ASTRO 2016: Reduced Radiation Boost Volume Recommended for Average-Risk Pediatric Medulloblastoma, but Craniospinal Axis Dose Remains Unchanged
In the largest trial conducted for average-risk medulloblastoma, survival rates following reduced radiation therapy boost volumes were comparable to standard treatment volumes for the primary tumor site, but lower doses of craniospinal axis irradiation were associated with higher event rates and worse survival, according to research presented at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO).
Findings from a phase III randomized trial indicate that physicians can adopt smaller boost volumes for posterior fossa radiotherapy, but should maintain the standard radiotherapy dose for craniospinal irradiation (CSI).
The most common type of brain malignancy in children, medulloblastoma is an aggressive tumor that originates in the lower, rear area of the brain but has a propensity to spread to the upper brain and spine. As a result, the standard of care following surgical resection for these children has included systemic chemotherapy and irradiation to both the posterior fossa (ie, the primary site) and the craniospinal axis. Complications of CSI, however, include considerable negative effects on patients’ neurocognitive abilities, endocrinologic function, and hearing.
Study Details
Researchers from the National Cancer Institute–supported Children’s Oncology Group conducted this phase III trial to assess outcomes from a reduced radiation boost volume to the posterior fossa among pediatric patients with average-risk medulloblastoma and a lower CSI dose, specifically in younger children. While several single-institution trials have found limited posterior fossa boost to be comparable to whole posterior fossa boost, this is the first trial that was sufficiently powered to state definitively that there is no survival difference between the two approaches.
Findings are based on data from 464 patients ages 3–21 with average-risk medulloblastoma. Eligible patients had complete or near-complete resection of their primary tumors and no evidence of anaplasia or spread of the cancer beyond the posterior fossa. Patients were randomized to receive either a standard radiation boost volume to the posterior fossa (PFRT group, n= 237) or a reduced dose of involved field radiotherapy (IFRT group, n= 227). The 226 patients who were ages 3–7 were also randomized to receive either a standard irradiation dose of 23.4 Gy to the craniospinal axis (SD-CSI group, n= 110) or a reduced dose of 18 Gy (LD-CSI group, n = 116). Following maximum surgery and within 31 days following resection, patients began 6 weeks of radiotherapy. After a 1-month break, patients began to receive alternating cycles of cisplatin and cytoxan-based chemotherapy.
Primary outcomes included the amount of time from study entry to disease progression, disease recurrence, death from any cause, or second malignant neoplasm. Researchers compared rates of overall survival, event-free survival, local failure, and distant failure by computing hazard ratios (HR) and performing intent to treat analysis.
Study Findings
With a median follow-up of more than 6.5 years, reduction in the volume of radiotherapy boost to the posterior fossa did not compromise overall survival or event-free survival in pediatric patients with average-risk medulloblastoma. Overall survival at 5 years was 84.1 ± 2.8% for patients who received the reduced volume with IFRT, and 85.2 ± 2.6% for patients who received the standard volume with PFRT. Event-free survival at 5 years was 82.2 ± 2.9% for IFRT and 80.8 ± 3.0% for PFRT. Rates of local failure also did not vary significantly between treatment arms. Local failure at 5 years was 1.9 ± 0.1% for IFRT and 3.7 ± 1.3% for PFRT (P = .178).
“This trial—the largest of its kind to date—indicates that it is safe to adopt a limited posterior fossa boost for patients receiving radiation therapy for average-risk medulloblastoma, and that these children can have similar positive outcomes with lower chances of radiation affecting surrounding brain tissue,” said Jeff M. Michalski, MD, MBA, FASTRO, Professor of Radiation Oncology at Washington University in St. Louis and lead author of the study. “Additional data are needed, however, to address the appropriate volume for patients with higher risk disease or those who have metastasis at the time of diagnosis.”
Event-Free and Overall Survival
While reduced radiotherapy volume to the posterior fossa did not impact survival rates, a low dose of craniospinal irradiation was associated with lower rates of event-free and overall survival for the youngest pediatric patients. Overall survival at 5 years was 78.1 ± 4.4% for patients ages 3–7 who received low-dose irradiation therapy to the CSI vs 85.9 ± 3.8% for the standard CSI dose. Event-free survival at 5 years was 72.1 ± 4.8% for the LD-CSI group, compared to 82.6 ± 4.2% for SD-CSI. Rates of distant failure did not vary significantly between treatment groups. Isolated distant failure at 5 years was 12.8 ± 3.2% for LD-CSI and 8.2 ± 2.8% for SD-CSI (P = .115).
“Unfortunately, we were disappointed to find that a lower dose of irradiation therapy was associated with increased rate of failure in the younger children,” said Dr. Michalski. “Reducing the treatment by just three fractions from 23.4 Gy to 18 Gy was associated with a higher rate of events and diminished overall survival. Patients with average-risk medulloblastoma should continue to receive a standard dose of 23.4 Gy to the craniospinal axis, unless they are enrolled in a clinical trial.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
