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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.

The aims of this study were to characterize and quantify time-frequency changes in transient-evoked otoacoustic emissions (TEOAEs) recorded in children diagnosed with retinoblastoma who were receiving carboplatin chemotherapy. A signal processing technique, the wavelet transform (WT), was used to analyze TEOAE waveforms in narrow-band frequency components. Ten children (aged 3-72 months) diagnosed with unilateral or bilateral retinoblastoma were enrolled in the study. TEOAEs were acquired from the children with linear sequences of 70 dB peak equivalent SPL clicks. After WT analysis, TEOAE energy, latency and normalized energy in the narrow-band frequency components were compared before and during carboplatin chemotherapy treatment (average dose 1693 mg/m2). On a group basis, no significant differences (p>0.05) in the TEOAE energy, latency or normalized energy before and after carboplatin treatment were observed. There were decreases in normalized energy on an individual basis in 10 out of 18 ears in the sample. Exposure to carboplatin chemotherapy did not cause significant changes in TEOAE energy, latency and normalized energy during treatment. However, long-term monitoring of hearing with measurements of TEOAEs is warranted, given the risks of delayed hearing loss in some children receiving carboplatin chemotherapy., (Copyright © 2012 S. Karger AG, Basel.)

Background: New, effective chemotherapeutic agents are needed for intraocular retinoblastoma., Methods: This institutional clinical trial sought to estimate the rate of response to 2 courses of vincristine and topotecan (VT) window therapy in patients with bilateral retinoblastoma and advanced disease (Reese-Ellsworth group IV or V) in at least 1 eye. The topotecan dose started at 3 mg/m(2) /day for 5 days and was adjusted to target a systemic exposure of 140 ± 20 ng/mL · hour. The vincristine dose was 0.05 mg/kg for patients <12 months of age and 1.5 mg/m(2) for those >12 months of age at diagnosis., Results: From February 2005 to June 2010, 27 patients received VT window therapy. Median age at enrollment was 8.1 months (range, 0.7-22.1 months). Twenty-four patients (88.9%) responded to window therapy (95% confidence interval = 71.3%-96.9%). Hematologic toxicity comprised grade 4 neutropenia (n = 27), grade 3 anemia (n = 19), and grade 3/4 thrombocytopenia (n = 16). Thirteen patients had grade 3 nonhematologic toxicity. Granulocyte colony-stimulating factor support was added after 10 patients had been treated, and it significantly reduced the duration of grade 4 neutropenia (median, 7 vs 24 days; P < .001). Pharmacokinetic studies showed rapid changes in topotecan clearance rates during the first year of life., Conclusions: The combination of topotecan and vincristine is effective for the treatment of advanced intraocular retinoblastoma. Granulocyte colony-stimulating factor treatment alleviates the duration of grade 4 neutropenia. Appropriate topotecan starting doses for patients 0-3, 3-6, 6-9, 9-12, and >12 months of age are specified., (Copyright © 2012 American Cancer Society.)

Background: Accurate diagnosis is critical for optimal management of pediatric cancer. Pathologists with experience in pediatric oncology are in short supply in the developing world. Telepathology is increasingly used for consultations but its overall contribution to diagnostic accuracy is unknown., Procedure: We developed a strategy to provide a focused training in pediatric cancer and telepathology support to pathologists in the developing world. After the training period, we compared trainee's diagnoses with those of an experienced pathologist. We next compared the effectiveness of static versus dynamic telepathology review in 127 cases. Results were compared by Fisher's exact test., Results: The diagnoses of the trainee and the expert pathologist differed in only 6.5% of cases (95% CI, 1.2-20.0%). The overall concordance between the telepathology and original diagnoses was 90.6% (115/127; 95% CI, 84.1-94.6%)., Conclusions: Brief, focused training in pediatric cancer histopathology can improve diagnostic accuracy. Dynamic and static telepathology analyses are equally effective for diagnostic review., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series., Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis., Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ≥ 50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ≥ 52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ≥ 54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively., Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: In order to predict whether tumor markers assist in the histopathologic diagnosis of germ cell tumors (GCTs), we analyzed the correlation of beta human chorionic gonadotropin (βhCG) and alpha-fetoprotein (AFP) in serum and cerebrospinal fluid (CSF) samples at baseline and subsequent follow-up examinations., Method: A retrospective study of patients diagnosed with intracranial GCTs between July 1985 and February 2011 at our institution was conducted to review clinical, surgical, radiological, laboratory, and histopathologic data., Results: Of the 67 patients eligible for the study, 42 had germinomas and 25 non-germinomatous GCTs. At baseline, serum and CSF AFP agreed in 97.9 % of patients (Cohen's Kappa 0.93). Baseline βhCG samples agreed in only 72.5 % of patients (Cohen's Kappa 0.46). In most cases, values were higher in serum for AFP and in CSF for βhCG. ROC curves estimated from logistic regression model indicated that CSF and serum samples had almost equal diagnostic utility, and the DeLong test showed that the difference in area under curves was not statistically significant. During follow-up (185 paired CSF and serum values from 43 patients), 90.3 % of AFP values correlated between CSF and serum (Cohen's Kappa 0.22, showing fair agreement). For βhCG, 96.2 % of values agreed in serum and CSF (Cohen's Kappa 0.61)., Conclusions: In some patients, intracranial GCTs can be diagnosed based solely upon positive serum AFP values. In addition, marker values from serum only may be sufficient to predict tumor relapse at interval follow-up examinations.

Introduction: Retinoblastoma and uveal melanoma are the most common ocular tumors in children and adults, respectively. Enucleation and external beam radiation therapy are integral in the management of ocular tumors. However, these tumors could also be treated effectively by plaque therapy, which has the potential of preserving the globe and maintaining vision., Methods and Materials: We reviewed our experience with the introduction of this technique to our center. Furthermore, we highlighted the critical role of a specialized multidisciplinary team in the successful implementation of this procedure., Discussion: This review represents a detailed report addressing the practical steps for successfully establishing plaque therapy in developing countries., Results: Plaque therapy was successfully implemented at our center in 1.5 years. Integration with an advanced cancer center is crucial for the correct transfer of this complex technology., Conclusion: Complex brachytherapy procedures could be successfully established and implemented in developing countries., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Carboplatin-induced ototoxicity remains poorly defined but is of potential great consequence in children with retinoblastoma. We retrospectively assessed the incidence of ototoxicity and its risk factors in children with retinoblastoma who were treated with carboplatin., Patients and Methods: We reviewed the audiologic test results of 60 patients with retinoblastoma who received front-line treatment with systemic carboplatin and vincristine according to the St Jude RET-3 protocol (n = 23) or best clinical management (n = 37). Ototoxicity was evaluated by three different grading systems., Results: Twelve patients (20%) developed ototoxicity at some time after treatment initiation; however, ototoxicity resolved in two patients, and thus,10 patients (17%) had sustained hearing loss as documented at their most recent audiologic evaluation. Nine of these 10 patients had grade 3 or 4 ototoxicity, and nine patients were less than 6 months of age at the start of chemotherapy. Age at the start of chemotherapy was the only risk factor identified as a significant predictor of sustained hearing loss. Younger age was associated with an increased incidence of hearing loss. The different ototoxicity grading systems showed good overall agreement in the identification of patients with ototoxicity. Agreement was greatest between the Brock and Children's Cancer Group systems., Conclusion: We found that young patients with retinoblastoma who were treated with systemic carboplatin had a higher incidence of ototoxicity than previously reported. Younger patients (< 6 months of age at the start of treatment) were more likely to have ototoxicity than were older patients. Children treated with carboplatin should routinely undergo thorough, long-term audiologic monitoring.

Pilocytic astrocytoma (PA) is one of the most common glial neoplasms in the pediatric population, and its gross total resection can be curative. Treatment of partially resected or recurrent tumors is challenging, and the factors associated with increased recurrence risk are not well defined. Identification of favorable and unfavorable factors can lead to a better understanding and management of patients with PA. We studied the pathologic characteristics of 116 intracranial PAs from 4 institutions representing 3 distinct geographic regions to identify factors that may be associated with biological behavior. The study included 65 boys and 51 girls with a median age of 6 years. Median follow-up for all patients was 101 months, during which time 38 patients had recurrence. Progression-free and overall survivals were better in patients who underwent gross total resection. We were not able to identify any differences in pathologic and molecular markers among the 4 institutions from 3 different countries. However, progression-free survival varied significantly among institutions. Sox-2 was the most prevalent stem cell marker in PA, and many tumors showed synaptophysin positivity. BRAF immunostaining was not useful in determining BRAF duplication. BRAF duplication was more typical of posterior fossa tumors. There was a strong correlation between BRAF duplication and pERK immunostaining, suggesting that the RAF/MEK/ERK pathway is active in these tumors. This finding has significant implications given its role in oncogen-induced senescence and possible influence on treatment decisions of subtotally resected tumors.

Purpose: To determine the impact of chemotherapy or external beam radiotherapy (EBRT) on pediatric anophthalmic sockets., Design: A retrospective, nonrandomized, interventional cohort study., Participants: A total of 135 sockets of 133 children undergoing enucleation from late 1999 to early 2009 at the St. Jude Children's Research Hospital were included., Methods: A retrospective chart review of outcomes after enucleation in patients treated with systemic chemotherapy or orbital EBRT either before or after removal of the eye compared with patients who received no other treatment., Main Outcome Measures: Incidence of implant exposure, migration, extrusion, socket contracture, and pyogenic granuloma formation., Results: Retinoblastoma was the primary diagnosis in 128 eyes (95%). Median follow-up was 3.6 years (range, 0.1-9.3 years). Event-free course was observed in 94 sockets (69.6%). Complications included implant exposure (n = 28, 20.7%), socket contracture (n = 16, 11.9%), pyogenic granuloma (n = 9, 6.7%), implant extrusion (n = 3, 2.2%), and migration (n = 2, 1.5%). Exposure resolved in 21 sockets (77.8%) and improved in 2 sockets (11.1%); 1 patient with exposure died. Use of prior, adjuvant, or subsequent chemotherapy increased the long-term risk of exposure (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.4-9.4), and contracture (OR could not be calculated, P<0.0001). External beam radiotherapy greatly increased the risk of contracture (OR 24.0; 95% CI, 6.9-82.8) and exposure (OR 2.89; 95% CI, 1.1-7.9)., Conclusions: In this unique pediatric population with cancer, chemotherapy and EBRT had an additive effect, significantly increasing the incidence of exposure and socket contracture., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: Information about pediatric survivors of brain tumors in developing countries is scant., Purpose: In this study, we aimed to investigate the availability of resources for treatment and long-term follow-up of children with central nervous system tumors in developing countries., Materials and Methods: A web-based questionnaire on available services and follow-up of brain tumor survivors was posted at www.cure4kids.org , and registered users were invited to participate., Results: A total of 140 evaluable responses from developing countries (n = 103) and high-income countries (n = 37) were obtained. There was a significant correlation between gross national income and the availability of services for treatment and follow-up and between patient load and the availability of some services., Conclusion: The resources for treatment and long-term follow-up of children with brain tumors need to be improved in developing countries.

Little is known about brain tumors in early infancy. Investigators reviewed the records of 27 patients (12 boys and 15 girls) diagnosed within 120 days of birth. The median age was 66 days (range, 0-110 days) at diagnosis. All patients underwent surgery; 18 received adjuvant chemotherapy, and 3 received adjuvant chemotherapy and radiation therapy. The median follow-up was 2.1 years (range, 0.2-21.6 years). At last encounter, 15 patients were alive, and 11 had no evidence of disease. Ten patients died of progressive disease, and 2 died of treatment-related complications. All survivors experienced late effects, including endocrine, neurologic, and cognitive deficits. Of the 13 patients who completed neurocognitive assessments, 7 had an IQ score less than 70. Children in whom brain tumors arise during early infancy can be cured with conventional therapy; however, contemporary approaches can adversely affect long-term function, and families need to be aware of these effects when making therapeutic decisions.

Background: Retinoblastoma (RB) is a rare and unique cancer that affects the eyes of very young children. There are few reports on RB in Sudan., Materials and Methods: We performed a retrospective study of data from patients diagnosed with retinoblastoma between January 1999 and December 2009 at the National Cancer Institute in Gezira (NCI-Gezira)., Results: Of the 519 cases of childhood cancer treated at NCI-Gezira during the study period, 25 (4.8%) were retinoblastoma. Of these 25 patients with retinoblastoma, there were 13 boys and 19 cases were unilateral. The median age at diagnosis was 36 months (range, 8-60 months). The disease was localized in 9 patients, regional in 5 patients, and metastatic in 11 patients. The most frequent symptoms were enlarged eye (n = 14) and leukocoria (n = 8). Nine patients (36%) have been lost to follow-up; 9 were alive at last follow-up (7 in remission, 2 progressed); and 7 have died (5 from disease and 2 from unrelated causes). Twenty-two eyes were enucleated in 16 patients (6 bilateral and 10 unilateral). Pathologic examination of the enucleated eyes could only be completed in 11 patients. Diagnostic imaging in the form of computerized tomography scans or ultrasonography of the brain and orbit was done for 10 patients (40%)., Conclusions: Although these findings are not surprising, and similar to reports from other developing countries, we hope our work will provide a foundation for strategies to improve outcome for retinoblastoma in our center such as proper training, public awareness, team approach, and twinning.

Purpose: To use functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to investigate visual system development in children being treated for retinoblastoma., Methods: Informed consent was obtained for all participants (N = 42) in this institutional review board-approved study. Participants were imaged with a 1.5-T scanner while under propofol sedation. Diagnostic brain and orbital imaging was followed by investigational functional neuroimaging, which included fMRI during photic stimulation through closed eyelids, to measure functional activation in the visual cortex, and DTI, to evaluate diffusion parameters of white matter tracts in the corpus callosum and the periventricular optic radiations. Analysis included 115 examinations of 39 patients with a median age of 16.4 months and age range from 1.5 to 101.5 months at first evaluation., Results: The blood oxygen level-dependent signal was predominantly negative and located in the anterior visual cortex. Activation was affected by tumor lateralization (unilateral or bilateral), macular involvement, and retinal detachment. Patients who had undergone unilateral enucleation showed cortical dominance corresponding to the projection from the nasal hemiretina in the unaffected eye. Diffusion parameters followed a normal developmental trajectory in the optic radiations and corpus callosum, but variability was greater in the splenium than in the genu of the corpus callosum., Conclusions: Longitudinal functional neuroimaging demonstrated important effects of disease and treatment. Therefore, fMRI and DTI may be useful for characterizing the impact of retinoblastoma on the developing visual system and improving the prediction of visual outcome in survivors.

Aims: To correlate the clinical and histopathological findings of eyes primarily enucleated for advanced intraocular retinoblastoma., Methods: In a retrospective study, the authors identified patients primarily enucleated for advanced intraocular retinoblastoma. The authors retrieved patient demographics, clinical findings, subsequent treatments and outcomes, and reviewed the histopathology of each eye for invasion of the anterior chamber, iris, ciliary body, choroid, sclera and optic nerve, and extraocular extension. The authors used the Fisher exact, exact Jonkheere-Terpstra, exact Wilcoxon rank sum and Kruskal-Wallis statistical tests (p<0.05) to study associations between clinical and histopathological findings., Results: The authors identified 67 eyes of 67 patients (33 males) primarily enucleated for retinoblastoma between March 1997 and January 2008. Corneal diameter, intraocular pressure and Reese-Ellsworth Classification had no significant association with invasive disease. The International Classification, however, was associated with optic nerve (p=0.026), choroid (p<0.001), ciliary body (p=0.002), iris (p=0.002), anterior chamber (p=0.025) and scleral (p<0.001) invasion. Eyes classified as International Classification Group E were more likely to have invasion of these sites and have more severe optic-nerve invasion., Conclusions: Corneal diameter, intraocular pressure and Reese-Ellsworth Classification do not correlate with histopathological evidence of invasive retinoblastoma. Eyes classified as International Classification Group E are more likely to have elevated intraocular pressure, invasion of the anterior chamber, uveal tract, optic nerve and sclera. The findings warrant primary enucleation with meticulous histopathological examination of such eyes prior to any adjuvant therapy.

Survival of retinoblastoma is >90% in developed countries but there are significant differences with developing countries in stage at presentation, available treatment options, family compliance, and survival. In low-income countries (LICs), children present with advanced disease, and the reasons are socioeconomic and cultural. In middle-income countries (MICs), survival rates are better (>70%), but there is a high prevalence of microscopically disseminated extraocular disease. Programs for eye preservation have been developed, but toxicity-related mortality is higher. Although effective treatment of microscopically extraocular disease improved the outcome, worldwide survival will be increased only by earlier diagnosis and better treatment adherence., (Copyright © 2010 Wiley-Liss, Inc.)

Background and Objective: The epidemiological characteristics of retinoblastoma have been extensively studied in developed countries, however epidemiological data is scarce in the Middle East. We present a de- tailed epidemiological analysis of retinoblastoma in Jordan in an attempt to aid national and regional strategies for improved cancer surveillance and control., Design and Setting: Retrospective review of retinoblastoma cases presenting to the sole and exclusive ocular oncology referral center in Jordan., Patients and Methods: Forty children (59 eyes) presenting with clinically and/or histologically confirmed retinoblastomas were treated at King Hussein Cancer Center (Amman, Jordan) between January 2006 and December 2010. This case series included 28 boys and 12 girls. Data relating to age at diagnosis, laterality, gender, treatment modality and survival were recorded., Results: The mean age-adjusted incidence of retinoblastoma in Jordan was 9.32 cases per million children per year for children aged 0-5 years. The male: female ratio was 2.3:1. Bilateral cases were encountered in 19 pa- tients (47.5%) while 21 patients (52.5%) harbored unilateral retinoblastoma. At the time of follow-up, 38 patients (95%) were alive. Overall, 40 eyes (67.8%) were successfully preserved without the need for enucleation., Conclusions: The national epidemiological data gathered in this study indicates that the incidence of retinoblastoma in Jordan is similar to that reported in various countries of the world. Jordanian boys, however, are at significantly higher risk for developing retinoblastoma than age-matched girls. Furthermore, Jordanian patients are more likely to harbor bilateral retinoblastoma.

Objective: Carboplatin is a common chemotherapy agent with potential ototoxic side effects that is used to treat a variety of pediatric cancers, including retinoblastoma. Retinoblastoma is a malignant tumor of the retina that is usually diagnosed in young children. Distortion-product otoacoustic emission tests offer an effective method of monitoring for ototoxicity in young children. This study was designed to compare measurements of distortion-product otoacoustic emissions obtained before and after several courses of carboplatin chemotherapy in order to examine if (a) mean distortion-product otoacoustic emission levels were significantly different; and (b) if criterion reductions in distortion-product otoacoustic emission levels were observed in individual children., Methods: A prospective repeated measures study. Ten children with a median age of 7.6 months (range, 3-72 months) diagnosed with unilateral or bilateral retinoblastoma were examined. Distortion-product otoacoustic emissions were acquired from both ears of the children with 65/55 dB SPL primary tones (f(2)=793-7996 Hz) and a frequency resolution of 3 points/octave. Distortion-product otoacoustic emission levels in dB SPL were measured before chemotherapy treatment (baseline measurement) and after 3-4 courses of chemotherapy (interim measurement). Comparisons were made between baseline and interim distortion-product otoacoustic emission levels (collapsed across ears). Evidence of ototoxicity was based on criterion reductions (≥ 6 dB) in distortion-product otoacoustic emission levels., Results: Significant differences between baseline and interim mean distortion-product otoacoustic emission levels were only observed at f(2) = 7996 Hz. Four children exhibited criterion reductions in distortion-product otoacoustic emission levels., Conclusions: Mean distortion-product otoacoustic emission levels at most frequencies were not changed following 3-4 courses of carboplatin chemotherapy in children with retinoblastoma. However, on an individual basis, children receiving higher doses of carboplatin exhibited criterion reductions in distortion-product otoacoustic emission level at several frequencies. These findings suggest that higher doses of carboplatin affect outer hair cell function, and distortion-product otoacoustic emission tests can provide useful information when monitoring children at risk of developing carboplatin ototoxicity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Trilateral retinoblastoma is characterized by the presence of retinoblastoma with an intracranial tumor. The incidence is low and prognosis poor. Due to the paucity of information regarding successful treatment, we report the case of a 6 month old female referred for leukocoria and found to have an associated suprasellar tumor and pineal enhancement. The patient, treated with standard infant brain tumor therapy, remains alive without signs of active disease 35 months after diagnosis; no surgery or irradiation was used. Early diagnosis of trilateral retinoblastoma may facilitate the use of less intensive therapeutic approaches and result in excellent outcomes in these patients., (2010 Wiley-Liss, Inc.)

Despite multiple advances in the management of retinoblastoma, enucleation remains an essential therapeutic modality. We studied patients who underwent enucleation at the King Hussein Cancer Center in Jordan. We retrospectively reviewed medical records of children with retinoblastoma who were treated at our center from June 2002 to February 2008. Twenty-eight eyes from 27 patients were enucleated. Median age at diagnosis was 1.1 years (range, 0.3-6.3 years). Twenty-six eyes (93%) had advanced disease (RE groups IV and V). Seventeen patients (61%) had unilateral retinoblastoma, and 11 (39%) had bilateral retinoblastoma. The median time from diagnosis to enucleation was 0.45 months (range, 0-45 months; mean, 4.4 months) and was longer for patients with bilateral retinoblastoma (median, 2.2 vs. 0.2 months; P = 0.034). Twenty enucleated eyes (71%) did not show high-risk pathologic features. Seventeen eyes with advanced intraocular disease were enucleated at the time of presentation, whereas chemoreduction was attempted for the other 19 eyes with advanced intraocular disease. Enucleation was then recommended for nine (47%) of those eyes. Enucleation at the time of diagnosis was feasible for most patients with advanced disease. Attempted salvage of eyes with advanced disease is justified, particularly in patients with bilateral disease. We were able to salvage almost half of these eyes. We hope our study provides new insights for counseling patients.

Background: Carboplatin is the most effective drug in retinoblastoma but systemic clearance is variable in young patients. While most regimens use a flat dose, individualized targeting may provide a more adjusted systemic exposure., Patients and Methods: We compared carboplatin doses between two groups of children with retinoblastoma that were treated using a flat dose of 560 mg/m(2) or a targeted AUC of 6.5 using a modified Calvert formula., Results: Ninety-eight patients with retinoblastoma received a total of 576 cycles of carboplatin (median 8 cycles). Fifty patients (51%) received a fixed dose per m(2), 32 (33%) received a dose based on AUC, 1 patient received fixed dose per kilogram, and in 15 patients a combination AUC and fixed doses was used. The median cumulative carboplatin dose (mg/m(2)) for patients who received eight cycles using fixed per m(2) dosing was 2151.8 (range, 1414.2-2852.0), compared to 1104.1 for nine patients who received eight cycles using Calvert dosing (range, 779.0-1992.7) (P < 0.001). For cycles given using AUC, the median percentage of the hypothetical fixed per m(2) dose was 70% (range, 48-134%). Younger patients had larger differences. Patients receiving carboplatin based on fixed per m(2) dosing were 3.0 times more likely to have a platelet transfusion (95% confidence interval, 1.3-7.3)., Conclusions: Carboplatin administration needs to consider the changes in renal function occurring during the first months of life. The use of a targeted AUC provides the most accurate method; however, mg per kg of body weight dosing is a very reliable alternative method.

Access to quality cancer care is often unavailable in low-income and middle-income countries, and also in rural or remote areas of high-income countries. Teleoncology-oncology applications of medical telecommunications, including pathology, radiology, and other related disciplines-has the potential to enhance access to and quality of clinical cancer care, and to improve education and training. Implementation of teleoncology in the developing world requires an approach tailored to priorities, resources, and needs. Teleoncology can best achieve its proposed goals through consistent and long-term application. We review teleoncology initiatives that have the potential to decrease cancer-care inequality between resource-poor and resource-rich institutions and offer guidelines for the development of teleoncology programmes in low-income and middle-income countries., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Malignant rhabdoid tumors (MRTs) are aggressive and often fatal; the Surveillance, Epidemiology, and End Results (SEER) database offers an opportunity to study this rare malignancy., Methods: From the SEER database, we extracted records of patients with a reported diagnosis of MRT and analyzed them for clinical features and survival rates by univariate and multivariate analyses., Results: For the 229 patients included in our data, who were diagnosed from 1986 to 2005, primary tumors were located in the central nervous system (CNS) (35%), kidneys (20%), and extra-renal non-cranial sites (ERNC-MRTs) (45%). Most patients with renal and CNS tumors were less than 18 years old (87% and 96%, respectively) while more than half of the patients with ERNC-MRTs (61%) were adults. Among staged tumors, 23% were localized, 34% regional, and 43% distant. Renal tumors had significantly more metastatic disease (47%; P = 0.006) than ERNC-MRTs. The estimated 5-year survival for the entire group was 33 +/- 3.4% (SE). Univariate and multivariate analyses showed that age at diagnosis (2-18 years), localized stage of tumors, and use of radiotherapy were significantly associated with improved survival. Adults had a better outcome than young children (<2 years old) but a poorer outcome than older children (2-18 years old); tumor stage, but not radiotherapy use, affected outcome in adults. The survival and prognostic factors of children diagnosed before and after 2000 did not differ significantly., Conclusion: Our population-based study indicates that age at diagnosis, tumor stage, and use of radiotherapy favorably impact survival rates of patients with MRTs., (Copyright 2009 Wiley-Liss, Inc.)

There is a growing gap between developing and developed countries in the availability of treatment for pediatric subspecialties. Twinning and telemedicine are effective ways to improve the quality of healthcare in developing countries. We evaluated the impact of e-mail exchanges on the development of a neuro-oncology twinning program between the King Hussein Cancer Center (KHCC), Amman, Jordan, and the Hospital for Sick Children, Toronto, Canada. We conducted a retrospective review of all e-mail communications between KHCC and the Hospital for Sick Children from August 2003 to December 2005 for subject, attachments, and responses. Over a period of 29 months, 356 e-mail exchanges (average, 12.3/month) occurred. Subjects discussed were specific consults (88), videoconferencing (65), general neuro-oncological questions (54), personal (45), exchange visits related (44), research projects related (28), articles or treatment guidelines (21), and Web site translation (11). Our study suggests that e-mails promote effective communication between twinning partners and enable discussion of complex cases, organization of teleconferences and workshops, aid other research activities, and further personal relationships between partners. Use of e-mail in telemedicine can be especially useful to improve the quality of care for children with cancer in developing countries.

Background: Although screening for familial retinoblastoma has been shown to be beneficial we suspected that such screening programs may be less than optimal in developing countries (DC)., Methods: Retrospective cohort study comparing patients with familial retinoblastoma from five centers in DC (Argentina, Brazil, Turkey, Jordan, and Venezuela) versus a reference center in the USA., Results: Ninety-two (32 from the USA and 60 from DC) patients were included. Forty-one (44.6%) patients avoided enucleation, 42 (45.7%) had 1 eye removed, and 9 (9.8%) underwent bilateral enucleation. Eleven (11.9%) had major pathology risk factors at enucleation. There were no cases of metastatic disease at diagnosis. Detection via screening was significantly less common in DC than in the USA (23.3% vs. 71.8%, P < 0.0001). Patients in DC were diagnosed at a significantly later age and with more advanced intraocular disease that led to increased risk of bilateral enucleation. Patients detected by screening in DC were significantly younger at diagnosis, had less advanced intraocular disease, better ocular preservation rates and survival results than those whose retinoblastoma was not detected via early screening. Five-year pEFS was 0.92 for the patients treated in the USA and 0.81 for the patients in DC (P = 0.42). Seven events occurred (extraocular relapse four in patients from DC and second malignancies in three)., Conclusions: Patients with familial retinoblastoma are less likely to be diagnosed by screening in DC and had higher morbidity and mortality caused by recurrent extraocular retinoblastoma., ((c) 2009 Wiley-Liss, Inc.)

Pineal gland tumors are rare and account for less than 1% of all primary brain tumor diagnoses. They are more commonly seen in pediatric patients than in adults. We analyzed the available SEER data on pineal gland tumors that were diagnosed during the period 1973-2005. The cohort was subdivided into groups on the basis of tumor histology: germ cell tumors, pineal parenchymal tumors, gliomas, and other pineal tumors. Analyses of incidence, survival, factors influencing survival, and treatment modalities are provided. Among the 633 patients with pineal tumors, male sex was predominant, i.e., sex ratio was 3:1 for the whole group and 11.8:1 for those with germ cell tumors. The 5-year overall survival (OS) for the cohort was 65% +/- 2.1%. Those with germ cell tumors experienced the best survival (OS = 78.9% +/- 2.3%), followed by those with gliomas (OS = 61% +/- 9.3%), and those with pineal parenchymal tumors (OS = 47.2% +/- 4.2%). Non-germ cell tumors, absence of radiotherapy from treatment regimen, and diagnosis before 1993 were the only factors associated with a negative impact on survival. The extent of surgical tumor resection did not affect survival in any histologic subgroup. We conclude that, although pineal tumors are histologically diverse, they share some similarities due to their unique location. An aggressive surgical approach should be considered with caution in this region. Further studies on different pineal tumors subtypes are needed.

For patients with diffuse pontine glioma, our institution offers local radiotherapy and supportive care only. The prognosis and do-not-resuscitate orders are discussed upfront with patients' parents. To investigate the effectiveness of this policy, we retrospectively reviewed records of patients with diffuse pontine glioma treated at the institution over a 49-month period. This study included 19 children (16 girls and 3 boys). The median age at diagnosis was 7 years. One patient remained alive at the end of the study, 2 were lost to follow-up, and 16 were confirmed dead. The median survival was 8.2 months. Do-not-resuscitate discussion was documented for 14 patients and successfully initiated for 11. None of those confirmed dead had been offered life support. Contrary to the common belief, our study showed that do not resuscitate should be addressed in Muslim patients with high-risk malignancies. We also found that diffuse pontine glioma warrants further study in developing countries.

Despite the important role of nurses in a pediatric oncology team, the marginalization of nursing is common, especially in developing countries. At the King Hussein Cancer Center (KHCC) in Jordan, the position of the clinical nurse coordinator (CNC) was created in the pediatric neuro-oncology and ocular oncology services to empower the role of nursing. Our advanced nursing practice is based on the domains of the Strong Model of Advanced Practice, which are direct patient care, support of systems, education, research and publications, and professional leadership. There is strong involvement of the CNC in clinical care, patient education, follow-up, and interdisciplinary collaboration, which has resulted in improved survival, reduced morbidity, and increased compliance of patients and also their successful reintegration into society. The coordination of twinning initiatives and telemedicine activities has helped ensure the quality of treatment and supported research initiatives in the services. Such a positive impact has led to a significant increase in the recruitment of CNCs at KHCC. We propose that the role of nursing be strengthened in developing countries to improve the level of care provided to patients and their families.

Pediatric low-grade gliomas are the most common tumors of the central nervous system in children, accounting for almost 50% of all childhood brain tumors. They are a heterogeneous group of tumors with different histologic subtypes. Most treatment studies address low-grade gliomas as a single entity, depriving us of histology-specific treatment outcomes. This is mostly due to a lack of understanding of tumor biology at the molecular level. Pediatric low-grade gliomas are not benign, and most incompletely resected tumors will progress and negatively affect quality of life. The advancements made in understanding sporadic pilocytic astrocytoma and neurofibromatosis 1-associated pilocytic astrocytoma in particular have paved the way for potential targeted therapy and biological stratification. Such progress in pilocytic astrocytoma needs to be consolidated and expanded to other histologic varieties of pediatric low-grade gliomas.

Background: The prognosis for children with M1 medulloblastoma (positive CSF cytology) has not been well-defined., Methods: We retrospectively reviewed the records of 285 newly diagnosed medulloblastoma patients treated between 1984 and 2006. Older children received post-operative craniospinal and tumor bed irradiation; radiotherapy for younger children depended on treatment era and physician/family preference., Results: 55 patients were <3 years old and 230 patients were >or= 3 years old at diagnosis. We detected significant (P < 0.0001) associations between M1 disease and EFS for the entire cohort and for both younger and older patients. Among younger children, M1 patients had lower EFS than M0 (P = 0.0044)., Conclusions: Children <3 years old with M1 medulloblastoma fared poorly in our small series. Survival for older children with M1 disease treated with higher-dose CSI was better than that of M2/M3 patients, but still less than optimal; our findings do not support reduction in therapy for either cohort.

Retinoblastoma is curable when diagnosed early and treated appropriately; however, the prognosis is dismal when the basic elements of diagnosis and treatment are lacking. In developing countries, poor education, lower socioeconomic conditions, and inefficient health care systems result in delayed diagnosis and suboptimal care. Furthermore, the complexity of multidisciplinary care required is seldom possible. Whereas ocular salvage is a priority in the Western world, death from retinoblastoma is still a major problem in developing countries. To bring the 2 ends of this spectrum together and provide a forum for discussion, the "One World, One Vision" symposium was organized, at which clinicians and researchers from various cultural, geographic, and socioeconomic backgrounds converged to discuss their experiences. Strategies for early diagnosis in developing countries were discussed. Elements of the development of retinoblastoma centers in developing countries were discussed, and examples of successful programs were highlighted. An important component in this process is twinning between centers in developing countries and mentor institutions in high-income countries. Global initiatives by nongovernmental organizations such as the International Network for Cancer Treatment and Research, Orbis International, and the International Agency for Prevention of Blindness were presented. Treatment of retinoblastoma in developing countries remains a challenge; however, it is possible to coordinate efforts at multiple levels, including public administrations and nonprofit organizations, to improve the diagnosis and treatment of retinoblastoma and to improve the outcome for these children.

Central nervous system tumors are the most common pediatric solid tumors and a leading cause of cancer-related mortality and morbidity in this age group. Survival rates have improved significantly over the last decades for most of the tumor types, as a consequence of improvements in neuroimaging, neurosurgery and neuroanesthesia, radiation oncology, and medical oncology. The complexity of the management of these patients requires a multidisciplinary approach and has led to the emergence of a new subspecialty of pediatric neuro-oncologists who are dedicated to the management and follow-up of this population. This review highlights the most critical advances in the diagnostic and treatment modalities of pediatric brain tumors. A specific review of the most common tumor types discusses treatment options, controversies, and ongoing developments, with an emphasis on cooperative trials.

Background: This study evaluated the outcome of retinoblastoma patients, when employing a telemedicine-based twinning program in Jordan., Procedure: This cohort study included patients at the King Hussein Cancer Centre (KHCC; Amman, Jordan) who received consultations for retinoblastoma from March 2003 to September 2006. A collaborative program was established with the International Outreach Program at St. Jude Children's Research Hospital in Memphis, Tennessee. Cases were discussed using an Internet consultation service where fundus images, clinical history, and proposed treatment were reviewed. Selected cases were further discussed via videoconferencing and electronic mail., Results: Thirty-three children with retinoblastoma (20 bilateral) were treated at KHCC. The median age at diagnosis was 7 months for patients with bilateral retinoblastoma and 35 months for patients with unilateral retinoblastoma. Of the 20 patients with bilateral disease, 12 were newly diagnosed and 8 had received prior treatment. Our success in the bilateral cases was most evident in the previously untreated group, in which only six eyes (25%) were enucleated and four eyes (17%) were irradiated. Of the 13 patients with unilateral retinoblastoma, 12 underwent enucleation, and 6 required radiation. Neither group experienced mortality., Conclusions: Twinning has positively impacted survival and ocular salvage in Jordan. By partnering a team of professionals with mentors willing to provide close supervision, the highly specialized management of retinoblastoma can be successfully implemented in a developing country.

Successful twinning initiatives have been reported in childhood leukemia. Pediatric neuro-oncology requires a complex multidisciplinary approach and the feasibility of similar twinning programs is unknown. Twinning between King Hussein Cancer Center in Amman and the Hospital for Sick Children in Toronto started with e-mail communications, and subsequently included monthly videoconferences and exchanges between institutions. The outcome of 35 newly diagnosed medulloblastoma patients (22 high-risk and 13 average-risk) treated during this period is reported. The 3-year overall survival for average risk and high-risk patients was 100 and 81%, respectively. This experience suggests that twinning may facilitate the implementation of multidisciplinary neuro-oncology programs in low-income countries. Videoconferencing allows interactive exchanges with a significant learning impact., ((c) 2007 Wiley-Liss, Inc.)

Following from the publication of the International Retinoblastoma Staging System, an open internet discussion group was created at the www.cure4kids.org resource. The results of a survey distributed among participants are discussed. Although most patients with retinoblastoma were treated under prospective protocols, there was a wide variation in the definition of risk criteria and in the criteria for giving adjuvant chemotherapy following enucleation. Definition of high-risk histological features and the criteria for use of adjuvant therapy will be standardized in future studies. Internet meetings are a valuable mechanism for enabling participation from under-resourced countries in the development of cooperative studies., ((c) 2007 Wiley-Liss, Inc.)

Background: Telemedicine is widely used in industrialized countries for educational purposes. Twinning experiences using telemedicine between institutions in industrialized and developing countries (DC) have been limited. Pediatric neuro-oncology is a complex multidisciplinary discipline that is underserved in most of DC and provides a model to test the feasibility of such tool for twinning purposes., Methods: A computer, an EMLO visual presenter HV-7600SX document camera, and a TANDBERG 6000 model videoconference unit were used to present data. For connectivity, we used a six-channel ISDN telephone line. Each channel is 64 megabytes/sec., Results: Between December 2004 and May 2006, 20 sessions of videoconference were held between King Hussein Cancer Center and the Hospital for Sick Children to discuss 72 cases of 64 patients with various brain tumors (5 patients were discussed twice and 1 patient four times). In 23 patients (36%), major changes from original plan were recommended on different aspects of the care. In 21 patients (91%), those recommendations were followed, with potentially significant positive impact on patients' care., Conclusions: Videoconferencing is a feasible and practical twinning tool in pediatric neuro-oncology with a potentially major impact on patient care., ((c) 2006 Wiley-Liss, Inc.)

Desmoplastic infantile ganglioglioma is a rare superficial supratentorial tumor that occurs within the first two years of life. Despite the worrisome radiological and histological appearance, the tumors are often curable following gross total resection. Tumors with similar characteristics are exceedingly rare in the noninfantile population. We present a six-year-old boy with seizures, weakness, and unsteady gait. Radiographic imaging confirmed a very large, solid and cystic mass in the right temporal-parietal region. Pathological examination demonstrated a tumor with severe desmoplasia identical to those reported as "desmoplastic infantile ganglioglioma." This case adds to the limited data available for desmoplastic gangliogliomas in the noninfantile population. It is not clear, yet likely, that the noninfantile form of this neoplasm is biologically similar to the infantile form. It is also unclear whether the desmoplastic noninfantile ganglioglioma has characteristics similar to classical ganglioglioma. This rare case highlights the remarkable versatility of glioneuronal tumors in children.

Background: Carboplatin-based regimens have demonstrated activity in unresectable low-grade glioma (LGG) in children. Despite an interesting toxicity profile, the use of these regimens has been limited by the development of carboplatin hypersensitivity reaction (HSR) in up to 30% of patients. Desensitization has been the recommended approach for HSR. However, no guidelines have existed to aid physicians when carboplatin desensitization techniques fail., Methods: A pilot study of monotherapy with weekly vinblastine for LGG in 9 children who developed carboplatin HSR on a carboplatin and vincristine regimen was performed., Results: Vinblastine toxicity was moderate and readily manageable. None of the 9 patients had disease progression on therapy. Magnetic resonance imaging evaluation of tumor size from diagnosis to the end of vinblastine treatment showed 1 complete response (CR), 1 partial response (PR), 5 objective effects (OE), and 2 stable diseases (SD)., Conclusions: This experience suggested that weekly vinblastine has a good efficacy to toxicity ratio in the treatment of LGG and can be a valuable option for children who develop severe HSR., (Copyright 2005 American Cancer Society.)