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ABSTRACT: Proton therapy offers dosimetric advantage of decreased dose to non-target tissues. This study explored the potential benefits of proton radiation therapy versus photon based intensity modulated radiation therapy (IMRT) for patients with low grade gliomas (LGG) through dosimetric comparison and biological modeling of potential radiation-induced toxicities. Eleven patients were treated with fractionated proton radiation therapy on a prospective protocol assessing for feasibility and treatment toxicity of proton radiation therapy in patients with LGG. IMRT treatment plans were created for each patient using the same CT planning data set and defined structures. The prescription dose to clinical target volume (CTV) was 54 Gy(RBE). The toxicity risk of IMRT and protons was estimated based upon equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) modeling. The risk of secondary tumors for each modality was estimated. Proton EUD for most immediate normal tissue structures was between 10-20 Gy lower than the EUD delivered by IMRT. However, the difference in NTCP was negligible for both modalities. The mean excess risk of proton radiation-induced second tumor in the brain per 10,000 cases per year is 47 (range 11-83), while the mean risk for IMRT is 106 (range 70-134). The mean ratio of excess risk IMRT/protons is 2.2 (range 1.6-6.5), demonstrating that the risk of secondary tumors is consistently higher for IMRT. Proton therapy effectively reduces the dose to surrounding normal tissues in LGG patients. IMRT has a twofold higher risk of secondary intracranial tumors as compared to proton therapy. In most cases, NTCP is negligible for both modalities. The benefit of proton therapy over IMRT may be more substantial in patients with tumors in proximity to critical structures.
Technology in cancer research & treatment 07/2012; · 2.02 Impact Factor
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ABSTRACT: This study was designed to estimate the risk of radiation-associated tumors and clinical toxicity in the brain following fractionated radiation treatment of pituitary adenoma. A standard case of a patient with a pituitary adenoma was planned using 8 different dosimetric techniques. Total dose was 50.4 Gy (GyE) at daily fractionation of 1.8 Gy (GyE). All methods utilized the same CT simulation scan with designated target and normal tissue volumes. The excess risk of radiation-associated second tumors in the brain was calculated using the corresponding dose-volume histograms for the whole brain and based on the data published by the United Nation Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and a risk model proposed by Schneider. The excess number of second tumor cases per 10,000 patients per year following radiation is 9.8 for 2-field photons, 18.4 with 3-field photons, 20.4 with photon intensity modulated radiation therapy (IMRT), and 25 with photon stereotactic radiotherapy (SRT). Proton radiation resulted in the following excess second tumor risks: 2-field 5 5.1, 3-field 5 12, 4-field 5 15, 5-field 5 16. Temporal lobe toxicity was highest for the 2-field photon plan. Proton radiation therapy achieves the best therapeutic ratio when evaluating plans for the treatment of pituitary adenoma. Temporal lobe toxicity can be reduced through the use of multiple fields but is achieved at the expense of exposing a larger volume of normal brain to radiation. Limiting the irradiated volume of normal brain by reducing the number of treatment fields is desirable to minimize excess risk of radiation-associated second tumors.
Technology in cancer research & treatment 06/2011; 10(3):243-51. · 2.02 Impact Factor
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ABSTRACT: To identify MR spectroscopic changes in the rat hippocampus following proton radiosurgery.
A group of 12 rats were treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 30 CGE, 50 CGE, 70 CGE, 90 CGE were delivered to groups of 3 animals using single fraction technique. Animals were imaged using a standard 3 T GE Signa MRI at 4 months following treatment. An untreated animal was also studied. A 3'' surface coil was employed to obtain T1 weighted coronal pre- and post-gadolinium images (TR 600 and TE 30) and dual echo T2 weighted coronal images (TR 3000, TE 30/90). Volumetric analysis with custom software was done to evaluate areas of increased signal on T2 weighted images and the development of hydrocephalus was examined. Animals were sacrificed and specimens of the treated hippocampus were harvested for High Resolution Magic Angle Spinning MR Spectroscopy (HRMAS) followed by histopathology of the tissue samples. Peak values of choline, creatine, N-acetyl aspartate and lipids were evaluated and compared.
Peak tissue injury occurred in the surviving 90 CGE animal by both T2 weighted and post-gadolinium imaging. Gadolinium enhancement was seen in decreasing volumes of tissue at dosage levels from 90 to 50 CGE. Hydrocephalus was seen on the untreated side in the 90 CGE animal likely because of mass effect, while it was seen in small degrees in the side of treatment in the 70 and 50 CGE animals. Histopathology showed changes at 90 and 70 CGE, but not at 50 or 30 CGE at this time point using H and E stains. HRMAS showed spectroscopic changes in the surviving 90 and 70 CGE animals but not in the 50 and 30 CGE animals. Statistical significance was not reached because of the small sample size.
Following single dose proton radiosurgery of rat hippocampus, HRMAS is able to identify metabolic changes induced by radiation. Studies built on these principles may help develop non-invasive MR spectroscopic methods to distinguish radiation changes from tumor recurrence.
Stereotactic and Functional Neurosurgery 02/2006; 84(4):147-54. · 1.85 Impact Factor
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ABSTRACT: Atypical and malignant meningiomas are at high risk for local failure. The role of radiation therapy (RT) and dose levels required to improve tumor control are poorly defined. This study reviews our experience with RT.
Thirty-one patients underwent fractionated RT for atypical (AM, 15 patients) or malignant meningioma (MM, 16 patients) of the cranium. Sixteen patients presented with primary and 15 with recurrent disease. Eight patients received RT following total resection, 21 patients after subtotal resection and 2 patient following biopsy only. RT was given using megavoltage photons in 15 patients and combined photons and 160 MeV protons in 16 patients. Total target doses ranged from 50 to 68 (AM, mean 62) and from 40 to 72 (MM, mean 58) Gy or CGE (= cobalt-gray-equivalent).
With mean observation time of 59 months (range: 7-155 months) actuarial local control rates at 5- and 8-years were similar for both histologies (38% and 19% for AM and 52 and 17% for MM). However, significantly improved local control was observed for proton versus photon RT (80% versus 17% at 5 years, p = 0.003) and target doses > or = 60 Gy for both, atypical (p = 0.025) and malignant meningioma (p = 0.0006). At time of analysis, 14/15 patients (93%) with AM and 6/16 (38%) with MM were alive. Three patients (19%) with MM developed distant metastasis. Actuarial 5- and 8-year survival rates for MM were significantly improved by use of proton over photon RT and radiation doses > 60 CGE. Three patients developed symptomatic radiation damage after 59.3, 68.4 and 72 Gy/CGE.
Conformal, high dose RT resulted in significant improvement of local control for atypical and malignant meningiomas. Increased local control resulted also in improved rates of survival for patients with malignant meningioma.
Journal of Neuro-Oncology 06/2000; 48(2):151-60. · 3.21 Impact Factor
