A case-control study of linear energy transfer and relative biological effectiveness related to symptomatic brainstem toxicity following pediatric proton therapy.

BACKGROUND AND PURPOSE: A fixed relative biological effectiveness (RBE) of 1.1 (RBE1.1) is used clinically in proton therapy even though the RBE varies with properties such as dose level and linear energy transfer (LET). We therefore investigated if symptomatic brainstem toxicity in pediatric brain tumor patients treated with proton therapy could be associated with a variable LET and RBE. MATERIALS AND METHODS: 36 patients treated with passive scattering proton therapy were selected for a case-control study from a cohort of 954 pediatric brain tumor patients. Nine children with symptomatic brainstem toxicity were each matched to three controls based on age, diagnosis, adjuvant therapy, and brainstem RBE1.1 dose characteristics. Differences across cases and controls related to the dose-averaged LET (LETd) and variable RBE-weighted dose from two RBE models were analyzed in the high-dose region. RESULTS: LETd metrics were marginally higher for cases vs. controls for the majority of dose levels and brainstem substructures. Considering areas with doses above 54 Gy(RBE1.1), we found a moderate trend of 13% higher median LETd in the brainstem for cases compared to controls (P =.08), while the difference in the median variable RBE-weighted dose for the same structure was only 2% (P =.6). CONCLUSION: Trends towards higher LETd for cases compared to controls were noticeable across structures and LETd metrics for this patient cohort. While case-control differences were minor, an association with the observed symptomatic brainstem toxicity cannot be ruled out.

Implementation of a double scattering nozzle for Monte Carlo recalculation of proton plans with variable relative biological effectiveness.

A constant relative biological effectiveness (RBE) of 1.1 is currently used in clinical proton therapy. However, theRBEvaries with factors such as dose level, linear energy transfer (LET) and tissue type. MultipleRBEmodels have been developed to account for this biological variation. To enable recalculation of patients treated with double scattering (DS) proton therapy, includingLETand variableRBE, we implemented and commissioned a Monte Carlo (MC) model of a DS treatment nozzle. The main components from the IBA nozzle were implemented in the FLUKA MC code. We calibrated and verified the following entities to experimental measurements: range of pristine Bragg peaks (PBPs) and spread-out Bragg peaks (SOBPs), energy spread, lateral profiles, compensator range degradation, and absolute dose. We recalculated two patients with different field setups, comparing FLUKA vs. treatment planning system (TPS) dose, also obtainingLETand variableRBEdoses. We achieved good agreement between FLUKA and measurements. The range differences between FLUKA and measurements were for the PBPs within ±0.9 mm (83% ⩽ 0.5 mm), and for SOBPs ±1.6 mm (82% ⩽ 0.5 mm). The differences in modulation widths were below 5 mm (79% ⩽ 2 mm). The differences in the distal dose fall off (D80%-D20%) were below 0.5 mm for all PBPs and the lateral penumbras diverged from measurements by less than 1 mm. The mean dose difference (RBE= 1.1) in the target between the TPS and FLUKA were below 0.4% in a three-field plan and below 1.4% in a four-field plan. A dose increase of 9.9% and 7.2% occurred when using variableRBEfor the two patients, respectively. We presented a method to recalculate DS proton plans in the FLUKA MC code. The implementation was used to obtainLETand variableRBEdose and can be used for investigating variableRBEfor previously treated patients.

Reducing Anesthesia and Health Care Cost Through Utilization of Child Life Specialists in Pediatric Radiation Oncology.

PURPOSE: To analyze the effectiveness of a certified child life specialist (CCLS) in reducing the frequency of daily anesthesia at our institution, and to quantify the potential health care payer cost savings of CCLS utilization in the United States. METHODS AND MATERIALS: From 2006 to 2014, 738 children (aged ≤21 years) were treated with radiation therapy at our institution. We retrospectively analyzed the frequency of daily anesthesia before and after hiring a CCLS in 2011 after excluding patients aged 0 to 2 and >12 years. In the analyzed cohort of 425 patients the median age was 7.6 years (range, 3-12.9 years). For the pre-CCLS period the overall median age was 7.5 years; for the post-CCLS period the median age was 7.7 years. An average 6-week course of pediatric anesthesia for radiation therapy costs $50,000 in charges to the payer. The average annual cost to employ one CCLS is approximately $50,000. RESULTS: Before employing a CCLS, 69 of 121 children (57%) aged 3 to 12 years required daily anesthesia, including 33 of 53 children (62.3%) aged 5 to 8 years. After employing a CCLS, 124 of 304 children (40.8%) aged 3 to 12 years required daily anesthesia, including only 34 of 118 children (28.8%) aged 5 to 8 years (P<.0001). With a >16% absolute reduction in anesthesia use after employment of a CCLS, the health care payer cost savings was approaching $50,000 per 6 children aged 3 to 12 years treated annually with radiation therapy in our institution. This reduction resulted in a total of only 6 children aged 3 to 12 years required anesthesia to be treated per year at our center to achieve nearly break-even cost savings to the health care payer if the payer were to subsidize the employment expense of a CCLS. Overall, the CCLS intervention can provide an average annualized health care payer cost savings of "$[(anesthesia cost to payer during radiation therapy course/6) - (CCLS expense to payer/N)]" per child (N) treated with radiation therapy, where N equals the number of children aged 3 to 12 years treated in 1 year. This formula assumes that the payer subsidizes the cost for the employment of a CCLS, although our institution absorbed this expense for this data cohort. The predicted annualized health care system cost savings from reducing the frequency of anesthesia with radiation therapy when treating 100 children aged 3 to 12 years per year could exceed $775,000. CONCLUSIONS: These data suggest that a CCLS significantly reduces the frequency of daily anesthesia for children treated with radiation therapy. Health care system payers may achieve significant cost savings by financially supporting the employment of a CCLS in high-volume pediatric radiation therapy centers.

Proton therapy for the treatment of children with CNS malignancies.

Proton therapy is a novel technique for treating pediatric malignancies. As a tool to reduce normal-tissue dose, it has the potential to decrease late toxicity. Although proton therapy has been used for over five decades, most pediatric dosimetry studies and clinical series have been published over the last 10 years. The purpose of this article is to review the physical, radiobiological and economic rationales for proton therapy in pediatric CNS malignancies, and provide an overview of the current challenges and future direction of research and utilization of this approach.

Proton therapy dose distribution comparison between Monte Carlo and a treatment planning system for pediatric patients with ependymoma.

PURPOSE: Compare dose distributions for pediatric patients with ependymoma calculated using a Monte Carlo (MC) system and a clinical treatment planning system (TPS). METHODS: Plans from ten pediatric patients with ependymoma treated using double scatter proton therapy were exported from the TPS and calculated in our MC system. A field by field comparison of the distal edge (80% and 20%), distal fall off (80% to 20%), field width (50% to 50%), and penumbra (80% to 20%) were examined. In addition, the target dose for the full plan was compared. RESULTS: For the 32 fields from the 10 patients, the average differences of distal edge at 80% and 20% on central axis between MC and TPS are -1.9 ± 1.7 mm (p < 0.001) and -0.6 ± 2.3 mm (p = 0.13), respectively. Excluding the fields that ranged out in bone or an air cavity, the 80% difference was -0.9 ± 1.7 mm (p = 0.09). The negative value indicates that MC was on average shallower than TPS. The average difference of the 63 field widths of the 10 patients is -0.7 ± 1.0 mm (p < 0.001), negative indicating on average the MC had a smaller field width. On average, the difference in the penumbra was 2.3 ± 2.1 mm (p < 0.001). The average of the mean clinical target volume dose differences is -1.8% (p = 0.001), negative indicating a lower dose for MC. CONCLUSIONS: Overall, the MC system and TPS gave similar results for field width, the 20% distal edge, and the target coverage. For the 80% distal edge and lateral penumbra, there was slight disagreement; however, the difference was less than 2 mm and occurred primarily in highly heterogeneous areas. These differences highlight that the TPS dose calculation cannot be automatically regarded as correct.

Effectiveness and morbidity associated with reirradiation in conservative salvage management of recurrent soft-tissue sarcoma.

PURPOSE: The management of isolated local recurrence of soft-tissue sarcoma is therapeutically complex, and functional conservative management is preferable to radical or amputative salvage surgery. This study reviews the University of Florida experience using conservative resection and reirradiation to manage isolated local recurrences of soft-tissue sarcoma. METHODS AND MATERIALS: Between 1976 and 2005, a total of 14 patients who underwent primary conservative resection and irradiation developed isolated local recurrence and were managed with salvage conservative resection and reirradiation. Of the patients treated, 3 had tumors of the distal extremity, 8 had tumors of the proximal extremity, and 3 had tumors of the trunk. At the time of recurrence, 64% of tumors were greater than 5 cm and 79% were high grade. In combination with gross total resection, 13 of 14 patients received external beam radiotherapy with or without brachytherapy, and 1 patient was treated with brachytherapy alone. Two patients received chemotherapy. RESULTS: The median follow-up was 30 months, and no living patients were lost during follow-up. From retreatment, the 5-year actuarial overall survival, cause-specific survival, and local control rates were 40%, 40%, and 18% respectively. There was a 50% incidence of serious complication requiring either reoperation or leading to permanent functional impairment. Of the 14 patients, only 1 has remained disease free and without significant complications. No treatment factors, including achieving wide surgical margins or delivering higher radiation dosages, seemed to confer an advantage in local control. CONCLUSIONS: Salvage therapy for management of locally recurrent soft-tissue sarcoma is challenging, and the effects of reoperation and reirradiation can be severe.