura et al. found the risk of secondary
cancer from proton therapy to be statistically lower in thoracic and abdominal regions
than it would have been if treated by intensity-modulated X-ray therapy.
● Miralbell et al. found that proton beams reduced the expected incidence of radiationinduced
secondary cancers for a parameningeal rhabdomyosarcoma pediatric patient
by a factor of ≥2 and for a medulloblastoma pediatric patient by a factor of 8 to 15
when compared with either intensity-modulated or conventional X-ray plans.
● Paganetti et al. found that in optic glioma and vertebral body Ewing’s sarcoma
pediatric patients, lifetime attributable risks for developing a secondary malignancy
from proton therapy was lower at least by a factor of 2 and up to a factor of 10 when
compared to intensity-modulated photon therapy.
● In a study of six pediatric medulloblastoma patients, Stokkevag et al. found that both
double-scattering protons and intensity-modulated proton therapy achieved a
significantly better dose conformity compared to the photon and electron irradiation
techniques resulting in a six times lower overall risk of radiation-induced cancer.
● In a study of 86 pediatric retinoblastoma patients, Roshan et al. show that proton
therapy may significantly reduce the risk of secondary malignancy.
Proton therapy may spare pediatric patients from some of the neurocognitive effects of
traditional irradiation.
Kahalley et al. studied intelligence quotient (IQ) scores in 150 childhood brain tumor
survivors. While those treated with radiation therapy experienced an IQ decline of 1.1
points per year, those treated with proton therapy experienced no change in IQ over
time.
● In a study of modeling changes in cognitive function in 40 child brain tumor survivors,
Merchant et al. found clinically significant higher IQ scores in former medulloblastoma and craniopharyngioma patients, and clinically significant higher academic reading
scores in optic pathway glioma patients.
Fortin et al. found hearing loss probability to be systematically less for pediatric brain
tumor patients treated with protons over photon radiation therapy.
In a study of 77 pediatric medulloblastoma patients, Eaton et al. found that, compared
to those receiving photon radiation, patients receiving proton therapy had a reduced
risk for hypothyroidism, sex hormone deficiency, requirement for endocrine
replacement therapy, and a greater height standard deviation score.
Zhang et al. found decreased lifetime attributable risks of cardiac mortality when
treated with proton craniospinal irradiation over photon CSI in a study of 17 pediatric
medulloblastoma patients.
The search for evidence-based indications for proton therapy in pediatric oncology
continues. As of July 2018, 110 active proton therapy clinical trials for pediatric patients listed
on clinicaltrials.gov.
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