A comprehensive method for calculating total body irradiation.

PURPOSE: To provide means for calculating the dose received by various tissues of the patient, calculate lung shield, and verify received dose using a phantom as a tool for quality assurance for a planned Total Body Irradiation (TBI) procedure in radiotherapy. METHOD: Using Microsoft Visual Basic, MATLAB, and Python, a program for Total Body Irradiation Calculation in Radiotherapy (TBICR) is constructed. It uses patient translation and beam zone method for total body irradiation calculations to compute the proper dose received by the patient and determine the lung shield thickness. There are three main user-friendly interfaces in the application. The first one allows the user to upload the TBI topography and estimate the distances needed for TBI calculations. The second one enables the user to count the number of beam zones needed for each point and estimate the effective area (Aeff) for each level. The third interface estimates the velocity required to deliver the relative dose depending on patient separation, Monitor Units (MU), couch speed and travel distance. It allows the user to compute the required lung shield thickness, read any patient's CT DICOM file and acquire dose in any distinct location using machine learning model to predict the dose. RESULTS: The TBICR software has been successfully validated by reproducing all of the manual calculations in an exact and timely manner. TBICR generated more accurate results and confirmed the absorbed dose to patient through measurements on Anderson phantom. CONCLUSIONS: A computer program for the calculation of total body irradiation (TBI) is described in full. The dose received at each point on the patient, the calculation of lung shield and the determination of the velocity and time required for the couch movement are all made possible using the software. The ease of use, precision, data storage and printing are some important features of the present software.

Palliative and end-of-life symptoms management for children with diffuse intrinsic pontine glioma.

Background: This study aimed to investigate diffuse intrinsic pontine glioma-specific symptoms in the last 12 weeks before death and to describe current palliative care. Materials & methods: A retrospective study included 80 pediatric diffuse intrinsic pontine glioma patients diagnosed between January 2018 and December 2019. Results: The most frequently encountered symptoms were headache, gait disturbance, vomiting, dysphagia, sensory loss, seizures and constipation. Steroids were used in 96% of patients with a high success rate, as well as analgesics (67.5%), antiemetics (59%), neuropathic medication (42.5%) and anticonvulsants (37.5%). Re-irradiation improved symptoms in 50% of patients. Conclusion: Steroids were efficient in managing many symptoms, with tolerated side effects. The symptomatic treatment succeeded in relieving end-of-life symptoms. Re-irradiation should be considered a good palliative tool in addition to regular symptomatic treatment.

This study aimed to describe symptoms in 80 patients with aggressive brain tumors in the brain stem, as well as proper management of the symptoms at the end of life. The symptoms encountered were headache, imbalance during walking, vomiting and fits. They were managed successfully with steroids, painkillers, nausea and vomiting medications and anti-fit medication. Giving radiotherapy for a second time improved symptoms in 50% of patients, and steroids can be used efficiently to improve the misery of these patients. These data can help to put a strategy for managing these devastating symptoms in the end-of-life period.

Aggresomes predict poor outcomes and implicate proteostasis in the pathogenesis of pediatric choroid plexus tumors.

PURPOSE: Protein misfolding and aggregation result in proteotoxic stress and underlie the pathogenesis of many diseases. To overcome proteotoxicity, cells compartmentalize misfolded and aggregated proteins in different inclusion bodies. The aggresome is a paranuclear inclusion body that functions as a storage compartment for misfolded proteins. Choroid plexus tumors (CPTs) are rare neoplasms comprised of three pathological subgroups. The underlying mechanisms of their pathogenesis remain unclear. This study aims to elucidate the prognostic role and the biological effects of aggresomes in pediatric CPTs. METHODS: We examined the presence of aggresomes in 42 patient-derived tumor tissues by immunohistochemistry and we identified their impact on patients' outcomes. We then investigated the proteogenomics signature associated with aggresomes using whole-genome DNA methylation and proteomic analysis to define their role in the pathogenesis of pediatric CPTs. RESULTS: Aggresomes were detected in 64.2% of samples and were distributed among different pathological and molecular subgroups. The presence of aggresomes with different percentages was correlated with patients' outcomes. The ≥ 25% cutoff had the most significant impact on overall and event-free survival (p-value < 0.001) compared to the pathological and the molecular stratifications. CONCLUSIONS: These results support the role of aggresome as a novel prognostic molecular marker for pediatric CPTs that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients' outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control.

Management of pediatric craniopharyngioma: 10-year experience from high-flow center.

PURPOSE: To report our experience and management strategies during 10 years for 137 childhood craniopharyngiomas treated at a single institution. METHODS: Medical records of children with craniopharyngioma treated at Children's Cancer Hospital Egypt (CCHE-57357) from July 2007 to December 2017 were retrospectively reviewed. Beta-catenin as an immunohistochemical marker was assessed also in available specimens. RESULTS: Our registry included 137 patients. Headache (n = 122), visual failure (n = 118), and hypothyroidism(n = 78) were the most common findings on presentation. Three management protocols were identified; 65 patients were primarily followed up after surgery, 71 patients had radiotherapy after surgery, and one patient underwent surgery for Ommaya insertion with intracystic interferon injection. Overall, gross total resection/near total resection was achieved in 48 cases (35.04%), subtotal resection was achieved in 58 patients (42.33%), 29 (21.16%) had biopsy and Ommaya reservoir, and two patients with calcified lesions had no operations. Fifty-four patients showed recurrence/progression of their lesions. Allover, 5-year progression-free survival (PFS) was 52.3%, while it was 34.49% and 72.25% for the follow-up group and the radiotherapy group, respectively. Beta-catenin mutations were positive in 61/95 patients; 5-year PFS for beta-catenin negative and positive cases was 65.5% and 39.4% respectively (p = 0.087). Mortality was reported in eight patients. Intraoperative endoscopy-assisted assessment was the cornerstone of tailored decision-making. CONCLUSION: The concepts of conservative surgery and multimodal management should be applied to reach the perfect balance between the quality of life and the best tumor control rates. Beta-catenin mutations more than 5% are associated with statistically trending aggressive clinical behavior. The CCHE-57357 algorithm of individualized management protocol was presented.

Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas.

Pediatric high-grade gliomas (HGG) are rare aggressive tumors that present a prognostic and therapeutic challenge. Diffuse midline glioma, H3K27M-mutant is a new entity introduced to HGG in the latest WHO classification. In this study we evaluated the presence of H3K27M mutation in 105 tumor samples histologically classified into low-grade gliomas (LGG) (n = 45), and HGG (n = 60). Samples were screened for the mutation in histone H3.3 and H3.1 variants to examine its prevalence, prognostic impact, and assess its potential clinical value in limited resource settings. H3K27M mutation was detected in 28 of 105 (26.7%) samples, and its distribution was significantly associated with midline locations (p-value < 0.0001) and HGG (p-value = 0.003). Overall and event- free survival (OS and EFS, respectively) of patients with mutant tumors did not differ significantly, neither according to histologic grade (OS p-value = 0.736, EFS p-value = 0.75) nor across anatomical sites (OS p-value = 0.068, EFS p-value = 0.153). Detection of H3K27M mutation in pediatric gliomas provides more precise risk stratification compared to traditional histopathological techniques. Hence, mutation detection should be pursued in all pediatric gliomas. Meanwhile, focusing on midline LGG can be an alternative in lower-middle-income countries to maximally optimize patients' treatment options.

Pediatric diffuse intrinsic pontine glioma: where do we stand?

Pediatric diffuse intrinsic pontine glioma (DIPG) represents approximately 20% of all pediatric CNS tumors. However, disease outcomes are dismal with a median survival of less than 1 year and a 2-year overall survival rate of less than 10%. Despite extensive efforts to improve survival outcomes, progress towards clinical improvement has been largely stagnant throughout the last 4 decades. Focal radiotherapy remains the standard of care with no promising single-agent alternatives and no evidence for improvement with the addition of a long list of systemic therapies. A better understanding of the biology of DIPG, though not easy due to obstacles in obtaining pathological material to study, is promising for the development of specific individualized treatment for this fatal disease. Recent studies have found epigenetic mutations to be successful predictors and prognostic factors for developing future management policies. The aim of this review is to give a global overview about the epidemiology, diagnosis, and treatment of DIPG. We further examine the controversial biopsy and autopsy issue that is unique to DIPG and assess the subsequent impact this issue has on the research efforts and clinical management of DIPG.

Outcome predictors of autologous hematopoietic stem cell transplantation in children with relapsed and refractory Hodgkin lymphoma: Single-center experience in a lower-middle-income country.

BACKGROUND: Children and adolescents with HL have excellent long-term survival exceeding 95% after combined modality treatment. However, about 20% will either relapse or have PRF. Salvage HDCT followed by AHSCT is considered to be the preferential treatment. OBJECTIVE: To describe the outcome (OS and EFS) and prognostic factors in pediatric patients with relapsed or refractory HL (r/rHL) who underwent AHSCT. METHODS: We retrospectively included 43 pediatric patients with r/rHL who underwent AHSCT from July 1, 2007, till December 31, 2016, at the Children's Cancer Hospital of Egypt. MAC regimen given was CMV. RESULTS: Of the whole cohort, 88.4% of patients achieved CR, while 11.6% had a positive PET scan prior to transplantation. The 3-year OS and EFS were 85% and 70.6%, respectively. The 3-year OS for patients > 10 years was 94% versus 65.5% for patients 10 years of age or younger (P = 0.046). There is strong tendency toward better 3-year OS for patients with negative PET scan as compared to those with positive PET scan before AHSCT, 89.4% vs 60%, respectively (P = 0.059). This tendency is also applicable when looking at the 3-year EFS for the two groups, 78.3% vs 40%, respectively (P = 0.069). CONCLUSION: Poor predictors of OS were younger age and positive PET scan before AHSCT. The latter, along with single modality treatment before AHSCT, were poor predictors of EFS.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt.

AIM: The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neuroblastoma patients treated at the Children Cancer Hospital - Egypt and their relation to various clinical and pathological factors. METHODS: The study included stage 3 patients <1.5 years, children 1.5 years or older with stage 3 disease and favorable histopathological features, infants (<1 year) with International Neuroblastoma Staging System (INSS) stage 4 disease, stage 4 children 1-1.5 years with favorable biology, and infants stage 4 s (with unfavorable biologic features). Patients received systemic chemotherapy, in the form of etoposide and carboplatin alternating with cyclophosphamide, doxorubicin and vincristine, administered at 3-week intervals, with a total of 6 or 8 cycles guided by reaching objective overall response (complete/very good partial/partial response). RESULTS: The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal masss and 7 with masses in the neck; 68% were stage 3 and the remaining (n = 44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94% ±â€¯2% and 90.9% ±â€¯2.5%, respectively. OS and EFS by gender, age, pathology and INPC were all statistically not significantly different. Moreover, OS for patients having surgery versus no surgery (inoperable residual only) was statistically significant (98.4% ±â€¯1.6% & 88.7% ±â€¯5.3%, respectively, p = .034). CONCLUSION: A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors.

A change roadmap towards research paradigm in low-resource countries: retinoblastoma model in Egypt.

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients' awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting.

Treatment and Outcome in 65 Children with Optic Pathway Gliomas.

INTRODUCTION: Optic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clinical course. There is significant controversy regarding the optimal management and outcome of these patients. METHODS: Charts of all patients with OPG diagnosed and treated at Children's Cancer Hospital Egypt between July 2007 and July 2014 were retrospectively reviewed. We evaluated the roles of surgical, ophthalmologic, endocrinologic, neurologic, and treatment aspects of care. RESULTS: Sixty-five patients were included in this study, with a mean age of 5.3 years. OPGs were chiasmatic (n = 25), optic nerve (n = 18), hypothalamic (n = 7), and chiasmatic/hypothalamic (n = 7). Extensive involvement of the optic pathway was seen in an additional 8 patients. Twenty cases had neurofibromatosis type 1. Four cases underwent surgical debulking, and 28 were biopsied (16 open, 11 stereotactic, and 1 endoscopic). Nine of the 18 optic nerve tumors were managed by total excision. Twenty-four patients did not undergo any surgical intervention. Forty-five patients received chemotherapy. Histopathology revealed pilocytic (n = 20), pilomyxoid (n = 15), fibrillary astrocytoma (n = 4), and grade I papillary-glioneuronal tumor (n = 1). Nonrepresentative sample (n = 1). The 4-year overall survival rate was 86.3% with mean follow-up period of 32.2 months. CONCLUSION: The initial role of surgery in newly developed OPG is biopsy for tissue diagnosis and relief of the hydrocephalus, if present, followed by chemotherapy. Chemotherapy decreases or stabilizes the tumor size in most cases, leading to preservation of both visual and endocrinal functions. The most significant prognostic factor confirmed in this study was the age of the patient.

Pediatric brain tumors in a low/middle income country: does it differ from that in developed world?

Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescents. The epidemiology of these tumors differs in areas of the world. However, very little data is available in the low/middle income countries (LMIC). The aim of this study is to describe the characteristics of primary childhood brain tumors treated at a leading LMIC pediatric cancer hospital and its difference from that in other countries. One thousand one hundred fourteen children and adolescent having CNS tumors were treated in the largest pediatric cancer hospital in the Middle East during a period of 5½ years. They were diagnosed histopathologically in 80.2 %, through medical imaging in 19.4 % and via both tumor markers and imaging in the remaining 0.4 % of cases. Through epidemiological analysis was performed using all available patients' data revealed that 96 % of the patients had primary brain tumors, while only 4 % the primary lesion was in the spinal cord. The most common histological type was astrocytic tumor (30.0 %, pilocytic (GI) = 13.2 %, GII = 10.5 % and GIII + IV (high grade) = 6.3 %) followed by embryonal tumor (23.2 %, medulloblastoma = 18.7 %, PNET = 2.8 %, ATRT = 1.5 % and ependymoblastoma = 0.2 %) then ependymoma in 8.7 %, craniopharyngeoma in 5.3 %. The mean age at diagnosis was 7.1 ± 4.2 years which did not differ significantly by gender nor residency but it differed by the pathological subtype. The frequency of each pathological type was different among different age groups. Though the present study was a hospital-based analysis in a low/middle income country, yet it did not differ from the well-established population-based study reports in the high income countries.

Corrigendum to "Outcome of Rhabdomyosarcoma in First Year of Life: Children's Cancer Hospital 57357 Egypt".

[This corrects the article DOI: 10.1155/2013/439213.].

Bilateral clear cell sarcoma of the kidney.

Clear cell sarcoma of the kidney (CCSK) accounts for 2-5% of all pediatric renal malignancies, and is known for its propensity to metastasize to bone and other sites. We are reporting two cases with bilateral CCSK that were diagnosed at our institution. One patient initially presented with bilateral renal masses, as well as pulmonary, hepatic and bone metastasis; while other present only with bilateral masses with no evident distant metastasis. Both patients received aggressive neo-adjuvant chemotherapy to decrease tumor size. One patient completed his designated treatment and initially showed complete remission (CR); eventually suffering from relapse. The other patient's tumor progressed during the course of chemotherapy. Both cases manifested brain dissemination at the time of relapse or progression. This emphasizes the importance of staging stratification in CCSK. This also illustrates CCSK's ability to metastasize to bone and other sites including the brain (a primary relapse site in our cases).

Intraspinal neuroblastoma: Treatment options and neurological outcome of spinal cord compression.

Malignant spinal cord compression (MSCC) is a common complication of cancer. Paraspinal neuroblastoma (NB) in the thoracic, abdominal and pelvic regions may extend into the neural foramina causing compression of nerve roots and even the spinal cord. The prompt initiation of specific treatment can improve the neurological outcome. The aim of the present study was to review the clinical features, the management received and the factors that may affect the outcome of patients with MSCC caused by paraspinal NB. During a period between July 2007 and December 2012, a total of 576 NB patients were treated at the Children's Cancer Hospital (Cairo, Egypt). Intraspinal disease extension was present in 51 patients (9%). The children with intraspinal disease extension were reviewed for disease pattern, neurological manifestations and treatment outcome. Children with intraspinal disease extension had an equal male to female ratio (1:1), and approximately two-thirds of patients (34/51) had a clinically manifested cord compression. The duration of neurological manifestations was >4 weeks in 58.8% (20/34) of symptomatic patients and ≤4 weeks in 41.2% (14/34). Subsequent to starting treatment, neurological manifestations showed a complete recovery in 16 patients (47.1%), partial in 11 (32.4%), and stationary course was found in 7 (20.6%). Manifestations of ≤4 weeks in duration carried an improved outcome compared with longer time compression, with a complete recovery in 78.6%, versus 25% for patients with a longer symptom duration (P=0.008). The upfront treatment, patient age and site of the primary tumor did not significantly affect the neurological outcome. Spinal cord compression in NB can be effectively managed with upfront chemotherapy. Initial surgical decompression should be reserved for benign variants only, including ganglioneuroma. Neurological manifestations of <4 weeks duration upon presentation are usually reversible.

Clear cell sarcoma of the kidney: patients' characteristics and improved outcome in developing countries.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive tumor accounting for 5% of pediatric renal tumors with an incidence of 20 patients per year in the USA. It is bone metastasizing with poor prognosis. Our aim was to show characteristics of patients in relation to improved outcome in one of the developing countries. PROCEDURE: We included all patients diagnosed as CCSK in the period between July 2007 and March 2012 at Children's Cancer Hospital, Egypt. Patients' demographics, clinical presentation, pathology, and management were reviewed. Follow up was continued until April 2013. RESULTS: Twenty-five patients were identified in the defined time interval, accounting for 7% all renal tumors diagnosed at the hospital. Mean age was 36 months. Abdominal swelling and hematuria were the most common presentations. Stages I, II, III, IV, and V represented 9 (36%), 3 (12%), 8 (32%), 3 (12%), and 2 (8%), respectively. Twenty-four patients had radical nephrectomy either upfront or after neo-adjuvant chemotherapy. Surgery was followed by adjuvant chemotherapy. Abdominal radiotherapy was given for local stages II and III. Twenty-two patients reached complete remission, while one patient had stationary disease and two patients died due to progression and relapse. Overall survival was 88.5% and event-free survival was 87.8% at 45 months. CONCLUSION: Although previous studies indicate poor prognosis of CCSK, our experience shows that those patients can be treated using extensive chemotherapy combined with proper local control.

Outcome of Rhabdomyosarcoma in First Year of Life: Children's Cancer Hospital 57357 Egypt.

Background. Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. Fifty percent of RMS cases occur in the first 10 years of life and less commonly in infants younger than one-year old. These infants require adapted multimodality treatment approaches. Patients and Methods. We analyzed patients' characteristics, treatment modalities, and the outcome for RMS infants treated at Children's Cancer Hospital Egypt (CCHE) between July 2007 and December 2010 and compared them to patients above one year treated on the same protocol. Results. Out of the 126 RMS treated during this period, 18 were below the age of one year. The male: female ratio was 1.25 : 1. The median age at diagnosis was 0.7 ± 0.2 years. Most of the cases (27.8%) were presented in head and neck regions. The estimated 4-years failure-free survival and overall survival for infants were 49 ± 12% and 70 ± 12%, respectively. These failure-free survival rate and overall survival rate did not differ from those for older patients (P = 0.2). Conclusion. Infants with RMS are a unique group of RMS who needs special concerns in tailoring treatment in addition to concerns regarding toxicity and morbidity in infants.

Joint genitourinary cancer symposium between Egyptian and American centers.

A joint symposium between Mansoura and Cleveland Universities, and the University of California, San Francisco (CA, USA) was held by the Egyptian Cancer Society in Mansoura, Egypt. The Symposium extensively discussed two topics: prostate and bladder cancer. The experiences of American and Egyptian scientists were shared in a trial to increase understanding, improve management, increase treatment outcome and decrease morbidity. Comparisons between treatment policies, management techniques and survival end results in Egypt and the USA, as well as internationally, were performed in both bladder and prostate cancer in order to determine the best policies for their management.

GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt.

BACKGROUND: Bladder cancer is the most common male malignancy in Egypt, consists predominantly of urothelial cell carcinoma (UCC) and squamous cell carcinoma (SCC), and disparities in incidence exist between men and women regardless of geographic region. Tobacco smoke exposure and Schistosoma haematobium (SH) infection and the presence of GSTM1, GSTT1, and GPX1 genotypes, as modulators of the carcinogenic effect of reactive oxidative species, were hypothesized to modify bladder cancer risk and possibly explain these gender differences. METHODS: We evaluated the association between bladder cancer risk and functional polymorphisms in the GSTM1, GSTT1, and GPX1 genes in 625 cases and 626 matched population-based controls in Egypt and assessed for potential interactions between these candidate genes and environmental exposures, such as smoking and SH infection. We analyzed the risk for developing UCC and SCC separately. RESULTS: None of these functional polymorphisms were significantly associated with bladder cancer risk. There were no significant interactions between genotypes and smoking or SH infection in this population, nor was any difference detected in genotypic risk between men and women. CONCLUSIONS: Our findings suggest that common genetic variations in GSTM1, GSTT1, and GPX1 are not associated with bladder cancer risk overall and that well-known environmental risk factors, such as smoking and SH infection, do not interact with these genes to modulate the risk. IMPACT: Our data indicate that common genetic variations in GSTM1, GSTT1, and GPX1 were not associated with bladder cancer risk.