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Trial record 35 of 73 for:    DIPG

Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma

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ClinicalTrials.gov Identifier: NCT02359565
Recruitment Status : Recruiting
First Posted : February 10, 2015
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I trial studies the side effects and best dose of pembrolizumab and to see how well it works in treating younger patients with high-grade gliomas (brain tumors that are generally expected to be fast growing and aggressive), diffuse intrinsic pontine gliomas (brain stem tumors), brain tumors with a high number of genetic mutations, ependymoma or medulloblastoma that have come back, progressed, or have not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells.

Condition or disease Intervention/treatment Phase
Constitutional Mismatch Repair Deficiency Syndrome Lynch Syndrome Malignant Glioma Progressive Ependymoma Progressive Medulloblastoma Recurrent Brain Neoplasm Recurrent Childhood Ependymoma Recurrent Diffuse Intrinsic Pontine Glioma Recurrent Medulloblastoma Refractory Brain Neoplasm Refractory Diffuse Intrinsic Pontine Glioma Refractory Ependymoma Refractory Medulloblastoma Procedure: Diffusion Tensor Imaging Procedure: Diffusion Weighted Imaging Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging Other: Laboratory Biomarker Analysis Procedure: Magnetic Resonance Spectroscopic Imaging Biological: Pembrolizumab Procedure: Perfusion Magnetic Resonance Imaging Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Preliminary Efficacy Trial of MK-3475 (Pembrolizumab; Anti-PD-1) in Children With Recurrent, Progressive or Refractory Diffuse Intrinsic Pontine Glioma (DIPG), Non-Brainstem High-Grade Gliomas (NB-HGG), Ependymoma, Medulloblastoma or Hypermutated Brain Tumors
Actual Study Start Date : May 22, 2015
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2020


Arm Intervention/treatment
Experimental: Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 34 courses in the absence of disease progression or unacceptable toxicity.
Procedure: Diffusion Tensor Imaging
Correlative studies
Other Names:
  • DIFFUSION TENSOR MRI
  • DT-MRI
  • DTI

Procedure: Diffusion Weighted Imaging
Correlative studies
Other Names:
  • Diffusion Weighted MRI
  • Diffusion-Weighted Magnetic Resonance Imaging
  • Diffusion-Weighted MR Imaging
  • Diffusion-Weighted MRI
  • DW-MRI
  • DWI
  • DWI MRI
  • DWI-MRI
  • MR Diffusion-Weighted Imaging

Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Correlative studies
Other Names:
  • DCE MRI
  • DCE-MRI
  • DYNAMIC CONTRAST ENHANCED MRI

Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
Correlative studies
Other Names:
  • DSC-MRI
  • Dynamic Susceptibility Contrast-Enhanced MRI
  • DYNAMIC SUSCEPTIBILITY-CONTRAST MRI

Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Magnetic Resonance Spectroscopic Imaging
Correlative studies
Other Names:
  • 1H- Nuclear Magnetic Resonance Spectroscopic Imaging
  • 1H-nuclear magnetic resonance spectroscopic imaging
  • Magnetic Resonance Spectroscopy
  • MRS
  • MRS Imaging
  • MRSI
  • Proton Magnetic Resonance Spectroscopic Imaging

Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Procedure: Perfusion Magnetic Resonance Imaging
Correlative studies
Other Name: magnetic resonance perfusion imaging




Primary Outcome Measures :
  1. Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 [ Time Frame: Within 30 days of treatment ]
    All adverse events observed during the dose finding period as well as during later courses will be summarized by stratum and by dose (if applicable). Separate tables for adverse events attributable to pembrolizumab will also be provided for each of the three strata.

  2. Sustained objective response (partial response [PR] + complete response [CR]) [ Time Frame: Within 12 courses (approximately 9 months) ]
    Stratum specific exact confidence interval estimates will be provided for the sustained objective response rates. In addition, if adequate number of responses is observed to make such analyses meaningful, stratum-specific confirmed sustained objective response rates observed during treatment will be estimated by cumulative incidence functions.

  3. Change in the percentage of CD8+ T cells that are PD-1+ due to treatment with pembrolizumab (Stratum C) [ Time Frame: Baseline to after 6 weeks of treatment ]
    A 1-sample t-distribution-based confidence interval (or its non-parametric counterparts, as needed) will be used to estimate the average change in the percentage of CD8+ T cells that are PD-1+ due to treatment with pembrolizumab.


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Date of initial treatment to the earliest date of disease progression or death from any cause for patients who fail and to the date of last contact for patients who remain at risk for failure, assessed bi-annually up to 3 years and then yearly thereafter ]
    Log-ranks tests or Cox regression models will be used to explore associations between biomarkers and PFS and OS.

  2. Event-free survival [ Time Frame: Up to 3 years ]
    Kaplan-Meier estimates of event free survival distribution for all evaluable patients within each stratum will be provided.

  3. Overall survival (OS) [ Time Frame: Date of diagnosis to the earliest date of death from any cause or to the date of last contact for patients who remain at risk for failure, assessed bi-annually up to 3 years and then yearly thereafter ]
    Kaplan-Meier estimates of OS distribution for all evaluable patients within each stratum will be provided. Log-ranks tests or Cox regression models will be used to explore associations between biomarkers and progression free survival (PFS) and OS.

  4. Radiologic response (Stratum C) [ Time Frame: Up to 3 years ]
    Will report any objective radiological responses observed in subjects who were not part of the primary cohort of progressive/recurrent high-grade gliomas (HGGs).

  5. Biomarker expression levels [ Time Frame: Up to 18 courses (approximately 13.5 months) ]
    The biomarker data generated as part of this study will be summarized via descriptive statistics and plots. The association between response and potential biomarkers will be evaluated by Fisher's exact or Chi-square test for categorical outcomes and two sample t-tests (or appropriate non-parametric counterparts) for continuous outcomes. Log-ranks tests or Cox regression models will also be used to explore associations between biomarkers and PFS and OS. These analyses will be done in a stratum specific fashion.

  6. Changes in quantitative imaging parameters [ Time Frame: Baseline to up to 34 courses (approximately 25.5 months) ]
    Observed values of the proposed quantitative imaging parameters as well as changes in these parameters across time will be described and summarized via descriptive statistics and plots. Mixed effects models will be used to explore differences in estimated slope parameters of the quantitative imaging. Pairwise changes in these imaging parameters across various time points will also be described. T-tests (or their non-parametric equivalent) will be used to compare differences in pairwise changes between patients with progression vs. pseudoprogression/tumor inflammation.



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Ages Eligible for Study:   1 Year to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • INCLUSION CRITERIA FOR STRATA A, B, D AND E
  • Tumor: patient must have one of the following diagnoses to be eligible:
  • Stratum A, currently closed to enrollment: Patients must have a recurrent, progressive or refractory DIPG following radiation therapy with or without chemotherapy

    • Histologic diagnosis is not required for patients with typical imaging findings of DIPG (defined as patients with a diffuse expansile mass centered in and involving at least 2/3 of the pons); patients with brainstem tumors who have undergone biopsy with a diagnosis of high-grade glioma or diffuse infiltrating glioma are also eligible
  • Stratum B: Patients must have a histologically confirmed diagnosis of a non-brainstem high-grade glioma (NB-HGG) that is recurrent, progressive or refractory following therapy which included radiotherapy; spinal primary disease is eligible
  • Stratum D: Patients must have a histologically confirmed diagnosis of ependymoma that is recurrent, progressive or refractory following therapy which included radiotherapy
  • Stratum E: Patients must have a histologically confirmed diagnosis of medulloblastoma that is recurrent, progressive or refractory following therapy which included radiotherapy
  • Patients must have adequate pre-trial formalin-fixed paraffin-embedded (FFPE) tumor material available for use in the biology studies mutational analysis and genome wide sequencing for each stratum

    • Patients with DIPG who have tissue available are requested to submit similar tissue as patients in other strata; however, this is not required for eligibility
  • All subjects must have measurable disease in 2-dimensions on MRI scan of the brain; disease should be consistently measured with the two largest perpendicular dimensions
  • Patients must have received prior radiation therapy and/or chemotherapy and recovered from the acute treatment related toxicities (defined as =< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study; there is no upper limit to the number of prior therapies that is allowed
  • Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks prior to study enrollment or at least six (6) weeks if prior nitrosourea
  • Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment

    • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration must be discussed with and approved by the study chair
    • Monoclonal antibody treatment and/or agents with prolonged half-lives: at least three half-lives must have elapsed prior to enrollment
  • Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment
  • Patients must have had their last fraction of:

    • Craniospinal irradiation >= 3 months prior to enrollment
    • Other substantial bone marrow irradiation >= 6 weeks prior to enrollment
    • Local palliative radiation therapy (XRT) (small port) >= 2 weeks
  • Patient must be >= 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment
  • Patients must be fully recovered from all acute effects of prior surgical intervention
  • All races and ethnic groups are eligible for this study
  • Patients with neurological deficits should have deficits that are completely stable for a minimum of 1 week (7 days) prior to enrollment
  • Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within two weeks of enrollment must be >= 70; patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Absolute neutrophil count >= 1000 cells/uL
  • Platelets >= 75,000 cells /uL (unsupported, defined as no platelet transfusion within 7 days)
  • Hemoglobin >= 8 g/dl (may receive transfusions)
  • Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
  • Albumin >= 2 g/dl
  • Serum creatinine based on age/gender as noted below; patients that do not meet the criteria below but have a 24 hour creatinine clearance or glomerular filtration rate (GFR) (radioisotope or iothalamate) >= 70 ml/min/1.73 m^2 are eligible

    • 1 to < 2 years: 0.6 mg/dl
    • 2 to < 6 years: 0.8 mg/dl
    • 6 to < 10 years: 1 mg/dl
    • 10 to < 13 years: 1.2 mg/dl
    • 13 to < 16 years: 1.5 mg/dl (male), 1.4 mg/dl (female)
    • >= 16 years: 1.7 mg/dl (male), 1.4 mg/dl (female)
  • Pulse oximetry > 93% on room air and no evidence of dyspnea at rest
  • Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (e.g. filgrastim, sargramostim, erythropoietin); 2 weeks must have elapsed for long-acting formulations
  • Patients must be willing to use brief courses (at least 72 hours) of steroids as directed for potential inflammatory side effects of the therapy if recommended by their treating physician
  • Female subjects of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is to be treated with MK-3475 (pembrolizumab)
  • Patients of childbearing or child fathering potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity while being treated on this study and for 6 months after the last dose of study medication
  • The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document, inclusive of assent where appropriate, according to institutional guidelines
  • INCLUSION CRITERIA FOR STRATUM C: Diagnosis of hypermutated brain tumors Patients with brain tumors and increased tumor mutation burden as determined by

    • Confirmed diagnosis of CMMRD syndrome by Clinical Laboratory Improvement Act (CLIA)-certified germline gene sequencing OR
    • Confirmation of high mutation burden by whole genome/exome sequencing performed in a CLIA-certified laboratory and/or the use of Foundation One next generation sequence panel or another CLIA approved targeted sequencing lab with publicly available correlations between number of mutations found in the panel and mutations per megabase and/or genome; for protocol purposes a high mutation burden will be defined as at least 100 non-synonymous coding-region mutations by whole exome/genome sequencing (well above two standard deviations of the number of median similar mutations described in pediatric CNS cancers) AND/OR a high tumor mutation burden (TMB) or intermediate TMB based on the reporting parameters of the panel; TMB parameters provided for the Foundation One reports are high tumor mutation burden is >= 20 mutations per megabase or intermediate TMB is between 6 to 19 mutations per megabase
    • Confirmed diagnosis of Lynch syndrome by CLIA-certified germline gene sequencing; patients with Lynch syndrome will not be accounted for in primary objective unless their tumors are determined to have the minimum number of mutations described above but they will still be eligible for this study
    • Low-grade tumors in patients with CMMRD or Lynch syndrome do not have to reach the threshold of 100 mutations for study inclusion
  • INCLUSION CRITERIA FOR STRATUM C: Patients must have a histologically confirmed primary brain tumor that is recurrent, progressive or refractory; inclusion criteria encompasses all types of brain tumors (e.g. gliomas, embryonal tumors or any other type of brain tumor as long as other eligibility criteria are met;

    • Patients with high-grade gliomas are eligible for this clinical trial at least 2 weeks after completion of radiotherapy independent of tumor progression/recurrence as long as they are not enrolled on any other therapeutic clinical trial and there is macroscopic residual disease
    • Patients with other concomitant tumors associated with CMMRD syndrome including gastrointestinal polyps/adenomas and carcinomas, lymphomas and leukemias will be eligible as long as they are not requiring anticancer therapy directed against these other cancers and meet all other eligibility criteria
  • INCLUSION CRITERIA FOR STRATUM C: Patients must have adequate pre-trial FFPE tumor material available and be willing to provide a blood sample for use in the genome wide sequencing studies; while tissue is required for genome-wide sequencing of tumor and germline samples, patients will be deemed eligible for the study with a minimum of approximately 10 unstained slides for the planned analysis
  • INCLUSION CRITERIA FOR STRATUM C: All subjects must have measurable disease in 2-dimensions on MRI scan of the brain and/or spine; disease should be consistently measured with the two largest perpendicular dimensions
  • INCLUSION CRITERIA FOR STRATUM C: Patients must have received prior radiotherapy and/or chemotherapy with the following exceptions:

    • Patients with secondary CNS cancers after a previous medical problem/malignancy who cannot receive full dose of radiotherapy (> 50 Gy) as long as they meet all other eligibility criteria
    • Patients with progressive low-grade gliomas and CMMRD or Lynch syndrome Patients must have recovered from the acute treatment related toxicities (defined as =< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study; there is no upper limit to the number of prior therapies that is allowed
  • INCLUSION CRITERIA FOR STRATUM C: Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks prior to study enrollment or at least six (6) weeks if prior nitrosourea
  • INCLUSION CRITERIA FOR STRATUM C: Patient must have received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment

    • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration must be discussed with and approved by the study chair
    • Monoclonal antibody treatment and/or agents with prolonged half-lives: at least three half-lives must have elapsed prior to enrollment
  • INCLUSION CRITERIA FOR STRATUM C: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment
  • INCLUSION CRITERIA FOR STRATUM C: Patients must have had their last fraction of:

    • Craniospinal irradiation >= 3 months prior to enrollment
    • Other substantial bone marrow irradiation >= 6 weeks prior to enrollment
    • Local palliative radiation therapy (XRT) (small port) >= 2 weeks
  • INCLUSION CRITERIA FOR STRATUM C: Patient must be:

    • >= 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment
    • >= 5 years since allogeneic bone marrow transplant prior to enrollment with no evidence of active graft versus (vs.) host disease
  • INCLUSION CRITERIA FOR STRATUM C: Patients must be fully recovered from all acute effects of prior surgical intervention
  • INCLUSION CRITERIA FOR STRATUM C: All races and ethnic groups are eligible for this study
  • INCLUSION CRITERIA FOR STRATUM C: Patients with neurological deficits should have deficits that are completely stable for a minimum of 1 week (7 days) prior to enrollment
  • INCLUSION CRITERIA FOR STRATUM C: Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within two weeks of enrollment must be >= 60; patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • INCLUSION CRITERIA FOR STRATUM C: Absolute neutrophil count >= 1000 cells/uL
  • INCLUSION CRITERIA FOR STRATUM C: Platelets >= 75,000 cells/uL (unsupported, defined as no platelet transfusion within 7 days)
  • INCLUSION CRITERIA FOR STRATUM C: Hemoglobin >= 8 g/dl (may receive transfusions)
  • INCLUSION CRITERIA FOR STRATUM C: Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)
  • INCLUSION CRITERIA FOR STRATUM C: ALT (SGPT) =< 3 x institutional upper limit of normal
  • INCLUSION CRITERIA FOR STRATUM C: Albumin >= 2 g/dl
  • INCLUSION CRITERIA FOR STRATUM C: Serum creatinine based on age/gender as noted below; patients that do not meet the criteria below but have a 24 hour creatinine clearance or GFR (radioisotope or iothalamate) >= 70 ml/min/1.73 m^2 are eligible

    • 1 to < 2 years: 0.6 mg/dl
    • 2 to < 6 years: 0.8 mg/dl
    • 6 to < 10 years: 1 mg/dl
    • 10 to < 13 years: 1.2 mg/dl
    • 13 to < 16 years: 1.5 mg/dl (male), 1.4 mg/dl (female)
    • >= 16 years: 1.7 mg/dl (male), 1.4 mg/dl (female)
  • INCLUSION CRITERIA FOR STRATUM C: Pulse oximetry > 93% on room air and no evidence of dyspnea at rest
  • INCLUSION CRITERIA FOR STRATUM C: Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (i.e. filgrastim; sargramostim; erythropoietin); 2 weeks must have elapsed for long-acting formulations
  • INCLUSION CRITERIA FOR STRATUM C: Patients must be willing to use brief courses (at least 72 hours) of steroids as directed for potential inflammatory side effects of the therapy if recommended by their treating physician
  • INCLUSION CRITERIA FOR STRATUM C: Female subjects of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is to be treated with MK-3475 (pembrolizumab)
  • INCLUSION CRITERIA FOR STRATUM C: Patients of childbearing or child fathering potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity while being treated on this study and for 6 months after the last dose of study medication
  • INCLUSION C

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02359565


Locations
United States, California
Children's Hospital Los Angeles Suspended
Los Angeles, California, United States, 90027
Lucile Packard Children's Hospital Stanford University Suspended
Palo Alto, California, United States, 94304
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Site Public Contact    888-823-5923    ctsucontact@westat.com   
Principal Investigator: Kathleen M. Dorris         
United States, District of Columbia
Children's National Medical Center Suspended
Washington, District of Columbia, United States, 20010
United States, Georgia
Children's Healthcare of Atlanta - Egleston Suspended
Atlanta, Georgia, United States, 30322
United States, Illinois
Lurie Children's Hospital-Chicago Suspended
Chicago, Illinois, United States, 60611
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Site Public Contact    212-639-7592      
Principal Investigator: Ira J. Dunkel         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Site Public Contact    888-823-5923    ctsucontact@westat.com   
Principal Investigator: Maryam Fouladi         
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Suspended
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Site Public Contact    888-823-5923    ctsucontact@westat.com   
Principal Investigator: Zsila S. Sadighi         
United States, Texas
Texas Children's Hospital Suspended
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Eugene Hwang Pediatric Brain Tumor Consortium

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02359565     History of Changes
Other Study ID Numbers: NCI-2015-00130
NCI-2015-00130 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PBTC-045
PBTC-045 ( Other Identifier: Pediatric Brain Tumor Consortium )
PBTC-045 ( Other Identifier: CTEP )
UM1CA081457 ( U.S. NIH Grant/Contract )
First Posted: February 10, 2015    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: June 2018

Additional relevant MeSH terms:
Syndrome
Neoplasms
Glioma
Brain Neoplasms
Ependymoma
Medulloblastoma
Colorectal Neoplasms, Hereditary Nonpolyposis
Neoplastic Syndromes, Hereditary
Colorectal Neoplasms
Disease
Pathologic Processes
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroectodermal Tumors, Primitive
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases