Technical Note: Design and characterization of a large diameter parallel plate ionization chamber for accurate integral depth dose measurements with proton beams.

PURPOSE: The goal was to develop and test a large diameter parallel plate ionization chamber capable of intercepting at least 98% of the proton beamlets tested with the system. METHODS: A commercial synchrotron proton therapy system was used for the study (Hitachi, Ltd, Hitachi City, Japan; Model: Probeat-V). The energies investigated were in the range of 100 to 192 MeV. Three beam spot options available from the system were used. A PTW Bragg peak IC of diameter 84 mm (BP84) (Model PTW34070) was employed for comparison in a scanning water phantom. A prototype of 150 mm diameter was produced (PTW, Freiburg, Germany; model: T34089) and used for the testing. Monte Carlo calculations were also performed with FLUKA to guide the BP150 design and for comparison to the radiological measurements. For comparison, a 40 cm diameter ideal virtual detector was included in the Monte Carlo model. RESULTS: The measured proton range R90 agrees between the BP84 and BP150 ionization chambers within +0.06/-0.27 mm across the energies 100-192 MeV, which is less than the daily experimental setup uncertainty of 0.4 mm. The differences in the absolute integral depth dose curves (IDDs) between the BP84 and BP150 ranged from 0.3% to 1.0% for the spot sizes and beam energies tested. As predicted by the Monte Carlo modeling, the greatest differences were found in the plateau region of the IDDs. Also, the IDDs measured with the BP150 were very similar to those of the ideal 40 cm diameter detector Monte Carlo simulations. CONCLUSIONS: We conclude that the BP150 offers a small, but a useful reduction in uncertainty from the nuclear halo effect for the system under test.

Critical combinations of radiation dose and volume predict intelligence quotient and academic achievement scores after craniospinal irradiation in children with medulloblastoma.

PURPOSE: To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects. METHODS AND MATERIALS: Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irradiation followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years after treatment) that included intelligence quotient (estimated intelligence quotient, full-scale, verbal, and performance) and academic achievement (math, reading, spelling) tests. Craniospinal irradiation consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for high-risk patients (metastatic or residual disease >1.5 cm(2)). The primary site was treated using conformal or intensity modulated radiation therapy using a 2-cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment. RESULTS: A decline with time for all test scores was observed for the entire cohort. Sex, race, and cerebrospinal fluid shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25 Gy and 55 Gy at 10-Gy increments according to brain volume and age. CONCLUSIONS: The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain subvolumes will improve treatment planning, guide intervention, and help estimate the value of newer methods of irradiation.

Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors.

PURPOSE: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. PATIENTS AND METHODS: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. RESULTS: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥ 50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ≥ 52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ≥ 54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively. CONCLUSIONS: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.

Predicting the probability of abnormal stimulated growth hormone response in children after radiotherapy for brain tumors.

PURPOSE: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. METHODS AND MATERIALS: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. RESULTS: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. CONCLUSIONS: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

Image quality & dosimetric property of an investigational imaging beam line MV-CBCT.

To measure and compare the contrast to noise ratio (CNR) as a function of dose for the CBCTs produced by the mega-voltage (MV) imaging beam line (IBL) and the treatment beam line (TBL), and to compare the dose to target and various critical structures of pediatric patients for the IBL CBCT versus standard TBL orthogonal port films. Two Siemens Oncor linear accelerators were modified at our institution such that the MV-CBCT would operate under an investigational IBL rather than the standard 6MV TBL. Prior to the modification, several CBCTs of an electron density phantom were acquired with the TBL at various dose values. After the modification, another set of CBCTs of the electron density phantom were acquired for various doses using the IBL. The Contrast to Noise Ratio (CNR) for each tissue equivalent insert was calculated. In addition, a dosimetric study of pediatric patients was conducted comparing the 1 cGy IBL CBCT and conventional TBL orthogonal pair port films. The CNR for eight tissue equivalent inserts at five different dose settings for each type of CBCT was measured. The CNR of the muscle insert was 0.8 for a 5 cGy TBL CBCT, 1.1 for a 1.5 cGy IBL CBCT and 2.8 for a conventional CT. The CNR of the trabecular bone insert was 2.9 for a 5 cGy TBL CBCT, 5.5 for a 1.5 cGy IBL CBCT and 14.8 for a conventional CT. The IBL CBCT delivered approximately one-fourth the dose to the target and critical structures of the patients as compared to the TBL orthogonal pair port films. The IBL CBCT improves image quality while simultaneously reducing the dose to the patient as compared to the TBL CBCT. A 1 cGy IBL CBCT, which is used for boney anatomy localization, delivers one-fourth the dose as compared to conventional ortho-pair films.