BACKGROUND: WBRT significantly improves tumor control in the brain after SRS, yet the role of adjuvant WBRT remains undefined due to concerns regarding neurocognitive risks. METHODS: Patients with 1-3 brain metastases, each 1 SD from baseline in any of the 6 cognitive tests at 3 months. Time to CP was estimated using cumulative incidence adjusting for survival as a competing risk. RESULTS: 213 patients were enrolled with 2 ineligible and 3 cancels prior to receiving treatment. Baseline characteristics were well-balanced between study arms. The median age was 60 and lung primary the most common (68%). CP at 3 months was more frequent after WBRT + SRS vs. SRS alone (91.7% vs. 63.5% respectively, p = 0.0007). There was more deterioration in the WBRT + SRS arm in immediate recall (30% vs. 8%, p = 0.0043), delayed recall (51% vs. 20%, p = 0.0009), and verbal fluency (19% vs. 2%, p = 0.0098). After WBRT + SRS there was more deterioration in overall QOL (p = 0.001) and functional well-being (p = 0.006) at 3months. Intracranial tumor control at 3 and 6 months were 75.3% and 64.7% with SRS alone vs. 93.7% and 88.4% with SRS + WBRT (p < 0.0001). Median OS was 10.4 for SRS alone vs. 7.4 months for SRS + WBRT respectively (HR = 1.02, p = 0.92). CONCLUSIONS: Decline in QOL and cognitive function, specifically immediate recall, memory and verbal fluency, was more frequent with the addition of WBRT to SRS. Adjuvant WBRT did not improve OS despite better brain control. Initial treatment with SRS and close monitoring is recommended to better preserve cognitive function in patients with newly diagnosed brain metastases that are amenable to SRS.
A symptom cluster comprises three or more concurrent symptoms. There is a paucity of symptom cluster research in cancer patients. Data from a previously conducted clinical trial were analyzed to search for symptom clusters. This phase III, placebo-controlled, double-blind, prospective, randomized clinical trial of 66 patients assessed the effect of prophylactic d-threo-methylphenidate (d-MPH) on quality of life (QOL) in newly diagnosed brain tumor patients receiving brain radiation therapy. Patients received 5-15 mg of d-MPH or placebo twice daily starting on week 1 of radiation therapy and continuing for 8 weeks post radiotherapy. QOL data were collected at baseline; the end of radiation therapy; and 4, 8, and 12 weeks following radiation therapy using the Functional Assessment of Cancer Therapy (FACT), the FACT-Brain subscale, and the Center for Epidemiologic Studies Depression Scale. Exploratory factor analysis, multidimensional scaling (MDS), and cluster analysis were used to search for symptom clusters. The trial failed to show a treatment effect; patients receiving d-MPH or placebo were analyzed together to search for clusters. Two symptom clusters were identified using exploratory factor analysis--a language cluster including difficulty reading, writing, and finding the right words and a mood cluster including feelings of sadness, anxiety, and depressed mood; these clusters were supported by MDS and cluster analysis. Our results suggest that interventions that target both cognitive function and mood should be considered in this patient population. Further research on symptom clusters in brain tumor patients is needed.
Abstract Background A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma. Methods Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided Z test for 2 proportions. Adverse events (AEs) were evaluated per CTCAE version 4. Results One hundred and fifty-eight patients were randomized, out of which 9 were ineligible and 12 were not evaluable for the primary endpoint, leaving 137 eligible and evaluable. 6-month PFS was 46.6% in the cediranib arm versus 24.5% in the placebo arm (P = .005). There was no significant difference in overall survival between the 2 arms. There was more grade ≥ 3 AEs in the cediranib arm than in the placebo arm (P = .02). Conclusions This study met its primary endpoint of prolongation of 6-month PFS with cediranib in combination with radiation and temozolomide versus placebo in combination with radiation and temozolomide. There was no difference in overall survival between the 2 arms.
Stereotactic body radiation therapy (SBRT) simulations using a Stereotactic Body Frame (SBF: Elekta, Stockholm, Sweden) were expanded to include 18F-deoxyglucosone positron-emission tomography (FDG PET) for treatment planning. Because of the length of time that staff members are in close proximity to the patient, concerns arose over the radiation safety issues associated with these simulations. The present study examines the radiation exposures of the staff performing SBRT simulations, and provides some guidance on limiting staff exposure during these simulations. Fifteen patients were simulated with PET/CT using the SBF. Patients were immobilized in the SBF before the FDG was administered. The patients were removed from the frame, injected with FDG, and allowed to uptake for approximately 45 minutes. After uptake, the patients were repositioned in the SBF. During the repositioning, exposure rates were recorded at the patient's surface, at the SBF surface, and at 15 cm, 30 cm, and 1 m from the SBF. Administered dose and the approximate time spent on patient repositioning were also recorded. The estimated dose to staff was compared with the dose to staff performing conventional diagnostic PET studies. The average length of time spent in close proximity (<50 cm) to the patient after injection was 11.7 minutes, or more than twice the length of time reported for diagnostic PET staff. That time yielded an estimated average dose to the staff of 26.5 microSv per simulation. The annual occupational exposure limit is 50 mSv. Based on dose per simulation, staff would have to perform nearly 1900 SBRT simulations annually to exceed the occupational limit. Therefore, at the current rate of 50-100 simulations annually, the addition of PET studies to SBRT simulations is safe for our staff. However, ALARA ("as low as reasonably achievable") principles still require some radiation safety considerations during SBRT simulations. The PET/CT-based SBRT simulations are safe and important for treatment planning that optimizes biologic dose distribution with highly accurate and reproducible target definition.
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.
Purpose: The EF-14 trial demonstrated that adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) significantly extends progression-free survival (PFS) and overall survival (OS) for newly-diagnosed glioblastoma (GBM) patients. This study assessed the cost-effectiveness of TTFields and TMZ for newly-diagnosed GBM from the US healthcare system perspective. Methods and materials: Outcomes for newly-diagnosed GBM patients were estimated over a lifetime horizon using an area under the curve model with three states: stable disease, progressive disease, or death. The survival model integrated the 5-year EF-14 trial results with long-term GBM epidemiology data and US background mortality rates. Adverse event rates were derived from the EF-14 trial data. Utility values to determine quality-adjusted life-years, adverse event costs, and supportive care costs were obtained from published literature. A 3% discount rate was applied to future costs and outcomes. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability. Results: Treatment with TTFields and TMZ was estimated to result in a mean increase in survival of 1.25 life years (95% credible range [CR] = 0.89-1.67) and 0.96 quality-adjusted life years (QALYs) (95% CR = 0.67-1.30) compared to treatment with TMZ alone. The incremental total cost was $188,637 (95% CR = $145,324-$225,330). The incremental cost-effectiveness ratio (ICER) was $150,452 per life year gained and $197,336 per QALY gained. The model was most sensitive to changes in the cost of TTFields treatment. Conclusions: Adding TTFields to maintenance TMZ resulted in a substantial increase in the estimated mean lifetime survival and quality-adjusted survival for newly-diagnosed GBM patients. Treatment with TTFields can be considered cost-effective within the reported range of willingness-to-pay thresholds in the US.
