Neuroprotective and anxiolytic potential of green rooibos (Aspalathus linearis) polyphenolic extract.

South African rooibos (Aspalathus linearis) tea is globally consumed for its health benefits and caffeine free nature, but no information is available on the neuroprotective capacity of (unfermented) green rooibos. Our aim was to investigate the cytoprotective activity of green rooibos in neuronal cells, including probing antioxidant and enzyme inhibitory properties that could explain observed effects in these cells. We also investigated the anxiolytic potential of green rooibos using zebrafish larval models. Green rooibos extract (Green oxithin™) was assessed for its neuroprotective potential in Neuro-2a cells treated with different concentrations of the extract (12.5-25-50-100 µg mL-1) and different concentrations of hydrogen peroxide (250 or 125 µM) as oxidizing agent. Cell viability (MTT) and redox status (intracellular ROS) were also quantified in these cells. Antioxidant properties of the extract were quantified using cell-free systems (DPPH, ORAC and xanthine/xanthine oxidase), and potential neuroprotection evaluated in terms of its potential to inhibit key enzymes of the CNS (monoamine oxidase A (MOA-A), acetylcholinesterase (AChE) and tyrosinase (TYR)). Results demonstrated that green rooibos extract exerted significant cytoprotective properties in Neuro-2a cells, particularly when exposed to lethal 250 µM hydrogen peroxide, increasing cell survival by more than 100%. This may be ascribed (at least partially) to its capacity to limit intracellular ROS accumulation in these cells. Data from cell-free systems confirmed that green rooibos was able to scavenge free radicals (synthetic and physiological) in a dose dependent manner with a similar profile activity to vitamins C and E. Green rooibos also acted as a moderate MAO-A inhibitor, but had no significant effect on AChE or TYR. Finally, zebrafish larvae treated with lower doses of green rooibos demonstrated a significant anxiolytic effect in the light-dark anxiety model. Using the PTZ excitotoxicity model, green rooibos was shown to rescue GABA receptor signalling, which together with its demonstrated inhibition of MAO-A, may account for the anxiolytic outcome. Current data confirms that green rooibos could be considered a "functional brain food" and may be a good option as starting ingredient in the development of new nutraceuticals.

Target volume delineation for partial breast radiotherapy planning: clinical characteristics associated with low interobserver concordance.

PURPOSE: To examine variability in target volume delineation for partial breast radiotherapy planning and evaluate characteristics associated with low interobserver concordance. METHODS AND MATERIALS: Thirty patients who underwent planning CT for adjuvant breast radiotherapy formed the study cohort. Using a standardized scale to score seroma clarity and consensus contouring guidelines, three radiation oncologists independently graded seroma clarity and delineated seroma volumes for each case. Seroma geometric center coordinates, maximum diameters in three axes, and volumes were recorded. Conformity index (CI), the ratio of overlapping volume and encompassing delineated volume, was calculated for each case. Cases with CI

Consistency in seroma contouring for partial breast radiotherapy: impact of guidelines.

PURPOSE: Inconsistencies in contouring target structures can undermine the precision of conformal radiation therapy (RT) planning and compromise the validity of clinical trial results. This study evaluated the impact of guidelines on consistency in target volume contouring for partial breast RT planning. METHODS AND MATERIALS: Guidelines for target volume definition for partial breast radiation therapy (PBRT) planning were developed by members of the steering committee for a pilot trial of PBRT using conformal external beam planning. In phase 1, delineation of the breast seroma in 5 early-stage breast cancer patients was independently performed by a "trained" cohort of four radiation oncologists who were provided with these guidelines and an "untrained" cohort of four radiation oncologists who contoured without guidelines. Using automated planning software, the seroma target volume (STV) was expanded into a clinical target volume (CTV) and planning target volume (PTV) for each oncologist. Means and standard deviations were calculated, and two-tailed t tests were used to assess differences between the "trained" and "untrained" cohorts. In phase 2, all eight radiation oncologists were provided with the same contouring guidelines, and were asked to delineate the seroma in five new cases. Data were again analyzed to evaluate consistency between the two cohorts. RESULTS: The "untrained" cohort contoured larger seroma volumes and had larger CTVs and PTVs compared with the "trained" cohort in three of five cases. When seroma contouring was performed after review of contouring guidelines, the differences in the STVs, CTVs, and PTVs were no longer statistically significant. CONCLUSION: Guidelines can improve consistency among radiation oncologists performing target volume delineation for PBRT planning.

Prospective evaluation of the prevalence and severity of fatigue in patients with prostate cancer undergoing radical external beam radiotherapy and neoadjuvant hormone therapy.

OBJECTIVE: To prospectively evaluate the prevalence and severity of fatigue and its impact on quality of life (QOL) during and after radical external beam radiotherapy (RT) for prostate cancer. METHOD AND MATERIALS: Twenty-eight men with prostate cancer undergoing RT over 6-8 consecutive weeks were prospectively accrued. The Brief Fatigue Inventory (BFI), a validated fatigue assessment tool, was administered at five time points: baseline (week 1), middle of RT (week 3-4), end of RT (last week of RT), and follow-up (median 6.5 weeks after RT). The BFI contained nine questions, each using 0-10 ratings to quantify fatigue severity and interference with six QOL domains. The prevalence of moderate-severe fatigue was plotted as a function of time. Mean sum and subscale scores at each time point were compared to baseline scores using Wilcoxon tests. Linear regression analyses were performed to assess associations between fatigue scores and age, tumor and treatment characteristics. RESULTS: The median age was 69 years (range 57-84), Gleason score 7 (range 6-10), and presenting PSA 9.0 ng/mL (range 2.5 ng/mL-103.0 ng/mL). Patients were treated once daily to a median dose of 74 Gy (range 60 Gy-78 Gy) over a median of 37 fractions (range 30-39). Hormone therapy was used in all patients (median duration 12.2 months). The prevalence of moderate-severe present fatigue increased from 7% at baseline to 8% at mid-RT and 32% at RT completion. Compared to baseline (mean score 11.5), fatigue increased significantly mid-RT (mean score 14.6, p = 0.03) and peaked at the end of RT (mean score 23.5, p = 0.001). Fatigue significantly interfered with walking ability, normal work, daily chores, and enjoyment of life only at the end of RT. After RT completion, fatigue improved but remained higher compared to baseline at 6.5 weeks of follow-up (mean score 15.0, p = 0.02). On linear regression analysis, age, Gleason score, PSA, T-stage, hormone therapy duration, RT dose and fractions were not significantly associated with mean fatigue scores. CONCLUSION: Patients undergoing 6-8 weeks of RT experienced significant fatigue adversely affecting QOL persisting after therapy completion. Since walking ability was not affected until the end of RT, a walking exercise intervention to combat fatigue is likely feasible and is being investigated.

Prospective evaluation of a 12-week walking exercise program and its effect on fatigue in prostate cancer patients undergoing radical external beam radiotherapy.

OBJECTIVE: To evaluate tolerability and compliance to a walking exercise program and its effect on fatigue during and after radical external beam radiation therapy (EBRT) for prostate cancer. METHODS: A total of 50 subjects with prostate cancer undergoing EBRT over 6 to 8 weeks were prospectively accrued to an exercise intervention group, matched for age and clinical characteristics to 30 subjects in a historical control group who underwent EBRT with no specific exercise intervention. Starting 1 week before EBRT, exercise participants performed moderate-intensity walking targeting 60% to 70% age-predicted maximum heart rate, at least 20 min/d, 3 d/wk over 12 weeks. The Brief Fatigue Inventory was administered at baseline, mid-EBRT (week 3-4), end-EBRT (week 6-8), and 6 months post-EBRT. RESULTS: Of 50, 42 (84%) of exercise participants completed the walking program. There were no cardiovascular complications, musculoskeletal injuries, or other adverse events. A total of 89% subjects reported "Good-Excellent" satisfaction during and up to 6 months post-EBRT. Fatigue in control subjects escalated from baseline to end-EBRT, remaining high at 6 months post-EBRT (P[r] = 0.03). In contrast, mean total fatigue scores in exercise subjects were stable from baseline up to 6 months post-EBRT (P = 0.52). Trends for higher fatigue interference with quality of life were observed in the control group as compared with the exercise group. CONCLUSIONS: Moderate-intensity walking exercise during radical EBRT is safe and feasible. The high convenience and satisfaction ratings, in conjunction with the observed fatigue trends, indicate that this activity has the potential to attenuate fatigue and improve quality of life for patients with localized prostate cancer undergoing curative therapy.

Prognostic significance of blood transfusions in patients with esophageal cancer treated with combined chemoradiotherapy.

OBJECTIVE: Anemia occurs commonly in patients with esophageal cancer. This study evaluates the effect of blood transfusion on survival outcomes in patients with esophageal cancer treated with combined chemoradiotherapy (CRT). PATIENTS AND METHODS: Fifty-six consecutive patients with unresectable esophageal cancer received 50 Gy in 25 fractions over 5 weeks concurrent with cycles 2 and 3 of cisplatin and 5-fluorouracil chemotherapy. Data on hemoglobin before and during radiation therapy (RT) and blood transfusion use were abstracted by chart review. Each patient had a blood count before every chemotherapy cycle, and the test was repeated if the blood count was low. Five-year Kaplan-Meier overall survival (OS) and relapse-free survival (RFS) estimates were compared according to pre-RT hemoglobin levels and transfusion use. Multivariate analysis using Cox regression modeling was performed to determine the prognostic significance of pre-RT hemoglobin and transfusion use on survival outcomes. RESULTS: The 5-year OS and RFS rates were 30% and 37%, respectively. Seventeen patients (30%) received transfusions during CRT. Among 18 patients (32%) with a hemoglobin of < or =12 g/dL at the start of RT, 9 received transfusions. Pre-RT hemoglobin levels of < or =12 g/dL were strongly associated with the use of blood transfusions (P = 0.03). Five-year Kaplan-Meier OS was 65% versus 21% in patients treated with, versus without, a transfusion (P = 0.006). On multivariate analysis, the use of blood transfusion was associated with improved OS (hazard ratio, 0.26; 95% confidence interval, 0.09-0.75, P = 0.01). CONCLUSIONS: The use of blood transfusion is a significant treatment-related factor associated with improved survival in patients undergoing CRT for esophageal cancer.