Favorable outcomes in locally advanced and node positive prostate cancer patients treated with combined pelvic IMRT and androgen deprivation therapy.

BACKGROUND: The most appropriate treatment for men with prostate cancer and positive pelvic nodes, N+, is an area of active controversy. We report our 5-years outcomes in men with locally advanced prostate cancer (T1-T4N0-N1M0) treated with definitive radiotherapy encompassing the prostate and pelvic lymph nodes (intensity modulated radiotherapy, IMRT) and long-term androgen deprivation therapy (ADT). MATERIAL AND METHODS: Of the 138 consecutive eligible men all living patients have been followed up to almost 5 years. Survival endpoints for 5-year biochemical failure-free survival (BFFS), relapse-free survival (RFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were assessed by Kaplan-Meier analysis. Univariate and multivariate Cox regression proportional hazards models were constructed for all survival endpoints. The RTOG morbidity grading system for physician rated toxicity was applied. RESULTS: Patients with locally advanced T3-T4 tumors (35 %) and N1 (51 %) have favorable outcome when long-term ADT is combined with definitive radiotherapy encompassing pelvic lymph nodes. The 5-year BFFS, RFS, PCSS and OS were 71.4, 76.2, 94.5 and 89.0 %, respectively. High Gleason sum (9-10) had a strong independent prognostic impact on BFFS, RFS and OS (p = 0.001, <0.001, and 0.005 respectively). The duration of ADT (= > 28 months) showed a significant independent association with improved PCSS (p = 0.02) and OS (p = 0.001). Lymph node involvement was not associated with survival endpoints in the multivariate analysis. The radiotherapy induced toxicity seen in our study population was moderate with rare Grade 3 GI side effects and up to 11 % for Grade 3 GU consisting mainly of urgency and frequency. CONCLUSION: Pelvic IMRT in combination with long-term ADT can achieve long-lasting disease control in men with N+ disease and unfavorable prognostic factors.

Postradiotherapy plasma lutein, alpha-carotene, and beta-carotene are positively associated with survival in patients with head and neck squamous cell carcinoma.

The aim of our study was to compare plasma carotenoids (i.e., biomarkers of fruits and vegetables intake) and tocopherols in 29 head and neck squamous cell carcinoma (HNSCC) patients with 51 healthy controls and to explore the possibility whether these plasma antioxidants could be related to outcome among patients. The patients' blood samples were taken at the end of radiotherapy. We observed that plasma lutein, zeaxanthin, alpha-carotene, beta-carotene, lycopene, and total carotenoids were significantly lower in HNSCC patients than controls. Among the patients, 18 died and 11 were still alive during median follow-up of 55 mo for survivors. We found a significant positive association between postradiotherapy plasma carotenoids (lutein, alpha-carotene, and beta-carotene) and progression-free survival in these patients. This study indicates that increasing postradiotherapy plasma carotenoid concentration may reduce risk of premature death or recurrence of tumor in HNSCC patients. Increasing plasma carotenoid concentration should be done by increasing intake of carotenoid-rich fruits and vegetables, as other studies have shown either no or negative effects due to use of carotenoid supplements.

Post-radiotherapy plasma total glutathione is associated to outcome in patients with head and neck squamous cell carcinoma.

We have studied the role of systemic oxidative stress for survival of patients with head and neck squamous cell carcinomas (HNSCC). Patients with lowest plasma total GSH levels had the lowest 36 months survival. In patients with post-radiotherapy concentrations of plasma total GSH less than median value, about 73% died during the 36 months follow-up compared to about 21% of patients with GSH values above median. Systemic oxidative stress as assessed by low GSH in post-radiotherapy plasma is associated to outcome in HNSCC patients.

Simultaneous quantification of reduced and oxidized glutathione in plasma using a two-dimensional chromatographic system with parallel porous graphitized carbon columns coupled with fluorescence and coulometric electrochemical detection.

A method for the simultaneous quantification of reduced and oxidized glutathione in human plasma employing a two-dimensional chromatographic system with parallel porous graphitized carbon (PGC) columns coupled with fluorescence (FLD) and coulometric electrochemical detection (ED) has been developed. Post-sampling oxidation of reduced glutathione (GSH) was prevented by derivatizing the -SH group with monobromobimane (MBB) and the glutathione-bimane adduct (GSMB) was detected by FLD. Oxidized glutathione (GSSG) was detected by ED optimized to give lowest possible limits of detection (LOD). The method is fully validated and is currently used for determination of GSH, GSSG and its redox potential in different clinical studies.