More than five years ago, I treated a four-year-old child with a large low-grade glioma at MD Anderson's Proton Therapy Center in Houston. His parents contacted us to see if proton therapy might be an option after chemotherapy and surgery had failed and his referring physician recommended hospice.

I recently saw this child for a follow-up; he's now 10 years old, going to school and enjoying life. His case is just one example-and I see many such success stories-that proton therapy can be an effective way to treat certain types of childhood cancers. It has several potential benefits, especially when it comes to decreasing late effects, which ultimately may lead to better outcomes and survival rates.

Advanced technology

Proton therapy is the delivery of high-energy subatomic particles that are extracted from a hydrogen atom. They are accelerated through a synchrotron or cyclotron and then magnetically directed toward the treatment room, where they're delivered to the tumor with sub-millimeter accuracy.

Proton therapy can be especially effective in tumor sites that require a higher degree of dose conformality, such as when the tumor is contiguous to clinical structures. Children with tumors in the brain, head, neck, spinal cord, heart, lungs and other areas that are sensitive to radiation can benefit from proton therapy because we can target treatment directly to the tumor area.

Decreased acute, late effects

Conventional radiotherapy can have a negative impact on the physical, intellectual and emotional development of children. Survivors who received conventional therapy as children are 10 to 20 times more likely to develop secondary cancers, and 40% have physical or neurocognitive issues severe enough to alter their lifestyles.

Highly-targeted delivery makes proton therapy a viable modality for many pediatric cancers. It allows pinpoint accuracy to treat tumors near or within sensitive areas, while sparing healthy tissue and organs, such as the brain stem, hippocampus, visual apparatus, reproductive organs and lungs. This may reduce acute side effects and help children better tolerate chemotherapy and other treatments.

A mother leans down to kiss her son before his daily proton therapy treatment at the MD Anderson Proton Therapy Center in Houston. image/courtesy MD Anderson

Comparative research regarding radiation outcomes has shown that proton therapy may lead to fewer late effects. This is particularly important because patients are surviving longer. Another advantage for proton therapy, though definitely a lesser factor in children, is the ability to increase dose delivery to certain areas, such as the skull base, while avoiding healthy structures.

Innovation

As one of the few proton therapy centers in the nation, MD Anderson has treated more than 500 children with it since opening in 2006. We're fortunate to have access to state-of-the-art technology, which allows us to implement innovative approaches.

MD Anderson has adopted pencil beam scanning proton therapy and become one of the world leaders in this approach. It is an even more precise form of proton therapy also called spot scanning, which could be valuable in treating children. Pencil beam is directed to move throughout the tumor's depth to "paint" the treatment volume with spots of radiation, conforming to the shape of the tumor and delivering thousands of spots of radiation within minutes. With pencil beam and, most recently, intensity-modulated proton therapy (IMPT), we are able to offer children and their families the most advanced radiation options available for difficult-to-treat tumors.

The vast majority of our pediatric patients have brain or spinal tumors. About half of these are medulloblastomas, which usually require surgery, chemotherapy and radiation. Other types of brain tumors that benefit from proton treatment include low-grade gliomas and germ cell tumors, sarcomas, rhabdomyosarcoma and occasionally retinoblastoma.

Barriers to care

So why doesn't every child who could benefit from proton therapy receive it? Since there are only a few proton therapy centers in the U.S., families sometimes find it difficult to put their lives on hold to travel to another city. Insurance is sometimes an issue, although less often with children.

While we get many referrals from physicians who think proton therapy is the best option for their patients, others are still hesitant. We make it a point to establish an open dialogue. Many children return to their communities for chemotherapy, and treatment and follow-up can be long term. It's a win-win for us to stay in touch to ensure seamless care and monitor any late effects.

Investigating efficacy, effects

While positive data about early outcomes and side effects have been published, investigation of the impact of potential late effects will require several years. In a small-sample study comparing 3-D CRT, electrons, IMRT and protons, protons were found to be the optimal treatment for retinoblastomas, medulloblastomas (posterior fossa and craniospinal) and pelvic sarcomas, both in target dose coverage and sparing of normal structures. MD Anderson researchers have published articles in major journals about early ototoxicity after medulloblastoma therapy; decreased esophagitis, pneumonitis and higher radiation dose for lung cancer; and decreased cytopenias during CSI.¹

Also, we have seen encouraging results in toxicity in medulloblastoma and endocrine and neurocognitive outcomes. That data will be published within the next several months.

The Proton Therapy Center's pediatric patients are enrolled in a national protocol that follows survivors for tumor control, as well as acute and late effects. We also collaborate with cooperative groups for pediatric cancer, including the Children's Oncology Group (COG) and the Pediatric Brain Tumor Consortium. Our physicians worked with COG to refine proton radiation guidelines for the organization's protocols. Proton therapy is now an acceptable form of radiation for nearly all COG clinical trials that call for it.

The future

As proton therapy technology develops, techniques are refined and new methods continue to decrease toxicity, it will play an even greater role in treatment of childhood cancers. In proton therapy as well as other modalities, we are working to define the cancers we treat and how we treat them. We partner with basic scientists to understand which children may need more therapy and which may need less. As a radiation oncologist who sits in exam rooms with parents who are searching for hope for their children, proton therapy offers an effective option for many of these families facing cancer.

Reference

1. Moeller, B.J., Chintagumpala, M., Philip, J.J., et al. (2011) Low early ototoxicity rates for pediatric medulloblastoma patients treated with proton radiotherapy. Radiation Oncology, 6: 58; via http://http://www.ro-journal.com/content/6/1/58

Anita Mahajan, MD, is the medical director of the MD Anderson Proton Therapy Center in Houston. She also serves as associate professor in the Department of Radiation Oncology, director of Pediatric Radiation Oncology, and co-section head of Pediatric and CNS Radiation Oncology at the MD Anderson Cancer Center.