Clinical and radiographic course of arrested cerebral adrenoleukodystrophy.

OBJECTIVE: To gain insight into the natural history of arrested cerebral adrenoleukodystrophy (CALD) by quantifying the change in Neurologic Function Score (NFS) and Loes Score (LS) over time in patients whose cerebral lesions spontaneously stopped progressing. METHODS: We retrospectively reviewed a series of 22 patients with arrested CALD followed longitudinally over a median time of 2.4 years (0.7-17.0 years). Primary outcomes were change in radiographic disease burden (measured by LS) and clinical symptoms (measured by NFS) between patients who never developed a contrast-enhancing lesion (gadolinium enhancement (GdE)- subgroup) and those who did (GdE+ subgroup). Secondary analyses comparing patterns of neuroanatomic involvement and lesion number, and prevalence estimates, were performed. RESULTS: Cerebral lesions were first detected at a median age of 23.3 years (8.0-67.6 years) with an initial LS of 4 (0.5-9). NFS was 0.5 (0-6). Overall change in NFS or LS per year did not differ between subgroups. No patients who remained GdE- converted to a progressive CALD phenotype. The presence of contrast enhancement was associated with disease progression (r s = 0.559, p < 0.001). Four patients (18.2%) underwent step-wise progression, followed by spontaneous resolution of contrast enhancement and rearrest of disease. Three patients (13.6%) converted to progressive CALD. Nineteen patients (86.4%) had arrested CALD at the most recent follow-up. The prevalence of arrested CALD is 12.4%. CONCLUSION: Arrested CALD lesions can begin in childhood, and patients are often asymptomatic early in disease. The majority of patients remain stable. However, clinical and MRI surveillance is recommended because a minority of patients undergo step-wise progression or conversion to progressive CALD.

Assessment of Pediatric Neurotrauma Imaging Appropriateness at a Level I Pediatric Trauma Center.

PURPOSE: The aim of this study was to assess the prevalence of appropriate neuroimaging on the basis of the ACR Appropriateness Criteria among pediatric patients presenting after head trauma to a level I emergency department. METHODS: A retrospective emergency department record review was performed for patients <18 years of age undergoing head CT or MRI for the indication "head trauma" between January 2013 and December 2014. Clinical history and symptoms were compared with the ACR Appropriateness Criteria; the indication was deemed appropriate for ratings of ≥7. Patients were analyzed by age, gender, presentation, imaging obtained, follow-up, treatment, and outcomes. RESULTS: Among 207 patients, 120 (58%) were imaged with CT and 107 (52%) with MRI; 20 patients underwent both CT and MRI. One hundred eighty-seven patients (90.3%) were appropriately imaged, with 90.0% of CT studies (108 of 120) deemed appropriate and 91.6% of MRI studies (98 of 107) deemed appropriate. Younger patients were more likely to be inappropriately imaged with CT or MRI than older patients (P = .02 and P < .01, respectively). Patients undergoing CT were older (mean age 9.9 ± 5.8 years) and more likely to be male (85.2%) than those undergoing MRI (5.6 ± 5.6 years and 55.1%, respectively) (P < .01 and P < .001, respectively). The diagnostic yield of positive imaging findings for intracranial trauma was significantly lower in the MRI group (P < .01), and patients undergoing MRI were significantly more likely to return to baseline with conservative management (P < .01). CONCLUSIONS: Most pediatric patients undergoing neuroimaging for head trauma did so appropriately per ACR guidelines and had symptom resolution with conservative management. The minority not imaged appropriately represent a target for quality improvement efforts.

Incidence of CNS Injury for a Cohort of 111 Patients Treated With Proton Therapy for Medulloblastoma: LET and RBE Associations for Areas of Injury.

BACKGROUND: Central nervous system (CNS) injury is a rare complication of radiation therapy for pediatric brain tumors, but its incidence with proton radiation therapy (PRT) is less well defined. Increased linear energy transfer (LET) and relative biological effectiveness (RBE) at the distal end of proton beams may influence this risk. We report the incidence of CNS injury in medulloblastoma patients treated with PRT and investigate correlations with LET and RBE values. METHODS AND MATERIALS: We reviewed 111 consecutive patients treated with PRT for medulloblastoma between 2002 and 2011 and selected patients with clinical symptoms of CNS injury. Magnetic resonance imaging (MRI) findings for all patients were contoured on original planning scans (treatment change areas [TCA]). Dose and LET distributions were calculated for the treated plans using Monte Carlo system. RBE values were estimated based on LET-based published models. RESULTS: At a median follow-up of 4.2 years, the 5-year cumulative incidence of CNS injury was 3.6% for any grade and 2.7% for grade 3+. Three of 4 symptomatic patients were treated with a whole posterior fossa boost. Eight of 10 defined TCAs had higher LET values than the target but statistically nonsignificant differences in RBE values (P=.12). CONCLUSIONS: Central nervous system and brainstem injury incidence for PRT in this series is similar to that reported for photon radiation therapy. The risk of CNS injury was higher for whole posterior fossa boost than for involved field. Although no clear correlation with RBE values was found, numbers were small and additional investigation is warranted to better determine the relationship between injury and LET.

Patterns of failure after proton therapy in medulloblastoma; linear energy transfer distributions and relative biological effectiveness associations for relapses.

PURPOSE: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. METHODS AND MATERIALS: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. RESULTS: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. CONCLUSIONS: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.