Proton therapy offers hope to pediatric brain cancer patients

By Cynthia E. Keen, staff writer

May 22, 2012 -- At Massachusetts General Hospital, the Francis H. Burr Proton Therapy Center allocates 40% of its available treatment time to 10% of its cancer patients. Who are these patients? They're children fighting to survive and someday be able to live a normal life.

Proton therapy treatment delivers a high, conformal radiation dose to tumor volume, while almost completely sparing normal tissue. It minimizes the exposure of healthy tissue for children whose bodies are more susceptible to damage caused by radiation. For children with brain tumors who have a strong likelihood of surviving their disease, proton therapy theoretically offers a better chance than photon-based radiotherapy for preserving brain function and quality of life.

However, there's been little research published to quantify this assumption. The first report of an ongoing study by researchers at Massachusetts General Hospital (MGH), published online May 7 in the Journal of Clinical Oncology, evaluated the health-related quality-of-life assessments of children younger than 18 prior to and three years after completing treatment.

Although the number of patients in the study is quite small (142 at baseline and 43 at three years), the research revealed that their overall quality-of-life scores improved significantly. In fact, they approached the scores of healthy children who have never had cancer or a chronic health condition.

For pediatric oncologists and radiation oncologists, this supports the premise that proton therapy is the preferred radiotherapy treatment of choice for children who have high odds of being cured of their cancer. The MGH study is following for a period of 10 years all pediatric patients -- not only those with brain cancer -- who received proton therapy treatment at its center between March 2004 and February 2010. Data collection is ongoing, lead author Dr. Karen Kuhlthau, associate professor of pediatrics, told

Why proton therapy?

It's been known for decades that children treated for tumors of the central nervous system with cranial radiation therapy or conventional photon-beam radiotherapy are at high risk of neurocognitive impairment. The younger the child at the time of treatment, the greater the risk, because of the early stage of brain development and the fact that younger children are disproportionately susceptible to radiation damage.

For this reason, chemotherapy and/or surgery may be the first treatments deployed, with radiotherapy deferred as long as possible. In an editorial accompanying the article, F. Daniel Armstrong, PhD, professor and associate chair of pediatrics at the University of Miami, noted that the Pediatric Oncology Group demonstrated decades ago that delaying cranial radiation therapy of young patients benefited their neurocognitive functions. Reduction in dose was also beneficial.

Proton therapy offers another option. Because protons have larger mass than photons, proton therapy delivers radiation in a narrower beam with a targeted delivery that is focused on tumor shape. And because protons have a limited range of penetration, proton therapy can be configured to stop at its target tumor. By comparison, photons hit the tumor target but then pass through it while exiting the body. As a result, healthy tissues in the path of photons are affected.

The Burr Proton Therapy Center treats approximately 900 adult and pediatric cancer patients annually. In 2011, it treated 138 patients younger than 22. Most children younger than 15 are sedated during treatment, which typically lasts 20 to 40 minutes. The center reserves 40% of available treatment time for pediatric patients, but it could operate at capacity by only treating pediatric patients.

Senior author and principle investigator Dr. Torunn Yock, director of pediatric radiation oncology, told in an interview that only 15% of children who could benefit from proton therapy actually receive the treatment. Leonard Arzt, executive director of the National Association for Proton Therapy, concurs.

There are currently 39 active proton therapy centers in the world, nine of which are in the U.S. -- not nearly enough to meet demand. Proton therapy centers are extraordinarily expensive to build, costing from $20 million to $30 million for single-gantry facilities and more than $100 million for sites with multiple gantries. The cost of treatment is also extraordinarily high.

Central nervous system tumors are the most common type of solid cancers in children. They include gliomas, medulloblastomas, germ cell tumors, and ependymoma. Pediatric patients with these types of cancers represent the majority of children treated at the Boston center. In an unrelated article published in the June issue of Technology in Cancer Research and Treatment, Yock and colleagues described this treatment in depth (Vol. 11:3, pp. 267-278).

Medulloblastomas are the most common brain tumors treated. Treatment typically includes surgical resection followed by craniospinal irradiation and platinum-based chemotherapy. Patients at standard risk receive a dose of 23.4 Gy, and patients at high risk receive 36 Gy. All patients also receive additional radiation to a total dose of 54 Gy to 55.8 Gy to the posterior fossa or tumor bed.

Yock cited one case of treatment to a 3-year-old boy, for whom proton radiotherapy decreased radiation dose to the cochlea, pituitary gland, hypothalamus, temporomandibular joints, parotid glands, and heart compared to if he had conventional intensity-modulated radiation therapy (IMRT). Yock explained that while chemotherapy is beneficial to treat brain cancers, it can cause more hearing loss than conformal radiotherapy treatment.

New treatment programs that can reduce chemotherapy and radiation dose to healthy tissue may make a world of difference in the lives of pediatric medulloblastoma patients, who have up to an 80% to 85% chance of living at least five years following treatment.

"The true benefit of protons with respect to late effects is that the treatment spares two to three times the volume of the normal brain compared to photons," she said. "Everything is age related. A 3-year-old is in a very different situation compared to a 15-year-old because the 15-year-old has had an additional 12 years of brain development. The 5-year-old children treated with proton therapy for medulloblastomas are still struggling a little in school and may require some accommodations, but they are not in special education classes dealing with radiation-induced disabilities."

Quality-of-life study

The quality-of-life study published in the Journal of Clinical Oncology reported on the baseline measurements of 142 patients ranging in age from 2 to 18 years. They were assessed twice during treatment, on the first and last weeks, and annually thereafter.

Twelve patients were eliminated from follow-up analysis because their tumor had either recurred or they had died. Twenty-three patients chose not to participate in the three-year follow-up. Fifty-seven patients had not yet reached the third anniversary of treatment completion.

A battery of neuropsychiatric testing was performed, including intelligence tests and the core PedsQL, a generic pediatric health-related quality-of-life tool for use with both healthy and ill children. It measures physical, emotional, social, and school functioning. Scores are scaled from 0 to 100 -- 82.3 is the average score for healthy children and 73.1 for ill children.

The PedsQL brain tumor module was also used, which reported levels of cognitive problems, movement and balance, pain, nausea, procedural anxiety, and worry. The research team measured perceived physical appearance, treatment anxiety, and communication about the disease using the PedsQL cancer module. Behavior and problem behavior assessment tests were also performed.

"It's important to test for IQ, processing speed, memory, and behavior at the beginning of treatment," Yock said. "A brain tumor impairs normal functioning, and surgery can change the neural track. We need a comprehensive baseline to measure against."

Overall, health-related quality-of-life scores as reported by patients older than 5 rose from an average of 68.1 at the beginning of treatment to an average of 76.5 at year 3. Parents were also asked to participate in some of the quality-of-life assessment surveys, or on behalf of children younger than 5 years. On average, they consistently reported lower scores in all categories at all times than their children did.

Within the psychosocial score category, school functioning received the lowest score for children surveyed during their treatment. Kuhlthau said this was expected, in view of the fact that treatment disrupts schooling or makes it impossible. Procedure anxiety also generated a low score, again an expected finding considering the severity of the disease.

What somewhat surprised the researchers were low rankings by patients and parents in the "communication" category. This encompassed discussions with caregivers and explaining the disease to others. Worry about treatment, adverse effects, and tumor recurrence also had poor ratings by parents and their children. The researchers are trying different ways of communicating with patients and their families to improve these scores.

The severity of treatment also correlated with the quality-of-life score: Patients with the most intense treatments had lower scores. Children with medulloblastomas or primitive neuroectodermal tumors also consistently had lower scores than children with other brain tumors. The small sample size prevented socioeconomic differences from being assessed, but Yock said that this could have a confounding effect and that the research team was collecting data to assess its impact in future analyses.

"This study provides support for the possibility that reducing neurotoxicity and associated late neurocognitive effects will result in better long-term health-related quality of life," Armstrong observed. "For many children, these [neurocognitive] deficits can affect school performance, vocation, social function, and later employment and relationships."

"Ultimately, the goal is prevention of late effects while sustaining and improving survival and quality of survival," he said. "A challenge for the field is to determine ways to make proton therapy treatment, if it is as effective and beneficial as it first seems, available for all children with central nervous system tumors who may benefit."



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