Amal Refaat

Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): A randomized controlled trial

BACKGROUNDnThe pediatric diffuse intrinsic pontine glioma (DIPG) outcome remains dismal despite multiple therapeutic attempts.nnnPURPOSEnTo compare the results of treatment of pediatric diffuse intrinsic pontine glioma (DIPG) using hypofractionated versus conventional radiotherapy.nnnPATIENTS AND METHODSnSeventy-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).nnnRESULTSnThe 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.nnnCONCLUSIONSnHypofractionated 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.

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.

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 5½xa0years. They were diagnosed histopathologically in 80.2xa0%, through medical imaging in 19.4xa0% and via both tumor markers and imaging in the remaining 0.4xa0% of cases. Through epidemiological analysis was performed using all available patients’ data revealed that 96xa0% of the patients had primary brain tumors, while only 4xa0% the primary lesion was in the spinal cord. The most common histological type was astrocytic tumor (30.0xa0%, pilocytic (GI)xa0=xa013.2xa0%, GIIxa0=xa010.5xa0% and GIIIxa0+xa0IV (high grade)xa0=xa06.3xa0%) followed by embryonal tumor (23.2xa0%, medulloblastomaxa0=xa018.7xa0%, PNETxa0=xa02.8xa0%, ATRTxa0=xa01.5xa0% and ependymoblastomaxa0=xa00.2xa0%) then ependymoma in 8.7xa0%, craniopharyngeoma in 5.3xa0%. The mean age at diagnosis was 7.1xa0±xa04.2xa0years 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.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt

AIMnThe 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.nnnMETHODSnThe study included stage 3 patients <1.5u202fyears, children 1.5u202fyears or older with stage 3 disease and favorable histopathological features, infants (<1u202fyear) with International Neuroblastoma Staging System (INSS) stage 4 disease, stage 4 children 1-1.5u202fyears with favorable biology, and infants stage 4u202fs (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).nnnRESULTSnThe 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 (nu202f=u202f44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94%u202f±u202f2% and 90.9%u202f±u202f2.5%, 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%u202f±u202f1.6% & 88.7%u202f±u202f5.3%, respectively, pu202f=u202f.034).nnnCONCLUSIONnA 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.

Role of surgery in localized initially unresectable neuroblastoma

PURPOSEnEvaluating the role of surgery and the extent of tumor resection on the outcome of patients with localized initially unresectable neuroblastoma (NB).nnnPATIENTS AND METHODSnThis was a retrospective case review study including patients with localized initially unresectable NB. The primary tumor was considered unresectable according to imaging defined risk factors (IDRFs). Surgical resection was attempted after four to six courses of chemotherapy. The extent of resection was classified as follows: ≥90% resection, incomplete resection (50-90%) and cases with <50% resection or just a biopsy. Survival analysis was performed using an intention-to-treat approach.nnnRESULTSnA total of 202 patients with NB were included. Surgical resection was done in 106 patients. It was ≥90% in 89 patients (83.9%). Surgical resection was not performed in 96 patients (47.5%). Fifty-five (57.2%) were in good response after primary chemotherapy and 41 patients (42.7%) had persisting IDRFs, nine of them had biopsy only, and a follow-up strategy was considered in the other 32 patients. The overall 5-year event-free survival (EFS) and overall survival (OS) were 89.1xa0±xa02.4% and 94.9xa0±xa01.7%, respectively, with significantly better OS and EFS for patients who had resection versus no resection (pxa0=xa00.003 and 0.04, respectively). There was no impact of extent of resection on EFS and OS in the whole group (pxa0=xa00.91, pxa0=xa00.9) and in subgroup analysis stratified by site, histology, and age of the patients.nnnCONCLUSIONnIn children with localized initially unresectable NB, surgical resection was the only significant risk factor associated with better survival. The extent of tumor resection had no impact on EFS and OS. The concept of accepting incomplete resection to avoid serious complications was successful.

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 patients 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 CCSKs ability to metastasize to bone and other sites including the brain (a primary relapse site in our cases).

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

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.

Histopathology and prognosos of clear cell sarcoma of the kidney

Background: Clear cell sarcoma of the kidney (CCSK) is an uncommon renal neoplasm of childhood. CCSK has a wide histologic spectrum that mimics other pediatric renal neoplasms with considerable diagnostic difficulty. Our aim is to show various histopathologic CCSK patterns, pitfalls, diagnostic utilities and outcome in one of the developing countries. Methods: We included all patients diagnosed as CCSK in the period between July 2007 and May 2013 at Childrens Cancer Hospital, Egypt. Patient demographics, clinical presentation, pathology and management were reviewed. Follow up was continued until March 2013. Results: Thirty-two patients were found within that interval, accounting for 6.4% of all renal tumors. Median age was 28.5 months. Stages I, II, III, IV and V represented 11 (34.4%), 3 (9.4%), 13 (40.6%), 3 (9.4%) and 2 (6.3%), respectively. The majority of tumors showed classic pattern either solely or focally. Other patterns were myxoid, spindle, cellular, epithelioid, haemangiopericytomatous, palisading and anaplastic. Wide immunohistochemical panels were done including vimentin, INI-1, WT1, CK, CD99, Synaptophysin, Desmin, LCA, CD34, P53 and EGFR. Fluorescence in situ hybridization (FISH) for EWS break apart translocation was done for 5 cases (suspected PNET) and synovial sarcoma breakapart translocation in 4 cases. Overall survival and event-free survival was 93% (95% CI 92.06–93.94%) for 16 months. Conclusion: CCSK has many histologic patterns that highlight the diagnostic pathologic dilemma. In addition, our institution showed increased survival of CCSK.