Trial Information

The Evaluation of Focal Contrast-Enhancing Brain Lesions in HIV-Infected Patients

Epstein Barr Virus (EBV)-associated primary central nervous system lymphoma (PCNSL) remains
a major problem among AIDS patients. The clinical presentation is often clinically
indistinguishable from toxoplasmic encephalitis. The method of choice for establishing the
definitive diagnosis is brain biopsy. This procedure can be associated with a significant
morbidity and mortality, and therefore less invasive means of diagnosing cerebral mass
lesions have been studied.

Currently, an accepted standard of care for HIV-infected patients that present with signs
and symptoms of focal brain lesions is to empirically treat for toxoplasmic encephalitis.
Brain biopsy is often deferred until there is demonstration of lack of clinical response or
progression on empiric therapy. As a result, treatment initiation is frequently delayed.
During this time it is not unusual for further clinical deterioration to occur before
appropriate therapies can be initiated. Frequently, the alternative approaches then become
a question of appropriate palliation rather than curative intent therapy.

Less invasive diagnostic tests to assist in the diagnosis have been investigated. Based on
the finding that essentially 100% of HIV-related PCNSL are EBV-associated, the detection of
EBV DNA by PCR amplification in the cerebrospinal fluid (CSF) has demonstrated clinical
usefulness in the diagnosis, as has the use of neuroradiologic imaging to detect the
malignancy. Prior studies have demonstrated that the use of a combination of
neuroradiologic, immunologic, and clinical variables in the workup of focal brain lesions in
HIV-infected patients to be quite accurate in identifying patients in need of brain biopsy,
but a diagnostic algorithm that incorporates the combination of the most sensitive and
specific tests in a timely manner has not yet been explored.

This study seeks to evaluate an algorithm for the workup of HIV infected patients with focal
brain lesions so as to expedite the diagnosis and subsequent treatment of PCNSL. The goals
of the study are to 1) determine the specificity, sensitivity, and positive predictive value
of a diagnostic algorithm that entails the use of the combination of EBV detection in the
CSF and FDG-PET scanning to diagnose PCNSL; 2) evaluate the time to response to
anti-toxoplasmic encephalitis therapy, and 3) evaluate the sensitivities and specificities
of FDG-PET and (201)Tl-SPECT scanning in identifying PCNSL. Up to one hundred HIV-infected
patients with history of at least one focal brain lesion will be screened for enrollment.
All patients will be treated empirically for toxoplasmic encephalitis until an alternative
diagnosis is confirmed. All enrolled patients will be treated concurrently with
antiretroviral therapy. Patients identified to have PCNSL will be referred to the NCI
Treatment of PCNSL Protocol for further treatment if the study is open for enrollment.