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Spot-Scanning based proton radiation therapy for pediatric ependymoma: clinical outcome of 25 patients treated at Paul Scherrer Institute (PSI)
Reporter: Arpi Thukral, MD MPH
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 12 de mayo del 2011
Presenter: Ares, C.
Presenter's Affiliation: Center for Proton Therapy, Paul Scherrer Institute (PSI), Switzerland
- Ependymomas are rare brain tumors that occur in young children.
- They arise from ependymal cells which form the lining of the ventricular system and the central spinal canal.
- United States: <150 cases/year among children < 14 yo
- <10% of pediatric brain tumors, incidence peaks at age 5
- Most are posterior fossa tumors and arise from the 4th ventricle.
- The mainstay of treatment for this disease is maximal safe resection followed by radiation therapy. Gross total resection is curative, however it is often not possible given the site of the tumor and its proximity to critical structures.
- Side effects of brain radiation treatment (RT) in these young children can be detrimental as well. These include:
- Cognitive dysfunction
- Neurologic dysfunction
- Hearing loss
- Prior trials examining chemotherapy after surgery to avoid RT in these children have not been successful.
- It is believed that proton RT may be superior to photon RT for these children due to a reduction in dose to normal tissues, which would lead to an improvement long-term side effects.
- This is due to the ability of proton radiation to deliver less exit dose to normal structures due to its characteristic Bragg peak and sharp dose-fall off.
- Previous work by Merchant, et. al. in 2008 has demonstrated a 7 year event free survival of 69.1% in patients with ependymoma treated with surgical resection + radiation. Factors that impacted local control included extent of surgery (GTR vs. STR) and gender.
- The purpose of this study was to evaluate the efficacy and safety of proton radiation in patients with ependymoma, using a spot-scanning technique at the Paul Scherrer Institute (PSI) in Switzerland.
Materials and Methods
- 25 patients with ependymoma were treated at PSI with proton therapy using a spot-scanning technique at PSI between July 2004 and September 2010.
- Patient characteristics:
- Grade 3: 24 patients; Grade 2: 1 patient
- Infratentorial: 17 patients; Supratentorial: 8 patients
- 18 male, 7 female
- Mean age: 3.2 years (range 1.1-15.2); 92% were less than 4 yo and required general anesthesia.
- Tumor resection:
- GTR: 17 patients (68%)
- STR: 8 patients (32%)
- GTV=tumor bed +/-residual tumor
- CTV= GTV+10mm – anatomically confined margin
- PTV=CTV+5 mm (anatomic 3D expansion)
- Prescribed median dose: 59.4 Gy (RBE); range 54-60 Gy
- Late toxicity assessed via CTCAE v. 4.0.
- Mean follow-up= 29 months (range 3.5 to 63.4)
- Local in-field failure was seen in 3 patients.
- 2 patients had infratentorial location and residual macroscopic tumor
- 1 patient had supratentorial location and had GTR
- No spinal axis failures.
- Two deaths seen due to tumor progression.
- Kaplan Meier Analysis:
- 3 year local control (LC): 82+/-9.2% (82% for infratentorial and 83% for supratentorial tumors, respectively)
- 3 year overall survival (OS): 83+/-9.1% (84% for infratentorial and 83% for supratentorial tumors, respectively)
- Grade > 3 toxicity free survival rate: 87 +/- 6.8%
- > Grade 3 toxicity seen in 3 patients.
- 2 patients had unilateral deafness after RT for infratentorial tumors infiltrating the internal auditory canal.
- 1 patient died of brainstem necrosis, however the cause of this was thought to be multifactorial (not only due to RT).
- No toxicity was seen due to general anesthesia.
- The authors conclude that their data demonstrate the efficacy and safety of spot-scanning based proton treatment for ependymomas in this population of children.
- They state that local control was excellent, especially given that almost all of these patients were young and had high grade (grade 3) ependymoma.
- The authors acknowledge the limited sample size and agree that a larger series and long-term follow-up is warranted.
- Radiation is a mainstay of treatment in patients with pediatric brain tumors, and can often lead to detrimental side effects including neuroendocrine abnormalities, cognitive defects, and visual disturbances.
- Proton radiation therapy offers a potential strategy to decrease long-term toxicity in pediatric brain tumor patients.
- The authors of this study were able to clearly demonstrate the efficacy and safety of proton radiation for the treatment of ependymomas in the acute setting in this small cohort of 25 pediatric patients.
- Although there were 3 patients with > Grade 3 toxicity, 2 of these patients who suffered unilateral deafness did have tumor of the internal auditory canal, where RT dose to this area could not be avoided.
- In the one patient that died of brainstem necrosis, this was thought to not be due to radiation, rather was likely the result of tumor progression or meningitis.
- The main limitation of this study is its small study population and short-term follow up. To fully evaluate long-term toxicity outcomes in this population, many more years of follow-up data will be needed
- However, even with its limitations, studies such as these are important to add to the growing body of literature regarding proton radiation in pediatric patients.