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TREATING PEDIATRIC CANCERS WITH PROTON THERAPY

INTRODUCTION

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.

HISTORY OF ACCEPTANCE

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.

PENCIL BEAM SCANNING

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.

INDICATIONS FOR THE USE OF PROTON THERAPY

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:

  • Basal cell carcinoma
  • Breast cancer
  • Gastrointestinal cancer
  • Meningioma
  • Salivary gland cancer
  • Thyroid cancer

BENEFITS OF PROTON THERAPY IN PEDIATRIC CANCER PATIENTS

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.

STUDY EVIDENCE

SECONDARY CANCER

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.

COGNITIVE FUNCTION

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.

HEARING LOSS

Fortin et al. found hearing loss probability to be systematically less for pediatric brain

tumor patients treated with protons over photon radiation therapy.

ENDOCRINE DYSFUNCTION

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.

CARDIAC MORTALITY

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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