Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients.

AIMS: Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait. METHODS: We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations. RESULTS: Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2-17.6) and 21 adult patients (median 37 years; 18.9-89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs. CONCLUSION: The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.

A regional virtual case discussion forum in pediatric oncology: Experience of the Pediatric Oncology East and Mediterranean Group.

BACKGROUND: The Pediatric Oncology East and Mediterranean (POEM) group that aims to share expertise among pediatric oncology providers across the Middle East, North Africa, and East Asia region initiated a virtual Case Discussion Forum (CDF) in 2013. METHODS: Meeting records from September 2013 till June 2021 were reviewed. Detailed minutes were available starting August 2016; case data were analyzed including diagnoses, purpose of presentation and recommendations. A 38-item survey assessing perception of benefits, challenges, and opportunities of the forum was distributed to members of the POEM group and results analyzed. RESULTS: A total of 140 cases were presented from 14 countries. After August 2016, 67 cases were presented, and those were analyzed regarding reasons for discussion, barriers, and recommendations. Details are presented in this report, and the most common challenges identified were related to histopathologic/molecular diagnosis (24%), imaging interpretation (18%), resource limitations (12%), and surgical difficulties (9%). A survey was distributed to all POEM members in 28 countries, and 76 responded. The main benefit reported was the provision of recommendations regarding treatment and evaluation, while the main challenges reported were time zone difference and workload. Recognized opportunities included conducting regionally relevant research studies based on clinical problems identified during discussions, and setting guidelines for resource-adapted treatment regimens. CONCLUSIONS: The POEM CDF identified areas for multi-institutional regional studies and led to a twinning project between two centers in the region for improving diagnostic infrastructure. Such forums can identify specific resource limitations in pediatric cancer and direct efforts for targeted capacity building.

Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry.

Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD.

Trends in Childhood Cancer in Kuwait: Data From the 2004-2017 Registry.

Background and objective There is a lack of updated data regarding pediatric cancer in Kuwait, with no separate childhood cancer registry available in the country prior to this study. We aimed to determine the trends in different cancer types with respect to international statistics, in order to understand their nature and identify gaps in their diagnosis and management. Methods This retrospective study was based on data obtained from the first national childhood cancer registry of the National Bank of Kuwait (NBK) Specialized Hospital for Children, the only hospital that manages pediatric cancer patients in Kuwait. The registry included the data of all children with cancer in Kuwait from 2004 to 2017 and had complete data files. Findings The total number of patients in the childhood cancer registry was 1,387. A total of 1,009 files met our eligibility criteria. In 2017, the incidence of childhood leukemia was determined to be six per 100,000 people, and for other cancers, it was 12.6 per 100,000 people. The most common cancer was leukemia (457 patients), followed by lymphoma (141 patients), and brain tumors (92 patients). The majority of children received chemotherapy (n=891, 88.3%). Post induction or treatment, the majority of patients achieved complete remission (n=790, 78.3%). The overall survival rate of children with cancer was around 80%. Major complications developed in 9% of patients. Conclusion These findings highlight the importance of hospital-based cancer registries. Active data management programs are essential to monitor outcomes, measure the effectiveness of current practice, and improve the quality of care.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.

Outcome of children with Hodgkin's disease. A 10-year experience from a single institution in Kuwait.

OBJECTIVE: To evaluate the outcome of children with Hodgkin's disease over a period of 10-years from a single institution in Kuwait. METHODS: Sixty-three children with previously untreated Hodgkin's disease, who were diagnosed at the Pediatric Oncology Unit of Kuwait Cancer Control Centre, Shuwaikh, Kuwait from January 1998 to December 2007 were included in the study. All cases were proved by histopathology, and staging was carried out according to the Ann Arbor system. RESULTS: Our series included 37 (59%) males and 26 (41%) females with a median age of 10 years (range 3-15 years). B symptoms were present in 20 (32%) children. Bulky disease was noted in 28 (44%) children, with stages III in 8 (13%) and IV in 12 (19%) children. Chemotherapy was administered as a primary treatment in 63 children. The median number of chemotherapy cycles given was 6 (range 2-8). Radiotherapy was used in 40 (63%) children. Grade III hematological toxicity was observed in 23 (37%) and grade IV in 14 (22%) children. Hypothyroidism was observed in 20 (32%) children. Fifty-five children achieved a complete remission (87%) and 2 children achieved a partial remission (3%) with an overall response rate of 90%. Three children achieved a progressive disease (5%) and response could not be evaluated in 3 (5%) children. At a median follow-up of 67 months (5.5 years), the overall survival was 91%. CONCLUSION: With moderate toxicity, combined modality therapy is effective in the treatment of childhood Hodgkin's disease.

Fetus in fetu: a case report.

INTRODUCTION: Fetus in fetu is a rare abnormality secondary to the abnormal embryogenesis in a diamniotic, monochorionic pregnancy. It is a rare pathological condition and fewer than 100 cases have been reported in the literature. CASE PRESENTATION: A 2 month old girl with an abdominal mass since birth, was referred to the Cancer Institute with a suspected diagnosis of a Wilms' tumor. Conventional radiograph of the abdomen revealed a mass containing numerous calcifications. CT scan showed a heterogeneous retroperitoneal mass containing well-defined calcified structures. The decision was made to recommend surgical exploration and the mass was successfully excised. Physical examination of the mass with review of literature confirmed the diagnosis of fetus in fetu. CONCLUSION: Although it is a rare condition imaging may play an important role in the correct prospective diagnosis of fetus in fetu. Surgical excision is the recommended treatment.