Radiotherapy For Brain Tumors Research Articles

Cerebral Radiation Necrosis in Pediatric Patients

Radiation necrosis is a well-described toxicity following radiation therapy in the brain. There is little data regarding the incidence of radiation necrosis in pediatric patients. We retrospectively reviewed our experience with 101 children with solid brain tumors. Radiation necrosis was diagnosed by examination of magnetic resonance imaging. Median follow-up for all patients was 13 months (range 3–51). Radiation necrosis occurred in 5% (5/101) of cases with a median time to onset of 1.2 months. In three of these children, the child was symptomatic, requiring management with steroids and bevacizumab. Radiation necrosis did not correlate with the administration of chemotherapy, age at treatment, or planning treatment volume. Our experience with pediatric patients treated with radiotherapy for solid brain tumor suggests that children may have an increased likelihood to develop radiation necrosis compared to adults.

Abstract 4438: Gold nanoparticle imaging and radiotherapy of brain tumors in mice.

Abstract Aims: To test intravenously injected gold nanoparticles for X-ray imaging and radiotherapy enhancement of large, imminently lethal intracerebral malignant gliomas. Materials & Methods: ∼11nm gold nanoparticles were injected intravenously and brains imaged by microCT. Fifteen hours after an iv dose of 4 g Au/kg, brains were irradiated with 30 Gy 100kVp X-rays. Results: Gold uptake gave a 19:1 tumor-to-normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by ∼300%. Mice receiving gold and radiation (30 Gy) showed 50% long-term (> 1 year) tumor-free survival, whereas all mice receiving radiation only died. In a second experiment using 35 Gy, long-term survival was 56% with AuNPs plus radiation versus 18% with radiation alone. Combining both experiments, the radiation plus AuNP treatments were statistically distinct from the radiation-only groups (p = 0.014). Conclusions: Intravenously injected gold nanoparticles cross the blood-tumor barrier but are largely blocked by the normal blood brain barrier, enabling high-resolution CT tumor imaging. Gold radiation enhancement significantly improved long-term survival compared to radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers. Citation Format: James F. Hainfeld, Michael J. O'Connor, Daniel N. Slatkin, F Avraham Dilmanian, Henry M. Smilowitz. Gold nanoparticle imaging and radiotherapy of brain tumors in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4438. doi:10.1158/1538-7445.AM2013-4438

Selective Targeting of Brain Tumors With Nanoparticle-induced Radiosensitization and Contrast Enhancement

Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood–brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, overall prognosis remains grim. We report pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). We characterize several versatile ways in which GNPs can be incorporated as adjuvants into brain tumor imaging and radiotherapy paradigms, serving as a potential “theranostic” agent.

Headache as a risk factor for neurovascular events in pediatric brain tumor patients

To determine whether severe recurrent headache is a risk factor for neurovascular events in children who received radiation for brain tumors. This is a retrospective cohort study of children with brain tumors who received cranial irradiation at a large tertiary care center, aged 0-21 years at diagnosis, with initial treatment between January 1, 1993 and December 31, 2002, and 2 or more follow-up visits. Patients were considered to have severe recurrent headache if this appeared as a complaint on 2 or more visits. Headaches attributed to tumor progression, shunt malfunction, or infection, or appearing at the end of life, were excluded. Medical records were reviewed for events of stroke or TIA. Of 265 subjects followed for a median of 6.0 years (interquartile range 1.7-9.2 years), stroke or TIA occurred in 7/37 (19%) with severe headaches compared to 6/228 (3%) without these symptoms (hazard ratio 5.3, 95% confidence interval 1.8-15.9, p = 0.003). Adjusting for multiple variables did not remove the significance of this risk. Median time to first neurovascular event for the entire cohort was 4.9 years (interquartile range 1.7-5.5 years). Severe recurrent headache appears to be a risk factor or predictor for subsequent cerebral ischemia in pediatric brain tumor survivors treated with radiation. This finding has clinical implications for both monitoring survivors and targeting a specific population for primary stroke prevention.

Radiation- and Chemotherapy-Induced Permanent Alopecia: Case Series

Radiation- and chemotherapy-induced alopecia is mostly temporary. However, permanent scalp alopecia is reported, albeit infrequently. The objective of this observational case series was to determine the kind and doses of chemotherapeutic agents and radiation in inducing permanent alopecia of the scalp. Eleven patients referred to our department over a period of 3 years for permanent alopecia after chemotherapy/radiotherapy or combination therapy were included. A detailed medical and therapeutic history was obtained from each patient and from medical records. Photography was done, and the scalp biopsies were taken. Patients were divided into three groups according to the type of therapy. The first group received conditioning chemotherapy prior to bone marrow transplantation. The second group had radiation for brain tumors, and the third group received both. A comprehensive multicenter and multidisciplinary study is required to determine the definite causative agents, doses, and other cofactors that induce permanent alopecia following chemotherapy/radiotherapy, as well as the means to avoid this distressing outcome in surviving patients.

An Integrated Method for Reproducible, Accurate Image-guided Stereotactic Cranial Irradiation of Brain Tumors Using the Small Animal Radiation Research Platform (SARRP)

An Integrated Method for Reproducible, Accurate Image-guided Stereotactic Cranial Irradiation of Brain Tumors Using the Small Animal Radiation Research Platform (SARRP)

Comparison of the effectiveness of MRI perfusion and fluorine-18 FDG PET-CT for differentiating radiation injury from viable brain tumor: a preliminary retrospective analysis with pathologic correlation in all patients

ObjectivesDifferentiating radiation injury from viable tumor is important for optimizing patient care. Our aim was to directly compare the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) and dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance (MR) perfusion in differentiating radiation effects from tumor growth in patients with increased enhancement following radiotherapy for primary or secondary brain tumors. Materials and methodsWe retrospectively identified 12 consecutive patients with primary and secondary brain tumors over a 1-year period that demonstrated indeterminate enhancing lesions after radiotherapy and that had undergone DSC MR perfusion, FDG PET-CT, and subsequent histopathologic diagnosis. The maximum standardized uptake value (SUV) of the lesion (SUVlesion max), SUVratio (SUVlesion max/SUVnormal brain), maximum relative cerebral blood volume, percentage of signal intensity recovery, and relative peak height were calculated from the positron emission tomography and MR perfusion studies. A prediction of tumor or radiation injury was made based on these variables while being blinded to the results of the surgical pathology. ResultsSUVratio had the highest predictive value (area under the curve=0.943) for tumor progression, although this was not statistically better than any MR perfusion metric (area under the curve=0.757–0.829). ConclusionsThis preliminary study suggests that FDG PET-CT and DSC MR perfusion may demonstrate similar effectiveness for distinguishing tumor growth from radiation injury. Assessment of the SUVratio may increase the sensitivity and specificity of FDG PET-CT for differentiating tumor and radiation injury. Further analysis is needed to help define which modality has greater predictive capabilities.

Concurrent cyclophosphamide and craniospinal radiotherapy for pediatric high-risk embryonal brain tumors

Embryonal tumors are an aggressive subtype of high-grade, pediatric central nervous system (CNS) tumors often with dismal survival rates. The 5-year survival for highest-risk embryonal tumors may be as low as 10 %. We report feasibility and efficacy from our experience using intravenous (IV) cyclophosphamide concurrently with craniospinal radiation (CSI) in high-risk embryonal CNS tumors of childhood. Ten consecutive children (aged: 3.5-15.5 years, median: 10.2 years, six male) with high-risk embryonal tumors, including: large cell/anaplastic medulloblastoma (6), atypical teratoid rhabdoid tumor (1), and leptomeningeal primitive neuroectodermal tumor (3), were treated with IV cyclophosphamide 1 g/M(2) on days 1 and 2 of CSI. Following a median of 36 Gy CSI plus tumor boosts, adjuvant treatment consisted of 21 doses of oral etoposide (7) and alkylator based chemotherapy from five to eight cycles in all. Of the ten patients thus treated, six remain alive with no evidence of disease and four are deceased. Median survival was 3.3 years, with a 3-year progression-free survival of 50 % (5/10). Median follow-up was: 3.3 years (range: 5 months-12.9 years) in the five patients with progression, median time-to-progression was: 1.3 years (range: 1 month-3 years). Median follow-up in the patients without progression is 8.8 years (range: 3-12.9 years). Complications due to adjuvant chemotherapy were typical and included myelosupression (10), necessitating shortened duration of chemotherapy in three, and hemorrhagic cystitis (1). In high-risk embryonal CNS tumors, cyclophosphamide given concurrently with CSI is well tolerated. Early results suggest that a phase II trial is warranted.

Light Flashes in Cancer Patients Treated with Heavy Ions

Light flashes (phosphenes) are reported by most of the astronauts during spaceflight and patients treated with radiotherapy for brain tumors. They are induced by cosmic ray traversals, but the target area is unknown. With a correlation analysis of the visual sensation and the position of the beam in patients treated with energetic carbon ions for skull base tumors, we demonstrate here that light flashes are elicited only when the energetic particles hit the retina.

Scattered dose to radiosensitive organs and associated risk for cancer development from head and neck radiotherapy in pediatric patients

The purpose of this study was to measure the scattered dose to out-of-field organs from head and neck radiotherapy in pediatric patients and to estimate the risk for second cancer induction to individual organs. Radiotherapy for thalamic tumor, brain tumor, acute leukemia and Hodgkin's disease in the neck region was simulated on 5 and 10-year-old pediatric phantoms with a 6 MV photon beam. The radiation dose to thyroid, breast, lung, stomach, ovaries, bladder, liver, uterus, prostate and colon was measured using thermoluminescent dosimeters. The methodology, provided by the BEIR VII report was used for the second cancer risk estimations. Peripheral dose range for a simulated 5-year-old patient was 0.019%–1.572% of the given tumor dose. The corresponding range at the advanced patient age was reduced to 0.018%–1.468%. The second cancer risk per fraction for male patients varied from 3 to 215 per 1,000,000 patients depending upon the age at the time of exposure, primary cancer site and organ scattered dose. The corresponding risk for females was 1–1186 per 1,000,000 patients. The higher risk values were found for breast, thyroid and lung cancer development. The current data concerning the risk magnitude for developing subsequent neoplasms to various out-of-field organs may be of value for health care professionals in the follow-up studies of childhood cancer survivors.

Precision radiotherapy for brain tumors: A 10-year bibliometric analysis.

OBJECTIVE:Precision radiotherapy plays an important role in the management of brain tumors. This study aimed to identify global research trends in precision radiotherapy for brain tumors using a bibliometric analysis of the Web of Science.DATA RETRIEVAL:We performed a bibliometric analysis of data retrievals for precision radiotherapy for brain tumors containing the key words cerebral tumor, brain tumor, intensity-modulated radiotherapy, stereotactic body radiation therapy, stereotactic ablative radiotherapy, imaging-guided radiotherapy, dose-guided radiotherapy, stereotactic brachytherapy, and stereotactic radiotherapy using the Web of Science.SELECTION CRITERIA:Inclusion criteria: (a) peer-reviewed articles on precision radiotherapy for brain tumors which were published and indexed in the Web of Science; (b) type of articles: original research articles and reviews; (c) year of publication: 2002-2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) Corrected papers or book chapters.MAIN OUTCOME MEASURES:(1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) top cited publications; (5) distribution according to journals; and (6) comparison of study results on precision radiotherapy for brain tumors.RESULTS:The stereotactic radiotherapy, intensity-modulated radiotherapy, and imaging-guided radiotherapy are three major methods of precision radiotherapy for brain tumors. There were 260 research articles addressing precision radiotherapy for brain tumors found within the Web of Science. The USA published the most papers on precision radiotherapy for brain tumors, followed by Germany and France. European Synchrotron Radiation Facility, German Cancer Research Center and Heidelberg University were the most prolific research institutes for publications on precision radiotherapy for brain tumors. Among the top 13 research institutes publishing in this field, seven are in the USA, three are in Germany, two are in France, and there is one institute in India. Research interests including urology and nephrology, clinical neurology, as well as rehabilitation are involved in precision radiotherapy for brain tumors studies.CONCLUSION:Precision radiotherapy for brain tumors remains a highly active area of research and development.

An Integrated Method for Reproducible and Accurate Image-Guided Stereotactic Cranial Irradiation of Brain Tumors Using the Small Animal Radiation Research Platform

Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform. We demonstrated that, in vivo, BLI correlated well with MRI for defining tumor volumes. Our novel restraint system enhanced setup reproducibility and precision, was atraumatic, and minimized artifacts on CT imaging used for treatment planning. We confirmed precise radiation delivery through immunofluorescent analysis of the phosphorylation of histone H2AX in irradiated brains and brain tumors. Assays with an intravenous near-infrared fluorescent probe confirmed that radiation of orthografts increased disruption of the tumor blood-brain barrier (BBB). This integrated model system, which facilitated delivery of precise, reproducible, stereotactic cranial RT in mice and confirmed RT's resultant histologic and BBB changes, may aid future brain tumor research.

Outcomes of hypofractionated stereotactic radiotherapy for metastatic brain tumors with high risk factors

The present study aimed to analyze outcomes of hypofractionated stereotactic radiotherapy (HFSRT) delivered in five fractions to metastatic brain tumors. Between June 2008 and June 2011, 39 consecutive patients with 46 brain metastases underwent HFSRT at Kyoto University Hospital. Selection criteria included high risk factors such as eloquent location, history of whole-brain radiotherapy (WBRT), or large tumor size. Given these factors, fractionated schedules were preferable in terms of radiobiology. The prescribed dose at the isocenter was basically 35 Gy in five fractions. Brainstem lesions with a history of WBRT were treated with 20-25 Gy in five fractions. Planning target volume was covered by the 80 % isodose line of the prescribed dose to the isocenter. Local-control probability and overall survival were estimated using the Kaplan-Meier method. For the analysis of local control, the response criteria were defined as follows: complete response (CR) was defined as no visible gross tumor or absence of contrast enhancement, partial response (PR) as more than a 30 % decrease in size, progressive disease as more than a 20 % increase in size, and stable disease (SD) as all other responses. Local control was defined as a status of CR, PR, or SD. Only patients with at least 3 months or longer follow-up (21 patients, 27 tumors) were included in the analysis. Median age and Karnofsky performance status were 59 years (range, 39-84 years) and 90 (range, 40-100), respectively. Tumor volumes and maximum diameters ranged from 0.08 to 15.38 cm(3) (median, 3.67 cm(3)) and from 3 to 34 mm (median, 18 mm), respectively. The median follow-up period was 329 days (range, 120-1,321 days). Local-control probabilities at 6 and 12 months were 92.1 and 86.7 %, respectively. Overall survival after HFSRT at 6 and 12 months was 85.4 and 64.5 %, respectively. Grade 3 radiation necrosis was observed in one patient according to the Common Terminology Criteria for Adverse Events version 3.0. The patient was successfully managed conservatively. HFSRT for metastatic brain tumors yields high local-control probabilities without increasing severe adverse events despite high risk factors.

SU-E-J-38: Rotational Setup Errors in Pediatric Patients Receiving Radiation Therapy for Intracranial Tumors.

We have clinically observed that larger rotational setup errors are more prominent in pediatric patients who received radiation therapy for brain tumors. In this work, we quantitatively evaluated the daily setup corrections in pitch, roll, and yaw axes for children who received intracranial radiation therapy under x-ray image guidance. Daily localization data of 43 patients between the ages of 10 months and 21.9 years were analyzed in this study. Patients were immobilized with thermoplastic mask during treatments, and 2D orthogonal x-ray images wereacquired for setup corrections before each treatment. Rotational setup corrections in pitch, roll, and yaw axes were extracted from 873 treatment fractions, and were analyzed for the whole group of patients and for two age groups: < 5 and = 5 years old. The mean values for the pitch corrections were 1.91° and 1.65° (p:0.02), roll corrections were 1.37° and 1° (p<0.001), and yaw corrections were 1.93° and 1.47° (p<0.001), respectively. For patients < 5 years, 21.7% of treatments had pitch corrections more than 3°, versus 15.6% of treatments required pitch corrections more than 3° for patients >= 5 years. Similarly, 10.6% of roll corrections and 20.9% of yaw corrections were more than 3° for patients < 5 years. On the other hand, 2.1% of roll and 13.8% of yaw corrections were more than 3° for patients = 5 years old. Data indicate that children less than 5 years old are more prone to rotational setup errors during intracranial radiation therapy. This can be attributed to reduced efficacy of immobilization devices due to smaller and rounder anatomicalfeatures of pediatric patients, and challenges in setup while the patient is under anesthesia. The role of daily image guidance and rotational setup corrections becomes important to ensure target coverage, especially for children < 5 years old.

Radiation Induces Acute Alterations in Neuronal Function

Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABAARs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.

Modeling radiation dose to circulating lymphocytes during brain tumor treatment: Effects of target volume, dose rate, and treatment technique.

2017 Background: Severe treatment-related lymphopenia (TRL) occurs in 40% of glioblastoma patients despite minimal radiation (RT) doses to bone marrow or nodal sites. In glioblastoma, TRL is associated with decreased survival. To explain the lymphopenia, we sought to estimate radiation doses received by circulating lymphocytes during partial brain RT. Methods: An in-house computer program linked to treatment planning software was used to calculate the mean radiation dose to circulating blood (DCB) and the fraction of blood receiving &gt;0.5 Gy. The model also studied the impact of different target volumes (PTV), dose rates (DR), and delivery techniques (IMRT, 3D-CRT). Results: The mean DCB for a 60-Gy course (8-cm diameter PTV, dose rate 600 MU/minute) was 2.2 Gy. With this the entire blood pool receives a lymphotoxic dose of &gt;0.5 Gy. DCB is correlated with fraction number, PTV size, and DR. Regardless of dose rate or delivery technique, the percent of circulating blood receiving &gt;0.5 Gy approached 100% as the number of fractions increased. Changing dose rate had minimal effects on mean DCB (3.1Gy for 300 MU/min vs 2.2 Gy for 1200 MU/min). Smaller PTV size reduced the percent of blood receiving &gt;0.5 Gy (15% for 2-cm diameter PTV vs 100% for 8-cm PTV). Conclusions: Standard RT for brain tumors delivers a lymphotoxic radiation dose to circulating blood. Altering dose rate may initially affect DCB, but advantages disappear over the course of 30 fractions. Marked reductions in target size appear to be the best way to avoid radiation injury to normal circulating lymphocytes. Other novel approaches are needed to limit radiation exposure to circulating lymphocytes given evidence associating lymphopenia with poorer outcomes in cancer patients.

Chalcone JAI-51 improves efficacy of synchrotron microbeam radiation therapy of brain tumors

Microbeam radiation therapy (MRT), a preclinical form of radiosurgery, uses spatially fractionated micrometre-wide synchrotron-generated X-ray beams. As MRT alone is predominantly palliative for animal tumors, the effects of the combination of MRT and a newly synthesized chemotherapeutic agent JAI-51 on 9L gliosarcomas have been evaluated. Fourteen days (D14) after implantation (D0), intracerebral 9LGS-bearing rats received either MRT, JAI-51 or both treatments. JAI-51, alone or immediately after MRT, was administered three times per week. Animals were kept up to ∼20 weeks after irradiation or sacrificed at D16 or D28 after treatment for cell cycle analysis. MRT plus JAI-51 increased significantly the lifespan compared with MRT alone (p = 0.0367). JAI-51 treatment alone had no effect on rat survival. MRT alone or associated with JAI-51 induced a cell cycle blockade in G2/M (p < 0.01) while the combined treatment also reduced the proportion of G0/G1 cells. At D28 after irradiation, MRT and MRT/JAI-51 had a smaller cell blockade effect in the G2/M phase owing to a significant increase in tumor cell death rate (<2c) and a proportional increase of endoreplicative cells (>8c). The combination of MRT and JAI-51 increases the survival of 9LGS-bearing rats by inducing endoreduplication of DNA and tumor cell death; further, it slowed the onset of tumor growth resumption two weeks after treatment.

The Family Impacts of Proton Radiation Therapy for Children With Brain Tumors

Children with brain tumors experience significant alterations to their health and well-being due to the tumors themselves and oncologic treatment. Caring for children with brain tumors can have significant impacts on families, especially during and shortly after treatment. In this study of the impacts on families caring for children undergoing proton radiation therapy for brain tumors, the authors found that families experienced a broad array of negative impacts. Families reported feeling like they were living on a roller coaster, feeling that others treated them differently, and having to give up things as a family. In the multivariable linear regression model, older age of the child and higher reported child health-related quality of life were associated with less family impact. The presence of concurrent chemotherapy was associated with increased family impact. This is the first study to specifically evaluate the families of children being treated with proton radiation therapy. The findings in this study are consistent with the findings in other studies of children treated with standard therapy that show that families experience a variety of stressors and negative impacts while their children are receiving treatment. Health care providers should be aware of the potential impacts on families of children with brain tumors and their treatment to provide robust services to meet the health, psychological, and social needs of such children and their families.

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

Clinicopathologic features of delayed radiation-induced brain injury after radiotherapy for brain tumor

To study the clinicopathologic features of delayed radiation-induced brain injury after radiotherapy for brain tumor. The clinical, histopathologic and immunohistochemical features of 9 cases with delayed radiation-induced injury were evaluated. The disease occurred from 6 months to 12 years after radiotherapy and often presented with headache and muscle weakness. Magnetic resonance imaging showed peripheral enhancing lesions with slight mass effect and surrounding edema. Microscopically, the major changes included coagulative necrosis, fibrinoid necrosis of vessels, vascular hyalinization with luminal stenosis and peripheral reactive gliosis. Immunostaining for hypoxia-inducible factors 1α was positive in reactive astrocytes. Delayed radiation-induced brain injury is a relatively common complication of radiation therapy. The lesion was frequently misdiagnosed as brain tumor. Correct diagnosis relies on clinical, radiologic and pathologic correlation.