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Tumor Virus Infections

Eugene Yu, MD

The standard treatment for nasopharyngeal cancer involves either radiation alone or radiation plus chemotherapy. Before the start of treatment,patients require an imaging scan to assess the extent of disease. The most commonly used test is a magnetic resonance imaging (MRI) scan.

The goal of the study is to examine the value of a new imaging technology that has recently become available at the University Health Network Hospitals called Positron Emission Tomography scanning (PET). PET scanning involves the injecting a small amount of a drug through a vein in the arm called 18-fluorodeoxyglucose (18FDG). This drug is special in that it is radioactive and will be detected by the PET machine. Cancer cells are believed to be more active than normal cells and have a high rate of metabolism. Therefore, cancer cells are thought to take up glucose (a kind of sugar) faster than normal cells in the body. Because 18FDG is a modified type of glucose, it is also taken up by cancer cells. Special imaging cameras will be able to visualize the areas of uptake and reveal sites of cancer involvement. The main goal of this study is to evaluate whteher the scan is able to detect the presence of nasopharyngeal carcinoma (NPC) both before and after treatment and to specifically compare it to findings on magnetic resonance imaging scans (MRI).

In addition to doing the PET scans, we are asking patients to have blood samples drawn throughout their treatment and follow-up, for a research test called Epstein Barr virus (EBV) DNA levels. The Epstein Barr virus is thought to have a role in the development of nasopharyngeal cancer, and many patients with nasopharyngeal carcinoma are found to have high levels of EBV DNA levels in their blood. The second goal of this study is to evaluate whether changes in EBV DNA levels are associated with the treatment and the disease course in nasopharyngeal cancer, and whether they help to predict any changes in the cancer. This part of the study involves the sampling of a small amount of venous blood at a time prior to the beginning of therapy and at regular intervals following treatment.

1. Patients with nasopharyngeal carcinoma are staged according to the 2002 American Joint Committee on Cancer (AJCC) criteria. MRI is the imaging modality of choice for staging and follow-up of nasopharyngeal carcinoma. The goal is to conduct a pilot study to compare the staging findings on MRI with those on PET scanning in both pre- and post-therapy patients. The end point is to document the degree of concordance between the two modalities with respect to the anatomic location and volume of disease at the time of initial staging and on follow up and to determine how any differences observed may alter staging and management including radiation planning. We hypothesize that PET scanning will be able to detect recurrence and residual disease within the radiated tissue earlier than MRI.
2. Nasopharyngeal carcinoma is associated with elevated titers of Epstein Barr virus (EBV) cell free, plasma DNA. Fluctuation i.e. - elevation in EBV DNA levels following therapy may serve as a potential marker for recurrent or residual disease. We believe that a change in EBV DNA titer precedes changes on conventional MRI and possibly PET scans in patients with recurrent disease. We also predict, that due to its sensitivity, that EBV titer levels will be more sensitive in the evaluation of tumor response to therapy, as well predicting tumor recurrence. The second goal is to conduct a trial to compare the sensitivity of MRI, PET and EBV titers in the assessment of recurrent disease.

Positron Emission Tomography Scanning and Epstein-Barr Virus DNA Levels in the Staging and Follow-up of Nasopharyngeal Carcinoma.

University Health Network, Toronto

This study will evaluate the ability of people of different ethnic backgrounds to develop immune responses against the Epstein-Barr virus (EBV). A common virus, EBV is present in 90 percent of healthy people and usually does not cause problems. Most people are infected in childhood, have no symptoms, and are unaware of their infection. People infected as adolescents or adults may develop infectious mononucleosis, which usually resolves completely. However, in immune suppressed people, like those who have had a transplant, EBV can cause fatal cancers. It can also cause certain cancers such as Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma in people who are not immune suppressed. Nasopharyngeal carcinoma is 100 times more common in people of Asian origin (particularly southern Chinese) compared with Caucasians. This difference may be the result of genetic, rather than environmental, factors. This study will examine whether the same proteins produced by EBV in the cancer cells react differently in people of different ethnic background in a way that could explain the differences in predisposition for this disease.

Healthy normal volunteers 18 years of age and older of Caucasian or Chinese ancestry may be eligible for this study. Candidates of Chinese ancestry must be born in China (including Taiwan, Hong Kong, and Singapore, or be first generation offspring of parents born in these places).

Participants will have a blood sample drawn and will undergo lymphapheresis - a procedure for collecting large numbers of white blood cells called lymphocytes. The blood sample is tested for blood counts and HLA type, a genetic marker of the immune system. HLA molecules help determine the way the body's immune cells respond to virus. HLA typing is similar to blood typing. Usually done to match stem cell or organ transplants, HLA testing may also be used to try to identify factors associated with an increased risk of certain diseases or conditions. HLA type is strongly associated with ethnic background.

For lymphapheresis, blood is collected through a needle in an arm vein, similar to donating blood. The blood flows from the vein through a catheter (plastic tube) into a machine that separates it into its components by centrifugation (spinning). The white cells are removed and the rest of the blood (red cells, plasma and platelets) is returned to the body through a needle in the other arm. The procedure takes 2 to 3 hours. The collected white cells are used for research for this study, including the ability to react to EBV proteins, and are then destroyed.

Epstein Barr virus (EBV) can induce in immune compromised patients fatal lymphoproliferative lesions that regress upon reversion of immune suppression or adoptive transfer of EBV-specific CD8+ T cells. EBV can also induce neoplastic lesions in immune competent hosts including Burkitt's lymphoma, Hodgkin's disease and nasopharyngeal cancer (NPC). EBV-specific CD8+ T cell responses can occur in patients with these cancers that are qualitatively similar but quantitatively diminished compared to EBV-primed normal individuals. Although these cancers share several features, they are characterized by divergent patterns of expression of EBV proteins. In particular, NPC expresses preferentially the latent membrane protein (LMP) 2 with or without expression of LMP 1 and intermediate expression of the Epstein-Barr nuclear antigen. Thus, there is interest to develop LMP 2-directed immunizations for patients with NPC with the hope that enhancement of the insufficient natural immunity may lead to tumor regression. Since, the incidence of NPC is tightly associated with ethnic background (principally Southern Chinese) and Human Leukocyte Antigen (HLA) phenotype, diverse populations may display distinct reactivity patterns toward EBV epitopes that may in turn be responsible for their respective predisposition to acquire NPC. Although, several LMP 2 epitopes have been described, to our knowledge, no systematic mapping across diverse ethnicity complemented with high-resolution HLA typing has ever been done. We, therefore, propose to map immune dominant epitopes of LMP 2 in EBV primed normal individuals of Caucasian or Asian (Chinese) ethnicity by measuring interferon (IFN)-gamma transcript levels in circulating lymphocytes exposed to a library of overlapping nonamer peptides encompassing the full sequence of LMP 2. High resolution, sequence-based HLA typing will complement the study.

Protein Studies of the Epstein-Barr Virus in Ethnically Diverse Populations

Comprehensive Epitope Mapping of the Epstein-Barr Virus Latent Membrane Protein-2 in Ethnically Diverse Populations

National Institutes of Health Clinical Center (CC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Positron Emission Tomography Scanning and Epstein-Barr Virus DNA Levels in the Staging and Follow-up of Nasopharyngeal Carcinoma.	NCT00188253	Nasopharyngeal ...		-	University Health Network, Toronto
Protein Studies of the Epstein-Barr Virus in Ethnically Diverse Populations	NCT00070785	Epstein-Barr Vi...		18 Years -	National Institutes of Health Clinical Center (CC)

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Spots Global Cancer Trial Database for ebv virus

Every month we try and update this database with for ebv virus cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ebv virus cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.