Pretreatment Normal WM Magnetization Transfer Ratio Predicts Risk of Radiation Necrosis in Patients with Medulloblastoma.

BACKGROUND AND PURPOSE: Radiation necrosis, for which abnormal WM enhancement is a hallmark, is an uncommon complication of craniospinal irradiation in children with medulloblastoma. The magnetization transfer ratio measures macromolecular content, dominated by myelin in the WM. We investigated whether the pretreatment supratentorial (nonsurgical) WM magnetization transfer ratio could predict patients at risk for radiation necrosis after radiation therapy for medulloblastoma. MATERIALS AND METHODS: Ninety-five eligible patients with medulloblastoma (41% female; mean age, 11.0 [SD, 5.4] years) had baseline balanced steady-state free precession MR imaging before proton or photon radiation therapy. Associations among baseline supratentorial magnetization transfer ratio, radiation necrosis (spontaneously resolving/improving parenchymal enhancement within the radiation field)3, age, and the presence of visible brain metastases were explored by logistic regression and parametric/nonparametric techniques as appropriate. RESULTS: Twenty-three of 95 (24.2%) children (44% female; mean age, 10.7 [SD, 6.7] years) developed radiation necrosis after radiation therapy (19 infratentorial, 1 supratentorial, 3 both). The mean pretreatment supratentorial WM magnetization transfer ratio was significantly lower in these children (43.18 versus 43.50, P = .03). There was no association between the supratentorial WM magnetization transfer ratio and age, sex, risk/treatment stratum, or the presence of visible brain metastases. CONCLUSIONS: A lower baseline supratentorial WM magnetization transfer ratio may indicate underlying structural WM susceptibility to radiation necrosis and may identify children at risk for developing radiation necrosis after craniospinal irradiation for medulloblastoma.

Anatomic Neuroimaging Characteristics of Posterior Fossa Type A Ependymoma Subgroups.

BACKGROUND AND PURPOSE: Posterior fossa type A (PFA) ependymomas have 2 molecular subgroups (PFA-1 and PFA-2) and 9 subtypes. Gene expression profiling suggests that PFA-1 and PFA-2 tumors have distinct developmental origins at different rostrocaudal levels of the brainstem. We, therefore, tested the hypothesis that PFA-1 and PFA-2 ependymomas have different anatomic MR imaging characteristics at presentation. MATERIALS AND METHODS: Two neuroradiologists reviewed the preoperative MR imaging examinations of 122 patients with PFA ependymomas and identified several anatomic characteristics, including extension through the fourth ventricular foramina and encasement of major arteries and tumor type (midfloor, roof, or lateral). Deoxyribonucleic acid methylation profiling assigned ependymomas to PFA-1 or PFA-2. Information on PFA subtype from an earlier study was also available for a subset of tumors. Associations between imaging variables and subgroup or subtype were evaluated. RESULTS: No anatomic imaging variable was significantly associated with the PFA subgroup, but 5 PFA-2c subtype ependymomas in the cohort had a more circumscribed appearance and showed less tendency to extend through the fourth ventricular foramina or encase blood vessels, compared with other PFA subtypes. CONCLUSIONS: PFA-1 and PFA-2 ependymomas did not have different anatomic MR imaging characteristics, and these results do not support the hypothesis that they have distinct anatomic origins. PFA-2c ependymomas appear to have a more anatomically circumscribed MR imaging appearance than the other PFA subtypes; however, this needs to be confirmed in a larger study.

Impact of radiation therapy and extent of resection for ependymoma in young children: A population-based study.

BACKGROUND: Young children with posterior fossa ependymoma (PF-EPN) have a worse prognosis than older children, and they have a unique molecular profile (PF-EPN-A subtype). Alternative treatment strategies are often used in these young patients, and their prognostic factors are less clear. METHODS: We characterized the prognostic factors and treatment outcomes of 482 patients between ages 0 and 3 years with the diagnosis of ependymoma identified from the Surveillance, Epidemiology, and End Results registry (1973-2013). RESULTS: Radiation therapy (RT) was delivered to 52.3% of patients, and gross total resection (GTR) was performed in 51.0% of patients. Overall survival (OS) at 10 years was 48.4% with median follow-up of 3.3 years. WHO grade was not predictive of OS. Extent of resection was significant for survival; the 10-year OS with GTR was 61.0%, and with subtotal resection (STR) and biopsy was 38.2% and 35.0%, respectively (P < 0.001). RT significantly benefitted OS for both grades II and III. The 10-year OS for grade II was 50.5% with RT and 43.4% without (P = 0.030); 10-year OS for grade III was 66.0% with RT and 40.0% without (P = 0.002). Multivariate analysis showed significantly improved OS with RT (hazard ratio [HR] 0.601, 95% CI: 0.439-0.820, P = 0.001) and GTR (HR 0.471, 95% CI: 0.328-0.677, P < 0.0001). CONCLUSIONS: Ependymoma outcomes in patients within 0-3 years of age significantly improved with RT and GTR. Histopathologic grading of ependymoma demonstrated no prognostic significance. Given the poor OS for this population and unique genetic profile, future prospective studies with molecular-based stratification should be performed to evaluate additional prognostic factors.

Tavaborole topical solution, 5% for the treatment of toenail onychomycosis.

Tavaborole topical solution, 5% (tavaborole) is a novel, boron-based, antifungal pharmaceutical agent indicated for treatment of toenail onychomycosis due to the dermatophytes Trichophyton rubrum or Trichophyton mentagrophytes. In preclinical studies, tavaborole effectively penetrated through full-thickness, non-diseased cadaver fingernails, including those with up to four layers of nail polish. Limited systemic absorption was observed following topical application of tavaborole. In phase III clinical trials involving patients with distal subungual onychomycosis affecting 20-60% of a target great toenail, significantly more patients treated with tavaborole versus vehicle achieved completely clear nail with negative mycology following daily application for 48 weeks. Treatment-emergent adverse events reported by at least 1% of patients treated with tavaborole and at a greater frequency versus vehicle included ingrown toenail, exfoliation, erythema and dermatitis. Treatment discontinuations were uncommon. Results from preclinical studies and phase III clinical trials establish tavaborole as a safe and efficacious treatment for toenail onychomycosis.

Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies.

T-cell depletion of an HLA-haploidentical graft is often used to prevent GVHD, but the procedure may lead to increased graft failure, relapse and infections due to delayed immune recovery. We hypothesized that selective depletion of the CD45RA+ subset can effectively reduce GVHD through removal of naive T cells, while providing improved donor immune reconstitution through adoptive transfer of CD45RA- memory T cells. Herein, we present results from the first 17 patients with poor-prognosis hematologic malignancy, who received haploidentical donor transplantation with CD45RA-depleted progenitor cell grafts following a novel reduced intensity conditioning regimen without TBI or serotherapy. Extensive depletion of CD45RA+ T cells and B cells, with preservation of abundant memory T cells, was consistently achieved in all 17 products. Neutrophil engraftment (median day +10) and full donor chimerism (median day +11) was rapidly achieved post transplantation. Early T-cell reconstitution directly correlated with the CD45RA-depleted graft content. T-cell function recovered rapidly with broad TCR Vß spectra. There was no infection-related mortality in this heavily pretreated population, and no patient developed acute GVHD despite infusion of a median of >100 million per kilogram haploidentical T cells.

Imaging changes in very young children with brain tumors treated with proton therapy and chemotherapy.

SUMMARY: PT promises to reduce side effects in children with brain tumors by sparing normal tissue compared with 3D conformal or intensity-modulated radiation therapy. Information is lacking about the combined effects of PT and chemotherapy in young children. We describe imaging changes in 8 very young children with localized brain tumors who received PT after chemotherapy. Mostly transient signal abnormalities and enhancement in brain parenchyma were observed by serial MR imaging, which were consistent with radiation-induced effects on normal-appearing tissue. Correlation with PT planning data revealed that the areas of imaging abnormality were located within or adjacent to the volume that received the highest radiation dose. Radiologists should be aware of these findings in children who receive PT after chemotherapy. In this report, we describe the time course of these PT-related imaging findings and correlate them with treatment and clinical outcomes.

Intensity-modulated radiation therapy for children with intraocular retinoblastoma: potential sparing of the bony orbit.

AIMS: We have evaluated the potential for intensity-modulated radiation therapy (IMRT) to reduce dose to surrounding normal tissues in children with retinoblastoma confined to the globe of the eye. MATERIALS AND METHODS: Treatment planning computed tomography (CT) scans from five children were used for comparison of four radiotherapy techniques to treat the eye. IMRT, conformal, anterior-lateral photon and en face electron plans were generated using the Corvus (NOMOS) and PLUNC treatment planning systems. Doses to surrounding critical structures were compared after normalisation of target coverage. RESULTS: The IMRT treatment technique allowed the greatest sparing of the surrounding bony orbit, with an average of 60% of the ipsilateral bony orbit treated above 20 Gy and 48% treated above 24 Gy when 45 Gy is prescribed to the globe. IMRT techniques reduced dose to the surrounding bony orbit by more than one-third compared with anterior-lateral photon and electron techniques, and by 23% compared with conformal techniques. The application of IMRT also reduced dose to other surrounding normal tissues, including the temporal lobe and contralateral orbit. CONCLUSION: IMRT shows potential for protecting normal tissues in patients requiring external beam radiation therapy for retinoblastoma.

Differences in ICAM-1 and TNF-alpha expression between large single fraction and fractionated irradiation in mouse brain.

PURPOSE: To elucidate the brain molecular response to irradiation. The expression of the intercellular adhesion molecule (ICAM-1) and tumour necrosis factor-alpha (TNF-alpha) in the mouse brain was compared after single-dose and fractionated whole-brain irradiation. MATERIALS AND METHODS: Mice received a single dose of 2, 10 or 20 Gy or a fractionated dose (2 Gy day(-1)) of 10, 20 or 40 Gy. ICAM-1, and TNF-alpha mRNA expression were quantified by the highly sensitive real-time polymerase chain reaction technique. Expression of ICAM-1 protein was quantified by dual-labelled monoclonal antibody assay. RESULTS: After a 20-Gy single dose, there was an increase in ICAM-1 and TNF-alpha mRNA levels (14- and 11-fold, respectively) as well as a significant increase in the level of ICAM-1 protein (p=0.0243). The expression of ICAM-1 and TNF-alpha mRNA increased at the end of the 40-Gy fractionated regimen (3.55- and 2.30-fold, respectively). CONCLUSIONS: The molecular response of the brain to single-dose irradiation was rapid, while its response to fractionated irradiation was slow. This finding is consistent with clinical observations and could be of use when designing strategies to mitigate radiation sequelae.

Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma.

PURPOSE: To evaluate the efficacy of multiagent chemotherapy in the neoadjuvant treatment of retinoblastoma. DESIGN: Noncomparative, prospective case series. PARTICIPANTS: Twenty consecutive patients with multifocal intraocular retinoblastoma (4 unilateral, 16 bilateral [36 eyes]). INTERVENTION: Eight cycles of chemotherapy with carboplatin and vincristine were administered at 3-week intervals over a 6-month period. Supplemental therapy was withheld until disease progression was documented. MAIN OUTCOME MEASURES: Disease progression (defined as tumor growth, vitreous or subretinal seed progression, and new tumor formation), delay of external beam radiotherapy, and ocular survival. RESULTS: Thirty-six eyes were treated. Eighteen eyes had Reese-Ellsworth group I-III tumors, and 16 eyes had Reese-Ellsworth group IV-V tumors at diagnosis. Two patients, who had unilateral disease at diagnosis, subsequently had tumors develop in the contralateral eye. Nineteen of 20 patients (95%) completed eight cycles of chemotherapy without disease progression. Three eyes of three different patients were successfully treated with chemotherapy alone. Thirty-three of 36 eyes (92%) progressed after completion of chemotherapy: 15 of the 18 eyes (83.3%) with Reese-Ellsworth group I-III and 16 of 16 eyes (100%) with Reese-Ellsworth group IV-V tumors. Seventeen eyes (52%) had growth of a tumor, whereas 14 eyes (42%) had progressive vitreous seeding, and 2 eyes (6%) had new tumors develop. Fifteen eyes (42%) required external beam radiotherapy. Twenty-nine of 36 (80.5%) eyes were salvaged. The median follow-up after chemotherapy was 19 months (range, 3-42 months). CONCLUSIONS: Multiagent chemotherapy alone does not ensure a cure for multifocal intraocular retinoblastoma. Supplemental focal therapy is needed to control disease progression.

Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection.

To describe the clinical features, histologic characteristics, and management of patients with pleomorphic xanthoastrocytoma (PXA), we reviewed data on 13 children who had histologically confirmed PXA and were referred to the neuro-oncology service between 1985 and 1999. Neuro-imaging with CT and/or MRI documented the anatomic location, tumor extent, and degree of resection. There were 3 males and 10 females; median age was 12.9 years (range, 8.2-17.2 years). The most frequent presentations included seizures (n = 8) and headache (n = 5). Tumor sites included temporal (n = 5), parietal (n = 3), frontal (n = 1), frontoparietal (n = 1), parietooccipital (n = 1), and temporoparietal (n = 1) lobes and the spinal cord (n = 1). CT/MRI revealed a cystic component in 6 patients, with cyst wall enhancement in 3 patients. The solid component was uniformly enhancing in 11 patients. Vasogenic edema was present in 9 patients, and calcification was noted in 4 patients. Histopathologic findings included meningeal invasion in 12 patients, calcifications in 4, and necrosis in 2. Mitotic figures (1-12 per high-power field) were seen in 8 patients. Gross total resection was achieved in 8 patients, near total resection in 1, and subtotal resection in 4. Ten patients were alive with a median follow-up of 41 months at this writing. Two patients died of progressive disease, and 1 died of an unrelated cause. In conclusion, pleomorphic xanthoastrocytoma is a rare neoplasm in childhood, commonly presenting with seizures. Gross total resection without adjuvant therapy provides prolonged disease control, as seen in 6 of 7 patients (85%) in our series.

Primary Ewing tumor of the vertebrae: clinical characteristics, prognostic factors, and outcome.

BACKGROUND: Fewer than 10% of Ewing family of tumors (EFT) arise in the vertebrae. Little information is available regarding the clinical presentation and outcome of these tumors. PROCEDURE: We reviewed the clinical features, prognostic factors, and outcome of EFT of the spine identified at our institution between 1962 and 1999. RESULTS: Thirty-three (10%) of 344 patients with EFT had a primary vertebral tumor. There were 21 (64%) males. Median age at diagnosis was 13.3 years. Six patients had metastatic disease and 10 had tumors > or = 8 cm in diameter. Primary sites were sacral (13), thoracic (10), lumbar (8), and cervical (2) vertebrae. We found no association between the affected spinal region and outcome, although sacral tumors were associated with delayed diagnosis (4 vs. 2 months after onset of symptoms, P = 0.076). Pain (n = 32) and neurologic deficits (n = 31; 82% motor, 58% sensory, 42% bladder, 27% bowel) were the most common presenting features. All patients received combination chemotherapy and local radiotherapy. With a median follow up of 9.7 years, 5-year survival and event-free survival ( +/- SD) estimates were 48.1% (8.9%) and 35.6% (8.6%), respectively, comparable to those of other patients with EFT. Outcome was better for patients with tumor size < 8 cm (P = 0.008) or localized disease (P = 0.084). Treatment era and specific tumor site did not affect outcome. CONCLUSIONS: Outcomes are similar for primary EFT of the spine and primary EFT in other sites. Unlike others, we found that patients with sacral tumors did not fare worse than patients with tumors at other spinal sites.

Patterns of intellectual development among survivors of pediatric medulloblastoma: a longitudinal analysis.

PURPOSE: To examine two competing hypotheses relating to intellectual loss among children treated for medulloblastoma (MB): Children with MB either: (1) lose previously learned skills and information; or (2) acquire new skills and information but at a rate slower than expected compared with healthy same-age peers. PATIENTS AND METHODS: Forty-four pediatric MB patients were evaluated who were treated with postoperative radiation therapy (XRT) with or without chemotherapy. After completion of XRT, a total of 150 examinations were conducted by use of the child version of the Wechsler Intelligence SCALES: These evaluations provided a measure of intellectual functioning called the estimated full-scale intelligence quotient (FSIQ). Changes in patient performance corrected for age (scaled scores) as well as the uncorrected performance (raw scores) were analyzed. RESULTS: At the time of the most recent examination, the obtained mean estimated FSIQ of 83.57 was more than one SD below expected population norms. A significant decline in cognitive performance during the time since XRT was demonstrated, with a mean loss of 2.55 estimated FSIQ points per year (P =.0001). An analysis for the basis of the intelligence quotient (IQ) loss revealed that subtest raw score values increased significantly over time since XRT, but the rate of increase was less than normally expected, which resulted in decreased IQ scores. CONCLUSION: These results support the hypothesis that MB patients demonstrate a decline in IQ values because of an inability to acquire new skills and information at a rate comparable to their healthy same-age peers, as opposed to a loss of previously acquired information and skills.

Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer.

PURPOSE: To test if methylphenidate (MPH) has an objective beneficial effect on immediate performance on tests of neurocognitive functions among learning-impaired survivors of childhood acute lymphoblastic leukemia (ALL) and malignant brain tumors (BT). PATIENTS AND METHODS: From July 1, 1997 through December 31, 1998, 104 long-term survivors of childhood ALL or a malignant BT completed neurocognitive screening for learning impairments and concurrent problems with sustained attention. Eligibility criteria for the MPH trial included an estimated intelligence quotient greater than 50, academic achievement in the 16(th) percentile or lower for age in reading, math, or spelling, and an ability to sustain attention on a computerized version of the Conners' Continuous Performance Test (CPT) in the 16(th) percentile or lower for age and sex. Of the 104, 32 (BT, n = 25; ALL, n = 7) were eligible on the basis of these a priori criteria for a randomized, double-blinded, placebo-controlled trial of MPH. The patients ingested a placebo (lactose) or MPH (0.6 mg/kg; 20 mg maximum) and repeated selected portions of the screening battery 90 minutes later. RESULTS: Compared to the 17 patients randomized to the placebo group, the 15 patients randomized to the MPH group had a significantly greater improvement on the CPT for sustained attention (errors of omission, P =.015) and overall index (P =.008) but not for errors of commission (indicative of impulsiveness) nor reaction times. A trend for greater improvement in the MPH group on a measure of verbal memory failed to reach statistical significance. No trend was observed for MPH effectiveness in improving learning of a word association task. No significant side effects from MPH were observed. CONCLUSION: MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.

Effect of ionizing radiation on the human brain: white matter and gray matter T1 in pediatric brain tumor patients treated with conformal radiation therapy.

OBJECTIVE: To test a hypothesis that fractionated radiation therapy (RT) to less than 60 Gy is associated with a dose-related change in the spin-lattice relaxation time (T1) of normal brain tissue, and that such changes are detectable by quantitative MRI (qMRI). METHODS: Each of 21 patients received a qMRI examination before treatment, and at several time points during and after RT. A map of brain T1 was calculated and segmented into white matter and gray matter at each time point. The RT isodose contours were then superimposed upon the T1 map, and changes in brain tissue T1 were analyzed as a function of radiation dose and time following treatment. We used a mixed-model analysis to analyze the longitudinal trend in brain T1 from the start of RT to 1 year later. Predictive factors evaluated included patient age and clinical variables, such as RT dose, time since treatment, and the use of an imaging contrast agent. RESULTS: In white matter (WM), a dose level of greater than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant about 3 months following treatment. In gray matter (GM), there was no significant change in T1 over time, as a function of RT doses < 60 Gy. However, GM in close proximity to the tumor had an inherently lower T1 before therapy. Neither use of a contrast agent nor a combination of chemotherapy plus steroids had a significant effect on brain T1. CONCLUSION: Results suggest that T1 mapping may be sensitive to radiation-related changes in human brain tissue T1. WM T1 appears to be unaffected by RT at doses less than approximately 20 Gy; GM T1 does not change at doses less than 60 Gy. However, tumor appears to have an effect upon adjacent GM, even before treatment. Conformal RT may offer a substantial benefit to the patient, by minimizing the volume of normal brain exposed to greater than 20 Gy.

Comparison of three patellar tendon anterior cruciate ligament reconstruction techniques with emphasis on tunnel location and outcome. Are our results improving?

In order to determine if recent changes in tunnel placement during anterior cruciate ligament reconstruction are producing better outcomes, the results of three different "bone-patellar tendon-bone" anterior cruciate ligament reconstruction techniques were compared. These techniques were: two-incision with the tibial tunnel at the anterior "footprint" of the anterior cruciate ligament (group I), two-incision with freehand placement of the tibial tunnel in the central or posterior "footprint" (group II), and endoscopic single incision utilizing a guide keying on the posterior cruciate ligament to achieve posterior tibial tunnel location (group III). The femoral tunnel was established with a rear-entry guide for the two-incision techniques. A guide keying off the posterior intercondylar shelf or roof was used for femoral tunnel placement with the endoscopic technique. Subjective rating, Lysholm scores, range of motion, manual and instrumented laxity, and radiographic tibial and femoral tunnel location in the sagittal plane were studied for 33 patients (twelve in group I, nine in group II, twelve in group III) at minimum follow-up of two years. Patients had uniform rehabilitation programs. Statistically significant differences were found between the groups for a number of the variables: the mean maximum manual KT-1000 score was 3.7 millimeters for group I compared to 1.4 millimeters for group III; the mean flexion deficit was 0.5 degrees for group I and 8.3 degrees for group III; tibial tunnels were located 31% posteriorly along the sagittal tibial articular length for group I, while groups II and III were 38% and 43% respectively. Femoral tunnels for groups I and II were located 83% and 79% posteriorly along Blumensaat's line respectively, where as the mean for group III was 69%. Recent techniques (group III) for anterior cruciate ligament reconstruction successfully achieved "posterior" tibial tunnel placement. This was associated with superior results as judged by instrumented laxity measurements. The significance of the endoscopic technique's anterior femoral tunnel location relative to that of the two-incision techniques is uncertain but warrants further study.

Effect of therapeutic ionizing radiation on the human brain.

We test a hypothesis that fractionated radiation therapy within a therapeutic dose range is associated with a dose-related change in normal brain, detectable by quantitative magnetic resonance imaging. A total of 33 patients were examined by quantitative magnetic resonance imaging to measure brain tissue spin-lattice relaxation time (T1) before treatment, and at various times during and after radiation therapy. A T1 map was generated at each time point, and radiation therapy isodose contours were superimposed on the corresponding segmented T1 map. Changes in white matter and gray matter T1 were analyzed as a function of radiation therapy dose and time since treatment, controlling for patient age and tumor site. In white matter, a dose level of more than 20 Gy was associated with a dose-dependent decrease in T1 over time, which became significant 6 months after treatment. There was no significant change in T1 of gray matter over time, at radiation therapy doses of less than 60 Gy. However, GM in close proximity to the tumor had a lower T1 before therapy. Our results represent the first radiation dose-response data derived from pediatric brain in vivo. These findings confirm that white matter is more vulnerable to radiation-induced change than is gray matter, and suggest that T1 mapping is sensitive to radiation-related changes over a broad dose range (20 to 60 Gy). Human white matter T1 is not sensitive to radiation therapy of less than 20 Gy, and gray matter T1 is unchanged over the dose range used to treat human brain tumor. The reduction of gray matter T1 near the tumor could result from compression of cortical parenchyma near the growing tumor mass, or from tumor cell invasion directly into the parenchyma. If brain T1 is a surrogate for radiation effect, reducing the volume of normal white matter receiving more than 20 Gy could be an important treatment planning goal.

Fractures in pediatric Ewing sarcoma.

PURPOSE: To determine the incidence, timing, and clinical significance of long-bone fractures in children with Ewing sarcoma family of tumors (ESFT). PATIENTS AND METHODS: We retrospectively reviewed 93 consecutive cases of ESFT of the long bones seen at a single institution over the course of a 37-year period. RESULTS: Fracture occurred in 14 (15%) of 93 patients with long-bone ESFT, most commonly in the femur. Approximately 30% of patients with tumors of the femur had fractures at some point in the course of their disease. The incidence of fracture was highest among patients with tumors of the proximal third of the femur (50%); these fractures were usually present at the time of initial diagnosis. Nine (64%) of the 14 fractures occurred after the start of radiotherapy, and three of these were associated with either local recurrence or second malignancy. CONCLUSIONS: Patients with femoral ESFT are at high-risk for fracture. If fractures occur after the completion of therapy, recurrence or second malignancy should be suspected.

Comparison of two immobilization techniques using portal film and digitally reconstructed radiographs for pediatric patients with brain tumors.

PURPOSE: To compare the accuracy of two immobilization techniques for pediatric brain tumor patients. METHODS AND MATERIALS: We analyzed data from 128 treatments involving 22 patients. Patients were immobilized with either a relocatable head frame (12 patients) or a vacuum bag (10 patients). Orthogonal portal films were used as verification images. Errors in patient positioning were measured by comparing verification images with digitally reconstructed radiographs generated by a three-dimensional treatment-planning system. RESULTS: With the head frame, systematic errors ranged from 1.4 mm to 2.1 mm; random errors, from 1.7 mm to 2.1 mm. With the vacuum bag, systematic errors ranged from 2.1 mm to 2.5 mm; random errors, from 2.0 mm to 2.6 mm. For the head frame, the mean length of the radial displacement was 4.4 mm; 90% of the total three-dimensional deviation was less than 6.8 mm. The corresponding values for the vacuum bag were 5.0 and 6.6 mm, respectively. CONCLUSIONS: The head frame and vacuum bag techniques limit the random and systematic errors in each of the three directions to within +/- 5 mm. We have used these results to determine the margin used to create the planning target volume for conformal radiation therapy.

Subtle white matter volume differences in children treated for medulloblastoma with conventional or reduced dose craniospinal irradiation.

Medulloblastoma is the most common malignant brain tumor in children, and approximately seventy percent of average-risk patients will achieve long-term survival. Craniospinal irradiation (CSI), combined with chemotherapy and surgery, is currently the mainstay of treatment but places children who survive at risk for serious neurocognitive sequelae. These sequelae are intensified with a younger age at treatment, greater elapsed time following treatment, and an increased radiation dose. Many newer treatment approaches have attempted to address this problem by reducing the dose of the CSI component of radiation therapy while maintaining the current survival rates. This study evaluates longitudinal MR imaging during therapy to assess the impact of the two CSI doses (conventional [36 Gy] and reduced [23.4 Gy]) on normal appearing white matter volumes (NAWMV) evaluated in a single index slice. Twenty-six children and young adults at least three years of age enrolled on an institutional protocol for newly diagnosed, previously untreated primary medulloblastoma had at least four MR examinations over a minimum nine month period following CSI. These serial volumes were evaluated as a function of time since CSI in three analyses: 1) all subjects, 2) subjects stratified by age at CSI, and 3) subjects stratified by CSI dose. The first analysis demonstrated that medulloblastoma patients treated with CSI have a significant loss of NAWMV in contradistiction to normally expected maturation. Stratifying the patients by age at CSI found no significant differences in the rate of NAWMV loss. The final analysis stratified the patients by CSI dose and revealed that the rate of NAWMV loss was 23% slower in children receiving reduced-dose. Serial quantitative MR measures of NAWMV may provide a neuroanatomical substrate for assessing functional impact of CSI on normal brain function following treatment for medulloblastoma.