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Biomedical subjects

Igor T Gavrilovic

Publications and source records attributed to Igor T Gavrilovic.

4 recordsLinked to original sources

Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma.

PURPOSE: We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity. PATIENTS AND METHODS: Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations. RESULTS: The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy. CONCLUSION: Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.

Adult↗

Brain metastases: epidemiology and pathophysiology.

Metastases are the most common tumors of the central nervous system (CNS), but cancer databases are often incomplete leading to underestimation of the incidence of even symptomatic brain metastases. Brain imaging studies are not routinely performed on neurologically asymptomatic cancer patients and autopsy studies are outdated. Furthermore, while incidence rates for cancers are stable and mortality is decreasing due to earlier detection and better therapy, the incidence of brain metastases appears to be increasing. The pathophysiology of brain metastases is a complex multistage process, mediated by molecular mechanisms; from the primary organ, cancer cells must transform, grow and be transported to the CNS where they can lay dormant for various lengths of time before invading and growing further. Understanding the pathophysiology of brain metastases is of great importance, because it may lead to the development of more efficient therapies to combat brain tumor growth or to possibly make the CNS an undesirable environment for tumor progression.

Brain Neoplasms↗

Diagnosis and treatment of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is an uncommon form of non-Hodgkin's lymphoma (NHL) that has been increasing in incidence over the past three decades. Unlike systemic extranodal NHL, the response to therapy for PCNSL patients has been somewhat unsatisfactory. However, methotrexate-based chemotherapy and whole-brain radiotherapy have improved the outcome of patients. Unfortunately, treatment-related neurotoxicity is common, especially in the elderly. Although progress has been made in treating PCNSL, there remains no optimal methotrexate dose or frequency. Treatment of recurrence also remains controversial. These important questions have prompted several clinical studies looking at novel ways to intensify chemotherapy and limit neurotoxicity.

Antineoplastic Agents↗

Primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare variant of non-Hodgkin's lymphoma that is increasing in incidence. Methotrexate-based chemotherapy in combination with whole-brain radiotherapy (WBRT) has dramatically improved the outcome of patients. However, treatment-related neurotoxicity is a significant complication, especially after radiotherapy in the elderly. Despite advances in therapy, several important questions remain regarding optimal methotrexate dose, dosing frequency, adjunct chemotherapy, and the impact of deferring WBRT. Advances in biologic therapy and strategies to intensify the delivery of chemotherapy may help to limit the use of radiotherapy, thus lessening potential neurotoxicity. Studies looking at oncogenic proteins as potential prognostic markers for PCNSL may help us to develop risk-adapted therapies.

Antineoplastic Agents↗