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Effects of vertebral-body-sparing proton craniospinal irradiation on the spine of young pediatric patients with medulloblastoma.

ABSTRACT: To investigate the long-term effects of vertebral-body-sparing proton craniospinal irradiation (CSI) on the spine of young patients with medulloblastoma.Six children between the ages of 3 and 5 years with medulloblastoma were treated with vertebral-body-sparing proton CSI after maximal safe resection. Radiation therapy was delivered in the supine position with posterior beams targeting the craniospinal axis, and the proton beam was stopped anterior to the thecal sac. Patients were treated with a dose of either 23.4 Gy or 36 Gy to the craniospinal axis followed by a boost to the posterior fossa and any metastatic lesions. Chemotherapy varied by protocol. Radiographic effects on the spine were evaluated with serial imaging, either with magnetic resonance imaging scans or plain film using Cobb angle calculations, the presence of thoracic lordosis, lumbar vertebral body-to-disc height ratios, and anterior-posterior height ratios. Clinical outcomes were evaluated by patient/family interview and medical chart review.Overall survival and disease free survival were 83% (5/6) at follow-up. Median clinical and radiographic follow-up were 13.6 years and 12.3 years, respectively. Two patients were clinically diagnosed with scoliosis and treated conservatively. At the time of follow-up, no patients had experienced chronic back pain or required spine surgery. No patients were identified to have thoracic lordosis. Diminished growth of the posterior portions of vertebral bodies was identified in all patients, with an average posterior to anterior ratio of 0.88, which was accompanied by compensatory hypertrophy of the posterior intervertebral discs.Vertebral-body-sparing CSI with proton beam did not appear to cause increased severe spinal abnormalities in patients treated at our institution. This approach could be considered in future clinical trials in an effort to reduce toxicity and the risk of secondary malignancy and to improve adult height.

SUBMITTER: MacEwan I

PROVIDER: S-EPMC5514252 | biostudies-other | 2017 Apr-Jun

REPOSITORIES: biostudies-other

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Project description:PurposeAt present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma.Methods and materialsFive plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system.ResultsIMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher.ConclusionsAdvanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children.

Project description:BackgroundHippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB).Methods and materialsWe identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10 mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans.ResultsThirty-eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy.ConclusionsPeri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB.Plain language summaryIn this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Project description:PurposeProton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT.MethodsIntelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups.ResultsLongitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose (P < .001) and boost margin (P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed (P = .003).ConclusionTo our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.

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Effects of vertebral-body-sparing proton craniospinal irradiation on the spine of young pediatric patients with medulloblastoma.

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