Dose Escalation in Pediatric Brain Tumors with Radiation Therapy. A dosimetric Evaluation on The Potential Role of Proton Beam Therapy

Reviewer: William Levin
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 29, 2007

Presenter: J.L. Habrand
Presenter's Affiliation: Centre De Proton Therapie d'Orsay, Orsay, France
Type of Session: Scientific

Background

Historically, local control of most pediatric brain tumors following surgery and conventional radiation have been disappointing.
Extrapolating from adult brain tumor data it seems that dose escalation would be worthwhile.
However, because of significant dose to uninvolved brain tissue, the use of conventional photon radiation therapy has been limited in this regard.
Typical side effects have included lifelong neurocognitive defects, as well as damage to the hypothalamic-pituitary axis resulting in growth deficits.
Proton beam radiation with its precise targeting and significant sparing of normal tissue has renewed interest in dose escalation in pediatric brain tumors.

Materials and Methods

Fifteen cases with tumors located in the supra tentorium were studied.
Two pathologic subtypes were included: Group 1, craniopharyngioma and Group 2, malignant ependymoma.
Comparison plans were then generated for the two groups using proton planning versus photon (conventional) planning.
The dose was then escalated on subsequent plans and DVH's were then generated for critical structures.

Results

In group 1, dose escalation up to 59 CGE (cobalt Gy equivalent) was possible in 10 of 11 cases while still observing dose constraints to all critical structures: Max 56 Gy to chiasm and left and right optic nerves, 45 Gy to cochlea, 60/45 Gy to surface/mid-brainstem.
1 of 11 cases could not tolerate dose escalation above 56.6 CGE without jeopardizing optic tolerance.
In group 2, improved coverage of the PTV using protons versus photons ranged between 19 and 48 percent.
There was also a significant sparing of the uninvolved cerebral hemispheres with protons. For example, at the 65 CGE tumor dose, the V20 (dose of 20Gy to the cerebral hemispheres) was reduced by 30% for the protons; V20-35 reduced by 10%; V35-65 by 20%.
The dose to the pituitary gland was also significantly reduced.

Author's Conclusions

Dose escalation may be possible in the treatment of pediatric brain tumors while significantly reducing the risk to uninvolved tissue.
This dose escalation may translate into improved local control and possibly improved survival.

Clinical/Scientific Implications

As the author indicated, pediatric brain tumors like many other sites of disease may benefit from increased dose.
However, dose escalation has been limited by potential and realized toxicity to nearby structures.
While IMRT has been used in the treatment of adult tumors and has allowed for dose escalation, many clinicians are hesitant to use this technique in the pediatric population. This is because with IMRT, low doses of radiation are spread out across normal structures, allowing dose to be escalated in the region of the tumor.
But we still do not know the potential side effects of this low dose exposure to normal tissues and there is clear concern that this may stimulate second malignancies.
Proton radiation, on the other hand, minimizes dose to all areas except for the site of disease.
In pediatric brain tumors dose escalation appears to be possible while still reducing the risk of cognitive deficits, growth retardation, and damage to optic structures.
Another avenue of research should be the combination of proton radiation with biologic agents and chemotherapeutics