MRI Changes in Pediatric Patients with Low Grade Gliomas Treated with Proton or Photon Radiotherapy

Reporter: J. Taylor Whaley, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 21, 2012

Presenter: Murali Chintagumpala, Anita Mahajan
Presenter's Institution: Baylor Pediatric Oncology, University of Texas M.D. Anderson Cancer Center


  • Astrocytomas are the most common primary brain tumor in children. Low grade gliomas are a class of astrocytomas that tend to be very curable, with 95% survival at 5 years after complete resection of low-grade tumors.
  • Generally, radiation is reserved for tumor progression or symptomatic disease in the setting of low grade glioma in pediatric patients.
  • Because long-term side effects of radiation can be significant in pediatric patients, proton therapy has been utilized to limit the amount of normal brain that receives radiation. Proton therapy can potentially limit long-term side effects seen with photon-based radiation. This is related to improved dose conformality and dose distribution because of steep dose fall-off beyond the Bragg peak.
  • Pseudoprogression is a known development following radiation therapy for high grade gliomas and has been documented to occur in 30-40% of patients after chemoradiation. Pseudoprogression is classically associated with an increase in contrast enhancement seen following completion of chemoradiation in Glioblastoma multiforme. This phenomenon may mislead the clinician as the tumor appears to expand on follow up imaging; however, given time, pseudoprogression will demonstrate improvement in contrast enhancement.
  • The authors from the M.D.Anderson Cancer Center noted several patients with pseudoprogression in low grade gliomas following proton therapy.
  • In order to further evaluate this phenomenon in pediatric low grade glioma, the current study was undertaken to evaluate MRI changes that were noted in a group of pediatric patients with low grade glioma treated with either proton therapy or photon-based radiation.


  • All patients treated with radiation for low grade glioma from 2001 to 2011 at 2 institutions were identified.
  • Patients were required to have pre-and post-radiation MRI imaging.
  • Two neuroradiologists were blinded to the radiation modality given and evaluated the MRI scans for changes in bi-dimensional measurements relative to pre-radiation measurements.


  • 66 patients (27 females and 39 males) were treated during the period of interest.
  • 31 patients received photon-based radiation, and 35 patients received proton therapy.
  • There were no significant differences in demographic data between patients that received photon-based vs. proton therapy.
  • The median age was 8.7 years (Range, 3-17 yrs). Median follow up was 6 years in patients receiving photon-based radiation, and 3.9 years in proton therapy patients.
  • 44 patients had pilocystic astrocytoma or optic glioma, 15 patients had grade II astrocytoma, and 6 patients had other low grade glioma.
  • 55 tumors were midline.
  • 25 patients had pre-radiation chemotherapy.
  • All patients underwent radiation for either progressive disease or symptomatic disease.
  • The median radiation dose was 50.4 Gy/ GyRBE (Range, 45-54 Gy).
  • Following radiation, enlargement of the tumor was noted in 33% of all patients between 1.5- 11 months.
  • Median peak increase in enlargement was 16% (Range, 5-259%).
  • Enlargement was seen in 29% and 37% of patients that received photon-based vs. proton therapy, respectively.
  • Patients that received photon-based treatment had an 18% median increase noted at a median of 6 months, while patients receiving proton therapy had a 16% median increase at a median of 4 months.
  • Median time to tumor stabilization was 15 months and 11.5 months for photon-based and proton therapy, respectively.
  • At the last follow up, median tumor size was 56% and 45% for photon-based vs. proton therapy. Patients receiving photon-based therapy demonstrated stable disease 87% of the time, while patients receiving proton therapy had stable disease 91% of the time.
  • Two patients underwent resection for possible progression. Four additional patients had confirmed progression.

Authors' conclusions

  • Proton therapy is a good option for patients with low grade glioma that demonstrate progressive disease.
  • Pseudo-progression was noted in 33% of pediatric patients with low grade glioma after radiation within the first 6 months of follow up with subsequent stabilization over the following year.
  • There was no significant difference noted in incidence of early radiographic changes between photon-based and proton-based radiation therapy.
  • This phenomenon should be recognized and interventions should be delayed unless the patient becomes symptomatic.

Scientific/Clinical Implications

  • Pseudoprogression is a common phenomenon that develops following radiation therapy for brain tumors. It is often impossible to differentiate pseudoprogression from progressive disease and requires additional follow up to distinguish from true progression.
  • This scenario presents a very difficult challenge for the treating physician, as well as the patient; however, when possible, interventions should be avoided as the majority of patients will improve with additional follow up.
  • Although anecdotal experience has suggested an increase in pseudoprogression following proton therapy, there was no such trend noted in the current study.
  • Additional studies should are needed to continue to investigate this challenging clinical scenario.