Robustness and dosimetric verification of hippocampal-sparing craniospinal pencil beam scanning proton plans for pediatric medulloblastoma

Background and Purpose Hippocampal-sparing (HS) is a method that can potentially reduce late cognitive complications for pediatric medulloblastoma (MB) patients treated with craniospinal proton therapy (PT). The aim of this study was to investigate robustness and dosimetric plan verification of pencil beam scanning HS PT. Materials and Methods HS and non-HS PT plans for the whole brain part of craniospinal treatment were created for 15 pediatric MB patients. A robust evaluation of the plans was performed. Plans were recalculated in a water phantom and measured field-by-field using an ion chamber detector at depths corresponding to the central part of hippocampi. All HS and non-HS fields were measured with the standard resolution of the detector and in addition 16 HS fields were measured with high resolution. Measured and planned dose distributions were compared using gamma evaluation. Results The median mean hippocampus dose was reduced from 22.9 Gy (RBE) to 8.9 Gy (RBE), while keeping CTV V95% above 95 % for all nominal HS plans. HS plans were relatively robust regarding hippocampus mean dose, however, less robust regarding target coverage and maximum dose compared to non-HS plans. For standard resolution measurements, median pass rates were 99.7 % for HS and 99.5 % for non-HS plans (p < 0.001). For high-resolution measurements, median pass rates were 100 % in the hippocampus region and 98.2 % in the surrounding region. Conclusions A substantial reduction of dose in the hippocampus region appeared feasible. Dosimetric accuracy of HS plans was comparable to non-HS plans and agreed well with planned dose distribution in the hippocampus region

Life years lost-comparing potentially fatal late complications after radiotherapy for pediatric medulloblastoma on a common scale

BACKGROUND: A framework for estimating and comparing risks of various long-term complications on a common scale is developed and applied to three different techniques for cranio-spinal irradiation of pediatric medulloblastoma patients. METHODS: Radiation dose-response parameters related to excess hazard ratios for secondary breast, lung, stomach and thyroid cancer, heart failure and myocardial infarction were derived from large published clinical series. Combined with age- and sex-specific hazards in the U.S. general population this yielded excess hazards of complications for a cancer survivor, as a function of attained age. After adjusting for competing risks of death, life years lost (LYL) were estimated based on excess hazard and prognosis of a complication, for 3D conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT). RESULTS: Lung cancer contributed most to the estimated LYL, followed by myocardial infarction and stomach cancer. Breast or thyroid cancer incidence was estimated higher than lung and stomach cancer incidence but LYL was lower due to the relatively good prognosis. Estimated LYL ranged between 1.90 years for 3D CRT to 0.28 years with IMPT. In a paired comparison, IMPT was associated with significantly fewer LYL than both photon techniques. CONCLUSIONS: Estimating the risk of late complications is associated with considerable uncertainty but including prognosis and attained age at an event, to obtain the more informative LYL estimate, adds relatively little to this uncertainty

Retrospective estimation of heart and lung doses in pediatric patients treated with spinal irradiation

Background and purpose: The purpose of this study was to investigate whether treatment information from medical records can be used to estimate radiation doses to heart and lungs retrospectively in pediatric patients receiving spinal irradiation with conventional posterior fields. Material and methods: An algorithm for retrospective dosimetry in children treated with spinal irradiation was developed in a cohort of 21 pediatric patients with available CT-scans and treatment plans. We developed a multivariable linear regression model with explanatory variables identifiable in case note review for retrospective estimation of minimum, maximum, mean and V10%–V80% doses to the heart and lungs. Doses were estimated for both linear accelerator (Linac) and 60Co radiation therapy modalities. Results: Age and spinal field width were identified as statistically significant predictors of heart and lung doses in multivariable analyses (p < 0.01 in all models). Models showed excellent predictive performance with R2 = 0.70 for mean heart dose and 0.79 for mean lung dose, for Linac plans. In leave-one-out cross-validation analysis the average difference between predicted and actual mean heart dose was 6.7% and 7.6% of the prescription dose for Linac and 60Co plans, respectively, and 5.2% and 4.9% for mean lung dose. Due to the small sample size and large inter-patient variation in heart and lung dose, prospective studies validating these findings are highly warranted. Conclusions: The models presented here provide retrospective estimates of heart and lung doses for historical cohorts of pediatric patients, thus facilitating studies of long-term adverse effects of radiation

Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma

We sought to assess the feasibility and estimate the benefit of sparing the neurogenic niches when irradiating the brain of pediatric patients with medulloblastoma (MB) based on clinical outcome data. Pediatric MB survivors experience a high risk of neurocognitive adverse effects, often attributed to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%–91.0%), 77.1% (range, 71.5%–81.3%), and 42.3% (range, 26.6%–51.2%) with IMAT, IMRT, and IMPT, respectively, while maintaining at least 95% of the prescribed dose in 95% of the whole-brain target volume. Estimated risks for developing memory impairment after a prescribed dose of 23.4 Gy were 47% (95% confidence interval [CI], 21%–69%), 44% (95% CI, 21%–65%), 41% (95% CI, 22%–60%), and 33% (95% CI, 23%–44%) with opposing fields, IMAT, IMRT, and IMPT, respectively. Neurogenic niche sparing during cranial irradiation of pediatric patients with MB is feasible and is estimated to lower the risks of long-term neurocognitive sequelae. Greatest sparing is achieved with intensity-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial