Increasing dose of radiotherapy for ependymoma could significantly improve survival

Two studies presented recently at the 3rd ESTRO Forum (24–28 April 2015, Barcelona, Spain) demonstrate that increasing the dose of radiotherapy given to children with an intracranial ependymoma can significantly improve survival rates.

Ependymoma is the third most common childhood brain tumor, and the overall 5-year survival rate following surgery and radiation therapy is approximately 70%. However, individual prognoses vary considerably according to a number of factors including patient age, extent of surgery, and radiotherapy technique and dose.  In 2004 the dose of radiotherapy recommended when treating pediatric patients increased from 54 to 59.4 Gy. The studies presented at the conference suggest that adding another radiotherapy dose can further improve survival rates in some patients.

In the first study, researchers from Istituto Nazionale dei Tumori (Italy) report the development of an innovative strategy for children who had measurable intracranial ependymoma following surgery. In addition to the 59.4 Gy radiotherapy dose to the tumor bed, a boost of 8 Gy divided into two fractions to the tumor residue was added.

Using a combination of highly sophisticated radiotherapy techniques, the researchers were able to deliver the radiation dose directly to the remaining malignant tissue, sparing the normal brain tissue as much as possible. The study reported that out of 143 children, 24 individuals with a median age of 4.5 years were eligible to receive this enhanced treatment, and 15 of them are still alive without disease progression at a median of 51 months postdiagnosis.

Lorenza Gandola from Istituto Nazionale dei Tumori commented: “Our strategy contributed significantly to obtaining durable local control of disease in these children, and this is more striking because they already had a poorer prognosis after surgery. The hypofractionated radiotherapy boost approach represents an effective alternative to surgery in cases where further surgery cannot be performed without the possibility of causing severe and perhaps life-long damage to the child.”

Researchers indicated that no deaths related to the treatment or major toxicity has been reported in the boost group. The technique demonstrated in this study will now be the subject of an international clinical trial organized by the International Society of Paediatric Oncology (SIOP), which will begin later this year. Gandola concluded: “We believe that our research has the potential to improve outcomes in children with poor-prognosis ependymoma, and we hope that the SIOP trial will confirm them further to the benefit of such patients.”

A second presentation from Anne Ducassou of the Institut Claudius Regaud, Institut Universitaire du Cancer Toulouse – Oncopole(France) reported findings from a study of all 177 children treated for ependymoma in France from 2000–2013. These individuals ranged in age from 1–23 years, and with a median age of 5 years. Ducassou explained: “We wanted to know whether metabolic characteristics might have a role in the prognosis of local control of disease and in survival, and whether they might also be able to help us predict relapse, where the disease returns or reoccurs after a period of improvement.”

Radiation oncologists in France who had treated pediatric patients with ependymoma provided information to the research team, which enabled the researchers to study the characteristics of the patients’ disease through MRI scans. The team focused on those related to metabolism, such as perfusion and the diffusion of intercellular water molecules, which also reflects the number of cells in the tumor.

Researchers discovered that children with localized disease who had received the higher radiation dose of 59.4 GY after 2004 had better outcomes than those who had received the lower dose in use prior to 2004. When comparing the 177 patients included in the study, the estimated overall survival and progression-free survival were 90 and 67% respectively for patients who had received a dose above 54 Gy, and 79 and 52% respectively for those who received the lower dose.

Ducassou commented: “Our work, which involved a large number of children with ependymoma, has confirmed that the treatment we carry out today is better than it was a few years ago, but there is still much work to be done. For example, we found that children younger than three, and those with more aggressive disease had a poorer outcome, and we need to look further at how we can improve their treatment, as well as identifying other children at high risk of relapse.”

President of the European Society for Radiotherapy and Oncology, Philip Poortmans added: “Both studies presented here demonstrate that a clear dose–effect relationship exists for tumor control and survival. While the increase from 54 to 59.4 Gy that was adopted first improves disease control and survival in a population-based study, a new study is planned to confirm the results of increasing the dose by a further 8 Gy, delivered with highly directed radiation therapy techniques that give a very localized dose to the target volume with a low dose to the surrounding normal tissues. We hope that this will bring about even better outcomes for these children.”

Source: European Society for Radiotherapy and Oncology press release via EurekAlert