Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma.

BACKGROUND: To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. METHODS: Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. RESULTS: The follow-up was a median of 53.5 months (range, 21-81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular. CONCLUSION: The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.

Effects of Single-Dose Versus Hypofractionated Focused Radiation on Vertebral Body Structure and Biomechanical Integrity: Development of a Rabbit Radiation-Induced Vertebral Compression Fracture Model.

PURPOSE: Vertebral compression fracture is a common complication of spinal stereotactic body radiation therapy. Development of an in vivo model is crucial to fully understand how focal radiation treatment affects vertebral integrity and biology at various dose fractionation regimens. We present a clinically relevant animal model to analyze the effects of localized, high-dose radiation on vertebral microstructure and mechanical integrity. Using this model, we test the hypothesis that fractionation of radiation dosing can reduce focused radiation therapy's harmful effects on the spine. METHODS AND MATERIALS: The L5 vertebra of New Zealand white rabbits was treated with either a 24-Gy single dose of focused radiation or 3 fractionated 8-Gy doses over 3 consecutive days via the Small Animal Radiation Research Platform. Nonirradiated rabbits were used as controls. Rabbits were euthanized 6 months after irradiation, and their lumbar vertebrae were harvested for radiologic, histologic, and biomechanical testing. RESULTS: Localized single-dose radiation led to decreased vertebral bone volume and trabecular number and a subsequent increase in trabecular spacing and thickness at L5. Hypofractionation of the radiation dose similarly led to reduced trabecular number and increased trabecular spacing and thickness, yet it preserved normalized bone volume. Single-dose irradiated vertebrae displayed lower fracture loads and stiffness compared with those receiving hypofractionated irradiation and with controls. The hypofractionated and control groups exhibited similar fracture load and stiffness. For all vertebral samples, bone volume, trabecular number, and trabecular spacing were correlated with fracture loads and Young's modulus (P < .05). Hypocellularity was observed in the bone marrow of both irradiated groups, but osteogenic features were conserved in only the hypofractionated group. CONCLUSIONS: Single-dose focal irradiation showed greater detrimental effects than hypofractionation on the microarchitectural, cellular, and biomechanical characteristics of irradiated vertebral bodies. Correlation between radiologic measurements and biomechanical properties supported the reliability of this animal model of radiation-induced vertebral compression fracture, a finding that can be applied to future studies of preventative measures.

Vertebral body and splenic irradiation are associated with lymphopenia in localized pancreatic cancer treated with stereotactic body radiation therapy.

OBJECTIVES: The purpose of this study was to determine if vertebral body and splenic dosimetry was associated with the development of lymphopenia in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation therapy (SBRT). METHODS: Patients with BRPC/LAPC who were treated with SBRT and who had lymphocyte counts and radiation treatment plans available for review were included in the study. Vertebral body levels T11-L3 and the spleen were retrospectively contoured for each patient. Univariate (UVA) and multivariable analyses (MVA) were performed to identify associations between vertebral body and splenic dosimetric parameters with absolute lymphocyte count (ALC) and grade ≥ 2 lymphopenia. Receiver operator characteristic curves were generated to identify dose-volume thresholds in predicting grade ≥ 2 lymphopenia. RESULTS: A total of 132 patients were included in the study. On UVA and MVA, vertebral V15 (regression coefficient [ß]: - 0.026, 95% CI - 0.044 to - 0.009, p = 0.003), vertebral V2.5 (ß: - 0.011, 95% CI - 0.020 to - 0.002, p = 0.015), and log10PTV (ß: - 0.15, 95% CI - 0.30 to - 0.005, p = 0.042) were associated with post-SBRT ALC. On UVA and MVA, vertebral V15 (odds ratio [OR]: 3.98, 95% CI 1.09-14.51, p = 0.027), vertebral V2.5 (OR: 1.04, 95% CI 1.00-1.09, p = 0.032), and spleen V10 (OR: 1.05, 95% CI 1.09-1.95, p = 0.004) were associated with development of grade ≥ 2 lymphopenia. Development of grade ≥ 2 lymphopenia was more likely in patients with vertebral V15 ≥ 5.84% (65.5% vs 34.0%, p = 0.002), vertebral V2.5 ≥ 48.36% (48.9% vs 23.8%, p = 0.005), and spleen V10 ≥ 4.17% (56.2% vs 26.9%, p < 0.001). CONCLUSIONS: Increasing radiation dose to vertebral bodies and spleen were associated with the development of lymphopenia in BRPC/LAPC treated with SBRT. Optimization of vertebral body and splenic dosimetry may reduce the risk of developing lymphopenia and improve clinical outcomes in this population.

Impact of lifetime attributable risk of radiation-induced secondary cancer in proton craniospinal irradiation with vertebral-body-sparing for young pediatric patients with medulloblastoma.

We used the method proposed by Schneider et al. Theor Biol Med Model 2011;8:27, to clarify how the radiation-induced secondary cancer incidence rate changes in patients after proton craniospinal irradiation (CSI) without and with vertebral-body-sparing (VBS). Eight patients aged 3-15 years who underwent proton CSI were enrolled in the study. For each case, two types of plan without and with VBS in the target were compared. The prescribed doses were assumed to be 23.4 Gy relative biological effectiveness (RBE) and 36 Gy (RBE). Using the dose-volume histograms of the two plans, the lifetime attributable risk (LAR) was calculated by both methods for each patient based on the dose data calculated using an XiO-M treatment planning system. Eight organs were analyzed as follows: lung, colon, stomach, small intestine, liver, bladder, thyroid and bone. When the prescribed dose used was 23.4 Gy (RBE), the average LAR differences and the average number needed to treat (NNT) between proton CSI without and with VBS were 4.04 and 24.8, respectively, whereas the average LAR difference and the average NNT were larger at 8.65 and 11.6, respectively, when the prescribed dose of 36 Gy (RBE) was used. The LAR for radiation-induced secondary cancer was significantly lower in proton CSI with VBS than without VBS in pediatric patients, especially for the colon, lung, stomach and thyroid. The results of this study could serve as reference data when considering how much of vertebral bodies should be included when performing proton CSI according to age in clinical settings.