Mohamed Zaghloul

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% ± 2% and 90.9% ± 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% ± 1.6% & 88.7% ± 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.

Importance: Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can decrease locoregional failure but has not been studied in the chemotherapy era.

Objective: To investigate if adjuvant sequential RT plus chemotherapy can improve locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy alone.

Design, Setting, and Participants: A randomized phase 3 trial was opened to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but a third arm was added later as a randomized phase 2 trial to compare chemotherapy plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat phase 2 trial reported herein enrolled patients from December 2002 to July 2008. Data were analyzed from August 3, 2015, to January 6, 2016. Routine follow-up and surveillance pelvic computed tomographic (CT) scans every 6 months during the first 2 years were performed. The setting was an academic center. Patients with bladder cancer 70 years or younger having 1 or more risk factors (≥pT3b, grade 3, or positive nodes) with negative margins after radical cystectomy plus pelvic lymph node dissection were eligible. Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, no evidence of distant metastases on CT scan of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and hematologic function. Ninety-one percent (109 of 120) had ≥ pT3 disease.

Interventions: Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day 2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of gemcitabine and cisplatin.

Main Outcome and Measure: Locoregional recurrence-free survival.

Results: The chemotherapy plus RT arm accrued 75 patients, and the chemotherapy-alone arm accrued 45 patients, with a weighted randomization to speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and 46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced except for age (median, 52 vs 55 years; P = .04) and tumor size (mean, 4.9 vs 5.8 cm; P < .01), both favoring chemotherapy plus RT. Two-year outcomes and overall adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were 96% vs 69% (HR, 0.08; 95% CI, 0.02-0.39; P < .01) for LRFS, 68% vs 56% (HR, 0.53; 95% CI, 0.27-1.06; P = .07) for disease-free survival, and 71% vs 60% (HR, 0.61; 95% CI, 0.33-1.11; P = .11) for overall survival (OS). Five patients (7%) had RT-associated late grade 3 gastrointestinal tract adverse effects in the chemotherapy plus RT arm.

Conclusions and Relevance: Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC. The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials.

Trial Registration: clinicaltrials.gov Identifier: NCT01734798.

BACKGROUND: Ewing sarcoma of the scapula is uncommon. Restoration of shoulder function after total scapulectomy is challenging. Extracorporeal irradiation and reimplantation is a well-known method of biological reconstruction in orthopaedic oncology; yet very few reports in the literature describe its specific use in tumors of the scapula.

PATIENTS AND METHODS: Ten patients with the diagnosis of Ewing sarcoma of the scapula were surgically treated by total scapulectomy and extracorporeal irradiation and reimplantation of the scapula. The mean age at presentation was 10 years (3 to 15 y). Six patients were male individuals and 4 were female individuals. An extracorporeal single dose of 5000 cGy was applied to each graft. At reimplantation, internal fixation was used in the first 2 cases, whereas, in the following 8 patients, stabilization was carried out by resuturing of the glenohumeral and acromioclavicular joint capsules without internal fixation. An ipsilateral Latissimus Dorsi muscle flap was used in all patients to cover the irradiated scapula.

RESULTS: The mean follow-up duration was 29.2 months (13 to 50 m). At the latest follow-up, 8 patients were continuously disease free and 2 patients had systemic relapse. No patient had local recurrence. The mean musculoskeletal tumor society functional score was 87% (66.6% to 100%). Eight of the 10 patients (80%) could actively elevate the upper limb up to and beyond 90 degrees in both the forward and scapular planes. Complications included wound gaping in 2 patients (20%), dislocation of the acromioclavicular joint in 3 patients (30%), and partial resorption of the scapular graft in 5 patients (50%). No patient showed any progressive deterioration of his or her shoulder function throughout the follow-up period.

CONCLUSIONS: The irradiated scapular graft provides a stable biological fulcrum for the reattached muscles of the shoulder joint after total scapulectomy, thereby providing an adequate postoperative range of shoulder elevation. A longer follow-up study is needed to evaluate the progression and effect of graft resorption on the functional outcome.

LEVEL OF EVIDENCE: Level IV.

PURPOSE: Was to evaluate the outcome of multimodality treatment in resectable primary Ewing sarcoma/primitive neuroectodermal tumor ES/PNET of the ribs and role of thoracoscopy in facilitating resection of these tumors.

PATIENTS AND METHODS: This was a retrospective study including 22 patients with primary ES/PNET of the ribs surgically treated at Children's Cancer Hospital Egypt (CCHE) between January 2008 until the end of December 2014.

RESULTS: Median age was 8.5years (range 5months to 16years.). All patients received neoadjuvant chemotherapy. Thoracoscopic exploration was performed in 15 (68%) patients. Resection included 1,2,3 and 4 ribs in (7,4,8 and 3 patients) respectively, parts of the diaphragm (3 patients), wedge resection of the lung (10 patients) and pleural nodules (2 patients). Primary closure was feasible in 11 patients and rib transposition was done in one patient. Reconstruction by proline mesh covered by muscle flap was done in 10 patients. Margins were microscopically positive in 3 patients and close in 2 patients. Postoperative radiotherapy was given in 8 patients. With a median follow-up of 38.5months, the 3-year event -free survival (EFS) and overall survival(OS) rates were 31.6% and 55.6%, respectively.

CONCLUSION: Multimodality treatment is essential in the management of ES-PNET of the ribs. Neoadjuvant chemotherapy facilitates adequate resection. The role of thoracoscopy and the indications of postoperative radiotherapy need further evaluation.

Local-regional recurrence for patients with ≥pT3 disease after radical cystectomy is a significant problem. Chemotherapy has not been shown to reduce the risk of local-regional recurrences in randomized prospective trials, and salvage therapies for local-regional failure are rarely successful. There is promising evidence, particularly from a recent Egyptian NCI trial, that radiation therapy plus chemotherapy can significantly reduce local recurrences compared to chemotherapy alone, and that this improvement in local-regional control may translate to meaningful improvements in disease-free and overall survival with acceptable toxicity. In light of the high rates of local failure following cystectomy for locally advanced disease and the progress that has been made in identifying patients at high risk of failure and the patterns of failure in the pelvis, the NCCN guidelines were revised in 2016 to include post-operative radiotherapy as an option to consider for patients with ≥pT3 disease. Despite advances in our understanding of the problem of local-regional failure after cystectomy and the potential role of adjuvant radiotherapy, the question of whether adjuvant radiotherapy should have a defined role for patients with locally advanced urothelial carcinoma has not yet been determined. The results of the NRG, European, Indian, and Egyptian trials on adjuvant radiotherapy are eagerly awaited. While none of these trials on their own may provide definitive conclusions, their aggregate outcomes will help clarify whether this treatment should have a role in the management of patients with locally advanced bladder cancer.

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.

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.

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.

We present a distributed fiber optic sensing scheme to image 3D strain fields inside concrete blocks during laboratory-scale hydraulic fracturing. Strain fields were measured by optical fibers embedded during casting of the concrete blocks. The axial strain profile along the optical fiber was interrogated by the in-fiber Rayleigh backscattering with 1-cm spatial resolution using optical frequency domain reflectometry (OFDR). The 3D strain fields inside the cubes under various driving pressures and pumping schedules were measured and used to characterize the location, shape, and growth rate of the hydraulic fractures. The fiber optic sensor detection method presented in this paper provides scientists and engineers an unique laboratory tool to understand the hydraulic fracturing processes via internal, 3D strain measurements with the potential to ascertain mechanisms related to crack growth and its associated damage of the surrounding material as well as poromechanically-coupled mechanisms driven by fluid diffusion from the crack into the permeable matrix of concrete specimens.

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).

BACKGROUND: The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma.

AIM: Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome.

PATIENTS AND METHODS: Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children's Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010.

RESULTS: Anaplasia was diagnosed in 18 patients (17.1%), focal in 10 (9.5%) and diffuse in 8 (7.6%). The distribution of anaplasia was found to be more common in older patients having age⩾10 years. Also it was more likely to occur in the high risk group and in tumors with unfavorable histology (alveolar subtype), and stage IV. The 3-year failure free survival rates for patients with and without anaplasia were 27.8±10.6% and 53.4±5.8%, respectively (p=0.014) and the 3-year overall survival rates were 35.3±11.6% and 61±6%, respectively (p=0.019).

CONCLUSIONS: The frequency of anaplasia in pediatric patients with rhabdomyosarcoma in our study was 17.1%. The presence of anaplasia had statistically significant worse clinical outcome.

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.

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

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.

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) (39Gy/13 fractions in 2.6weeks) and conventional (CF) arm (54Gy/30 fractions in 6weeks).

RESULTS: The median and one-year overall survival (OS) was 7.8months 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 6.6months 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.

Intensity-modulated radiotherapy is used for delivering more efficient homogenous dose to the target and lowering of dose to the surrounding normal tissues. However, a second malignant neoplasm may develop after prolonged latent period. The use of modern precise radiotherapy techniques in the pediatric age group has many controversial issues in spite of its proven dosimetric distribution advantages and the considerable decrease of normal tissue complication probability (NTCP). This concern is due to many factors; mainly the exposure of a larger volume of normal tissues to low dose radiotherapy. Children have more proliferating tissues compared to the adults. However, the epidemiological data did not detect an increase in the incidence of radiation-induced second malignancy. This issue is still controversial as IMRT and other precise radiotherapy techniques were not widely used except recently. This may entail a thorough careful follow up for children treated with these techniques to detect any incidence increase.

BACKGROUND: PM RMS represents a diagnostic and therapeutic problem as it is less visible than other superficial head and neck sites, and has tendency to local and intracranial extension.

OBJECTIVES: The aim of this work is to study the treatment outcome, overall survival (OS) and event free survival (EFS) of pediatric PM RMS patients diagnosed and treated at the Children Cancer Hospital-Egypt [CCHE-57357] during a 4 year period.

METHODS: Retrospective review of charts of newly diagnosed pediatric PM RMS patients diagnosed and treated in CCHE during the period between July 2007 and the end of June 2011.

RESULTS: Forty-two pediatric patients with PM RMS with age ranging from 3 months to 17.7 years (median 6.9 years) were studied. The follow up period ranged from 4 to 55 months with a median of 24.8 months. Twenty-one patients [50%] were stage III, while 11 patients [26.1%] were stage IV. The 3-year overall survival (OS) was 58.4 ± 8.9%. OS was 65.9 ± 10% for non metastatic tumors while it was 35.8 ± 16.2% for the metastatic ones (p=0.039). The 3-year event-free survival (EFS) was 48 ± 8.6% for the whole group. The non-metastatic and metastatic patients had 3-year EFS of 56.5 ± 9.7% and 24.9 ± 14.9% respectively. This difference was not statistically significant (p=0.127).

CONCLUSION: PM RMS remains a diagnostic and therapeutic problem. Late presentation and advanced local disease compromise treatment options and decrease OS and EFS.

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.

OBJECTIVES: To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men.

MATERIALS AND METHODS: We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively.

RESULTS: The study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer were lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women.

CONCLUSIONS: These findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt.

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 (D₉₅), 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.

Through the years, schistosoma-associated bladder cancer was believed to be a unique entity of disease, different from urothelial cancer. As carcinogenesis is a highly complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation and regulation process, confirmation of their minute differences or similarities are extremely difficult. In bladder cancer, many of these carcinogenic cascades were not fully documented in spite of the efforts undertaken. The control of schistosomiasis and the subsequent decrease in the intensity of infestation showed feature changes approaching that of urothelial tumors. However, schistosoma-associated bladder cancer still presents in more advanced stages than schistosoma-non-associated urothelial cancer. Furthermore, many data were collected proving that, upon applying the same treatment protocol and management care, stage-by-stage comparison of the treatment end results were found to be similar in bladder cancer patients with the different etiologies.

Schistosoma-associated bladder cancer was believed, for several decades, to be a completely unique entity of disease, different from urothelial cancer. This was probably due to its distinct clinicopathologic and demographic features that varied from those of urothelial entity. The carcinogenesis is an extremely complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation regulation process. In bladder cancer, many of these carcinogenic cascades were not fully documented or somewhat conflicting. Inspite of the efforts performed, much is still needed to explore the presence or absence of the carcinogenic difference with a different etiology. The control of schistosomiasis in certain countries and the subsequent decrease in the intensity of infestation showed changing of features approaching that of urothelial tumors. However the schistosoma-associated bladder cancer presented in more advanced stages than schistosoma-non associated urothelial cancer. More recently, data are gathered that, upon applying the same treatment protocol and management care, stage by stage comparison of the treatment end-results were found to be similar in bladder cancer patients with a different etiology. All treatment options; including radical cystectomy with or without adjuvant or neoadjuvant chemo- or radiotherapy or trimodality bladder preserving treatment seem to lead to similar end-results regardless of etiologic factor(s) implicated in bladder cancer development.

The improvement in conformal radiotherapy techniques enables us to achieve steep dose gradients around the target which allows the delivery of higher doses to a tumor volume while maintaining the sparing of surrounding normal tissue. One of the reasons for this improvement was the implementation of intensity-modulated radio therapy (IMRT) by using linear accelerators fitted with multi-leaf collimator (MLC), Tomo therapy and Rapid arc. In this situation, verification of patient set-up and evaluation of internal organ motion just prior to radiation delivery become important. To this end, several volumetric image-guided techniques have been developed for patient localization, such as Siemens OPTIVUE/MVCB and MVision megavoltage cone beam CT (MV-CBCT) system. Quality assurance for MV-CBCT is important to insure that the performance of the Electronic portal image device (EPID) and MV-CBCT is suitable for the required treatment accuracy. In this work, the commissioning and clinical implementation of the OPTIVUE/MVCB system was presented. The geometry and gain calibration procedures for the system were described. The image quality characteristics of the OPTIVUE/MVCB system were measured and assessed qualitatively and quantitatively, including the image noise and uniformity, low-contrast resolution, and spatial resolution. The image reconstruction and registration software were evaluated. Dose at isocenter from CBCT and the EPID were evaluated using ionization chamber and thermo-luminescent dosimeters; then compared with that calculated by the treatment planning system (TPS- XiO 4.4). The results showed that there are no offsets greater than 1 mm in the flat panel alignment in the lateral and longitudinal direction over 18 months of the study. The image quality tests showed that the image noise and uniformity were within the acceptable range, and that a 2 cm large object with 1% electron density contrast can be detected with the OPTIVUE/MVCB system with 5 monitor units (MU) protocol. The registration software was accurate within 2 mm in the anterior-posterior, left-right, and superior-inferior directions. The additional dose to the patient from MV-CBCT study set with 5 MU at the isocenter of the treatment plan was 5 cGy. For Electronic portal image device (EPID) verification using two orthogonal images with 2 MU per image the additional dose to the patient was 3.8 cGy. These measured dose values were matched with that calculated by the TPS-XiO, where the calculated doses were 5.2 cGy and 3.9 cGy for MVCT and EPID respectively.

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.

PURPOSE: To evaluate set-up variation of pediatric patients undergoing 3D conformal radiotherapy (3DCRT) using electronic portal image device (EPID), in an effort to evaluate the adequacy of the planning target volume (PTV) margin employed for the 3DCRT treatment of pediatric patients.

MATERIALS AND METHODS: Set-up data was collected from 48 pediatric patients treated with 3DCRTfor head and neck (31 patients), abdomino-pelvic (9 patients) and chest (8 patients) sites during the period between September 2008 and February 2009. A total of 358 images obtained by EPID were analyzed. The mean (M) and standard deviation (SD) for systematic and random errors were calculated and the results were analyzed.

RESULTS: All images were studied in anterior and lateral portals. The systematic errors along longitudinal, lateral and vertical directions in all patients showed an M equal to 1.9, 1.6, and 1.6mm with SD of 1.8, 1.4, and 1.8mm, respectively; (head and neck cases: M equal to 1.5, 1.2, and 1.6mm with SD 1.4, 1.2, and 1.8mm; chest cases: M equal to 2.5, 1.8, and 0.8mm with SD 2.7, 1.7, and 1.2mm, abdomino-pelvic cases: M equal to 2.9, 2.8 and 2.3mm with SD 1.6, 1.2, and 2.3mm). Similarly, the random errors for all patients showed SD of 1.9, 1.6, and 1.8mm, respectively (head and neck cases: SD 1.7, 1.3, and 1.5mm; chest cases: SD 1.2, 1.9, and 2.5mm; abdomino-pelvic cases SD 2.5, 2, and 2.4mm, respectively). Using Van Herk's formula the suggested (PTV) margin around the clinical target volume (CTV) of 5.5mm appears to be adequate.

CONCLUSION: The ranges of set-up errors are site specific and depends on many factors.

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.

To date, radical cystectomy has continued to be the treatment of choice for muscle-invasive bladder cancer. It is associated with a 5-year disease-free survival rate ranging from 27-55%. This outcome is significantly worse when reporting upon locally advanced cases. The independent prognostic factors include: tumor stage, grade, pelvic nodal involvement and some other additional factors. Beside the higher reported incidence of distant metastasis, local recurrence either alone or combined with systemic relapse has been shown to be experienced by 23-50% of locally advanced patients - a rate that was much more frequent than previously believed. Nonrandomized trials of preoperative radiotherapy have suggested improved survival rates. However, only one out of the six randomized preoperative trials in the literature published in English has proved to be significant. On the other hand, the only randomized trial and most retrospective studies dealing with postoperative radiotherapy revealed a significant increase in disease-free survival. Late complications of post operative radiotherapy, contrary to former belief, were acceptable and generally depended upon the volume of the irradiated normal tissues and the radiotherapy techniques used. Most of these adjuvant or neoadjuvant reports were performed in the 1970s and 1980s using conventional radiation techniques. Modern radiotherapy, delivering higher doses to the tumor while saving a significant amount of the surrounding normal structure, has not been rigorously tested. However, these techniques have already succeeded in improving treatment end results in other pelvic tumors.

OBJECTIVE: To examine associations between reproductive history and urinary bladder cancer in Egyptian women.

METHODS: We used questionnaire data from an ongoing, multicenter case-control study in Egypt. Controls were matched on age and residence area. This analysis focused on female cases with confirmed urothelial (UC) and squamous cell (SCC) carcinoma of the bladder.

RESULTS: We recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at menopause (<45 y) and older age at first pregnancy (>18 y) were factors significantly associated with increased risk of bladder cancer, even after adjusting for schistosomiasis history and other covariates in the multivariable logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41, 2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple pregnancies or use of oral contraceptives were associated with decreased odds of having bladder cancer. Similar associations were observed with UC and SCC when analyzed separately; however, the magnitude of association with SCC was lower than with UC.

CONCLUSION: Our data suggest that early estrogen exposure, or the relative lack of it, plays a role in urinary bladder carcinoma development among Egyptian women.

With the advancement in endoscopic surgery, radiation treatment planning and execution, as well as the use of new chemotherapeutic regimens, bladder conservation has evolved into a competing alternative to radical cystectomy. Trimodality treatment has the great advantage of preserving a normally functioning urinary bladder. Despite the absence of direct randomized trials comparing both modalities, trimodality treatment comprising maximal transuretheral resection of bladder tumors followed by different regimens of combined radiochemotherapy achieved comparable results to radical cystectomy in many trials. Those who did not achieve complete remission after induction radiochemotherapy were salvaged by radical cystectomy. Improving the radiotherapeutic window is a challenging issue. In radiotherapy for bladder cancer, uncertainties include set-up errors, patient movement, internal organ movement and volume changes due to bladder filling (both inter- and intrafraction). The advancement in treatment verification procedures in modern radiotherapy and the use of fiducial markers reduces set-up errors, while adaptive radiotherapy could decrease the unnecessary irradiation of normal tissues by tracking bladder volume changes. In addition, new radiotherapeutic techniques, such as intensity-modulated radiotherapy and volume-modulated radiotherapy, permit dose escalation to the target without increasing the dose to the surrounding normal tissues.

BACKGROUND: Zoledronic acid treatment reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from breast, lung, and urologic cancers including prostate and renal cancer. The aim of this study was to evaluate the effect of zoledronic acid on SREs in patients with bone metastases from bladder cancer.

PATIENTS AND METHODS: Patients with bone metastases from bladder cancer who were receiving palliative radiotherapy were randomized to placebo or zoledronic acid (4 mg intravenous monthly) for 6 months.

RESULTS: The patients (n = 40) were evenly distributed between the two treatment groups, and the baseline demographics of the two groups were similar. The follow-up varied from 8 to 65 weeks (median 24 weeks). Compared with patients receiving placebo, those receiving zoledronic acid had a lower mean incidence of SREs (2.05 +/- 1.0 vs. 0.95 +/- 0.9, respectively), and a larger proportion did not experience an on-study SRE (2 vs. 8 patients, respectively). Zoledronic acid also prolonged the median time to first SRE compared with the placebo (16 vs. 8 weeks, respectively). Multiple event analysis of SREs revealed that zoledronic acid decreased the risk of SRE development by 59% (hazard ratio 0.413). Zoledronic acid also increased the 1-year survival rate compared with placebo (36.3 +/- 11.2 vs. 0%, respectively). Zoledronic acid was generally well tolerated in our patient population.

CONCLUSIONS: Zoledronic acid therapy decreased the incidence of SREs and improved the 1-year survival rate of patients with bone metastases from bladder cancer, potentially through its anticancer activity.

A wide gathering of scientists, clinicians, pharmacists and nurses specialized in pediatric oncology practice met to celebrate the second anniversary of Children's Cancer Hospital, Egypt (CCHE). The celebration was in the form of high-brow teaching lectures and reports presented by international experts in the fields of pediatric CNS tumors, solid tumors (neuroblastoma, nephroblastoma, soft tissue and bone tumors, lymphoma, leukemia and pediatric oncology nursing. The conference extends its activities to hospital management, clinical pharmacy and telemedicine. Furthermore, CCHE experts presented the efforts performed to establish a state-of-the-art pediatric oncology hospital equipped with all needed facilities to raise the standard of care to the highest levels.

OBJECTIVE: To evaluate temporal changes in histopathological types of bladder cancer and to assess associated changes in demographic, epidemiologic, and lifestyle risk factors.

METHODS: We abstracted data from all available medical records from the National Cancer Institute of Cairo University (NCI-Cairo). Six calendar years representing 5-year periods between 1980 and 2005 were evaluated. Information on demographics, schistosomal infection, clinical symptoms of bladder cancer, and tumor pathology was abstracted.

RESULTS: During this 26-year period, important changes in the frequency of histopathological types of bladder cancer occurred. We found a statistically significant association between time period of diagnosis and histopathological type. Patients diagnosed in 2005 had a sixfold higher odds associated with transitional cell carcinoma compared to those patients diagnosed in 1980 (odds ratio (OR) 6.00 (95% CI 4.00-8.97)).

CONCLUSIONS: These data strongly suggest that the histopathological profile of bladder cancer in Egypt has changed significantly over the past 26 years. Historically, squamous cell carcinoma was the predominant form of bladder cancer in Egypt; however transitional cell carcinoma has become the most frequent type. These results corroborate findings from a few small-scale hospital-based studies which conclude that the etiology of bladder cancer in Egypt has changed significantly over the past 26 years.