Renin Lukose

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.

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 bony anatomy localization, delivers one‐fourth the dose as compared to conventional ortho‐pair films. PACS number: 87.57.Q, 87.57.cj, 87.53.Jw

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.

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.

SU-F-T-156: Monte Carlo Simulation Using TOPAS for Synchrotron Based Proton Discrete Spot Scanning System

PURPOSE This study provides an overview of the design and commissioning of the Monte Carlo (MC) model of the spot-scanning proton therapy nozzle and its implementation for the patient plan simulation. METHODS The Hitachi PROBEAT V scanning nozzle was simulated based on vendor specifications using the TOPAS extension of Geant4 code. FLUKA MC simulation was also utilized to provide supporting data for the main simulation. Validation of the MC model was performed using vendor provided data and measurements collected during acceptance/commissioning of the proton therapy machine. Actual patient plans using CT based treatment geometry were simulated and compared to the dose distributions produced by the treatment planning system (Varian Eclipse 13.6), and patient quality assurance measurements. In-house MATLAB scripts are used for converting DICOM data into TOPAS input files. RESULTS Comparison analysis of integrated depth doses (IDDs), therapeutic ranges (R90), and spot shape/sizes at different distances from the isocenter, indicate good agreement between MC and measurements. R90 agreement is within 0.15 mm across all energy tunes. IDDs and spot shapes/sizes differences are within statistical error of simulation (less than 1.5%). The MC simulated data, validated with physical measurements, were used for the commissioning of the treatment planning system. Patient geometry simulations were conducted based on the Eclipse produced DICOM plans. CONCLUSION The treatment nozzle and standard option beam model were implemented in the TOPAS framework to simulate a highly conformal discrete spot-scanning proton beam system.

MO-D-213-02: Quality Improvement Through a Failure Mode and Effects Analysis of Pediatric External Beam Radiotherapy

Purpose: To conduct a failure mode and effects analysis (FMEA) as per AAPM Task Group 100 on clinical processes associated with teletherapy, and the development of mitigations for processes with identified high risk. Methods: A FMEA was conducted on clinical processes relating to teletherapy treatment plan development and delivery. Nine major processes were identified for analysis. These steps included CT simulation, data transfer, image registration and segmentation, treatment planning, plan approval and preparation, and initial and subsequent treatments. Process tree mapping was utilized to identify the steps contained within each process. Failure modes (FM) were identified and evaluated with a scale of 1–10 based upon three metrics: the severity of the effect, the probability of occurrence, and the detectability of the cause. The analyzed metrics were scored as follows: severity – no harm = 1, lethal = 10; probability – not likely = 1, certainty = 10; detectability – always detected = 1, undetectable = 10. The three metrics were combined multiplicatively to determine the risk priority number (RPN) which defined the overall score for each FM and the order in which process modifications should be deployed. Results: Eighty-nine procedural steps were identified with 186 FM accompanied by 193 failure effects with 213 potential causes. Eighty-one of the FM were scored with a RPN > 10, and mitigations were developed for FM with RPN values exceeding ten. The initial treatment had the most FM (16) requiring mitigation development followed closely by treatment planning, segmentation, and plan preparation with fourteen each. The maximum RPN was 400 and involved target delineation. Conclusion: The FMEA process proved extremely useful in identifying previously unforeseen risks. New methods were developed and implemented for risk mitigation and error prevention. Similar to findings reported for adult patients, the process leading to the initial treatment has an associated high risk.