DOCSLIB.ORG

Risk-Adapted Therapy for Young Children with Embryonal Brain Tumors, High-Grade Glioma, Choroid Plexus Carcinoma Or Ependymoma (Sjyc07)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Risk-Adapted Therapy for Young Children with Embryonal Brain Tumors, High-Grade Glioma, Choroid Plexus Carcinoma Or Ependymoma (Sjyc07) SJCRH SJYC07 CTG# - NCT00602667 Initial version, dated: 7/25/2007, Resubmitted to CPSRMC 9/24/2007 and 10/6/2007 (IRB Approved: 11/09/2007) Activation Date: 11/27/2007 Amendment 1.0 dated January 23, 2008, submitted to CPSRMC: January 23, 2008, IRB Approval: March 10, 2008 Amendment 2.0 dated April 16, 2008, submitted to CPSRMC: April 16, 2008, (IRB Approval: May 13, 2008) Revision 2.1 dated April 29, 2009 (IRB Approved: April 30, 2009 ) Amendment 3.0 dated June 22, 2009, submitted to CPSRMC: June 22, 2009 (IRB Approved: July 14, 2009) Activated: August 11, 2009 Amendment 4.0 dated March 01, 2010 (IRB Approved: April 20, 2010) Activated: May 3, 2010 Amendment 5.0 dated July 19, 2010 (IRB Approved: Sept 17, 2010) Activated: September 24, 2010 Amendment 6.0 dated August 27, 2012 (IRB approved: September 24, 2012) Activated: October 18, 2012 Amendment 7.0 dated February 22, 2013 (IRB approved: March 13, 2013) Activated: April 4, 2013 Amendment 8.0 dated March 20, 2014. Resubmitted to IRB May 20, 2014 (IRB approved: May 22, 2014) Activated: May 30, 2014 Amendment 9.0 dated August 26, 2014. (IRB approved: October 14, 2014) Activated: November 4, 2014 Un-numbered revision dated March 22, 2018. (IRB approved: March 27, 2018) Un-numbered revision dated October 22, 2018 (IRB approved: 10-24-2018) RISK-ADAPTED THERAPY FOR YOUNG CHILDREN WITH EMBRYONAL BRAIN TUMORS, HIGH-GRADE GLIOMA, CHOROID PLEXUS CARCINOMA OR EPENDYMOMA (SJYC07) Principal Investigator Amar Gajjar, M.D. Division of Neuro-Oncology Department of Oncology Section Coordinators David Ellison, M.D., Ph.D. Eugene Reddick, Ph.D. Department of Pathology Department of Diagnostic Imaging Thomas E. Merchant, D.O., Ph.D. Arzu Onar-Thomas, Ph.D. Department of Radiation Oncology Department of Biostatistics Heather Conklin, Ph.D. Clinton F. Stewart, Pharm.D. Department of Psychology Department of Pharmaceutical Sciences Other Investigators Giles Robinson, M.D. Matthew J. Krasin, M.D. Ibrahim Qaddoumi, M.D. Department of Radiation Oncology Division of Neuro-Oncology Department of Oncology Noah Sabin, M.D. Zoltan Patay, M.D., Ph.D Greg Armstrong, M.D. Department of Diagnostic Imaging Department of Epidemiology & Cancer Control Catherine Billups, M.S. Fredrick Boop, M.D. Jie Huang, M.S. Department of Neurosurgery Department of Biostatistics Brent Orr, M.D. Ph.D. Department of Pathology St. Jude Children's Research Hospital 262 Danny Thomas Place Memphis, Tennessee 38105-2794 Telephone: (901) 595-3300 This is a confidential research document. No information may be extracted without permission of the Principal Investigator Amendment 9.0, dated: 08-26-2014 IRB Approved date: 10-24-2018 Protocol version dated: 10-22-2018 UNIVERSITY OF FLORIDA INVESTIGATORS Daniel J. Indelicato, M.D. Robert B. Marcus, Jr., M.D. Assistant Professor Professor Department of Radiation Oncology Department of Radiation Oncology University of Florida University of Florida Zuofeng Li, D.Sc. Nancy P. Mendenhall, M.D. Associate Professor Medical Director, UFPTI Department of Radiation Oncology Professor & Associate Chairman University of Florida Department of Radiation Oncology University of Florida Amendment 9.0, dated: 08-26-2014 IRB Approved date: 10-24-2018 Protocol version dated: 10-22-2018 COLLABORATING INVESTIGATORS: Daniel Bowers, MD University of Texas Southwestern Medical Center at Dallas Dallas, Texas Sonia Partap, MD Stanford University Palo Alto, California Anne Bendel, MD Children's Hospitals and Clinics of Minnesota Minneapolis, Minnesota Tim Hassall, MBBS, FRACP Royal Children’s Hospital in Brisbane Brisbane, Qld AUSTRALIA John Crawford, MD, MS University of California, San Diego San Diego, California Amendment 9.0, dated: 08-26-2014 IRB Approved date: 10-24-2018 Protocol version dated: 10-22-2018 Protocol summary SJYC07, Risk-Adapted Therapy for Young Children with Embryonal Brain Tumors, High-Grade Glioma, Choroid Plexus Carcinoma or Ependymoma Principal Investigator: Amar Gajjar, M.D. IND holder: Not applicable, non-IND study Brief overview: Children younger than 3 years of age with newly diagnosed medulloblastoma, supratentorial primitive neuroectodermal tumor (PNET), atypical teratoid/rhabdoid tumor (ATRT), high-grade glioma, choroid plexus carcinoma (CPC) or ependymoma. Children ≥ 3 and < 5 years of age with newly diagnosed non-metastatic medulloblastoma are also eligible Intervention: multi-modality, according to risk assignment Drugs: Methotrexate, vincristine, cisplatin, cyclophosphamide, vinblastine, carboplatin, etoposide, topotecan, erlotinib Other: Focal radiation therapy, craniospinal irradiation Brief outline of treatment plan: All participants will receive 4 identical cycles of induction chemotherapy including high-dose (5 g/m2 or 2.5g/m2 for patients less than or equal to 31 days of age at enrollment) intravenous methotrexate and standard dose vincristine, cisplatin, and cyclophosphamide. Patients enrolled on the high-risk arm will also receive low-dose vinblastine between induction cycles. Induction will be followed by risk-adapted consolidation therapy: low-risk patients will receive further conventional chemotherapy with carboplatin, cyclophosphamide, and etoposide; intermediate risk patients will receive focal radiotherapy (RT) to the tumor bed; high-risk patients will receive either chemotherapy with targeted intravenous topotecan and cyclophosphamide or optional craniospinal irradiation (CSI). CSI will be offered only to patients who reach 3 years of age by the end of induction only. After consolidation, all patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16). Induction Consolidation Maintenance (16 weeks) (8 weeks) (24 weeks) MTX/VCR/CDDP/CPM CPM/Carbo/VP16 (Low Risk) PO CPM/Topo alternating (+VBL for High-risk) Focal RT (Intermediate Risk) with Erlotinib or VP16 Topo/CPM or CSI (High Risk) Amendment 9.0, dated: 08-26-2014 IRB Approved date: 10-24-2018 Protocol version dated: 10-22-2018 Study design: Exploratory study utilizing risk-adapted multi-modality treatment. M Stage M1+ M0 Diagnosis Other Medulloblastoma High Grade (PNET, ATRT, Glioma Extent of Resection < GTR GTR Histologic Subtype Other Nodular (Classical, Desmoplastic anaplastic) Age at Diagnosis >3 to <5 yrs < 3 yrs High Risk Intermediate Risk Low Risk Sample size: Target accrual is 90 medulloblastoma patients. The projected total accrual for the entire study including patients with other tumor types is 315. Data management: Data management and statistical analysis will be provided locally by the Division of Neuro-Oncology and the Department of Biostatistics at St. Jude Children’s Research Hospital. Human subjects: The main risk to research participants will be the potential toxicities associated with the use of the multi-modality therapy. The research participants will be informed of the toxicities that have been associated with the study drugs and potential side effects of procedures recommended in this study. Adverse events will be monitored, treated, and reported following institutional and federal guidelines and regulations. Amendment 9.0, dated: 08-26-2014 IRB Approved date: 10-24-2018 Protocol version dated: 10-22-2018 TABLE OF CONTENTS 1.0 OBJECTIVES ......................................................................................................................... 1 1.1 PRIMARY OBJECTIVES .............................................................................................. 1 1.2 SECONDARY OBJECTIVES ......................................................................................... 1 2.0 BACKGROUND AND RATIONALE .................................................................................. 4 2.1 OVERVIEW ............................................................................................................... 4 2.2 RESULTS OF CLINICAL TRIALS FOR INFANTS AND YOUNG CHILDREN WITH BRAIN TUMORS ................................................................................................................... 6 2.3 RATIONALE FOR TUMOR BIOLOGY STUDIES .......................................................... 16 2.4 RATIONALE FOR TREATMENT ................................................................................ 21 2.5 RATIONALE FOR PHARMACOKINETIC/PHARMACOGENETIC STUDIES ...................... 44 2.6 RATIONALE FOR CNS NEUROTRANSMITTER STUDIES ............................................ 52 2.7 RATIONALE FOR NEUROCOGNITIVE STUDIES ......................................................... 54 2.8 RATIONALE FOR DIAGNOSTIC IMAGING STUDIES ................................................... 57 2.9 RATIONALE FOR GROWTH HORMONE SECRETION TESTING BEFORE AND AFTER RADIATION THERAPY ............................................................................................ 59 3.0 ELIGIBILITY CRITERIA AND STUDY ENROLLMENT ............................................ 60 3.1 INCLUSION CRITERIA FOR ALL PATIENTS............................................................... 60 3.2 CRITERIA FOR ASSIGNMENT TO THE LOW-RISK ARM OF THE PROTOCOL ............... 61 3.3 CRITERIA FOR ASSIGNMENT TO THE INTERMEDIATE-RISK ARM OF THE PROTOCOL62 3.4 CRITERIA FOR ASSIGNMENT TO THE HIGH-RISK ARM OF THE PROTOCOL .............. 63 3.5 SYNCHRONOUS EXTRANEURAL ATRT ................................................................... 63 3.6 ENROLLMENT ON STUDY ....................................................................................... 63 4.0 TREATMENT PLAN ..........................................................................................................
Load more

Recommended publications
  • Neurofibromatosis Type 2 (NF2)
    International Journal of Molecular Sciences Review Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis Suha Bachir 1,† , Sanjit Shah 2,† , Scott Shapiro 3,†, Abigail Koehler 4, Abdelkader Mahammedi 5 , Ravi N. Samy 3, Mario Zuccarello 2, Elizabeth Schorry 1 and Soma Sengupta 4,* 1 Department of Genetics, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA; [email protected] (S.B.); [email protected] (E.S.) 2 Department of Neurosurgery, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (S.S.); [email protected] (M.Z.) 3 Department of Otolaryngology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (S.S.); [email protected] (R.N.S.) 4 Department of Neurology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] 5 Department of Radiology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] * Correspondence: [email protected] † These authors contributed equally. Abstract: Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression.
    [Show full text]
  • Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies
    International Journal of Molecular Sciences Review Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies Maria Peleli 1,2,3,*, Aristidis Moustakas 1 and Andreas Papapetropoulos 2,3 1 Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden; [email protected] 2 Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece; [email protected] 3 Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, Greece * Correspondence: [email protected]; Tel.: +46-768-795-270 Received: 28 August 2020; Accepted: 3 October 2020; Published: 6 October 2020 Abstract: Glioblastoma and other brain or CNS malignancies (like neuroblastoma and medulloblastoma) are difficult to treat and are characterized by excessive vascularization that favors further tumor growth. Since the mean overall survival of these types of diseases is low, the finding of new therapeutic approaches is imperative. In this review, we discuss the importance of the interaction between the endothelium and the tumor cells in brain and CNS malignancies. The different mechanisms of formation of new vessels that supply the tumor with nutrients are discussed. We also describe how the tumor cells (TC) alter the endothelial cell (EC) physiology in a way that favors tumorigenesis. In particular, mechanisms of EC–TC interaction are described such as (a) communication using secreted growth factors (i.e., VEGF, TGF-β), (b) intercellular communication through gap junctions (i.e., Cx43), and (c) indirect interaction via intermediate cell types (pericytes, astrocytes, neurons, and immune cells).
    [Show full text]
  • Risk Factors for Gliomas and Meningiomas in Males in Los Angeles County1
    [CANCER RESEARCH 49, 6137-6143. November 1, 1989] Risk Factors for Gliomas and Meningiomas in Males in Los Angeles County1 Susan Preston-Martin,2 Wendy Mack, and Brian E. Henderson Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, California 90033 ABSTRACT views with proxy respondents, we were unable to include a large proportion of otherwise eligible cases because they were deceased or Detailed job histories and information about other suspected risk were too ill or impaired to participate in an interview. The Los Angeles factors were obtained during interviews with 272 men aged 25-69 with a County Cancer Surveillance Program identified the cases (26). All primary brain tumor first diagnosed during 1980-1984 and with 272 diagnoses had been microscopically confirmed. individually matched neighbor controls. Separate analyses were con A total of 478 patients were identified. The hospital and attending ducted for the 202 glioma pairs and the 70 meningioma pairs. Meningi- physician granted us permission to contact 396 (83%) patients. We oma, but not glioma, was related to having a serious head injury 20 or were unable to locate 22 patients, 38 chose not to participate, and 60 more years before diagnosis (odds ratio (OR) = 2.3; 95% confidence were aphasie or too ill to complete the interview. We interviewed 277 interval (CI) = 1.1-5.4), and a clear dose-response effect was observed patients (74% of the 374 patients contacted about the study or 58% of relating meningioma risk to number of serious head injuries (/' for trend the initial 478 patients).
    [Show full text]
  • Central Nervous System Cancers Panel Members Can Be Found on Page 1151
    1114 NCCN David Tran, MD, PhD; Nam Tran, MD, PhD; Frank D. Vrionis, MD, MPH, PhD; Patrick Y. Wen, MD; Central Nervous Nicole McMillian, MS; and Maria Ho, PhD System Cancers Overview In 2013, an estimated 23,130 people in the United Clinical Practice Guidelines in Oncology States will be diagnosed with primary malignant brain Louis Burt Nabors, MD; Mario Ammirati, MD, MBA; and other central nervous system (CNS) neoplasms.1 Philip J. Bierman, MD; Henry Brem, MD; Nicholas Butowski, MD; These tumors will be responsible for approximately Marc C. Chamberlain, MD; Lisa M. DeAngelis, MD; 14,080 deaths. The incidence of primary brain tumors Robert A. Fenstermaker, MD; Allan Friedman, MD; Mark R. Gilbert, MD; Deneen Hesser, MSHSA, RN, OCN; has been increasing over the past 30 years, especially in Matthias Holdhoff, MD, PhD; Larry Junck, MD; elderly persons.2 Metastatic disease to the CNS occurs Ronald Lawson, MD; Jay S. Loeffler, MD; Moshe H. Maor, MD; much more frequently, with an estimated incidence ap- Paul L. Moots, MD; Tara Morrison, MD; proximately 10 times that of primary brain tumors. An Maciej M. Mrugala, MD, PhD, MPH; Herbert B. Newton, MD; Jana Portnow, MD; Jeffrey J. Raizer, MD; Lawrence Recht, MD; estimated 20% to 40% of patients with systemic cancer Dennis C. Shrieve, MD, PhD; Allen K. Sills Jr, MD; will develop brain metastases.3 Abstract Please Note Primary and metastatic tumors of the central nervous system are The NCCN Clinical Practice Guidelines in Oncology a heterogeneous group of neoplasms with varied outcomes and (NCCN Guidelines®) are a statement of consensus of the management strategies.
    [Show full text]
  • Malignant Glioma Arising at the Site of an Excised Cerebellar Hemangioblastoma After Irradiation in a Von Hippel-Lindau Disease Patient
    DOI 10.3349/ymj.2009.50.4.576 Case Report pISSN: 0513-5796, eISSN: 1976-2437 Yonsei Med J 50(4): 576-581, 2009 Malignant Glioma Arising at the Site of an Excised Cerebellar Hemangioblastoma after Irradiation in a von Hippel-Lindau Disease Patient Na-Hye Myong1 and Bong-Jin Park2 1Department of Pathology, Dankook University College of Medicine, Cheonan; 2Department of Neurosurgery, Kyunghee University Hospital, Seoul, Korea. We describe herein a malignant glioma arising at the site of the resected hemangioblastoma after irradiation in a patient with von Hippel-Lindau disease (VHL). The patient was a 25 year-old male with multiple heman- gioblastomas at the cerebellum and spinal cord, multiple pancreatic cysts and a renal cell carcinoma; he was diagnosed as having VHL disease. The largest hemangioblastoma at the right cerebellar hemisphere was completely removed, and he received high-dose irradiation postoperatively. The tumor recurred at the same site 7 years later, which was a malignant glioma with no evidence of hemangioblastoma. The malignant glioma showed molecular genetic profiles of radiation-induced tumors because of its diffuse p53 immunostaining and the loss of p16 immunoreactivity. The genetic study to find the loss of heterozygosity (LOH) of VHL gene revealed that only the cerebellar hemangioblastoma showed allelic losses for the gene. To the best of our knowledge, this report is the first to show a malignant glioma that developed in a patient with VHL disease after radiation therapy at the site of an excised hemangioblastoma. This report also suggests that radiation therapy should be performed very carefully in VHL patients with hemangioblastomas.
    [Show full text]
  • Thiopurine Drug Therapy
    Thiopurine Drug Therapy Thiopurine drug therapy is used for autoimmune diseases, inflammatory bowel disease, acute lymphoblastic leukemia, and to prevent rejection after solid organ transplant. The inactivation of thiopurine drugs is catalyzed in part by thiopurine Tests to Consider methyltrasferase (TPMT) and nudix hydrolase 15 (NUDT15). Variants in the TPMT and/or NUDT15 genes are associated with an accumulation of cytotoxic metabolites Thiopurine Methyltransferase, RBC leading to increased risk of drug-related toxicity with standard doses of thiopurine 0092066 drugs, and the effects on thiopurine catabolism can be additive. Method: Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry The enzyme activity phenotype of TPMT can also be measured directly when Phenotype test to assess risk for severe performed prior to drug administration. Complementary to pretherapeutic tests, myelosuppression with standard dosing of concentrations of thiopurines and metabolites can be measured after initiation of thiopurine drugs therapy to optimize dose. Use for individuals being considered for thiopurine therapy Must be performed before thiopurine therapy is initiated Disease Overview Can also detect rapid metabolizer phenotype Prevalence TPMT and NUDT15 3001535 Method: Polymerase Chain Very low/absent TPMT activity: ~3/1,000 individuals Reaction/Fluorescence Monitoring Intermediate TPMT activity: ~10% of Caucasian individuals Normal TPMT activity: ~90% of individuals Genotyping test to assess genetic risk for severe myelosuppression
    [Show full text]
  • Charts Chart 1: Benign and Borderline Intracranial and CNS Tumors Chart
    Charts Chart 1: Benign and Borderline Intracranial and CNS Tumors Chart Glial Tumor Neuronal and Neuronal‐ Ependymomas glial Neoplasms Subependymoma Subependymal Giant (9383/1) Cell Astrocytoma(9384/1) Myyppxopapillar y Desmoplastic Infantile Ependymoma Astrocytoma (9412/1) (9394/1) Chart 1: Benign and Borderline Intracranial and CNS Tumors Chart Glial Tumor Neuronal and Neuronal‐ Ependymomas glial Neoplasms Subependymoma Subependymal Giant (9383/1) Cell Astrocytoma(9384/1) Myyppxopapillar y Desmoplastic Infantile Ependymoma Astrocytoma (9412/1) (9394/1) Use this chart to code histology. The tree is arranged Chart Instructions: Neuroepithelial in descending order. Each branch is a histology group, starting at the top (9503) with the least specific terms and descending into more specific terms. Ependymal Embryonal Pineal Choro id plexus Neuronal and mixed Neuroblastic Glial Oligodendroglial tumors tumors tumors tumors neuronal-glial tumors tumors tumors tumors Pineoblastoma Ependymoma, Choroid plexus Olfactory neuroblastoma Oligodendroglioma NOS (9391) (9362) carcinoma Ganglioglioma, anaplastic (9522) NOS (9450) Oligodendroglioma (9390) (9505 Olfactory neurocytoma Ganglioglioma, malignant (()9521) anaplastic (()9451) Anasplastic ependymoma (9505) Olfactory neuroepithlioma Oligodendroblastoma (9392) (9523) (9460) Papillary ependymoma (9393) Glioma, NOS (9380) Supratentorial primitive Atypical EdEpendymo bltblastoma MdllMedulloep ithliithelioma Medulloblastoma neuroectodermal tumor tetratoid/rhabdoid (9392) (9501) (9470) (PNET) (9473) tumor
    [Show full text]
  • Central Nervous System Tumors General ~1% of Tumors in Adults, but ~25% of Malignancies in Children (Only 2Nd to Leukemia)
    Last updated: 3/4/2021 Prepared by Kurt Schaberg Central Nervous System Tumors General ~1% of tumors in adults, but ~25% of malignancies in children (only 2nd to leukemia). Significant increase in incidence in primary brain tumors in elderly. Metastases to the brain far outnumber primary CNS tumors→ multiple cerebral tumors. One can develop a very good DDX by just location, age, and imaging. Differential Diagnosis by clinical information: Location Pediatric/Young Adult Older Adult Cerebral/ Ganglioglioma, DNET, PXA, Glioblastoma Multiforme (GBM) Supratentorial Ependymoma, AT/RT Infiltrating Astrocytoma (grades II-III), CNS Embryonal Neoplasms Oligodendroglioma, Metastases, Lymphoma, Infection Cerebellar/ PA, Medulloblastoma, Ependymoma, Metastases, Hemangioblastoma, Infratentorial/ Choroid plexus papilloma, AT/RT Choroid plexus papilloma, Subependymoma Fourth ventricle Brainstem PA, DMG Astrocytoma, Glioblastoma, DMG, Metastases Spinal cord Ependymoma, PA, DMG, MPE, Drop Ependymoma, Astrocytoma, DMG, MPE (filum), (intramedullary) metastases Paraganglioma (filum), Spinal cord Meningioma, Schwannoma, Schwannoma, Meningioma, (extramedullary) Metastases, Melanocytoma/melanoma Melanocytoma/melanoma, MPNST Spinal cord Bone tumor, Meningioma, Abscess, Herniated disk, Lymphoma, Abscess, (extradural) Vascular malformation, Metastases, Extra-axial/Dural/ Leukemia/lymphoma, Ewing Sarcoma, Meningioma, SFT, Metastases, Lymphoma, Leptomeningeal Rhabdomyosarcoma, Disseminated medulloblastoma, DLGNT, Sellar/infundibular Pituitary adenoma, Pituitary adenoma,
    [Show full text]
  • Adrenal Neuroblastoma Mimicking Pheochromocytoma in an Adult With
    Khalayleh et al. Int Arch Endocrinol Clin Res 2017, 3:008 Volume 3 | Issue 1 International Archives of Endocrinology Clinical Research Case Report : Open Access Adrenal Neuroblastoma Mimicking Pheochromocytoma in an Adult with Neurofibromatosis Type 1 Harbi Khalayleh1, Hilla Knobler2, Vitaly Medvedovsky2, Edit Feldberg3, Judith Diment3, Lena Pinkas4, Guennadi Kouniavsky1 and Taiba Zornitzki2* 1Department of Surgery, Hebrew University Medical School of Jerusalem, Israel 2Endocrinology, Diabetes and Metabolism Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Israel 3Pathology Institute, Kaplan Medical Center, Israel 4Nuclear Medicine Institute, Kaplan Medical Center, Israel *Corresponding author: Taiba Zornitzki, MD, Endocrinology, Diabetes and Metabolism Institute, Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Bilu 1, 76100 Rehovot, Israel, Tel: +972-894- 41315, Fax: +972-8 944-1912, E-mail: [email protected] Context 2. This is the first reported case of an adrenal neuroblastoma occurring in an adult patient with NF1 presenting as a large Neurofibromatosis type 1 (NF1) is a genetic disorder asso- adrenal mass with increased catecholamine levels mimicking ciated with an increased risk of malignant disorders. Adrenal a pheochromocytoma. neuroblastoma is considered an extremely rare tumor in adults and was not previously described in association with NF1. 3. This case demonstrates the clinical overlap between pheo- Case description: A 42-year-old normotensive woman with chromocytoma and neuroblastoma. typical signs of NF1 underwent evaluation for abdominal pain, Keywords and a large 14 × 10 × 16 cm left adrenal mass displacing the Adrenal neuroblastoma, Neurofibromatosis type 1, Pheo- spleen, pancreas and colon was found. An initial diagnosis of chromocytoma, Neural crest-derived tumors pheochromocytoma was done based on the known strong association between pheochromocytoma, NF1 and increased catecholamine levels.
    [Show full text]
  • Identification and Analysis of Single-Nucleotide Polymorphisms in the Gemcitabine Pharmacologic Pathway
    The Pharmacogenomics Journal (2004) 4, 307–314 & 2004 Nature Publishing Group All rights reserved 1470-269X/04 $30.00 www.nature.com/tpj ORIGINAL ARTICLE Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway AK Fukunaga1 ABSTRACT 2 Significant variability in the antitumor efficacy and systemic toxicity of S Marsh gemcitabine has been observed in cancer patients. However, there are 1 DJ Murry currently no tools for prospective identification of patients at risk for TD Hurley3 untoward events. This study has identified and validated single-nucleotide HL McLeod2 polymorphisms (SNP) in genes involved in gemcitabine metabolism and transport. Database mining was conducted to identify SNPs in 14 genes 1Department of Clinical Pharmacy and Pharmacy involved in gemcitabine metabolism. Pyrosequencing was utilized to Practice, Purdue University, W. Lafayette, IN, determine the SNP allele frequencies in genomic DNA from European and 2 USA; Departments of Medicine, Genetics, and African populations (n ¼ 190). A total of 14 genetic variants (including 12 Molecular Biology and Pharmacology, Washington University School of Medicine and SNPs) were identified in eight of the gemcitabine metabolic pathway genes. the Siteman Cancer Center, St Louis, MO, USA; The majority of the database variants were observed in population samples. 3Department of Biochemistry and Molecular Nine of the 14 (64%) polymorphisms analyzed have allele frequencies that Biology, Indiana University School of Medicine, were found to be significantly different between the European and African Indianapolis, IN, USA populations (Po0.05). This study provides the first step to identify markers Correspondence: for predicting variability in gemcitabine response and toxicity. Dr HL McLeod, Washington University The Pharmacogenomics Journal (2004) 4, 307–314.
    [Show full text]
  • Choroid Plexus Tumors: a Review
    UC San Diego UC San Diego Previously Published Works Title Perinatal (fetal and neonatal) choroid plexus tumors: a review. Permalink https://escholarship.org/uc/item/0sm7q5q7 Journal Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 35(6) ISSN 0256-7040 Authors Crawford, John R Isaacs, Hart Publication Date 2019-06-01 DOI 10.1007/s00381-019-04135-x Peer reviewed eScholarship.org Powered by the California Digital Library University of California Child's Nervous System (2019) 35:937–944 https://doi.org/10.1007/s00381-019-04135-x REVIEW ARTICLE Perinatal (fetal and neonatal) choroid plexus tumors: a review John R. Crawford1,2,3 & Hart Isaacs Jr3,4 Received: 13 September 2018 /Accepted: 20 March 2019 /Published online: 5 April 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Introduction The object of this review is to describe the choroid plexus tumors (CPTs) occurring in the fetus and neonate with regard to clinical presentation, location, pathology, treatment, and outcome. Materials and methods Case histories and clinical outcomes were reviewed from 93 cases of fetal and neonatal tumors obtained from the literature and our own institutional experience from 1980 to 2016. Results Choroid plexus papilloma (CPP) is the most common tumor followed by choroid plexus carcinoma (CPC) and atypical choroid plexus papilloma (ACPP). Hydrocephalus and macrocephaly are the presenting features for all three tumors. The lateral ventricles are the main site of tumor origin followed by the third and fourth ventricles, respectively. CPTs of the fetus are detected most often near the end of the third trimester of pregnancy by fetal ultrasound.
    [Show full text]
  • A Case of Intramedullary Spinal Cord Astrocytoma Associated with Neurofibromatosis Type 1
    KISEP J Korean Neurosurg Soc 36 : 69-71, 2004 Case Report A Case of Intramedullary Spinal Cord Astrocytoma Associated with Neurofibromatosis Type 1 Jae Taek Hong, M.D.,1 Sang Won Lee, M.D.,1 Byung Chul Son, M.D.,1 Moon Chan Kim, M.D.2 Department of Neurosurgery,1 St. Vincent Hospital, The Catholic University of Korea, Suwon, Korea Department of Neurosurgery,2 Kangnam St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea The authors report a symptomatic intramedullary spinal cord astrocytoma in the thoracolumbar area associated with neurofibromatosis type 1 (NF-1). A 38-year-old woman presented with paraparesis. Magnetic resonance imaging revealed an intramedullary lesion within the lower thoracic spinal cord and conus medullaris, which was removed surgically. Pathological investigation showed anaplastic astrocytoma. This case confirms that the diagnosis criteria set by the National Institute of Health Consensus Development Conference can be useful to differentiate ependymoma from astrocytoma when making a preoperative diagnosis of intramedullary spinal cord tumor in patients of NF-1. KEY WORDS : Astrocytoma·Intramedullary cord tumor·Neurofibromatosis. Introduction eurofibromatosis type 1 (NF-1), also known as von N Recklinghausen's disease, is one of the most common autosomal dominant inherited disorders with an incidence of 1 in 3,000 individuals and is characterized by a predisposition to tumors of the nervous system5,6,12,16). Central nervous system lesions associated with NF-1 include optic nerve glioma and low-grade gliomas of the hypothalamus, cerebellum and brain stem6,10). Since the introduction of magnetic resonance(MR) imaging, Fig. 1. Photograph of the patient's back shows multiple subcutaneous incidental lesions with uncertain pathological characteristic nodules (black arrow) and a cafe-au-lait spot (white arrow), which have been a frequent finding in the brain and spinal cord of are typical of NF-1.
    [Show full text]