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Craniopharyngioma: Early Response Evaluation of Patients Treated with Protons at the Midwest Proton Radiotherapy Institute in Bloomington, Indiana.
Reviewer: Christine Hill, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 23, 2008
Presenter: Markus Fitzek, MD
Presenter's Affiliation: Midwest Proton Radiotherapy Institute, Bloomington, IN and Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN
Type of Session: Scientific
- Craniopharyngioma is a benign tumor that represents the most common pituitary tumor in children.
- Affected children present most often with symptoms such as headache and visual disturbance; however, up to 80% have symptoms of endocrine dysfunction at the time of diagnosis.
- The intimate involvement of both the pituitary gland and the optic chiasm make treatment of craniopharyngioma with either surgery or radiotherapy challenging.
- Although more than half of patients experience visual improvement after surgery (Dhellemmes, 2006), tumors have a high propensity to recur after surgery. Visual and endocrine issues resulting from both treatment and tumor recurrence can significantly alter quality of life (Dekkers, 2006).
- Radiotherapy is generally included in the care of children who have only subtotal resection, or those who experience recurrence after gross total resection. Post-operative radiotherapy may contribute to hypothalamic dysfunction, IQ decline, short-term memory loss, and threat of visual loss (Merchant, 2006).
- Proton beam radiotherapy may allow improved dose distribution and precision because of steep dose fall-off beyond the Bragg peak, as well as the particulate nature of protons that allows improved dose conformality.
- Preliminary reports have demonstrated that fractionated proton-based radiotherapy may reduce the incidence of neurocognitive changes in patients requiring radiotherapy for treatment of craniopharyngioma (Luu, 2006).
- The study presented here was carried out in order to evaluate the early response to proton beam radiotherapy in children requiring radiotherapy for treatment of craniopharyngioma after surgical resection.
Materials and Methods
- Six children received proton-beam irradiation for craniopharyngioma at the Midwest Proton Radiotherapy Institue (MPRI) between 2005 and 2007.
- Radiotherapy was carried out for patients either after subtotal surgical tumor resection, or in the case of recurrent tumor after gross total resection.
- Median age was 11 years, with a range of 5 – 18 years. Five patients were male, and one was female.
- Five of six patients had had ventriculo-peritoneal shunts placed prior to beginning radiotherapy.
- Four patients had tumors of mixed histology, one had a purely solid tumor, and the last had a purely cystic tumor. Tumor volume ranged from 3 – 54 cc, with a median tumor volume of 17 cc.
- All children were treated with a 206 MeV fixed horizontal beam line.
- Patients were positioned in the supine position, and immobilized in an aquaplast mask, and positioning was assisted by a robotic patient positioning system.
- Four of six patients received total dose of 54 Cobalt Gray Equivalents (CGE); the remaining two received dose of 50.4 CGE. All treatment was delivered using conventional fractionation of 1.8 CGE delivered Monday through Friday.
- In the absence of new neurologic/ endocrine symptoms, MRI was obtained after week two of the planned radiotherapy course for evaluation of possible change in tumor volume.
- Median follow up was 20 months (range 3 – 28 months).
- All patients remain alive without tumor progression/ local failure.
- One child required cyst aspiration during the radiotherapy that did not require treatment interruption; a second child required cyst aspiration 9 months after completing radiotherapy.
- No unexpected treatment interruptions occurred. Acute toxicities included intermittent headaches, alopecia, and fatigue.
- No new endocrine/ visual effects have been observed following radiotherapy.
- All patients have continued in school without gross deficits or difficulties.
- Individual patient tumor response was as follows:
- Patient 1: 13 yo boy with 5 cc tumor volume, received 54 CGE and achieved complete response, stable at 13 months of follow-up.
- Patient 2: 15 yo girl with 19 cc tumor volume, received 54 CGE and achieved partial response, stable at 19 months of follow-up.
- Patient 3: 5 yo boy with 17 cc tumor volume, received 50.4 CGE and achieved partial response, stable at 25 months of follow-up.
- Patient 4: 11 yo boy with 3 cc tumor volume, received 54 CGE and achieved partial response, stable at 22 months of follow-up.
- Patient 5: 5 yo boy with 54 cc tumor volume, received 50.4 CGE and achieved partial response, stable at 33 months of follow-up.
- Patient 6: 18 yo boy with 30 cc tumor volume, received 54 CGE and achieved partial response, stable at 5 months of follow-up.
- The authors conclude that tumor response appears to be adequate with delivery of 50.4 – 54 CGE for partial resected or locally recurrent craniopharyngioma in children.
- They acknowledge the small size of the sample presented here, but note that acute tolerability was observed to be excellent, with no appreciable deterioration in quality of life due to radiotherapy observed.
- They acknowledge that much longer observation time is required for assessment of late CNS effects, but note that they expect them to be decreased when compared to late effects resulting from photon-based radiotherapy.
- Craniopharyngioma represents a benign tumor that may be devastating to quality of life in children.
- Much of the quality of life detriment associated with treatment of craniopharyngioma exists because of the intimate involvement of brain and visual structures with these tumors.
- In the small cohort of patients presented here, proton beam radiotherapy did not appear to be associated with any new endocrine, neurologic, or visual detriment; however, follow-up of this small population is quite short.
- Many potential risks of radiotherapy for craniopharyngioma, including neurocognitive impact and second malignant neoplasm, are acknowledged to occur years after completion of radiotherapy, and these risks are not addressed in the study presented here.
- The cystic nature of craniopharyngiomas causes these tumors to at times change in volume considerably during the course of radiotherapy. For this reason, MRI scanning is often performed during radiotherapy, as was done during this study. The authors acknowledge that re-planning proton radiotherapy for tumors which have changed considerably in size or shape could cause considerable treatment break or delay because of the considerable amount of time needed to develop proton radiotherapy plans. Although no child in the cohort presented here required such re-planning, awareness of this possibility is certainly important at the initiation of treatment. As proton treatment planning becomes more efficient and technologies more advanced, this risk of time delay is expected to decrease.
- Based on this small cohort of patients, delivery of proton beam radiotherapy for treatment of craniopharyngiomas appears to be feasible and safe in the acute setting. Information on late effects associated with this treatment remains unavailable, and will certainly contribute to the literature when longer follow-up permits analysis of potential neuroendocrine deficits and quality of life following proton beam radiotherapy as opposed to photon-based treatment delivery.