Symptoms and General Pathology

All Conditions

Diseases and Abnormalities at or Before Birth

Neoplasms

Nervous System Diseases

Heart and Blood Diseases

Blood and Lymph Conditions

Rare Diseases

Hemorrhage

Congenital Abnormalities

Hemangioma

Hemangioma, Cavernous, Central Nervous System

Hemangioma, Cavernous

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

Syndrome

Brain Diseases

Central Nervous System Diseases

Vascular Malformations

Central Nervous System Vascular Malformations

Nervous System Malformations

Cardiovascular Abnormalities

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Hemorrhagic Disorders

Hematologic Diseases

Familial Cerebral Cavernous Malformation

Cavernous Angioma (CA) without symptomatic hemorrhage cases scheduled for evaluation by their neurology or neurosurgery teams in an inpatient or outpatient setting

Cavernous Angioma (CA) with Symptomatic Hemorrhage (SH) cases scheduled for evaluation by their neurology or neurosurgery teams in an inpatient or outpatient setting

Young (\<30 years old) healthy control cohorts with seizures in the prior year

Young (\<30 years old) healthy control cohorts without seizures in the prior year

Older (\>50 years old) with hemorrhagic microangiopathy (HMA)

Older (\>50 years old) without hemorrhagic microangiopathy (HMA)

There is no intervention for any group in this observational study.

observational

Agnieszka Stadnik, MS

Jennifer Cibrian, MPH

Amanda Land, BSN

Michael T Lawton, MD

Helen Kim, PhD

Justine Hsu, BSN

Issam A Awad, MD

Kelly Flemming, MD

Issam Awad, MD

The project aims to develop prognostic and diagnostic blood tests for symptomatic brain hemorrhage in patients diagnosed with cavernous angiomas, a critical clinical challenge in a disease affecting more than a million Americans. We further examine whether blood biomarkers can replace or enhance the accuracy of advanced imaging in association with lesional bleeding. The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease, with a clinically relevant context of use.

Cerebral cavernous angioma (CA) is a capillary microangiopathy affecting more than a million Americans, predisposing them to a premature risk of brain hemorrhage. Fewer than 200,000 cases who have suffered a recent symptomatic hemorrhage (SH) are most likely to re-bleed again with serious clinical sequelae, and are the primary focus of therapeutic development. Genetic mechanisms of CA have been extensively studied, and consequent signaling aberrations in the neurovascular unit. These include proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammation and immune mediated processes, anticoagulant vascular domain, and gut microbiome-driven mechanisms. Plasma levels of molecules reflecting these mechanisms and measures of vascular permeability and hemorrhage leak on magnetic resonance imaging (MRI) have been correlated with CA hemorrhage in pilot studies. It would be desirable to optimize these biomarkers to accurately diagnose CASH, to prognosticate the risk of future SH, and to monitor cases after a bleed and in response to therapy. This would influence clinical management, and select higher risk cases for clinical trials. Additional candidate biomarkers are emerging from ongoing mechanistic and differential transcriptome studies, which would be expected to further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Weighed combinations of levels of plasma proteins and characteristic micro-ribonucleic acids (miRNA) may further strengthen biomarker associations. Plasma biomarkers may reflect (and potentially replace) more cumbersome and expensive imaging biomarkers for monitoring CA hemorrhage. We here assemble CA researchers and propose to deploy advanced statistical and computational biology approaches for the integration of novel candidate biomarkers. In Specific Aim 1 we assess these biomarkers in a large CA cohort to discover the best plasma biomarkers and validate them in sex, age and relevant clinical subgroups. In Specific Aim 2 we compare changes in MRI measures of vascular permeability and hemorrhage with plasma biomarkers over time. In Specific Aim 3 we query the biomarkers in non-CA subjects, to identify potential confounders in the clinical context. This project integrates analytic and computational biology expertise to develop blood tests for better CASH diagnosis and prognosis. The project tests a novel integrational approach of biomarker development in a mechanistically defined cerebrovascular disease with a relevant context of use. This approach is applicable to other neurological diseases with similar pathobiologic features.

Biomarkers of CASH

Biomarkers of Cerebral Cavernous Angioma With Symptomatic Hemorrhage (CASH)

Within the first year, we will publish the protocol paper. At the end of the 5 year study, we will publish the data dictionary along with study findings. The expression profile data will be made publicly available no later than the date of initial publication or six months after the receipt of the final sequencing data, whichever comes first.

To test whether individual and combined levels of candidate plasma proteins and miRNAs can be associated with diagnosis of CASH (cross sectional) and can predict/prognosticate future SH (longitudinal) in CAs

To assess whether changes in QSM (quantitative susceptibility mapping) and DCEQP (dynamic contrast enhanced quantitative permeability) used as monitoring biomarkers after a SH, are reflected by changes in plasma biomarkers and miRNAs

To assess the plasma biomarkers in non-CA young and older subjects, with and without seizures and hemorrhagic microangiopathy on MRI, to clarify potential confounders in the context of clinical use, and to motivate novel hypotheses for broader applications

Mayo Clinic

University of California, San Francisco

National Institute of Neurological Disorders and Stroke (NINDS)

Barrow Neurological Institute

University of Chicago

Behaviors and Mental Disorders

Respiratory Tract (Lung and Bronchial) Diseases

Adenocarcinoma

Aggression

Adenocarcinoma of Lung

Carcinoma

Neoplasms, Glandular and Epithelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Adenocarcinoma

Duel-energy CT, PET, copy number alteration

CT, PET, copy number alteration

Young Mog Shim, Dr.

Ho Yun Lee, Dr.

to determine the values of imaging and genetic biomarkers for prediction of tumor aggressiveness and prognosis in patient with early stage lung adenocarcinoma to Identify unique copy number alteration in patient with early stage lung adenocarcinoma to evaluate the long-term change of ground-glass nodule combined with lung adenocarcinoma to suggest a guideline for planning an appropriate follow-up examination and management

Study of Early-stage Lung Adenocarcinoma for Early Detection and Effective Treatment Strategy

Prospective Study of Early-stage Lung Adenocarcinoma for Early Detection and Effective Treatment Strategy

Korean Foundation for Cancer Research

Samsung Medical Center

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Topotecan

Bortezomib

Sirolimus

Temsirolimus

MTOR Inhibitors

Telbivudine

Antiviral Agents

Enzyme Inhibitors

FLT-PET scan uses the FLT solution (dosage of FLT in range between 1 and 10 mCi) with imaging performed 60-90 minutes after FLT intravenous injection.

FLT-PET

Sarina Piha-Paul, MD

The goal of this clinical research study is to learn if an imaging solution, \[F-18\]-fluoro-L-thymidine (FLT), when used with a positron emission tomography (PET) scan, can help doctors to better see changes in the growth of tumors in the body. Researchers want to learn if FLT-PET scans can show an early response to chemotherapy.

FLT-PET Scan:

An FLT-PET scan uses the FLT solution, which contains a small amount of radioactive material, to help locate cancer cells inside the body. This scan may help doctors find solid tumors as well as learn if these tumors are growing and how fast they are growing. This information could be used to help predict if the cancer will respond to treatment.

Study Visits:

Within 2 weeks before Day 1 of Cycle 1 and between Days 19 and 21 of Cycle 1, you will have a FLT-PET scan.

For at least 4 hours before the FLT-PET scan, you must not eat or drink anything. You will receive the FLT solution by vein. The FLT solution is a mildly radioactive material. The radioactive nature of the solution allows the scanner to "see" it in certain places in your body. After the injection, you will need to rest quietly until it is time for the scan. The amount of rest time may vary, but be prepared to wait for about 60 minutes. During the scan, you will lie flat on your back on a table. After the solution is injected into a vein, the PET scanner takes pictures of the radioactive solution as it moves through the body and collects at various sites in the body. By watching how the solution travels through the body and studying where the solution collects, researchers can learn the status of disease in the body. The scan itself may last about 40-60 minutes.

Your vital signs (blood pressure, heart rate, temperature, and breathing rate) will be measured before each injection of the FLT solution, 30 minutes after each injection, and before each PET scan. You will be allowed to leave 30 minutes after your scan, if your vital signs are acceptable.

Length of Study:

You will be off this study after the second FLT-PET scan. You will be taken off study early if you have intolerable side effects or the study doctor thinks it is in your best interest.

This is an investigational study. The FLT solution is not FDA approved or commercially available. At this time, FLT solution is only being used in research.

Up to 5 patients will take part in this study. All will be enrolled at MD Anderson.

FLT-PET as an Imaging Biomarker With Temsirolimus, Topotecan, and Bortezomib

FLT-PET as an Imaging Biomarker in Patients Receiving the Combination of Cell Cycle Inhibitors Temsirolimus, Topotecan, and Bortezomib

SUV measured on continuous scale at two specified time points (baseline and post-treatment phase, cycle 1, day 19-21).

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biomarkers of CASH	NCT04467489	Cerebral Cavern... Cavernous Angio... Hemorrhagic Mic...	observational	18 Years -	University of Chicago
Study of Early-stage Lung Adenocarcinoma for Early Detection and Effective Treatment Strategy	NCT01482585	Lung Adenocarci...	CT, PET, copy n...	20 Years -	Samsung Medical Center
FLT-PET as an Imaging Biomarker With Temsirolimus, Topotecan, and Bortezomib	NCT01143779	Advanced Cancer	FLT-PET	18 Years -	M.D. Anderson Cancer Center
Biomarkers of CASH	NCT04467489	Cerebral Cavern... Cavernous Angio... Hemorrhagic Mic...	observational	18 Years -	University of Chicago
FLT-PET as an Imaging Biomarker With Temsirolimus, Topotecan, and Bortezomib	NCT01143779	Advanced Cancer	FLT-PET	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for imaging biomarker