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Proton radiotherapy effective for childhood medulloblastoma

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Study points to clinical benefits of advanced radiation therapies

The prospective study by Dr. Yock and colleagues sets a new benchmark for treatment of medulloblastoma in pediatric patients and alludes to the clinical benefits of advanced radiation treatment. It becomes increasingly important for radiation oncologists to incorporate new findings in genomics and molecular subtyping for diseases such as medulloblastoma in the design of prospective studies, and to implement strategies to prevent cognitive decline in pediatric patients. The investigators demonstrate benefits of low-dose sparing afforded by proton therapy, but further improvements are possible. With newer delivery techniques, such as spot scanning proton therapy for the craniospinal component of treatment, more improvements in hearing outcomes can be expected.

The rarity of the disease, combined with the compelling results of Dr. Yock and colleagues, make randomized trials of photons versus protons for medulloblastoma unlikely. Without randomized trial data, some states require that all pediatric patients be treated with photon therapy, a requirement that could result higher rates of cardiovascular disease and other adverse effects. Radiation oncologists understand the potential for severe adverse effects of treatment, and many embrace new technologies that mitigate effects of radiation therapy on patients’ quality of life, a consideration that is particularly important in treatment of pediatric cancers.

Dr. David Grosshans is at the department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston. These remarks were part of an editorial accompanying the report by Dr. Yock and colleagues (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00217-X. Dr. Grosshans reported having no disclosures.


 

FROM THE LANCET ONCOLOGY

References

Treatment of childhood medulloblastoma with proton radiotherapy resulted in acceptable toxicity, with no observed cardiac, pulmonary, or gastrointestinal late effects, and achieved outcomes that were similar to those of photon (x-ray)-based therapy.

At a median follow up of 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16% (95% confidence interval, 6-29). The Full Scale Intelligence Quotient decreased significantly, particularly in children younger than 8 years, driven mostly by drops in processing speed and verbal comprehension. The cumulative incidence of any hormone deficit at 7 years was 63% (95% CI, 48-75).

For all patients, progression-free survival (PFS) at 5 years was 80% (95% CI, 67-88) and overall survival (OS) was 83% (95% CI, 70-90). For patients with standard-risk disease, PFS was 85% (95% CI, 69-93) and OS was 86% (95% CI, 70-94); for intermediate-risk disease, PFS was 67% (95% CI, 19-90) and OS was 67% (95% CI, 19-90); for high-risk disease, PFS was 71% (95% CI, 41-88) and OS was 79% (95% CI, 47-93). These rates are similar to previously published outcomes of 81%-83% for PFS and 85%-86% for OS (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00167-9).

“Therefore, the similar disease control coupled with similar patterns of failure should quell concerns raised about the differences in relative biologic effectiveness of passively scattered proton radiotherapy,” wrote Dr. Torunn Yock, chief of pediatric radiation oncology at Massachusetts General Hospital, Boston, and colleagues.

“Although there remain some effects of treatment on hearing, endocrine, and neurocognitive outcomes – particularly in younger patients – other late effects common in photon-treated patients, such as cardiac, pulmonary, and gastrointestinal toxic effects, were absent,” they said.

Medulloblastoma survivors often have treatment-related adverse late effects, and proton radiotherapy is used to mitigate late effects by decreasing the volume of normal tissue irradiated.

The estimated mean loss per year of IQ points, at –1.5, was less than IQ differences reported in previous studies, which ranged from –1.9 to –5.8 depending on age, craniospinal irradiation dosing, boost volumes, and length of follow-up.

There were no observed cardiac effects, and no patients had restrictive lung disease, which can occur in 24%-50% of long-term survivors treated with craniospinal photon irradiation. In addition, there were no new cases of gastrointestinal toxic effects that have occurred in up to 44% of photon-treated patients.

The prospective, nonrandomized phase II study carried out at Massachusetts General Hospital, Boston, evaluated 59 patients aged 3-21 years (median age 6.6 years) who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk). All patients received chemotherapy and 55 had a near or gross total resection.

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