Favourable safety, disease control for proton radiotherapy in paediatric medulloblastoma

By Shreeya Nanda, Senior medwireNews Reporter

Proton radiotherapy has an acceptable safety and disease control profile in paediatric medulloblastoma patients, according to research published in The Lancet Oncology.

Survival outcomes in the trial were comparable to previous studies of conventional photon radiotherapy, and thus the team led by Torunn Yock (Massachusetts General Hospital, Boston, USA) proposes that proton radiotherapy could be a viable alternative in this patient population.

The phase II trial included 59 medulloblastoma patients aged between 3 and 21 years who received proton craniospinal irradiation at a median dose of 23.4 Gy radiobiological equivalents (GyRBE) followed by a median boost dose of 54.0 GyRBE. All patients received chemotherapy, either prior to, concurrent with or after radiotherapy.

After a median 5 years of follow-up, 9% of 45 evaluable patients developed grade 3 or 4 hearing loss as per the Pediatric Oncology Group ototoxicity scale in both ears and 7% of patients in just one ear, but in one patient the severity decreased to grade 2 at a subsequent evaluation.

The cumulative incidence of grade 3–4 ototoxicity at 3 years was 12%, increasing to 16% at 5 years.

And at the most recent follow-up, the Pediatric Oncology Group hearing score remained unchanged from baseline or improved by 1 point in 35% of 98 ears, and worsened by 1, 2, 3 or 4 points in a respective 21%, 36%, 6% and 2% of ears.

The researchers assessed neurocognition using the Full Scale Intelligence Quotient (FSIQ), and found that the FSIQ score decreased significantly by an average of 1.5 points per year during a median follow-up of 5.2 years. This decrease was driven primarily by significant reductions in processing speed and the verbal comprehension index, with mean decreases of 2.4 and 1.3 points, respectively. By contrast, neither the perceptual reasoning index nor working memory were significantly altered, they report.

At 5 years from the initiation of proton radiotherapy, the cumulative incidence of any hormone deficit was 55%, and growth hormone deficits were most frequent, with a 5-year cumulative incidence of 46%.

No patient experienced any cardiac, pulmonary or gastrointestinal late toxic effects; however, the study authors point out that they did not perform electrocardiograms, echocardiograms or pulmonary function tests, and thus would not have detected asymptomatic cardiopulmonary disease.

Overall the 5-year progression-free survival rate was 80%, while 85% of those with standard-risk disease as per the Children’s Oncology Group criteria and 70% of participants categorised as high or intermediate risk were progression-free at 5 years. Yock et al note that these rates are similar to the findings of previous cooperative group studies, which commentator David Grosshans (University of Texas MD Anderson Cancer Center, Houston, USA) says “[quells] concerns regarding disease recurrence”.

He adds that “[i]n their assessment of late radiation-induced adverse effects, the investigators offer a glimpse of the benefits of the low-dose sparing afforded by proton therapy, yet further improvements are possible”, resulting from, for example, the use of newer delivery techniques, such as spot scanning proton therapy.

And Grosshans concludes: “This study sets a new benchmark for the treatment of paediatric medulloblastoma and alludes to the clinical benefits of advanced radiation therapies.”

Speaking to the press, Kevin Harrington (Institute of Cancer Research, London, UK), who was not involved in the study, commented: “This is an important set of observations that highlights the need to properly evaluate proton beam radiotherapy in the clinic.

“The reductions in toxicity suggested by the study are important, but this is an observational series of cases, not a prospective clinical trial – and while the results look promising, there remains a lack of data about the side-effects of proton beam radiotherapy in children.”

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