Variant histology of pediatric nodular lymphocyte-predominant Hodgkin lymphoma with IgD and CD30 expression.

BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), recently known as nodular lymphocyte-predominant B-cell lymphoma (NLPBL), accounts for 5%-10% of Hodgkin lymphoma (HL). Different morphologic patterns of NLPBL are identified and categorized as typical patterns (type A and B) and variant histologic patterns (types C, D, E, and F). PATIENTS AND METHOD: We investigated different morphologic patterns, CD30 and IgD expression in pediatric patients with NLPBL diagnosed at the Children's Cancer Hospital Egypt. RESULTS: Forty-six (53%) of the patients exhibited a typical histologic pattern, whereas the remaining (47%) exhibited variant histologic pattern. Variant histology is associated with unfavorable clinical characteristics, such as advanced stages, B-symptoms, and extranodal involvements, particularly bone marrow and bone infiltration, with p-values of .06, .05, and 0.01%, respectively. Additionally, 39% of patients with variant histology experienced disease progression or relapse, compared to only 15.2% of patients with typical patterns (p = .009). Types C and D are related to decreased event-free survival (EFS), as shown by a p-value of .05. The 5-year EFS for patients with variant histology was 94.4% for the rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone (RCHOP) versus 33.3% for the adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). IgD expression in lymphocyte-predominant (LP) cells was detected in 44 (50%) patients, while CD30 expression in LP cells was found in 39 (44%) patients. CONCLUSION: Variant histology of NLPBL was associated with advanced disease stages and a poor prognosis, while expression of IgD and CD30 in LP cells was not. The poor outcome of variant histology improved with the RCHOP regimen.

Cost-effectiveness of childhood cancer treatment in Egypt: Lessons to promote high-value care in a resource-limited setting based on real-world evidence.

Background: Childhood cancer in low-and middle-income countries is a global health priority, however, the perception that treatment is unaffordable has potentially led to scarce investment in resources, contributing to inferior survival. In this study, we analysed real-world data about the cost-effectiveness of treating 8886 children with cancer at a large resource-limited paediatric oncology setting in Egypt, between 2013 and 2017, stratified by cancer type, stage/risk, and disease status. Methods: Childhood cancer costs (USD 2019) were calculated from a health-system perspective, and 5-year overall survival was used to represent clinical effectiveness. We estimated cost-effectiveness as the cost per disability-adjusted life-year (cost/DALY) averted, adjusted for utility decrement for late-effect morbidity and mortality. Findings: For all cancers combined, cost/DALY averted was $1384 (0.5 × GDP/capita), which is very cost-effective according to WHO-CHOICE thresholds. Ratio of cost/DALY averted to GDP/capita varied by cancer type/sub-type and disease severity (range: 0.1-1.6), where it was lowest for Hodgkin lymphoma, and retinoblastoma, and highest for high-risk acute leukaemia, and high-risk neuroblastoma. Treatment was cost-effective (ratio <3 × GDP/capita) for all cancer types/subtypes and risk/stage groups, except for relapsed/refractory acute leukaemia, and relapsed/progressive patients with brain tumours, hepatoblastoma, Ewing sarcoma, and neuroblastoma. Treatment cost-effectiveness was affected by the high costs and inferior survival of advanced-stage/high-risk and relapsed/progressive cancers. Interpretation: Childhood cancer treatment is cost-effective in a resource-limited setting in Egypt, except for some relapsed/progressive cancer groups. We present evidence-based recommendations and lessons to promote high-value in care delivery, with implications on practice and policy. Funding: Egypt Cancer Network; NIHR School for Primary Care Research; ALSAC.

Temporal trends in childhood cancer survival in Egypt, 2007 to 2017: A large retrospective study of 14 808 children with cancer from the Children's Cancer Hospital Egypt.

Childhood cancer is a priority in Egypt due to large numbers of children with cancer, suboptimal care and insufficient resources. It is difficult to evaluate progress in survival because of paucity of data in National Cancer Registry. In this study, we studied survival rates and trends in survival of the largest available cohort of children with cancer (n = 15 779, aged 0-18 years) from Egypt between 2007 and 2017, treated at Children's Cancer Hospital Egypt-(CCHE), representing 40% to 50% of all childhood cancers across Egypt. We estimated 5-year overall survival (OS) for 14 808 eligible patients using Kaplan-Meier method, and determined survival trends using Cox regression by single year of diagnosis and by diagnosis periods. We compared age-standardized rates to international benchmarks in England and the United States, identified cancers with inferior survival and provided recommendations for improvement. Five-year OS was 72.1% (95% CI 71.3-72.9) for all cancers combined, and survival trends increased significantly by single year of diagnosis (P < .001) and by calendar periods from 69.6% to 74.2% (P < .0001) between 2007-2012 and 2013-2017. Survival trends improved significantly for leukemias, lymphomas, CNS tumors, neuroblastoma, hepatoblastoma and Ewing Sarcoma. Survival was significantly lower by 9% and 11.2% (P < .001) than England and the United States, respectively. Significantly inferior survival was observed for the majority of cancers. Although survival trends are improving for childhood cancers in Egypt/CCHE, survival is still inferior in high-income countries. We provide evidence-based recommendations to improve survival in Egypt by reflecting on current obstacles in care, with further implications on practice and policy.

Does Salvage Chemotherapy Regimen Intensity Embark on Clearance of Bone Marrow Neuroblastoma?

Introduction: Neuroblastoma (NBL) is the most common extracranial solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at "high risk" (HR) of treatment failure. This study aim was to evaluate the impact of salvage chemotherapy ICE (ifosfamide, carboplatin, and etoposide) versus TC (topotecan/cyclophosphamide) when administered to NBL HR patients having residual bone marrow disease after primary tumor control on the first line treatment regimen. Materials and Methods: The present retrospective study included two groups of eligible stage 4 NBL patients with persistent bone marrow disease. Group (1), 29 patients, received ICE whereas less intensive TC was administered to Group (2), 32 patients. Data analysis included epidemiological variables, pathology subtype, MYCN gene status, primary tumor response and their correlation with bone marrow disease clearance on each regimen. Results: A higher tendency of complete bone marrow clearance was reported in patients who received ICE compared to TC; 41.4% versus 25.0%, respectively. However, the difference was not statistically significant (p= 0.174). Conclusion: TC regimen appears to be a good alternative to ICE as salvage treatment in an attempt to clear NBL bone marrow residual, with the privilege of being less toxic and can be given on outpatient basis. Further randomized trials of larger study sample size with survival impact analysis are warranted.

Risk stratification and pattern of cardiotoxicity in pediatric Ewing sarcoma.

INTRODUCTION: Anthracycline chemotherapy contributes to improved outcomes in Ewing sarcoma; however, the most feared complication is cardiotoxicity. Echocardiograms were routinely used to monitor cardiac function after anthracycline treatment. Nevertheless, indices chosen to assess cardiac toxicity vary significantly among different centers, and no uniform protocol has been accepted as ideal. METHODS: This retrospective study included children with Ewing sarcoma treated at Children's Cancer Hospital Egypt over 4years. All echocardiograms and related clinical assessments were reviewed. RESULTS: In total, 149 patients (median age 11years; range 1-18years) were included. Although all patients had a reduced ejection fraction compared with their baseline echocardiogram, only 39 patients developed cardiotoxicity (26%): 43% acute-onset, 36% chronic early-onset, and 21% chronic late-onset. There were no statistically significant association between the frequency of myocardial dysfunction and risk factors, including age, sex, follow-up duration, cumulative doxorubicin dose, and mediastinal irradiation. Over one-third (39%) of the patients with cardiac toxicity regained normal cardiac parameters, whereas seven patients died of acute cardiac toxicity. CONCLUSION: The routine use of echocardiography to screen for anthracycline-induced cardiac toxicity before and during chemotherapy identified myocardial dysfunction. Early medical intervention can improve cardiac parameters. Improved screening techniques with better sensitivity and predictability are needed.

Role of FDG-PET scan in the management of pediatric mature B cell non-Hodgkin's lymphoma. CCHE experience.

AIM OF WORK: To evaluate the sensitivity (Se), specificity (Sp), and predictive values (PV) of PET scan during management of pediatric mature B cell non-Hodgkin's lymphoma (NHL) in comparison with conventional computed tomography (CT) scan. PATIENTS AND METHODS: A retrospective study enrolled on pediatric NHL patients at Children Cancer Hospital Egypt (CCHE) during the period from July 2007 to the end of June 2013. RESULTS: For 115 pediatric patients diagnosed with mature B cell NHL, 152 PET and 152 CT scans were done simultaneously. Median age was 5.7years. They were 85 males (74%) and 30 females (26%). One hundred twenty six scans (82.9%) were done for 100 (87%) Burkitt lymphoma (BL) patients, while 26 scans (17.1%) were done for 15 (13.0%) patients with diffuse large B cell NHL (DLBC). Nineteen examination (12.5%) were done before starting chemotherapy (group 1), 107 (70.3%) at time of evaluation (group 2), and 26 (17.1%) during follow up (group C). Overall sensitivity was 91.6% for PET and 70.0% for conventional CT (p=0.02). Specificity was 84.1% for PET and 58.9% for CT (p<0.001). Positive predictive value (PPV) for PET was 50%, while was 22% for CT scan (p<0.001). Negative predictive value (NPV) for PET was 98%, and 92% for CT (p=0.01). CONCLUSION: PET scan is significantly more sensitive than conventional CT in the management of aggressive pediatric mature B cell NHL. PET negativity is an excellent indicator of tumor response.

Comparison of toxicity following different conditioning regimens (busulfan/melphalan and carboplatin/etoposide/melphalan) for advanced stage neuroblastoma: Experience of two transplant centers.

The outcome for advanced neuroblastoma has improved with combined modality therapy: induction chemotherapy, surgery, and consolidation with high-dose chemotherapy/autologous HSCT, followed by local radiation, cisretinoic acid, and recently antibody therapy. In the United States, the most common conditioning regimen is CEM, while in Europe/Middle East, Bu/Mel has been widely used; it remains unclear which regimen has the best outcome. Assess renal, hepatic, and infectious toxicity through Day+100 in 2 different regimens. Retrospective comparison between CEM-DFCHCC Boston and Bu/Mel- CCHE-57357. Thirty-five patients, median age 4, in Boston (2007-2011) and 38 patients, median age 3, in Cairo (2009-2011). Renal toxicity; creatinine was significantly higher in CEM than Bu/Mel: 57% (median day+90) vs. 29% (median>day+100), p = 0.004. One CEM patient died from renal dialysis at day+19. Hepatic toxicity was significantly higher in CEM than Bu/Mel: 80% (median day+26) vs. 58% (median day+60), p = 0.04. In infectious complications with CEM 14%, bacteremia (n = 4) and fungemia (n = 1), 3 had culture-negative sepsis requiring vasopressors. With Bu/Mel 18%, bacteremia (n = 7), none required pressors, p = 0.4. Bu/Mel was associated with less acute hepatic and renal toxicity and thus may be preferable for preserving organ functions.

Langerhans Cell Histiocytosis (LCH) in Egyptian Children: Does Reactivation Affect the Outcome?

OBJECTIVE: To report a single centre outcome of management of Langerhans cell histiocytosis (LCH), a clonal disease with involvement of various body systems. METHODS: Retrospective analysis of 80 pediatric LCH patients at Children Cancer Hospital-Egypt between July 2007 and December 2011 was performed. Patients were stratified and treated according to LCH III protocol. The median follow up period was 42 mo (range: 1.18 to 71 mo). RESULTS: At wk 6 and 12, 'better' response was obtained in 61 (76 %) and 74 (93 %) patients respectively. Afterwards, reactivation occurred in 25 patients (38 %), of them multiple episodes occurred in 5 patients (6.25 %), managed by repetition of 1st line treatment for once or more. The 5 y overall survival (OS) and event free survival (EFS) was 96.3 and 55 % respectively. At last follow up, better status was reached in 70 patients, 3 in each 'intermediate' and 'worse' status. Three high risk patients died and one patient was lost to follow up. CONCLUSIONS: In a single Egyptian pediatric LCH experience, the response to treatment is satisfactory and survival remains the rule except in high risk organs disease that still needs a new molecule for salvage. However in multiple reactivations, patients do well with repetition of the 1st line of treatment with or without methotrexate.

Clinical presentation of intraocular retinoblastoma; 5-year hospital-based registry in Egypt.

PURPOSE: To study the presenting signs of Retinoblastoma in Egypt at Egypt's main pediatric oncology referral center. METHODS: This is a prospective descriptive study (hospital-based registry) conducted at Children's Cancer Hospital Egypt between July 2007 and December 2012. RESULTS: Out of 262 patients diagnosed with retinoblastoma, 244 were suffering from intra-ocular disease at presentation. One hundred thirty-nine (57%) patients presented with unilateral disease, while 105 (43%) suffered bilateral disease. The mean age at presentation was 20.6 ± 17 months, averaging 18.87 ± 11.76 months for bilateral and 25.72 ± 18.78 months for unilateral disease. The most common clinical presentation was leukocoria in 180 (73.8%) patients, strabismus in 32 (13.1%) patients and decreased visual acuity in 12 (4.9%) patients. Group D and E disease represented 62% of all affected eyes. Patients with advanced disease (Group C-E) had longer duration of symptoms. CONCLUSION: In Egypt, retinoblastoma patients present more frequently with advanced disease. There is an ever-increasing need to develop a national team dedicated to studying disease significance and formulating a national awareness program.

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.].

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.

Intracranial germ cell tumors: a single-institution experience.

BACKGROUND AND OBJECTIVES: Intracranial germ cell tumors (GCTs) are not a common disease. We reviewed the experience of a single institution to determine the variables that affect treatment outcome. DESIGN AND SETTING: A retrospective review of patients with the diagnosis of intracranial germ cell tumors treated in a single institution (KFSHRC) during the period from March 1985 to December 2007. PATIENTS AND METHODS: Fifty-seven patients with the diagnosis of intracranial GCT were recorded in the KFSHRC Tumor Registry during the period from 1985 to 2007. Seven patients with a pineal region tumor treated as germinomas in the earlier years without a tissue diagnosis were excluded. This retrospective study was restricted to the remaining 50 patients with a tissue or marker diagnosis: 31 germinomas and 19 non-germinomatous germ cell tumors (NGGCTs). RESULTS: The 10-year overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were 87%, 88% and 96% for patients with germinoma, with a median follow-up of 4.5 (range 2-17) years, compared with 26%, 29% and 46% for patients with NGGCT with a median follow-up of 3 (range 1.5-13) years. For NGGCT, variables favorably influencing OS were younger age (< 16 y vs ≥16 y, P=.01), higher radiation dose (>50 Gy vs ≤50 Gy; P=.03) and later year of diagnosis (>1990 vs <1990 P=.002). CONCLUSIONS: Tissue diagnosis of GCTs is mandatory prior to treatment except for patients with elevated markers. In germinoma, localized radiotherapy (RT) for M0 patients may be adequate. Long-term follow-up is needed to define the benefit of adding chemotherapy. For NGGCT, the use of combined modality treatment and RT dose ;gt;50 Gy are important factors that influence the outcome. Second-look surgery and resection of residual/ refractory tumors is always recommended.

Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage III/IV neuroblastoma?

BACKGROUND AND PURPOSE: Neuroblastoma is the most common extracranial and deadly solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at "high risk" of treatment failure. The aim of this study is to evaluate the response rate of salvage chemotherapy by the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary refractory or progressive high risk neuroblastoma patients. PATIENTS AND METHODS: Sixty-six patients from the National Cancer Institute (NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE) either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in 15/66 (22.8%). RESULTS: They were 40 males (60.6%) and 26 females (39.4%). Patients' age ranged between 3 months and 12.5 years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients (3%) died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in 29 patients (43.9%). Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients (78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy. By the end of the study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14 patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14 (85.8%) were in CCR. CONCLUSION: Chemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a good salvage therapy in the category of patients who are condemned for palliation.