Postoperative radiation therapy (RT), either alone or in combination with chemotherapy, is the mainstay of treatment for primary and/or metastatic brain tumors. The majority of patients with brain tumors will have significant symptoms of their disease and of RT that will have a negative impact on their quality of life and neurocognitive function. The symptoms of brain tumors depend on tumor location. Radiation-induced brain injury is a complex and dynamic process involving all cells in the brain, including endothelial and oligodendroglial cells, astrocytes, microglia, neurons, and neuronal stem cells. The symptoms of radiation-induced brain injury may be acute, subacute, or chronic, occurring hours, days, weeks, months, and even years after exposure to radiation, the pathogenesis of which is oxidative stress and inflammation. At present, there are no effective preventive approaches for radiation-induced brain injury. Rather, the management of radiation-induced fatigue, changes in mood, and cognitive dysfunction involves a multidisciplinary approach using pharmacologic, behavioral, and rehabilitative therapies. Given the prevalence of brain neoplasms and the high incidence of the radiation-induced symptom cluster and brain injury, clinical research to address these important clinical problems is critical.
8587 Background: A symptom cluster is 2 or more co-occurring symptoms. Patients with brain tumors experience disease and treatment-related symptoms that impact their health-related quality of life (QOL). Identifying symptom clusters will facilitate treatment and improve QOL outcomes. Methods: 66 patients were enrolled in a phase III, placebo-controlled, double-blind, prospective randomized clinical trial assessing the effect of prophylactic d-methylphenidate (d-MPH) on QOL in newly diagnosed brain tumor patients receiving brain radiation therapy (RT). Inclusion criteria were: age ≥ 13 years, primary or metastatic brain tumor, partial or whole brain RT with a total dose of ≥ 2,500 cGy in ≥ 10 fractions, KPS ≥ 70, and life expectancy ≥ 3 months. Patients received d-MPH 5–15 mg BID (or placebo) starting week 1 of RT and continuing for 8 weeks post-RT. QOL data were collected at baseline, the end of RT, and 4, 8, and 12 weeks following RT using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Center for Epidemiologic Studies Depression Scale (CES-D). Symptom data were analyzed using exploratory factor analysis, multi-dimensional scaling (MDS), and cluster analysis. Results: The study failed to show a treatment effect for d-MPH (Butler J et al, Int J Radiat Oncol Biol Physics 63 [Supp1]:80, 2005).Thus, both d-MPH and placebo patients were analyzed together. 58 and 48 patients were analyzed at baseline and the end of RT, respectively. Two symptom clusters were identified using exploratory factor analysis and supported by MDS and cluster analysis: an expressive language cluster including difficulty reading, writing, and finding the right words, and a mood cluster including feeling sad, anxious, and having depressed mood. Conclusions: Two symptom clusters were identified in patients undergoing brain RT: an expressive language cluster and a mood cluster. This suggests that interventions that target both cognitive function and mood should be utilized. Further research on symptom clusters in cancer patients is needed. This study was supported by NCI grant 1 U10 CA81851. No significant financial relationships to disclose.
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