Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers a... more Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1 3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). BRAF V600E mutations were observed in only 2/37 patients, while H3F3A (K27M) histone mutations were not detected. Interes...
BACKGROUND: There is limited data from Saudi Arabia on the demographic characteristics, outcomes ... more BACKGROUND: There is limited data from Saudi Arabia on the demographic characteristics, outcomes and effectiveness of different treatment modalities in children with intracranial ependymoma. OBJECTIVE: Study the characteristics of pediatric ependymoma and outcomes of treatment modalities in Saudi Arabia. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS AND METHODS: Children with intracranial ependymoma who were younger than 14 years of age and treated between 2006 and 2015 were included in the study. Patients with prior radiation, chemo-therapy, or surgical resection at other centers were excluded. MAIN OUTCOME MEASURES: Kaplan-Meier survival curves were used to estimate the event-free (EFS) and overall survival (OS) rates of the patients. SAMPLE SIZE: 22. RESULTS: Of the 22 children, 4 (18.2%) were less than three years old. All intracranial ependymomas had upfront surgical resection of the primary tumor. Gross total resection was achievable in 9 (42.9%) cases and sub...
Background: Hospital admission can be scary for a child, most especially for hospitalized pediatr... more Background: Hospital admission can be scary for a child, most especially for hospitalized pediatric cancer patients, but studies show that there is growing evidence that environmental modification has a great impact in patient experience and health outcomes. Majority of pediatric cancer patients and their family was not satisfied with the unit environment. The aim of this study was to explore the impact of creating a child-friendly hospital environment in pediatric cancer patients and their families. Method: General surveys were conducted. Performance improvement team studied the result of the surveys, a specific survey was formulated. Relevant data were collected. After studying the results, suggestions for improvement were considered. Contributing factors for their dissatisfaction were also analyzed in a form of Cause-and-Effect Diagram. A post-intervention survey was conducted. Result: Result of general, specific survey and repeated focus group discussion showed that we need to c...
Clinical behaviors, prognosis, and appropriate treatments of PTPR are not fully defined due to th... more Clinical behaviors, prognosis, and appropriate treatments of PTPR are not fully defined due to the rarity of these tumors. At diagnosis, PTPR may present with various clinical symptoms with obstructive hydrocephalus, as well as neurological signs including Parinaud’s syndrome. Radiological assessment of pineal region lesions is challenging with a wide range of potential differential diagnoses. PTPR typically presents as a heterogeneous, well circumscribed mass in the pineal region. we report 3 female pediatric cases of PTPR treated in our institution. Histological and immunohistochemical diagnosis was confirmed by analysis of genome-wide DNA methylation profiles. the first case presenting with spinal leptomeningeal dissemination with excellent tumor control with radiation therapy alone. The second patient had aggressive course with recurrent local tumor growth despite radiation therapy and 0repeated surgical resections and she responded well to Pineoblastoma like intensive chemother...
The Outcome for relapsed NGGCT is poor. Salvage therapy usually consist of reinduction platinum-b... more The Outcome for relapsed NGGCT is poor. Salvage therapy usually consist of reinduction platinum-based chemotherapy regimen followed by high-dose-chemotherapy and autologous-stem-cell-rescue (HDC/AuSCR) and re-irradiation with no consensus on optimal management and usually associated with remarkable toxicity. We present a 12-year-old boy diagnosed with a localized pineal Non-Germinaoteous Germ Cell Tumors NGGCTs of mixed origin with elevated AFP he had ETV and biopsy started on COG ACNS0122 protocol after receiving first cycle (carbo/Etoposide) he developed acute renal failure investigation showed small dysplastic kidney to avoid nephrotoxicity of platinum agents chemotherapy changed to VBE (Vinblastine, Bleomycin and Etoposide) post 3rd cycle MRI showed increase in size of the pineal mass with normal tumor markers representing Growing Teratoma Syndrome He had total surgical resection of the tumor Pathology showed predominant teratoma component He received radiation therapy CSI then ...
Diffuse midline glioma, H3 k27-altered (DMG) is a type of Paediatric- type diffuse high grade gli... more Diffuse midline glioma, H3 k27-altered (DMG) is a type of Paediatric- type diffuse high grade gliomas according to the 2021 WHO CNS tumors Classification. Diffuse intrinsic pontine glioma (DIPG) is another acceptable related term when it located in the pons with fatal prognosis. The combination of H3K27M with BRAF V600 mutations rarely reported in DMG although more commonly in Paediatric-type low grade gliomas (Diffuse low-grade glioma, MAPK pathway-altered). We present a twenty-month-old boy, previously healthy, presented with 2 weeks history of unsteady gait, drooling, cranial nerves palsy MRI imaging showed diffuse pontine mass with classic radiological features of DIPG. 2.6 x 1.6 x 3.2 (AP x TV x CC) with no evidence for spinal metastases. Patient underwent right retro sigmoid approach and open biopsy of lesion he received focal Radiation Therapy 54GY/30fx as stander of care of DIPG with mild neurogical improvement Pathological & molecular Diagnosis was Diffuse midline glioma, H...
BACKGROUND: The management of childhood central nervous system (CNS) tumors is complex and often ... more BACKGROUND: The management of childhood central nervous system (CNS) tumors is complex and often faces numerous challenges in low- and middle- income countries (LMICs), including delayed diagnosis and limited treatment resources. Twinning initiatives between LMICs with high- income countries are feasible and proven to be highly effective at exchanging skills and expertise to improve diagnosis, treatment and care for children with brain tumors. METHODS: A monthly multidisciplinary international pediatric neuro-oncology tumor board via zoom videoconferencing was established in January 2021. This effort is a collaboration between Washington University School of Medicine, in St. Louis, Missouri, USA and nine international sites. Given the significant contributions of this international effort, it has since grown to include 20 institutions and cancer centers from 12 countries in the Middle East, Europe, Australia and South America. RESULTS: As of January 2022, we have held 11 tumor board...
PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposit... more PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic...
BACKGROUND Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predispo... more BACKGROUND Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome resulting in early onset central nervous system (CNS) and other cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol. METHODS We surveyed all confirmed CMMRD patients in the International Replication Repair Deficiency Consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging (CNS and total body MRI) studies were employed. Survival analyses and efficacy of each method were assessed. RESULTS Surveillance data were collected from 105 CMMRD individuals from 41 countries. Of the 193 malignant tumors, CNS malignancies were the most common (44%). The surveillance protocol uncovered 49 asymptomatic tumors including 16 glioblastomas and medulloblastomas. Five-year overall survival was 89% for tumors discovered by surveillance, and 61% for symptomatic tumors (p<0.004)...
Objectives. This study is aimed at describing the epidemiological trends of primary CNS tumors in... more Objectives. This study is aimed at describing the epidemiological trends of primary CNS tumors in children and adults at the National Neurologic Institute in Saudi Arabia. Methods. A retrospective epidemiological approach was used where data was obtained from the department of pathology registry files and pathology reports. The records of all patients registered from January 2005 to December 2014 with a diagnosis of primary CNS tumor (brain and spinal cord) were selected. Data about sex, age, tumor location, and histologic type were collected. The classification was based on the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3). Results. Nine hundred and ninety-two (992) cases of primary CNS tumors throughout the ten years (2005 to 2014) were reviewed. There were 714 (71.97%) adults and 278 (28.02%) in the pediatric age group. Nonmalignant tumors dominated the adult population (60.08%) while malignant tumors were more frequent in the pediatric population. ...
e18218 Background: Oncology patients need to receive their course of treatment in a timely manner... more e18218 Background: Oncology patients need to receive their course of treatment in a timely manner. Increasing the efficiency of laboratory testing could potentially improve hospital operations and thus have a positive impact on patient care. One way of doing this is by initiating an installation of a satellite laboratory. The purpose of this study is to determine the advantages of having a satellite laboratory in an oncology unit. Moreover, it shall also try to determine whether the presence of satellite laboratory will help reduce the chemotherapy waiting time of oncology patients. Methods: This study utilized experimental study design in order to analyze and compare Laboratory Turnaround time (TAT) and the chemotherapy waiting time before and after establishment of satellite laboratory. The samples taken as base line data was 150 and compared to samples taken from 2013-2015. The population of this study included patients in Comprehensive Cancer Center of King Fahad Medical City di...
Purpose Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer predisposi... more Purpose Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer predisposition syndrome caused by biallelic mutations in mismatch repair (MMR) genes. As several cancer syndromes are clinically similar, accurate diagnosis is critical to cancer screening and treatment. As genetic diagnosis is confounded by 15 or more pseudogenes and variants of uncertain significance, a robust diagnostic assay is urgently needed. We sought to determine whether an assay that directly measures MMR activity could accurately diagnose CMMRD. Patients and Methods In vitro MMR activity was quantified using a 3′-nicked G-T mismatched DNA substrate, which requires MSH2-MSH6 and MLH1-PMS2 for repair. We quantified MMR activity from 20 Epstein-Barr virus–transformed lymphoblastoid cell lines from patients with confirmed CMMRD. We also tested 20 lymphoblastoid cell lines from patients who were suspected for CMMRD. We also characterized MMR activity from patients with neurofibromatosis type ...
Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers a... more Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1 3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). BRAF V600E mutations were observed in only 2/37 patients, while H3F3A (K27M) histone mutations were not detected. Interes...
BACKGROUND: There is limited data from Saudi Arabia on the demographic characteristics, outcomes ... more BACKGROUND: There is limited data from Saudi Arabia on the demographic characteristics, outcomes and effectiveness of different treatment modalities in children with intracranial ependymoma. OBJECTIVE: Study the characteristics of pediatric ependymoma and outcomes of treatment modalities in Saudi Arabia. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS AND METHODS: Children with intracranial ependymoma who were younger than 14 years of age and treated between 2006 and 2015 were included in the study. Patients with prior radiation, chemo-therapy, or surgical resection at other centers were excluded. MAIN OUTCOME MEASURES: Kaplan-Meier survival curves were used to estimate the event-free (EFS) and overall survival (OS) rates of the patients. SAMPLE SIZE: 22. RESULTS: Of the 22 children, 4 (18.2%) were less than three years old. All intracranial ependymomas had upfront surgical resection of the primary tumor. Gross total resection was achievable in 9 (42.9%) cases and sub...
Background: Hospital admission can be scary for a child, most especially for hospitalized pediatr... more Background: Hospital admission can be scary for a child, most especially for hospitalized pediatric cancer patients, but studies show that there is growing evidence that environmental modification has a great impact in patient experience and health outcomes. Majority of pediatric cancer patients and their family was not satisfied with the unit environment. The aim of this study was to explore the impact of creating a child-friendly hospital environment in pediatric cancer patients and their families. Method: General surveys were conducted. Performance improvement team studied the result of the surveys, a specific survey was formulated. Relevant data were collected. After studying the results, suggestions for improvement were considered. Contributing factors for their dissatisfaction were also analyzed in a form of Cause-and-Effect Diagram. A post-intervention survey was conducted. Result: Result of general, specific survey and repeated focus group discussion showed that we need to c...
Clinical behaviors, prognosis, and appropriate treatments of PTPR are not fully defined due to th... more Clinical behaviors, prognosis, and appropriate treatments of PTPR are not fully defined due to the rarity of these tumors. At diagnosis, PTPR may present with various clinical symptoms with obstructive hydrocephalus, as well as neurological signs including Parinaud’s syndrome. Radiological assessment of pineal region lesions is challenging with a wide range of potential differential diagnoses. PTPR typically presents as a heterogeneous, well circumscribed mass in the pineal region. we report 3 female pediatric cases of PTPR treated in our institution. Histological and immunohistochemical diagnosis was confirmed by analysis of genome-wide DNA methylation profiles. the first case presenting with spinal leptomeningeal dissemination with excellent tumor control with radiation therapy alone. The second patient had aggressive course with recurrent local tumor growth despite radiation therapy and 0repeated surgical resections and she responded well to Pineoblastoma like intensive chemother...
The Outcome for relapsed NGGCT is poor. Salvage therapy usually consist of reinduction platinum-b... more The Outcome for relapsed NGGCT is poor. Salvage therapy usually consist of reinduction platinum-based chemotherapy regimen followed by high-dose-chemotherapy and autologous-stem-cell-rescue (HDC/AuSCR) and re-irradiation with no consensus on optimal management and usually associated with remarkable toxicity. We present a 12-year-old boy diagnosed with a localized pineal Non-Germinaoteous Germ Cell Tumors NGGCTs of mixed origin with elevated AFP he had ETV and biopsy started on COG ACNS0122 protocol after receiving first cycle (carbo/Etoposide) he developed acute renal failure investigation showed small dysplastic kidney to avoid nephrotoxicity of platinum agents chemotherapy changed to VBE (Vinblastine, Bleomycin and Etoposide) post 3rd cycle MRI showed increase in size of the pineal mass with normal tumor markers representing Growing Teratoma Syndrome He had total surgical resection of the tumor Pathology showed predominant teratoma component He received radiation therapy CSI then ...
Diffuse midline glioma, H3 k27-altered (DMG) is a type of Paediatric- type diffuse high grade gli... more Diffuse midline glioma, H3 k27-altered (DMG) is a type of Paediatric- type diffuse high grade gliomas according to the 2021 WHO CNS tumors Classification. Diffuse intrinsic pontine glioma (DIPG) is another acceptable related term when it located in the pons with fatal prognosis. The combination of H3K27M with BRAF V600 mutations rarely reported in DMG although more commonly in Paediatric-type low grade gliomas (Diffuse low-grade glioma, MAPK pathway-altered). We present a twenty-month-old boy, previously healthy, presented with 2 weeks history of unsteady gait, drooling, cranial nerves palsy MRI imaging showed diffuse pontine mass with classic radiological features of DIPG. 2.6 x 1.6 x 3.2 (AP x TV x CC) with no evidence for spinal metastases. Patient underwent right retro sigmoid approach and open biopsy of lesion he received focal Radiation Therapy 54GY/30fx as stander of care of DIPG with mild neurogical improvement Pathological & molecular Diagnosis was Diffuse midline glioma, H...
BACKGROUND: The management of childhood central nervous system (CNS) tumors is complex and often ... more BACKGROUND: The management of childhood central nervous system (CNS) tumors is complex and often faces numerous challenges in low- and middle- income countries (LMICs), including delayed diagnosis and limited treatment resources. Twinning initiatives between LMICs with high- income countries are feasible and proven to be highly effective at exchanging skills and expertise to improve diagnosis, treatment and care for children with brain tumors. METHODS: A monthly multidisciplinary international pediatric neuro-oncology tumor board via zoom videoconferencing was established in January 2021. This effort is a collaboration between Washington University School of Medicine, in St. Louis, Missouri, USA and nine international sites. Given the significant contributions of this international effort, it has since grown to include 20 institutions and cancer centers from 12 countries in the Middle East, Europe, Australia and South America. RESULTS: As of January 2022, we have held 11 tumor board...
PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposit... more PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic...
BACKGROUND Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predispo... more BACKGROUND Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome resulting in early onset central nervous system (CNS) and other cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol. METHODS We surveyed all confirmed CMMRD patients in the International Replication Repair Deficiency Consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging (CNS and total body MRI) studies were employed. Survival analyses and efficacy of each method were assessed. RESULTS Surveillance data were collected from 105 CMMRD individuals from 41 countries. Of the 193 malignant tumors, CNS malignancies were the most common (44%). The surveillance protocol uncovered 49 asymptomatic tumors including 16 glioblastomas and medulloblastomas. Five-year overall survival was 89% for tumors discovered by surveillance, and 61% for symptomatic tumors (p<0.004)...
Objectives. This study is aimed at describing the epidemiological trends of primary CNS tumors in... more Objectives. This study is aimed at describing the epidemiological trends of primary CNS tumors in children and adults at the National Neurologic Institute in Saudi Arabia. Methods. A retrospective epidemiological approach was used where data was obtained from the department of pathology registry files and pathology reports. The records of all patients registered from January 2005 to December 2014 with a diagnosis of primary CNS tumor (brain and spinal cord) were selected. Data about sex, age, tumor location, and histologic type were collected. The classification was based on the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3). Results. Nine hundred and ninety-two (992) cases of primary CNS tumors throughout the ten years (2005 to 2014) were reviewed. There were 714 (71.97%) adults and 278 (28.02%) in the pediatric age group. Nonmalignant tumors dominated the adult population (60.08%) while malignant tumors were more frequent in the pediatric population. ...
e18218 Background: Oncology patients need to receive their course of treatment in a timely manner... more e18218 Background: Oncology patients need to receive their course of treatment in a timely manner. Increasing the efficiency of laboratory testing could potentially improve hospital operations and thus have a positive impact on patient care. One way of doing this is by initiating an installation of a satellite laboratory. The purpose of this study is to determine the advantages of having a satellite laboratory in an oncology unit. Moreover, it shall also try to determine whether the presence of satellite laboratory will help reduce the chemotherapy waiting time of oncology patients. Methods: This study utilized experimental study design in order to analyze and compare Laboratory Turnaround time (TAT) and the chemotherapy waiting time before and after establishment of satellite laboratory. The samples taken as base line data was 150 and compared to samples taken from 2013-2015. The population of this study included patients in Comprehensive Cancer Center of King Fahad Medical City di...
Purpose Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer predisposi... more Purpose Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer predisposition syndrome caused by biallelic mutations in mismatch repair (MMR) genes. As several cancer syndromes are clinically similar, accurate diagnosis is critical to cancer screening and treatment. As genetic diagnosis is confounded by 15 or more pseudogenes and variants of uncertain significance, a robust diagnostic assay is urgently needed. We sought to determine whether an assay that directly measures MMR activity could accurately diagnose CMMRD. Patients and Methods In vitro MMR activity was quantified using a 3′-nicked G-T mismatched DNA substrate, which requires MSH2-MSH6 and MLH1-PMS2 for repair. We quantified MMR activity from 20 Epstein-Barr virus–transformed lymphoblastoid cell lines from patients with confirmed CMMRD. We also tested 20 lymphoblastoid cell lines from patients who were suspected for CMMRD. We also characterized MMR activity from patients with neurofibromatosis type ...
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