Neoplasms

Nervous System Diseases

All Conditions

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Archived CNS neoplasm specimens, in which primary diagnostic studies are complete, and for which there is excess tissue for analysis in the form of unstained slides or paraffin blocks

Terri S Armstrong, C.R.N.P.

Background:

The number of people who get tumors of the brain or central nervous system (CNS) is lower than other cancers. But these tumors cause a higher rate of serious effects and even death. Researchers want to test existing samples of tissue from these tumors to learn more about them. This may lead to better treatment.

Objective:

To study stored samples of CNS tumors to learn more about the tumors and explore new ways to diagnose them.

Eligibility:

The study will use tissue samples already collected at NIH from people with brain or CNS tumors.

Design:

The participants will have given their consent in a previous study.

Researchers will review the tissue samples and any data collected about them.

Researchers will do lab tests and scans on the samples.

All data will be kept secure.

BACKGROUND

* Central Nervous System (CNS) and brain tumors are a heterogeneous group of neoplasms. They can be broadly categorized to tumors of neuroepithelial tissue, meninges, hematopoietic system, germ cells, and sella.
* The Central Brain Tumor Registry of the United States reports an overall average annual age-adjusted incidence rate for the years 2006-2010 for primary brain and CNS tumors as 21.03 per 100,000. This leads to an estimated mortality of over 13,000 deaths per year. Although this number is small compared to other more common cancers, due to the location of CNS (brain and spinal cord) tumors, they are responsible for disproportionately high morbidity and mortality among cancer patients.
* Although much progress has been made on overall understanding of CNS tumors, not much is known about mechanisms responsible for intratumoral heterogeneity, disease relapse, progression into higher grades, and in vivo invasive mechanisms. This may involve new mutations, selection of specific clones of cells by either therapeutic pressure or as part of natural tumor evolution leading to progression, microenvironmental cues or combinations.
* This study will review the molecular pathological alterations of archived human CNS tumor specimens at initial presentation and at subsequent relapse. We will request archived brain tumor tissue samples from the NCI CCR Laboratory of Pathology at multiple time points to determine the expression of cellular proteins and surrogate markers involved in growth, proliferation, differentiation, invasion, and survival of brain tumor cells. Such information will be pooled with imaging data (MRI, PET, etc.) to identify potential surrogate markers of disease resistance.
* This study has the potential to uncover key molecular events underlying disease progression and thereby contribute to the understanding of CNS tumor pathogenesis without active patient intervention.

OBJECTIVES

-To study archived specimens of CNS tumors from the NCI CCR Laboratory of Pathology to explore potential new biomarkers for diagnosis and to better understand CNS tumor pathogenesis.

ELIGIBILITY

* Diagnosis of CNS neoplasm.
* Eligible cases include those in which primary diagnostic studies are complete, and for which there is excess tissue for analysis in the form of unstained slides or paraffin blocks archived in the NCI CCR Laboratory of Pathology as well as imaging stored in the NIH medical records system.
* We also request permission to extend this analysis, as may be relevant in the future, to surplus materials to be accrued under existing NCI protocols, upon completion of all superseding diagnostic tests and medical/scientific studies.

DESIGN

* We anticipate obtaining approximately 500 archived specimens in the NCI CCR Laboratory of Pathology from patients with CNS neoplasms to analyze parameters in order to better understand the biology and pathogenesis of disease.
* To identify potential specimens, medical records of patients seen in the Neuro-Oncology and Neurosurgery Clinics will be reviewed. Additional medical records will be reviewed in order to identify archived specimens and to obtain ancillary information such as result of imaging studies.
* Existing biomarker data will be analyzed in conjunction with review of histological features and clinical data existing in laboratory and imaging data to arrive at improved criteria for diagnosis, and to recognize newly identified, as yet undescribed, disease entities. New biomarkers, as they may become available, will be utilized to improve on current diagnostic methods for disease definition.
* Tissue may be collected from pathology to be processed for specific research question at a future time point. Time of processing may be contingent on accumulating sufficient number of specimens.

Biomarker Analysis of Central Nervous System Tumors

To study archived specimens of CNS tumors from the NCI CCR Laboratory of Pathology to explore potential new biomarkers for diagnosis and to better understand CNS tumor pathogenesis.

National Cancer Institute (NCI)

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

We plan to perform PET scanning on the patients with high grade gliomas after the injection of the second generation of EGFR tracer ,89Zr-ABT806（1-2mCi）, which can be specifically binded to EGFR vⅢ . After fusing the PET and MRI images, we precisely obtained the tissue from the"hot-spot" on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status was detected by Sanger sequencing to analyze the correlation with the 89Zr-ABT806 PET image qualitatively and quantitatively. The final goal was to detect EGFR vⅢ by noninvasive molecular imaging procedure for the clinical outcome prediction and the selection of EGFR-targeted therapies.

Patients will be given IV bolus injection of 89Zr-ABT806(1-2mCi). The first 89Zr-ABT806 PET scan will be performed about 72 to 120 hours after injection of tracer. The second 89Zr-ABT806 PET scan will be performed about 120 to 168 hours after injection of tracer. Semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) and T/N ratio.

89Zr-ABT806 PET

Dongxiao Zhuang, Professor

Liangfu Zhou, Professor

Nijiati Kudulaiti, M.D.

Dongxiao Zhuang, M.D. Ph.D.

Zhemin Huang, M.D.

Chengjun Yao, M.D. Ph.D.

Tainming Qiu, M.D. Ph.D.

Junfeng Lu, M.D. Ph.D.

Huiwei Zhang, M.D.

Zhengwei Zhang, M.D.

Yihui Guan, M.D. Ph.D.

Jingsong Wu, M.D. Ph.D.

Zhifeng Shi, M.D. Ph.D.

Jie Zhang, M.D. Ph.D.

Fangyuan Gong, M.D.

Zhengda Yv, M.D.

The epidermal growth factor receptor variant Ⅲ(EGFR vⅢ) is commonly detected in high-grade gliomas, which is also an important epitope in EGFR-targeted therapies and correlated to poor prognosis. However, detection of this mutant usually needs resected tumor samples. For biopsy samples, test results may not represent the EGFR vⅢ status of the whole tumor tissues because of the heterogeneity of tumor. It is also not applicable for patients who are not suitable for surgical procedure due to the tumor location or patients' general conditions. Because of the importance of the epidermal growth factor receptor (EGFR) signal pathway in oncogenesis, maintenance, and progression of high grade glioma, there has been an intense effort to develop noninvasive molecular imaging approach for the selection and monitoring of EGFR-targeted therapies.

Based on investigators' previous study, investigators plan to perform PET scanning on the participants with high grade gliomas after the injection of the second generation of EGFR tracer ,89Zr-ABT806, which can be specifically binded to EGFR vⅢ . After fusing the PET and MRI images, investigators precisely obtain the tissue from the"hot-spot" on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status will be detected by molecular methods to analyze the correlation with the 89Zr-ABT806 PET image qualitatively and quantitatively. Investigators' final goal is to detect EGFR vⅢ by noninvasive molecular imaging procedure for the clinical outcome prediction and the selection of EGFR-targeted therapies.

The Research on 89Zr-ABT806 PET Imaging in High Grade Glioma

The Research on 89Zr-ABT806 PET Imaging in High Grade Glioma and Its Correlation to EGFRvIII

After fusing the 89Zr-ABT806 PET and MRI images, investigators precisely obtained the tissue from the"hot-spot" on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status will be analyzed by molecular methods. The sensitivity and specificity of 89Zr-ABT806 PET will be measured with statistic methods.

Huashan Hospital

Professor

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

For in vitro diagnostic use only.

The OSNA Breast Cancer System is an automated semi-quantitative, in vitro diagnostic test for the rapid detection of greater than (\>) 0.2 mm metastases in nodal tissue removed from sentinel lymph node biopsies of breast cancer patients. Results from the assay can be used to guide the intra-operative or post-operative decision to remove additional lymph nodes and to aid in patient staging. An assay positive + or ++ result indicates the presence of metastasis (\> 0.2 mm). An assay positive ++ result predicts the presence of macrometastasis (\> 2 mm).

Post-operative histological evaluation of permanent sections of the tissue specimen, in accordance with usual diagnostic practice and using the Sysmex lymph node cutting scheme, is required.

OSNA Breast Cancer System

The study will determine the sensitivity, specificity, negative predictive value and positive predictive value of the OSNA Breast Cancer System by comparing its performance to permanent section Hematoxylin and Eosin (H\&E) and IHC staining.

Samples of the tissue homogenate will be retained and may be used for for further testing.

Clinical Evaluation of OSNA Breast Cancer System to Test Sentinel Lymph Nodes From Patients With Breast Cancer

Clinical Evaluation of LS-03M/LS-04R for the Detection of Sentinel Lymph Node Metastasis From Breast Cancer

Sysmex America, Inc.

Carrie Pineda

Patients with previous diagnosis of breast cancer scheduled for sentinel lymph node dissection.

For in vitro diagnostic use only.

The GeneSearch™ Breast Lymph Node (BLN) Assay is a qualitative, in vitro diagnostic test for the rapid detection of greater than 0.2 mm metastases in nodal tissue removed from sentinel lymph node biopsies of breast cancer patients. Results from the assay can be used to guide the intra-operative or post-operative decision to remove additional lymph nodes.

Post-operative histological evaluation of permanent sections of the tissue specimen, in accordance with usual diagnostic practice and using the Veridex lymph node cutting scheme, is required.

GeneSearch™ Breast Lymph Node (BLN) Assay

Robert J. Goulet, MD

The purpose of this trial is to show adequate assay performance on clinical samples tested in real time at the clinical site.

This study will determine the sensitivity, specificity, negative predictive value, and positive predictive value of the GeneSearch™ BLN Assay in patient samples by comparing its performance to that of the current methods -- permanent section Hematoxylin and Eosin (H\&E) staining with IHC. Additional marker testing using probes associated with nodal metastases may be used in the assay performance calculations. The observed performance measures will be compared to those obtained in the larger U.S. registration trial to show that there are no differences in the assay's performance.

Samples of the tissue homogenate and extracted RNA will be retained and may be used for for further testing.

Validation Study Using the GeneSearch BLN Assay to Test Sentinel Lymph Nodes From Patients With Breast Cancer

GeneSearch™ Breast Lymph Node (BLN) Assay for Molecular Testing Protocol

Janssen Diagnostics, LLC

Retrospective frozen tissue and paired peripheral blood samples were obtained from the Huashan Glioma Biobank between October 2010 and August 2018. A total of 753 patients diagnosed with supratentorial diffuse glioma (WHO grade 2-4) aged 18-80 years were selected for the study.

From January to July 2021, 223 frozen tissue samples were retrieved from the Huashan Glioma Biobank. In addition, 107 frozen tumor samples were used to assess the detection accuracy of the IDH and TERTp mutation rapid test. The accuracy of this qPCR-based rapid test was further confirmed by Sanger and targeted sequencing.

Detection of IDH and TERT mutation using frozen glioma tissues

Detection of IDH and TERT mutation

Jin-song Wu, MD & PhD

Evaluate the diagnostic value of TERT promoter mutation in differ glioma subtypes and expend the application of the diagnostic algorithm to surgical practice

A total of 976 gliomas were enrolled in this study. First, in order to evaluate the diagnostic value of TERT promoter mutation in differ glioma subtypes, we conducted a retrospective cohort study included 753 frozen tissue samples of patients with different grades of glioma. According to WHO CNS5, all recommended alteration including IDH, 1p/19q, TERT, EGFRamp and 7+/10- were profiled using multiple approaches and a permanent diagnosis was obtained for each patient. Exploring the feasibility of the molecular pathology model of patients with glioma via retrospective research. Compare with the existing molecular pathology system, analyze the combination of IDH and TERT mutations and the feasibility of stratifying the prognosis of patients with glioma.

Moreover, to expend the application of the diagnostic algorithm to surgical practice, we developed a fast detection assay that could detect hotspot somatic mutations in IDH and TERT within 25 minutes and can discriminate TERT and IDH mutations from wild-type alleles with a minimum variant allele frequency (VAF) of 0.2% and 0.5%, respectively. We further validate the simplified diagnostic algorithm on frozen tissue of 223 patients with glioma in another retrospective cohort and performed this assay to evaluate the accuracy of the rapid assay.

Molecular Pathology Research Project of Glioma

Exploring the Feasibility of the Molecular Pathology Model of Patients With Glioma Via Retrospective Research

According to WHO CNS5, all recommended alteration including IDH, 1p/19q, TERT, EGFRamp and 7+/10- were profiled using multiple approaches and a permanent diagnosis was obtained for each patient. Exploring the feasibility of the molecular pathology model of patients with glioma

Derivation of a simplified diagnostic scheme based on IDH and TERT promoter (TERTp) mutations combined with histology and evaluation of its feasibility of stratifying the prognosis of patients with glioma when comparing with WHO CNS5 criteria.

Jinsong Wu

Prof.

The study will determine the sensitivity, specificity, negative predictive value and positive predictive value of the OSNA Breast Cancer System for patients receiving Sentinel Lymph Node biopsies after receiving neoadjuvant hormonal/chemotherapy as compared to permanent section Hematoxylin and Eosin (H\&E) and Immuno-histochemistry (IHC) staining.

Clinical Evaluation of OSNA Breast Cancer System in Breast Cancer Patients Receiving Neoadjuvant Therapy

OSNA Neoadjuvant Feasibility Study in Breast Cancer Patients

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neoplastic Processes

Genome analysis of tissue samples.

The project aims to compare the histopathological and molecular characteristics of tumour tissue from metastases with similar analyses of the primary tumour in the lung, where it is available.

The investigators will therefore perform analysis of blood samples if possible, to identify predictive markers in blood samples.

The investigators want to make genome analysis of tissue samples. This involves analysing the RNA, DNA methylation, for example in cancer cells. This will provide information regarding somatic changes in cancer cells, such as mutations. All of the investigators analysis will be cancer-focused, with the goal of increasing understanding of the heterogeneity.

The investigators will therefore perform analysis of blood samples if possible, to identify predictive markers in blood samples. This will then be the miRNA, RNA expression or protein expression in blood samples.

Identification of Predictive and Prognostic Markers for Lung Cancer With Metastases

We will do profiling of the mRNA (messenger ribonucleic acid) expression of microRNA and perform single nucleotide polymorphism analysis of cancer tissue and compare the expression using statistical methods such as SAM (Significance analysis and microarrays), PAM (Prediction analysis of microarrays). In addition, we wish to perform specific genetic analysis of cancer-related genes. These will be made with available methods like sequencing or TaqMan assays for specific mutations.

Blood samples will be analysed by microarray methods for RNA and microRNA in addition to serum analysis of proteins.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biomarker Analysis of Central Nervous System Tumors	NCT02692898	Central Nervous... Primary Brain N... Neoplasms, Brai... Cancer of the B... Brain Cancer		- 99 Years	National Institutes of Health Clinical Center (CC)
The Research on 89Zr-ABT806 PET Imaging in High Grade Glioma	NCT03058198	Glioma	89Zr-ABT806 PET	18 Years -	Huashan Hospital
Biomarker Analysis of Central Nervous System Tumors	NCT02692898	Central Nervous... Primary Brain N... Neoplasms, Brai... Cancer of the B... Brain Cancer		- 99 Years	National Institutes of Health Clinical Center (CC)
Clinical Evaluation of OSNA Breast Cancer System to Test Sentinel Lymph Nodes From Patients With Breast Cancer	NCT01136369	Breast Neoplasm... Breast Diseases	OSNA Breast Can...	18 Years -	Sysmex America, Inc.
Validation Study Using the GeneSearch BLN Assay to Test Sentinel Lymph Nodes From Patients With Breast Cancer	NCT00551278	Breast Cancer	GeneSearch™ Bre...	18 Years -	Janssen Diagnostics, LLC
Molecular Pathology Research Project of Glioma	NCT04924127	Glioma, Maligna...	Detection of ID...	18 Years - 80 Years	Huashan Hospital
Clinical Evaluation of OSNA Breast Cancer System in Breast Cancer Patients Receiving Neoadjuvant Therapy	NCT01140776	Breast Neoplasm... Breast Diseases		18 Years -	Sysmex America, Inc.
Identification of Predictive and Prognostic Markers for Lung Cancer With Metastases	NCT02301858	Lung Cancer Primary Tumor Metastases	Genome analysis...	18 Years - 90 Years	Sykehuset i Vestfold HF

Spots Global Cancer Trial Database for molecular pathology