Papers by Mohamed Zaghloul
JCO Global Oncology, 2020
PURPOSE Adequate clinical services have yet to be established in the majority of African countrie... more PURPOSE Adequate clinical services have yet to be established in the majority of African countries, where childhood cancer survival rates vary from 8.1% to 30.3%. The aim of this review is to describe the landscape of pediatric oncology trials in Africa, identify challenges, and offer future opportunities for research collaborations. METHODS The study includes data from the International Pediatric Oncology Society (SIOP) global mapping survey, meta-research identifying trials in Africa in ClinicalTrials.gov, and a literature overview of publications on the subject of pediatric oncology clinical research supported by expert opinions on the current situation and challenges. RESULTS The SIOP global mapping survey received responses from 47 of 54 African countries, of which 23 have active clinical research programs. A preliminary search of ClinicalTrials.gov showed that only 105 (12.1%) of 868 African oncology studies included children and adolescents. Of these, 53 (50.5%) were interven...
PeerJ, 2019
The incidence of pediatric cancer is lower than that of adult cancer worldwide. However, the form... more The incidence of pediatric cancer is lower than that of adult cancer worldwide. However, the former has detrimental side effects on the health of individuals, even after the cancer is cured, due to the impact of treatment on development. Recently, correlations have been made between the gut microbiome and cancer in several studies but only on adult participants. There is always a complication of dealing with pediatric cancer treatment protocols because they usually include a combination of chemotherapy, radiotherapy, and intensive prophylactic antibiotics. In the current study, a pilot study was conducted to analyze ten fecal samples from three pediatric cancer patients, suffering from rhabdomyosarcoma near their pelvic region, and two healthy individuals. A correlation between microbial composition and response to treatment was reported, in which the responders had generally a lower microbial diversity compared to non-responders. In addition, nucleotide changes and deletions in the...
World Neurosurgery, 2016
Optic pathway gliomas (OPG) are rare neoplasms in children with an unpredictable clinical course.... more Optic pathway gliomas (OPG) are rare neoplasms in children with an unpredictable clinical course. There is significant controversy regarding the optimal management and outcome of these patients. Charts of all patients with OPG diagnosed and treated at Children's Cancer Hospital Egypt between August 2007 and December 2013 were retrospectively reviewed. Evaluation of the role of surgical, ophthalmological, endocrinological, neurological and treatment aspects of care were reviewed. 65 patients were included in this study, with a mean age of 5.3 years. OPG 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 NF1. Four cases underwent surgical debulking and 28 were biopsied (16 open, 11 stereotactic and one 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). Non representative sample (n=1). The 4 years overall survival rate was 86.3% with mean follow-up period of 32.2 months. 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 of the 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.
Ophthalmic Genetics, 2015
Pediatric Oncology Department, Pathology Department, Ophthalmology Unit, Research Department, and... more Pediatric Oncology Department, Pathology Department, Ophthalmology Unit, Research Department, and Radiation Therapy Department, Children’s Cancer Hospital Egypt, Cairo, Egypt, National Eye Research Institute, Giza, Egypt, Egyptian National Cancer Institute, Cairo, Egypt, School of Medicine, Cairo University, Cairo, Egypt, and Institute of Neural Processing, Ulm University, Ulm, Baden-Württemberg, Germany
Expert Review of Anticancer Therapy, 2010
1. Expert Rev Anticancer Ther. 2010 Oct;10(10):1527-8. The need to revisit adjuvant and neoadjuva... more 1. Expert Rev Anticancer Ther. 2010 Oct;10(10):1527-8. The need to revisit adjuvant and neoadjuvant radiotherapy in bladder cancer. Zaghloul MS. Comment on Expert Rev Anticancer Ther. 2010 Jun;10(6):895-901. PMID: 20942623 [PubMed - indexed for MEDLINE]. ...
Expert Review of Anticancer Therapy, 2010
With the advancement in endoscopic surgery, radiation treatment planning and execution, as well a... more 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.
Cancers
In part one of this two-part paper, we present eight principles that we believe must be considere... more In part one of this two-part paper, we present eight principles that we believe must be considered for more effective treatment of the currently incurable cancers. These are addressed by multidrug adjunctive cancer treatment (MDACT), which uses multiple repurposed non-oncology drugs, not primarily to kill malignant cells, but rather to reduce the malignant cells’ growth drives. Previous multidrug regimens have used MDACT principles, e.g., the CUSP9v3 glioblastoma treatment. MDACT is an amalgam of (1) the principle that to be effective in stopping a chain of events leading to an undesired outcome, one must break more than one link; (2) the principle of Palmer et al. of achieving fractional cancer cell killing via multiple drugs with independent mechanisms of action; (3) the principle of shaping versus decisive operations, both being required for successful cancer treatment; (4) an idea adapted from Chow et al., of using multiple cytotoxic medicines at low doses; (5) the idea behind C...
Re-evaluation of the value of adjunctive modern radiotherapy in muscle-invasive bladder cancer
Journal of the Egyptian National Cancer Institute, 2020
Background Urinary schistosomiasis and its severe complications, mainly bladder cancer, are scarc... more Background Urinary schistosomiasis and its severe complications, mainly bladder cancer, are scarce in non-endemic areas. The deficiency in knowledge and clinical experience of schistosomiasis may lead to inadequate management. Highlighting these topics may be of value, especially with the increased immigration from endemic low-/middle-income countries (LMIC) to non-endemic high-income countries (HIC). Schistosomiasis is a parasitic infection endemic in many low- and middle-income countries. It can affect various systems but is best known for its effect on the urinary system. Main Body PubMed, Scopus, Google Scholar, and the Cochrane Library databases were searched for urinary schistosomiasis and its related bladder cancer published from 1980 till 2020. Schistosoma haematobium (SH) infecting the urinary bladder was considered by the IARC as group 1 definitive biological carcinogenic agent. Several carcinogenic pathways have been postulated but the exact mechanism(s) are not defined y...
Cancer and Metastasis Reviews, 2019
Pediatric diffuse intrinsic pontine glioma (DIPG) represents approximately 20% of all pediatric C... more 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.
Child's Nervous System, 2019
Journal of pediatric orthopedics, 2018
Ewing sarcoma of the scapula is uncommon. Restoration of shoulder function after total scapulecto... more 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. 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 patient...
Journal of the Egyptian National Cancer Institute, 2018
The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neurob... more 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. 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). The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal...
JAMA surgery, Jan 29, 2017
Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cyste... more 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. To investigate if adjuvant sequential RT plus chemotherapy can improve locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy alone. 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 y...
Journal of the Egyptian National Cancer Institute, 2017
Was to evaluate the outcome of multimodality treatment in resectable primary Ewing sarcoma/ primi... more 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 8.5 years (range 5 months to 16 years.). 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 38.5 months, the 3year 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.
Bladder cancer (Amsterdam, Netherlands), Jan 27, 2017
Local-regional recurrence for patients with ≥pT3 disease after radical cystectomy is a significan... more 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 disea...
International journal of radiation oncology, biology, physics, 2016
To the Editor: Reddy et al (1) focused on local-regional failure (LF) in muscle-invasive bladder ... more To the Editor: Reddy et al (1) focused on local-regional failure (LF) in muscle-invasive bladder cancer after radical cystectomy. Although the predominant site of failure is systemic relapse, up to 20% of cystectomized patients develop LF, more commonly in those presenting with advanced stages, reaching up to 50% to 60% in pT3 and pT4 patients (2, 3). Local-regional recurrence was underreported for a long time, for several reasons, mainly lack of intensified local investigation, especially whenever distant metastasis was evident; many investigators ignore reporting LF completely if it occurs simultaneously with or after systemic failure (4). With the recent awareness of the importance of LF, many investigators tried to determine the independent prognostic factors affecting LF and found them not much different from those affecting progressionfree and overall survival in bladder cancer patients undergoing radical cystectomy. These factors were tumor stage, nodal involvement, extent and number of nodal dissection, residual tumors, and tumor grade (1, 2, 4). Other factors proved to have no role in determining LF, such as tumor cell type and addition of chemotherapy either as neoadjuvant or adjuvant treatment. Perioperative chemotherapy did not decrease LF in many retrospective studies. After the original trial showing the value of postoperative radiation therapy in decreasing the incidence of LF, the same group compared postoperative with preoperative radiation therapy. They reached the conclusion that radiation therapy plays the major role in preventing or decreasing LF in bladder cancer, regardless of the tumor cell type (2, 5). Recently a prospective, randomized trial was performed at the National Cancer Institute, Cairo University, Cairo, Egypt, and presented at the 2016 American Society for Clinical Oncology Genitourinary Cancers Symposium. The trial included 198 patients randomized after radical cystectomy into 3 arms: (1) adjuvant radiation therapy; (2) adjuvant chemoradiotherapy; and (3) adjuvant chemotherapy. In this study, the local control rate was significantly superior in the arms including adjuvant radiation therapy. The 3-year local relapse-free survival
Asia-Pacific Journal of Clinical Oncology, 2016
Background: Nasopharyngeal carcinoma is rare in children and adolescents; however, it has a bette... more Background: Nasopharyngeal carcinoma is rare in children and adolescents; however, it has a better prognosis than in adults. Nevertheless, its prognostic factors are not clearly documented. Patients and methods: A prospective single-arm study was performed in 32 nonmetastatic Stages II-IV nasopharyngeal carcinoma (NPC) patients, below age 18 years. The treatment regimen included three courses of neoadjuvant chemotherapy (cisplatin and fluorouracil) followed by concomitant chemoradiotherapy (simultaneous integrated boost-intensity modulated radiotherapy [SIB-IMRT] with three cycles of cisplatin). Results: All patients completed their prescribed treatment with tolerable acute side-effects. The 3-year overall (OS), event-free (EFS), local recurrence-free (LRFS), and distant metastasis-free (DMFS) survival rates were 83 ± 8, 77 ± 8, 92 ± 6 and 77 ± 9 percent, respectively. Although the median initial (pretreatment) gross tumor volume of the primary site (GTVp) increased with increasing stage, yet these differences did not rank to the level of significance. However, GTVp (with a cutoff value of 54.5 mL) was the only significant prognostic factor determining OS, EFS, LRFS and DMFS. On the other hand, age, gender, T stage, AJCC stage and footprint histopathological EBV did not have statistical significant impact on any survival rate. The late toxicity of this regimen was much lower than that reported with the conformal treatment. Conclusion: Neoadjuvant chemotherapy and concomitant chemo-radiotherapy using SIB-IMRT led to excellent outcome with reduced late toxicity in juvenile nasopharyngeal carcinoma. GTVp is the sole prognostic factor that showed statistical impact on survival rates when applying this regimen.
Pediatric Blood & Cancer, 2016
To the Editor: Hankinson et al.[1] recently published a brief report of great importance about hy... more To the Editor: Hankinson et al.[1] recently published a brief report of great importance about hypofractionated radiotherapy for children with diffuse intrinsic pontine glioma (DIPG). The issue of hypofractionated radiotherapy for pediatric DIPG has become a point of interest at many centers and study groups and is now considered standard of care in some centers.[2] Although the series of Hankinson et al.[1] is a retrospective study that included only seven patients, it represents the first report of using hypofractionated radiotherapy in the United States. This study added to the three reports coming from the Netherlands and France [3-5], while pilot studies, support the feasibility of this practice. An Egyptian randomized study (Clinical Trial gov. # NTC01635140) comprising 80 patients allocated to the following two arms: hypofractionated and conventional fractionation, demonstrated no difference in outcome.[6] Hankinson et al.[1] treated their patients with 25 Gy in five fractions of 5 Gy given in 5-11 days, which may be considered as extreme hypofractionation. They reported symptomatic radiation necrosis in 43% (3/7) of their patients, which was not reported in neither the European nor the Egyptian series. Furthermore, the median overall survival (OS) reported as 6.6 months was much lower than that reported with the previously published hypofractionated regimens; 9.0,[3] 8.6,[4] 7.8[6], and 7.6[5]. The progressionfree survival (PFS) was 3.6 months, much lower than the previously published reports: 6.3,[6] 5.7,[5] 5.0,[4] and 4.9 months [3]. The one-year OS was also lower (28%) than that reported by Zaghloul et al. (36.4%) and the 9-month PFS was 0% compared to one-year PFS of 22.5% in the later study. These lower results could be anticipated in view of the lower biological effective dose (BED) calculated according to the following equation: Conflict of interest: Nothing to declare.
Journal of Neuro-Oncology, 2015
Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescent... more 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 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.
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Papers by Mohamed Zaghloul