Effectiveness of risk-adapted radiotherapy followed by a shortened period of dose-intense chemotherapy in children with medulloblastoma

 


The current treatment for medulloblastoma -- postoperative radiotherapy and one year of chemotherapy -- does not cure many of those children who have the high-risk form of this disease. Therefore, we investigated the effectiveness of risk-adapted radiotherapy followed by a shortened period of dose-intense chemotherapy in children with medulloblastoma.  

Using a risk-adapted approach to radiotherapy and chemotherapy in children with newly diagnosed medulloblastoma, as described in our paper, we achieved an increased overall five-year survival from the current rate of 70% to 85% among children with average-risk medulloblastoma; and raised the rate of survival among high-risk patients from 55% to 70%.  

We find these results to be especially significant for two reasons. First, they were achieved despite a reduction in the amount of radiation and length of chemotherapy following surgery in average risk patients from the levels used in standard treatments; and second, they represent a dramatic change from the 45% survival rate achieved 20 years ago using just surgery and irradiation. Therefore, we conclude that the use of risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue, offers a superior form of treatment for children with newly diagnosed medulloblastoma. 

Overall, we attribute our very promising results to the early use of high-dose radiotherapy after surgery—rather than waiting until after chemotherapy—in combination with short-term, intense chemotherapy. In fact, the shorter-term, intense chemotherapy is an especially important component of treatment that contributes to the improved survival of high-risk patients. 

We also believe that reducing radiation and chemotherapy treatment increases the possibility that a child will suffer less long-term, troublesome side effects on intellectual development.  

Moreover, our additional studies of medulloblastoma tissues obtained from these patients showed that genetic differences exist in medulloblastoma tissues among children. These differences might be useful in differentiating between children whose tumors are very aggressive and require novel experimental treatment and those children whose tumors are less aggressive and who could benefit from further reduction in treatment. Therefore, we believe that in the future we could further reduce the long-term effects of treatment among some children by further reducing the treatment intensity. We are currently working toward that goal.

 

Bibliographic reference:

Packer RJ et al.: "Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma", J Clin Oncol. 2006 Sep 1;24(25):4202-8

 

Amar Gajjar

Division of Neurology, Children's National Medical Center, Washington, USA