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Khatua S.,Childrens Cancer Hospital | Moore K.R.,Primary Childrens Medical Center | Vats T.S.,Childrens Cancer Hospital | Kestle J.R.W.,Primary Childrens Medical Center
Child's Nervous System | Year: 2011

Introduction Diffuse intrinsic pontine gliomas which constitute 15% of all childhood brain tumors are inoperable and response to radiation and chemotherapy has not improved long-term survival. Due to lack of newer effective therapies, mean survival after diagnosis has remained less than 12 months. Trials investigating chemotherapy and/or radiation have proven disappointing. As biopsy of these tumors are rarely performed due to the high eloquence of the brain stem, information about the pathology and biology remains elusive hindering development of novel biologic agents. Poor access of most chemotherapeutic agents to these tumors due to the blood-brain barrier continues to undermine therapeutic efficacy. Thus, to date, we remain at a virtual standstill in our attempts to improve the prognosis of children with these tumors. Methods An extensive review of the literature was performed concerning children with diffuse brain stem gliomas including clinical trials, evolving molecular biology, and newer therapeutic endeavors. Conclusion A pivotal approach in improving the prognosis of these tumors should include the initiation of biopsy and encouraging families to consider autopsy to study the molecular biology. This will help in redefining this tumor by its molecular signature and profiling targeted therapy. Continued advances should be pursued in neuroimaging technology including identifying surrogate markers of early disease progression. Defining strategies to enhance local delivery of drugs into tumors with the help of newer surgical techniques are important. Exhaustive research in all these aspects as a multidisciplinary approach could provide hope to children with these fatal tumors. © 2011 Springer-Verlag.

Wolff J.E.,Floating Hospital for Children | Brown R.E.,University of Texas Health Science Center at Houston | Buryanek J.,University of Texas Health Science Center at Houston | Pfister S.,German Cancer Research Center | And 2 more authors.
Pediatric Blood and Cancer | Year: 2012

Background: A new generation of anticancer drugs has reached clinical care in common diseases, but their use in rare diseases such as pediatric brain tumors lags behind since conventional clinical trial design requires larger patient numbers. Procedure: We designed individualized treatment protocols for pediatric patients with relapsed brain tumors, based upon the patient's treatment history. In addition, each tumor was analyzed with morphoproteomics using a panel of markers to show treatment targets, resulting in a list of potential novel drugs to be added to chemotherapy. Here, we present the concept and report the experiences of the first patients enrolled in the program. Results: Eleven treatment protocols were designed using morphoproteomic information and given to eight patients. The histological diagnoses included: medulloblastoma (n=3), glioblastoma multiforme (n=2), atypical teratoid rhabdoid tumor (n=1), choroid plexus carcinoma (n=1), and primitive neuroectodermal tumors (n=1). Tumor markers included p-ERK, Topoisomerase IIa, Bcl-2, VEGF-A, p-STAT3, ER-beta, p-mTOR, and p-NF-kappaBp65. The novel agents included sorafenib, bevacizumab, fulvestrant, rapamycin, bortezomib, and curcumin. The response to the first protocol was complete response: 1, partial response: 1, stable disease: 0, progressive disease: 4, and continuous complete remission: 2. The median Event-Free Survival was 0.32 year±0.4. For the comparison with the institutional control group, the individual response probability was calculated. The observed response was superior to the historical controls (P=0.006 Whitman U-test). Conclusion: This approach warrants further, systematic evaluation as proof of concept and then expansion to drug-specific hypotheses. © 2011 Wiley Periodicals, Inc..

Eldesoky I.,Childrens Cancer Hospital
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2012

This work aimed at evaluating the performance of three different intensity-modulated radiotherapy (IMRT) treatment planning systems (TPSs)--KonRad, XiO and Prowess--for selected pediatric cases. For this study, 11 pediatric patients with different types of brain, orbit, head and neck cancer were selected. Clinical step-and-shoot IMRT treatment plans were designed for delivery on a Siemens ONCOR accelerator with 82-leaf multileaf collimators (MLCs). Plans were optimized to achieve the same clinical objectives by applying the same beam energy and the same number and direction of beams. The analysis of performance was based on isodose distributions, dose-volume histograms (DVHs) for planning target volume (PTV), the relevant organs at risk (OARs), as well as mean dose (Dmean), maximum dose (Dmax), 95% dose (D 95), volume of patient receiving 2 and 5 Gy, total number of segments, monitor units per segment (MU/Segment), and the number of MU/cGy. Treatment delivery time and conformation number were two other evaluation parameters that were considered in this study. Collectively, the Prowess and KonRad plans showed a significant reduction in the number of MUs that varied between 1.8% and 61.5% (p-value = 0.001) for the different cases, compared to XiO. This was reflected in shorter treatment delivery times. The percentage volumes of each patient receiving 2 Gy and 5 Gy were compared for the three TPSs. The general trend was that KonRad had the highest percentage volume, Prowess showed the lowest (p-value = 0.0001). The KonRad achieved better conformality than both of XiO and Prowess. Based on the present results, the three treatment planning systems were efficient in IMRT, yet XiO showed the lowest performance. The three TPSs achieved the treatment goals according to the internationally approved standards.

Ray A.,Childrens Cancer Hospital | Gombos D.S.,University of Texas M. D. Anderson Cancer Center
Indian Journal of Pediatrics | Year: 2012

Retinoblastoma, the most common intraocular malignancy of childhood arises due to mutation of the retinoblastoma gene on chromosome 13q14. In the hereditary setting this mutation is present in all germ line cells and can occur as early as during development; however it requires a mandatory second "hit" or mutation of the remaining allele for retinoblastoma to develop. The nonhereditary form arises from spontaneous mutation affecting both alleles in a somatic cell of the retina. The tumor may present with leucocoria or strabismus. The diagnosis is best made by an ophthalmologist who examines the patient under sedation. Although tissue biopsy is not routinely performed, imaging studies like ultrasound and MRI scan can serve as useful adjuncts to help in establishing the diagnosis and also aid in staging. Group A tumors are smaller than 3 mm while group B tumors are ≥3 mm or those located in the macula. Groups C and D tumors are associated with localized and diffuse vitreous seeds respectively. Group E tumors occupy ≥50% of the globe and are generally not salvagable. Despite the fact that great advances have been made in the treatment of retinoblastoma in the last two decades, a large number patients undergo procedures associated with significant morbidity such as enucleation. Werecommend large multi institutional studies using newer therapeutic models and targeting novel pathways to improve the outcome in advanced stage retinoblastoma. © Dr. K C Chaudhuri Foundation 2012.

Elsherbini A.A.M.,Cairo University | El-Shahawy A.,Childrens Cancer Hospital
Journal of Nanomaterials | Year: 2013

Magnetic nanoparticles (MNPs) are being developed for a wide range of biomedical applications. In particular, hyperthermia involves heating the MNPs through exposure to an alternating magnetic field (AMF). These materials offer the potential for selectively by heating cancer tissue locally and at the cellular level. This may be a successful method if there are enough particles in a tumor possessing sufficiently high specific absorption rate (SAR) to deposit heat quickly while minimizing thermal damage to surrounding tissue. The current research aim is to study the influence of super paramagnetic iron oxides Fe 3O4 (SPIO) NPs concentration on the total heat energy dose and the rate of temperature change in AMF to induce hyperthermia in Ehrlich carcinoma cells implanted in female mice. The results demonstrated a linearly increasing trend between these two factors. © 2013 Alsayed A. M. Elsherbini and Ahmed El-Shahawy.

El Beltagy M.A.,Childrens Cancer Hospital | Aggag M.,Childrens Cancer Hospital | Kamal M.,Childrens Cancer Hospital
Child's Nervous System | Year: 2010

Purpose: In neurosurgery, ultrasound is useful in determination of the tumor location, differentiation between solid tumors and cystic components, as well as definition of the shortest and safest access to the mass. This study aims to evaluate the role of the intraoperative ultrasound in resection of pediatric brain tumors. Methods: Intraoperative ultrasonography (conventional B-Mode) was performed in 25 pediatric patients with brain tumors pre-, during, and post-resection, in whom eight patients were supratentorial and 17 were infratentorial. Post-op Grayscale images of the brain tumors on conventional ultrasound were compared with the results of immediate postoperative magnetic resonance imaging. Results: The border of the tumor and post-resection residual tumor were more distinguishable from healthy brain on ultrasound during the operation. Improved definition of the tumor tissue from normal brain with ultrasound was demonstrated in all cases aiding in tumor resection. Conclusion: Intraoperative ultrasound is suggested to be a useful imaging technique in defining the border between the tumor and healthy brain tissue pre-resection, in detecting residual tumor tissues after the resection of the mass, and in guiding to the shortest and safest access to the tumor during neurosurgery. © 2010 Springer-Verlag.

Zaghloul M.S.,Cairo University | Eldebawy E.,Cairo University | Ahmed S.,Cairo University | Mousa A.G.,Cairo University | And 5 more authors.
Radiotherapy and Oncology | Year: 2014

Background The pediatric diffuse intrinsic pontine glioma (DIPG) outcome remains dismal despite multiple therapeutic attempts. Purpose To compare the results of treatment of pediatric diffuse intrinsic pontine glioma (DIPG) using hypofractionated versus conventional radiotherapy. Patients and methods Seventy-one newly diagnosed DIPG children were randomized into hypofractionated (HF) (39 Gy/13 fractions in 2.6 weeks) and conventional (CF) arm (54 Gy/30 fractions in 6 weeks). Results The median and one-year overall survival (OS) was 7.8 months and 36.4 ± 8.2% for the hypofractionated arm, and 9.5 and 26.2 ± 7.4% for the conventional arm respectively. The 18-month OS difference was 2.2%. The OS hazard ratio (HR) was 1.14 (95% CI: 0.70-1.89) (p = 0.59). The hypofractionated arm had a median and one-year progression-free survival (PFS) of 6.6 months and 22.5 ± 7.1%, compared to 7.3 and 17.9 ± 7.1% for the conventional arm. The PFS HR was 1.10 (95% CI: 0.67-1.90) (p = 0.71). The 18-month PFS difference was 1.1%. These differences exceed the non-inferiority margin. The immediate and delayed side effects were not different in the 2 arms. Conclusions Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption. © 2014 Elsevier Ireland Ltd. All rights reserved.

Eldebawy E.,McGill University | Eldebawy E.,Childrens Cancer Hospital | Parker W.,McGill University | Abdel Rahman W.,McGill University | Freeman C.R.,McGill University
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To determine the best treatment technique for patients with retinoblastoma requiring radiotherapy to the whole eye. Methods and Materials: Treatment plans for 3 patients with retinoblastoma were developed using 10 radiotherapy techniques including electron beams, photon beam wedge pair (WP), photon beam three-dimensional conformal radiotherapy (3D-CRT), fixed gantry intensity-modulated radiotherapy (IMRT), photon volumetric arc therapy (VMAT), fractionated stereotactic radiotherapy, and helical tomotherapy (HT). Dose-volume analyses were carried out for each technique. Results: All techniques provided similar target coverage; conformity was highest for VMAT, nine-field (9F) IMRT, and HT (conformity index [CI] = 1.3) and lowest for the WP and two electron techniques (CI = 1.8). The electron techniques had the highest planning target volume dose gradient (131% of maximum dose received [D max]), and the CRT techniques had the lowest (103% D max) gradient. The volume receiving at least 20 Gy (V 20Gy) for the ipsilateral bony orbit was lowest for the VMAT and HT techniques (56%) and highest for the CRT techniques (90%). Generally, the electron beam techniques were superior in terms of brain sparing and delivered approximately one-third of the integral dose of the photon techniques. Conclusions: Inverse planned image-guided radiotherapy delivered using HT or VMAT gives better conformity index, improved orbital bone and brain sparing, and a lower integral dose than other techniques. © 2012 Elsevier Inc.

Zaghloul M.S.,Childrens Cancer Hospital
The Gulf journal of oncology | Year: 2012

Different craniospinal irradiation techniques are complex. The homogeneity of the dose to the target and the normal tissues at risk affect both the control rate and the level of adverse effects. Thirty one patients were treated with CSI in the supine position. Custom-made Styrofoam was tailored for each patient to straighten the convexity and concavity of the spinal axis allowing better dose distribution uniformity during CSI technique. In the first 6 patients, CT simulation were performed twice: one time with the patient lying directly on the vacuum mattress without the foam (the conventional way) and the second while lying on the foam. Dose distribution was calculated using a 3D conformal planning. The gap between the fields was determined using isodose alignment method. All treatment portals were verified during the first 3 treatment sessions and once weekly thereafter using either cone-beam or portal image device. Weekly feathering (shifting of the junction between the 2 adjacent radiation fields) was routinely performed. The 95% dose distribution had better coverage with the foam (p=0.042) while the hot volume of 110% and 105% dosage were significantly lesser than conventional technique (both p=0.028). The organs at risk received nearly similar radiation doses in the 2 positions. The CSI led to minimal immediate adverse effects that were reversible. Weight loss was experienced by 55% of patients. This modified technique of CSI is simple, ensuring better dose distribution to CSI target without increasing the dose to the surrounding organs at risk. It is tolerable and safe to apply.

Alfaar A.S.,Childrens Cancer Hospital
Telemedicine journal and e-health : the official journal of the American Telemedicine Association | Year: 2012

In developed countries, pharmacists play a crucial role in designing and implementing cancer treatments as part of a multidisciplinary oncology team. However, developing countries have a shortage of pharmacists, and their role is generally limited to dispensing and selling drugs. The aim of this study was to investigate the feasibility of providing clinical pharmacy educational activities via international teleconferencing to improve cancer care in developing countries. Meticulous preparation and intense promotion of the workshop were done in Egypt before the telepharmacy conferences began. Multiple connectivity tests were performed to resolve technical problems. Nine telepharmacy conferences were delivered during 3-h sessions that were held on three consecutive days. Talks were subsequently made available via Web streaming. Attendees were requested to complete a survey to measure their satisfaction with the sessions. The teleconference was attended by a total of 345 persons, and it was subsequently reviewed online via 456 log-in sessions from 10 countries. Technical issues (e.g., poor auditory quality) were resolved on the first day of the event. The rate of attendees' responses on the survey was 30.1%, and satisfaction with the event was generally good. Telecommunication is a relatively inexpensive approach that may improve pharmacy practices, especially those used to treat patients with cancer in developing countries. Special attention to patient-based telepharmacy education, including the use of cost-effective technology, should be considered.

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