IQ change within three years of radiation therapy in pediatric brain tumor patients treated with proton beam radiation therapy versus photon radiation therapy

Reporter: Jacob Shabason, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 6 de junio del 2013

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Presenter: Lisa Kahalley, PhD
Presenter's Affiliation: Baylor College of Medicine, Houston, TX
Abstract #: 10009

Background

  • There are approximately 4,000 new pediatric brain tumors diagnosed each year in children, accounting for approximately 20% of all pediatric malignancies.
  • Radiation therapy typically plays an integral role in the treatment of pediatric brain tumors.
  • However, radiation therapy can cause significant toxicity particularly to the developing brain of a child.
  • One of the major long-term toxicities from brain radiation is the increased risk of non-reversible cognitive impairment.
  • Risk factors for worsening neurocognitive decline are younger age of treatment, higher radiation dose and larger volume treated.
  • Recent advances in the delivery of radiation can reduce the exposure of normal tissue to radiation and therefore presumably decrease the risk of neurocognitive toxicity.
  • As compared to standard photon radiation, proton radiotherapy does not have an exit dose and therefore minimizes irradiation to the surrounding healthy brain tissue
  • Proton therapy therefore has the potential to better preserve cognitive function.
  • To date there have been no studies that describe neurocognitive outcomes of proton vs. photon radiation for pediatric brain malignancies.
  • In this retrospective study, the authors examine the change in IQ over time between patients treated for pediatric brain tumors with proton therapy compared to photon therapy.

Materials and Methods

  • IQ change was evaluated for the first three years post-radiation.
  • In order to avoid treatment selection bias patients in the photon cohort were chosen from 2000-2007 before the proton center was built at MD Anderson, and patients in the proton group were selected from 2008-2011, after the proton center was built.
  • The study included patients of ages 2-18 years.
  • Patients with high-grade gliomas, brainstem gliomas and atypical teratoid rhabdoid tumors (ATRT) were excluded, because of the poor tumor prognosis in these diseases.
  • IQ scores were used as a measure of cognitive function.
  • Patients were only included if they had baseline IQ scores, and then IQ scores at different time points for at least the first three years post-radiotherapy.
  • A linear regression model predicted follow-up IQ scores controlling for baseline IQ, age-at-RT, time-since-RT, and craniospinal irradiation (CSI), F (7,45)=23.4, p<0.001.

Results

  • 53 survivors of pediatric brain tumors were included in this study where baseline and follow up IQ scores were obtained retrospectively.
  • 31 patients were treated with proton therapy and 22 with conventional photon radiation techniques.
  • Overall patients treated with photon radiation were on average younger and received a higher dose of radiation.
  • There was no significant difference in tumor location between the 2 groups.
  • Follow-up IQ scores were significantly lower in the photon group compared to the proton group (p<0.05).
  • The photon group lost 10.3 IQ points on average with each additional year following radiation therapy (p<0.01), while the proton therapy group remained stable, losing only 0.1 points per year on average (p<0.05).
  • Craniospinal irradiation was associated with IQ decline in both groups (p<.0.05).
  • Age at time of radiation was not associated with IQ decline in either group (p=0.154).
  • Total radiation dose and location of tumor was not associated with IQ with the above variables in the model.

Author's Conclusions

  • Standard photon radiation can result in significant cognitive decline in patients with pediatric brain tumors with IQ scores declining by more than half a standard deviation with each additional year post-radiation.
  • On the other hand, patients treated with proton radiotherapy had a relatively stable IQ for three years, likely from improved sparing of normal brain tissue.
  • Therefore, proton therapy may spare cognitive function for at least the first 3 years post-radiation.
  • Limitations of this study include:
    • The small heterogeneous sample size.
    • The data was obtained retrospectively.
    • The study did not account for potential differences in surgery or chemotherapy.
    • The study did not take into account dosimetric differences.
    • There is a lack of long-term follow up.
  • This study needs to be verified with a larger sample size, with more dosimetric analysis and with longer follow up all preferably in a prospective manner.

Clinical Implications

  • This study is the first report evaluating neurocognitive toxicity in pediatric patients with brain tumors treated with photon vs. proton radiotherapy.
  • With 3 years of follow up, there is a clear advantage in terms of cognitive toxicity as measured by IQ in patients receiving partial brain proton radiation.
  • No difference in IQ was demonstrated between proton and photon treatment for patients receiving craniospinal irradiation. When craniospinal irradiation is required, the entire brain receives radiation regardless of modality used. For this reason, proton therapy does not provide normal brain sparing and is not expected to reduce IQ deficits. Proton radiation to the craniospinal axis provides sparing of many other tissues and is expected to be beneficial over photon therapy by measures not included as part of this study.
  • It is absolutely vital to continue to obtain long term follow up data and to begin to collect this data in a prospective manner.
  • Other measures of cognitive function as opposed to only IQ will be most interesting in future studies..
  • It is also important to take into account dosimetric factors in order to truly understand how volume of normal brain correlates with neurocognitive outcome.
  • Nonetheless, the information provided shows a significant benefit of proton radiotherapy in long-term survivors with pediatric brain tumors.
  • Due to the fact, that proton therapy is a limited resource with only a few centers open in the United States, it is important to ensure that these patients have access to this resource regardless of their geographic location due to the potential significant benefit of this therapy in this population.

Patient Summary: What Does This Mean For Me?

Radiation therapy is a standard treatment for pediatric brain tumors, yet there are concerns over radiation's long term effect on cognitive function. Proton therapy is a type of radiation therapy in use at a limited number of centers in the US that is theorized to significantly reduce toxicity to normal tissues. This study looked to compare the effects on patient IQ when using conventional radiation versus proton therapy for pediatric brain tumors.
The study found that kids who received conventional radiation lost an average of 10.3 IQ points per year over the 3 year study compared to only 0.1 IQ points lost per year in the proton group. The age of the patients did not affect the result (assuming that perhaps younger patients would be more severely affected). With 3 years of follow up, there is a clear advantage in terms of cognitive toxicity as measured by IQ in patients receiving partial brain proton radiation.
No difference in IQ was demonstrated between proton and photon treatment for patients receiving craniospinal irradiation, which treats the entire brain, regardless of which type of radiation is used. For this reason, in these cases, proton therapy does not provide normal brain sparing and is not expected to reduce IQ deficits.

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