A Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma
Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 21, 2003
Presenter: Thomas Merchant, MD Presenter's Affiliation: St. Jude Children's Research Hospital Type of Session: Scientific
Neurocognitive, endocrine, and otic toxicity are of primary concern in treating pediatric patients with radiation therapy (RT). Previous efforts to decrease the dose and volume of RT for patients with average-risk medulloblastoma have been successful in reducing the volume of normal tissue treated without compromising control. The current standard for this patient population includes craniospinal irradiation (CSI) to 23.4 Gy with a boost to the entire posterior fossa (PF) to a total dose of 54-55.8 Gy followed by dose-intensive chemotherapy. Despite this limited dose for CSI, pediatric patients continue to experience a loss of IQ of 4.3 points per year. This study attempts to decrease even further the volume of normal tissue treated by limiting the dose given to the entire PF and introducing a boost to the primary tumor volume.
Materials and Methods
84 patients with average-risk medulloblastoma (defined as having residual tumor after surgery <1.5 cm2 with no metastatic disease) were treated from 1996-2002.
RT was started 28 days following surgical resection of the primary disease.
RT consisted of CSI to 23.4 Gy with a conedown to the anatomic PF to a dose of 36.0 Gy followed by a final conedown to the primary tumor volume to a total dose of 55.8 Gy.
Volume definitions for the PF volume were as follows:
CTV includes the bilateral cerebellar hemispheres, the brainstem to the midbrain, and the cervical spinal cord to the foramen magnum
PTV = CTV + 0.3-0.5 cm for margin.
Volumes for the final tumor volume were defined as follows:
GTV was defined as the post-operative tumor bed (with MRI correlation)
CTV = GTV + 2.0 cm for margin
PTV = CTV + 0.3-0.5 cm for margin
6 weeks following completion of RT, patients underwent dose-intensive chemotherapy consisting of Cytoxan (2 mg/m2x2), Cisplatin (75 mg/m2), and vincristine (1.5mg/m2x2) x 4 cycles with peripheral blood stem cell support.
The median follow-up was 2.8 yrs.
Overall, the 3-yr local control rate was 93%
The 3-year event-free survival rate was 78%
The 3-yr PF failure as a component of failure was 6.3%.
The patterns of failure included 3 patients who failed in the PF alone, 1 patient who had both PF and neuraxis failure, and 10 patients who failed in the neuraxis alone.
This is the largest study to date showing equivalent local control for average risk medulloblastoma patients receiving decreased dose to the posterior fossa.
Additional follow-up is required to confirm these results.
A current trial further decreasing the volume of the final tumor boost is underway which defines the CTV as the GTV + 1 cm.
The need for decreasing toxicities from cranial irradiation in the pediatric population is of utmost importance. Although radiation has been shown to be very effective in controlling medulloblastoma, its use has been limited due to these toxicities. The results of this study follow recent results which showed equivalent control achieved with 23.4 Gy of CSI compared to 36 Gy. The current study represents a small but important step in further decreasing the volume of normal tissue treated. The ongoing trial of decreased final tumor volume boost represents an additional step limiting radiation volumes. Although equivalent results to historic rates of local control were found with the decreased PF volumes, longer follow-up is needed to confirm these results, and correlation with long-term neurocognitivce outcomes is necessary.
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