Outcomes and survival rates of childhood osteosarcoma in Iran, A report from MAHAK Pediatric Cancer Treatment and Research Center, from 2007 to 2020.

Background: Osteosarcoma is one of the most common childhood bone malignancies. Although chemotherapy protocol including methotrexate is an effective treatment for osteosarcoma, some other regimens have excluded it because of its complications. Methods: This retrospective study was conducted on 93 children younger than 15 years old who were diagnosed with osteosarcomafrom March 2007 to January 2020. Two chemotherapy protocols were administrated for patients, namely, DCM protocol (Doxorubicin-Cisplatin-Methotrexate) and German protocol (excluding methotrexate). All statistical analysis was conducted using SPSS-25 software. Results: Among patients, 47.31% were male. Patients' age ranged from 3 to 15 with the mean of 10.41 ± 0.32 years. Femur was the most frequent primary tumor site (59.14%), followed by tibia (22.58%). Metastasis rate at diagnosis was 17.20% in our study. Furthermore, the 5-year overall survival (OS) of total patients was 37.3 ± 7.5%, whereas the 5-year OS of males and females was 33.6 ± 10.9% and 39.8 ± 10.6%, respectively. The 5-year OS of methotrexate regimen was 15.6 ± 9.6%, whereas that of methotrexate-free protocol was 50.2 ± 9.0%. Conclusions: Female patients had better survival rates than males. In addition, the chemotherapy protocol excluding methotrexate significantly increased the overall and event free survival of patients.

Pediatric Cancer Registry at MAHAK Pediatric Cancer Treatment and Research Center: A Single-Center Study from Iran.

Background: The childhood cancer registry in Iran is a hospital-based system and there is not any unique and national registry system for pediatric malignancies in Iran. According to the limitations and requirements, this study was designed to clarify the aspect of childhood malignancies in Iran and promote establishing the Iranian national childhood cancer registry system. Materials and Methods: This cross-sectional longitudinal study was implied on 1500 patients younger than 20-years old diagnosed with any malignancy and admitted at MAHAK Pediatric Cancer Treatment and Research Center (MPCTRC) from 2007 to 2014. Data collection was based on a validated questionnaire with three categories including demographic data, clinical data and type of malignancy, and outcomes. Collected data were analyzed using methods for qualitative and quantitative variables (P < 0.05) by SPSS software version 22. The survival rate was calculated by the Kaplan-Meyer method. Results: This study was implied on 1500 children with a mean age of 6.1 years old. The most common malignancy was acute leukemia (30.7%) followed by central nervous system tumors (27%). At the onset of starting treatment, the rate of conferring with relapse, metastasis, and secondary malignancies was 29%, 19.5%, and 1% respectively. In addition, 52 patients had bone marrow transplantation of whom, 14 cases died. Totally, 42% of patients died and the 3-years, 5-years, and 10-years overall survival rates were 67.7% ± 0.01, 60.3% ± 0.01, and 53.8% ± 0.01, respectively. Conclusion: Establishing a population-based pediatric cancer registry in Iran is necessary and will be useful for improving the survival rate of mentioned patients.

Treatment and outcomes of pediatric patients with cancer and COVID-19 at MAHAK pediatric cancer treatment and research center, Tehran, Iran.

The COVID-19 pandemic has been particularly devastating for Iran. Children with cancer are generally immunosuppressed and especially vulnerable to SARS-CoV-2 infections. We report the treatment and outcomes of pediatric oncology patients with COVID-19 at the MAHAK Pediatric Cancer Treatment and Research Center (MPCTRC) in Tehran. We enrolled pediatric oncology patients who experienced SARS-CoV-2 infections from March 18, 2020, to January 28, 2021. The COVID-19 diagnostic criteria at MPCTRC were based on imaging and clinical presentation because of specific challenges diagnosing SARS-CoV-2 infections with molecular testing, which was locally developed and conducted at centers other than MPCTRC. We enrolled nine outpatients and eight inpatients (mean age = 9 years), seven of whom had a diagnosis of leukemias, and five who had brain tumors. COVID-19 symptoms were mild in fourteen patients, and three patients were asymptomatic. Of twelve patients who received molecular testing for SARS-CoV-2 infection, eight were negative and four were positive. Of nine patients tested for IgG and IgM antibodies, one was positive. Three patients died of COVID-19, all of whom were hospitalized. Mild COVID-19 symptoms did not appear to affect the outcomes of the pediatric patients with cancer who received treatment at MPCTRC during the study period.

Retinoblastoma presentation, treatment and outcome in a large referral centre in Tehran: a 10-year retrospective analysis.

BACKGROUND/OBJECTIVES: Early diagnosis, care and treatment of retinoblastoma is a challengeable issue for Iranian health system. This study was designed and conducted in a referral multidisciplinary centre in the capital city of Iran to evaluate management, care, prognosis and survival rates of paediatric patients with retinoblastoma. METHODS: In this retrospective study, a total number of 309 patients younger than 15 years, diagnosed with retinoblastoma, who referred for diagnosis and treatment to MAHAK's Pediatric Cancer Treatment and Research Center (MPCTRC) from 2007 to 2017 were evaluated. All data were analyzed via SPSS version 22 software in regard of parametric and non-parametric data. Survival rates were analyzed using the Kaplan-Meyer method. RESULTS: The mean age of patients was 20 months and the majority of patients (77%) had leukocoria as a common clinical symptom at the time of diagnosis. Primary treatment methods were systemic chemotherapy (94%), laser (35%) and primary enucleation (28%). Relapses occurred in nearly 42% of cases, and the median time from diagnosis to the first relapse was 9 months. At the time analyzing the data, 11% of patients died. Patients' 5-year OS and RFS rates were 79.6% and 41.5%, respectively. CONCLUSION: Comparing results with other conducted studies identifies that the recurrence rate was high in our considered patients. Also, OS and RFS rates in our study were not as considerable as other reports. Screening methods, updating protocols and follow-up of patients may lead to improvements in survival rates of patients with retinoblastoma.

Treatment challenges and outcomes for pediatric intracranial ependymoma at a single institution in Iran.

BACKGROUND: The scarcity of information on pediatric ependymoma in Iran motivated this study. Our main objectives were to determine outcomes, identify clinical management challenges at a nongovernment hospital in Iran, and devise guidelines for improving care. PROCEDURE: A retrospective chart review was performed for pediatric patients with ependymoma who were younger than 15 years and treated at MPCTRC between 2007 and 2015. Records included patient demographics, treatment regimens used, duration of follow-up, and outcomes. Clinical outcomes [ie, 3-year overall survival (OS) and progression-free survival (PFS)] were determined based on the age at diagnosis (younger or older than 3 years) by using the Kaplan-Meier method. RESULTS: In total, 73 eligible patients were enrolled; 20 patients were in the younger group, and 53 were in the older group. The majority (91.8%, n = 67) of patients underwent initial gross-total or partial surgical resection, and 6 (8.2%) had a biopsy. Twenty-one patients experienced ependymoma recurrence. The median time to relapse was 1 year. The median duration of follow-up and PFS were 25 and 17 months, respectively. The 3-year OS and PFS were 61% and 59.5%, respectively. At the time of this project, 27 patients had died, and 35 were alive with no evidence of disease. CONCLUSION: Our study demonstrated inferior outcomes of Iranian children with ependymoma. To improve our care for these children, a paradigm shift must occur that includes radiation therapy as standard of care, second-look surgery, a multidisciplinary team approach, and potentially twinning initiatives.

Management and outcomes of treating pediatric medulloblastoma: an eight years' experience in an Iranian pediatric center.

PURPOSE: The clinical management of pediatric medulloblastoma requires a multidisciplinary approach, which can be challenging, especially in low- and middle-income countries. The aim of this study was to identify current challenges and describe the treatment and outcomes of Iranian pediatric patients with medulloblastoma who were referred to our center in Tehran, Iran. METHODS: Our retrospective review included 126 patient records from April 2007 to May 2015. The records were analyzed for epidemiologic features, treatment modalities, overall survival, and progression-free survival. Data were analyzed using SPSS 22.0 software. RESULTS: Median age at diagnosis was 6 years (male:female ratio, 2.3:1). At the time of diagnosis, 7 patients were 2 years or younger, and 76 (60.3%) were categorized as having high-risk disease. Overall, 100 patients had gross or near-total surgical resection. Cerebral spinal fluid involvement was detected in 22.2% of the patients tested, and spinal involvement was detected in 25% of the patients who underwent spinal MRI. Metastasis stages at the time of diagnosis were as follows: M0: 48.4% patients, M1: 16.7%, M2: 5.5%, and M3: 21.4%. Median times of follow-up and progression-free survival were 16 and 12 months, respectively. Probability of 7-year overall survival and progression-free survival were 59 and 53.8%, respectively. CONCLUSIONS: Results of the current retrospective study emphasize the need for implementing measures to improve outcome for our patients with medulloblastoma. Such measures include a multidisciplinary approach, unified national treatment guidelines, better disease and metastasis staging, twinning initiatives, and seeking a second opinion when needed.

CD7 aberrant expression led to a lineage switch at relapsed childhood acute pre-B lymphoblastic leukemia.

Immunophenotypic changes and lineage switch between diagnosis and relapse in acute lymphoblastic leukemia are uncommon and accompanied by poor outcomes. In this report, a 12-year-old boy with diagnosis of pre-B ALL with an aberrant expression of CD 7 is described. Patient was treated with the ALL-BFM 2000 protocol and suffered an episode of relapse with a lineage switch from pre-B ALL to T cell ALL. This report concludes that presence of aberrant expression of CD7 at diagnosis of pre-B ALL can have prognostic value of lineage switch to T cell ALL at relapse.

Evaluation of Relationship Between Demographics and Dental Status in a Defined Group of Iranian Paediatric Patients Undergoing Cancer Therapy.

CONTEXT: Cancer is a major cause of death in children under 15 years of age. AIMS: This study aimed to evaluate relationship between demographics and dental status in a defined group of Iranian paediatric patients undergoing cancer therapy. SETTINGS AND DESIGN: This cross-sectional study was accomplished on 161 subjects age ranging 8-12 years. There were 76 cancerous patients hospitalized at Mahak Hospital (one of the major children's cancer centers in Tehran) as the study group and 85 healthy children attending at Dental School, International Branch of Shahid Beheshti University of Medical Sciences, Tehran, Iran from 2012 to 2013. MATERIALS AND METHODS: Demographics were gathered by using data-form. Oral examination and DMFT Index were used to describe teeth status in all teeth and in the first permanent molars. According to Becker's definition, "D" stands for untreated decayed teeth, "M" indicates missing teeth, and "F" shows Filled teeth. It is noteworthy that full coverage crowns are considered as "F" in this Index. STATISTICAL ANALYSIS: Chi-square, Mann-Whitney U, Student's t-tests and Logistic Regression were used for data analysis. RESULTS: The most frequent type of cancer was acute lymphoblastic/lymphocytic leukemia (33.3%). Patients were significantly shorter than controls (p=0.03), and their fathers and mothers were of lower educational achievement (p=0.01, p= 0.001). Although DMFT of all dentition showed significantly higher score in cancerous children (p=0.001), DMFT of four first permanent molars (left, right, upper, and lower) was borderline significantly higher in patients (p= 0.06). Moreover, frequency of cancer was borderline significantly higher in children with lower birth order (p= 0.05). According to Logistic Regression, in as much as patients grew elder 1 year, DMFT index increased 1.5 units. CONCLUSION: Patients under cancer therapy were shorter than healthy ones, and their parents were of lower educational levels. In addition, their teeth status was poorer than controls.

Family History and Relapse in Pediatric Acute Myeloid Leukemia.

We report the epidemiology and characteristics of acute myeloid leukemia and outcomes of its treatment with the AML-BFM 83 protocol at the Mahak Pediatric Cancer Treatment and Research Center, Tehran, Iran, from 2007 to 2012. A positive family history of cancer or leukemia was associated with the risk of relapse (family history of cancer in relapse: n = 11; 61%, P = 0.136, leukemia: n = 7; 39%; P = 0.016). Treatment-related mortality was 19% and associated with underweight patients (n = 5; 62.5%; P = 0.158). Event-free and overall survivals were 36% (SE = 3.5) and 44% (SE = 3.4), respectively. These data suggest a possible relationship between family history and relapse rate.

Cytomegalovirus Disease in Children With Acute Lymphoblastic Leukemia in the Nontransplant Setting: Case Series and Review of the Literature.

Cytomegalovirus (CMV) disease in pediatric acute lymphoblastic leukemia in the nontransplant setting is very rare. We report our experience with 4 such cases, and review the literature (n=12). The median age at diagnosis was 10 years and 50% of patients were males. Among the 11 cases with available information at the time of diagnosis, CMV disease occurred during maintenance therapy in 10 patients. Fever was present in 9 cases. CMV disease manifested as retinitis in 6, hepatosplenic disease in 3, pneumonitis in 1, and hemophagocytic lymphohistiocytosis in 1 patient. One patient had both CMV retinitis and CMV-related hemophagocytic lymphohistiocytosis. Four of the 7 patients with retinitis complained of visual disturbance at diagnosis. CMV viremia was present in 10 patients. Three patients had at least 1 relapse and developed permanent visual defects, and 1 patient developed recurrent retinal detachment. In conclusion, prolonged immunosuppression is the major etiology and retinitis is the most common manifestation of CMV disease. As a significant number of patients with retinitis are asymptomatic, early diagnosis and treatment is important to prevent permanent visual loss.

Features of Childhood Acute Myeloid Leukemia in Iran: a Report from Double Center Study.

Acute Myeloblastic Leukemia is one of the important malignancies in children. For better managing the prognosis of this disease, there should be enough information about common features of this malignancy. The aim of this study was to evaluate these common features in children with Acute Myeloblastic Leukemia. A total of 104 eligible children less than 15-year-old have been referred from 2007-2011 to two referral centers for childhood malignancies. Basic epidemiological information recorded in checklists for each individual. Analyzes have been done by SPSS version 22. Out of patients, 57 cases were males (54.8%). The male/female ratio was 1.2. The mean age of patients was 6.5 ± 4.3 years. The majority subtypes of patients were M3, M4, non-M3, and M2, respectively. The common molecular abnormalities were t (15;17) and inv (16). Of patients, 19.2% had an early relapse. The mean age of relapse in patients was 6.7 ± 3.9 years. Sixty patients (57.7%) were alive, and 44 cases (42.3%) died during or after therapy. The three years overall survival rate of patients was 42% in this study. According to our data, AML has the same frequency as compared with data from developing countries. But different epidemiological characteristic was a lower rate of three years overall survival in patients. These data may serve the health authorities for more effective environmental and preventive measurements, purposeful allocation of resources for facilitating up-to-date diagnostic and treatment modalities, psychological support programs for respective family members and educational purposes.

The effect of adjuvant zinc therapy on recovery from pneumonia in hospitalized children: a double-blind randomized controlled trial.

Objectives. Pneumonia is one of the common mortality causes in young children. Some studies have shown beneficial effect of zinc supplements on treatment of pneumonia. The present study aimed to investigate the effects of short courses of zinc administration on recovery from this disease in hospitalized children. Methods. In a parallel Double-Blind Randomized Controlled Trial at Ayatollah Golpaygani Hospital in Qom, 120 children aged 3-60 months with pneumonia were randomly assigned 1 : 1 to receive zinc or placebo (5 mL every 12 hours) along with the common antibiotic treatments until discharge. Primary outcome was recovery from pneumonia which included the incidence and resolving clinical symptoms and duration of hospitalization. Results. The difference between two groups in all clinical symptoms at admittance and the variables affecting the disease such as age and sex were not statistically significant (P < 0.05) at baseline. Compared to the placebo group, the treatment group showed a statistically significant decrease in duration of clinical symptoms (P = 0.044) and hospitalization (P = 0.004). Conclusions. Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia. In general, zinc administration, along with common antibiotic treatments, is recommended in this group of children. It can also reduce the drug resistance caused by multiple antibiotic therapies. This trial is approved by Medical Ethic Committee of Islamic Azad University in Iran (ID Number: 8579622-Q). This study is also registered in AEARCTR (The American Economic Association's Registry for Randomized Controlled Trials). This trial is registered with RCT ID: AEARCTR-0000187.

Childhood central nervous system tumors at MAHAK's Pediatric Cancer Treatment and Research Center (MPCTRC), Tehran, Iran.

PURPOSE: As central nervous system (CNS) tumors account for second most common childhood malignancies and the first cause of mortality in children with cancer, improving treatment modalities can lead to increase the health care of patients. In this study, we examined the prevalence of childhood brain tumors in patients who referred to MAHAK's Pediatric Cancer Treatment and Research Center (MPCTRC) for treatment. METHODS: A retrospective review of all children less than 15 years old with a CNS histologically proven tumor, who presented to MPCTRC from April 2007 to April 2010, was performed. Data was analyzed by SPSS version 19 with Kolmogorov-Smirnov and Chi-square tests. RESULTS: There were 198 (124 boys) children eligible for the study. The majority of the tumors were infratentorial (n = 134), and the rest were supratentorial (n = 60) and spinal (n = 4) cases. The median age was 6.11 ± 3.65 years old. Medulloblastoma (n = 66), low-grade glioma (n = 52), and high-grade glioma (n = 40) were the most common tumors. The mean duration of follow-up was 21 months. At the time of this analysis, there were 105 (53 %) children alive, 82 (41.4 %) deaths, and 11 (5.6 %) lost for follow-up. The survival rate was 51.68 ± 5.22 %. CONCLUSIONS: In contrast of high rate of death in this study, other general characteristics can serve as benchmark for improving our care for children with brain tumors in Iran.

Consequences of delayed diagnosis in treatment of retinoblastoma.

OBJECTIVE: One of the primary factors in managing patients with retinoblastoma is early diagnosis. The main idea of this study was to recognize the consequences of delay in diagnosis on therapy of the disease. METHODS: A retrospective review of all children with proven retinoblastoma, who had presented to MAHAK hospital in Tehran, from April 2007 to Dec 2011, was performed. Grouping of intraocular tumors was applied as A to E according to International Classification of Retinoblastoma. Findings : There were 157 (91 boys) children eligible for study. The mean age was 1.21±0.11 years with average delay in diagnosis of 3.4±0.53 months. Classification of D group in both unilateral (93 patients) and bilateral tumors was the largest category. A significant relation (P=0.05) between delayed diagnosis time and tumor grouping was evident. The most frequent symptoms were leukocoria and strabismus. Age was significantly lower in the subgroup of bilateral tumors than in unilateral retinoblastomas (0.6±0.12 year vs 1.6±0.15 years). The diagnosis was delayed in subgroup of extra ocular retinoblastoma more than in intraocular tumors (8.7±2.9 months vs 2.9±0.52 months). CONCLUSION: The authors recommend early referring of suspected cases to ophthalmologists and pediatric oncologists and to organize educational programs to publisize signs and symptoms of the disease such as leukocoria, strabismus and ocular inflammatory disorders through national media. In conclusion, early diagnosis of retinoblastoma can be the primary factor in managing the patients as the delay in diagnosis accounts for highly advanced disease and poor prognosis.

Presepsin (scd14) as a marker of serious bacterial infections in chemotherapy induced severe neutropenia.

OBJECTIVE: Timely detection of serious bacterial infections or prediction of sepsis and death is of paramount importance in neutropenic patients especially in oncology settings. The aim of this study was to determine a rapid and secure predictor of sepsis in severe neutropenic cancer children. METHODS: In addition to blood culture, we have evaluated serum soluble CD14 on this role and measured it in 39 neutropenic episodes in Mahak pediatric oncology center from September 2012 to January 2013. Fifteen episodes had positive bacterial cultures and 18 had fever. The mean sCD14 values were compared in the presence or absence of fever, positive blood culture and other clinical conditions. Also, mean levels compared in different white cell counts and different four combination settings of fever and blood culture. FINDINGS: It was statistically higher in febrile episodes, in the presence of oral mucositis, indwelling catheter infection, otitis media, and post toxic epidermal necrolysis sepsis and in instances of death within 15 days. Leukocyte count did not affect sCD14 level and in combinations of fever and blood culture, mean sCD14 values were ranked as follow: febrile culture negatives, febrile culture positives, afebrile culture positives and afebrile culture negatives. CONCLUSION: Although sCD14 was not sensitive in detection of bacteremia, in the absence of clinically detectable source of infection, it was significantly higher in culture positives.