Medulloblastoma, the most common malignant brain cancer in children, is a fast-growing tumour that develops in the cerebellum at the base of the brain and spreads through cerebrospinal fluid to the surface of the brain and spinal cord. Conventional treatment involves a combination of surgery, chemotherapy and radiotherapy. But because the entire brain and spine must be irradiated to minimize risk of recurrence, patients often suffer significant side effects. Toxic effects include hearing loss, learning and memory problems, and neuroendocrine disorders, as well as problems affecting the heart, lungs, thyroid, spine and reproductive organs. All of these tend to be more serious in children treated at younger ages.

The ability of proton therapy to deliver little entrance dose and no exit dose makes it particularly attractive for treating tumours in or near the brain, where protection of nearby healthy tissues is particularly critical. However, debate is ongoing as to the clinical benefits of this technique, and no previous study has examined the long-term results of children treated with proton therapy for medulloblastoma.

In this new study, the researchers examined 59 patients, aged 3 to 21, who received proton therapy for medulloblastoma at MGH between 2003 and 2009. All had previous surgery to remove as much of the tumour as possible, and all received chemotherapy before, during or after proton therapy. Patients received craniospinal irradiation of 18–36 GyRBE, delivered at 1–8 GyRBE per fraction followed by a boost dose.

At the outset of the study, participants underwent hearing tests. The researchers also measured a variety of cognitive functions, levels of important hormones, and height and weight. These tests were repeated at follow-up visits for an average of seven years after treatment.

Significant hearing loss was seen in 12% of patients three years after treatment and in 16% at five years. This compares with around 25% reported in studies using photon radiotherapy. The cognitive effects of proton therapy – primarily affecting verbal comprehension and processing speed – were also less serious than those reported with photon radiotherapy, and were primarily seen in children who were under the age of eight when treated.

The neuroendocrine effects of proton therapy – deficits in any hormone level – were seen in 55% of patients at five years, and 63% at seven years after treatment, similar to that reported with photon therapy. Growth hormone deficit was the most common occurrence. Importantly, no patients exhibited any cardiac, pulmonary or gastrointestinal toxic effects – all of which have been reported in photon radiotherapy studies.

Three years after treatment, progression-free survival was 83%. At five years, progression-free survival was 80% and overall survival was 83% – similar to previously published outcomes for photon radiotherapy.

"Our results indicate that proton therapy maintains excellent cure rates in paediatric medulloblastoma while reducing long-term side effects, particularly in hearing and neurocognitive function, and eliminating cardiac, pulmonary, gastrointestinal and reproductive effects," said lead author Torunn Yock, from MGH's Department of Radiation Oncology. "While we are currently investigating quality-of-life differences between proton and photon treatment, I truly believe that – particularly for the youngest children – the ability to offer them proton therapy can make a big difference in their lives."

Writing in a linked Comment, David Grosshans from the University of Texas MD Anderson Cancer Center said that the investigators "offer a glimpse of the benefits of the low-dose sparing afforded by proton therapy". He points out that further improvements are possible, particularly with the development of newer delivery techniques such as spot scanning proton therapy (Lancet Oncol. doi: 10.1016/S1470-2045(15)00217-X).

"I believe that radiation oncologists have always understood that our treatments are associated with the potential for severe adverse effects," Grosshans wrote. "I also believe that many in radiation oncology embrace new technology, not simply to have the latest and greatest innovations, but rather to reduce the effect of radiation therapy on patients' quality-of-life. Nowhere in oncology is this more important than for paediatric cancers. This study sets a new benchmark for the treatment of paediatric medulloblastoma and alludes to the clinical benefits of advanced radiation therapies."

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