Smoking and alcohol drinking effect on radiotherapy associated risk of second primary cancer and mortality among breast cancer patients.

BACKGROUND: Smoking and alcohol consumption are potential risk factors for breast cancer (BC) and may modify the risk of radiotherapy-associated second primary cancer (SPC) occurrence and total mortality. We explored the joint effect of smoking, or alcohol drinking, and radiotherapy on the risk of SPC and overall mortality among BC survivals. METHODS: We conducted a cancer registry-based study of 10,676 BC cases (stage 0-III) with data on smoking and alcohol consumption at time of diagnosis and clinical and therapeutics characteristics. Multivariable Cox proportional hazard models were used to estimate Hazard Ratios [HRs] and 95% confidence interval [CI] of total and site-specific SPC and mortality adjusting for demographic and cancer related characteristics. RESULTS: The SPC risk associated with radiotherapy was higher among ever-smokers than never-smokers (p for interaction = 0.04). Compared to never-smokers/unirradiated, the adjusted HR for ever-smokers/irradiated was 1.79 (95%CI, 1.43-2.23), and for never-smokers/irradiated was 1.31 (95%CI, 1.06-1.63). Analysis by cancer site showed that for ever-smokers/irradiated the risk for hematological, gastrointestinal, gynecological urological and lung/pulmonary cancer was significantly increased by two to five-fold. Mortality was significantly higher for ever-smokers/irradiated (HR = 1.25; 95%CI, 1.06-1.47), but was lower for never-smokers/irradiated (HR = 0.85; 95%CI, 0.73-0.99). Alcohol consumption did not alter the association between radiotherapy and SPC risk, but was associated with lower mortality risk. CONCLUSION: Patients who received radiotherapy and smoked before or at time of BC diagnosis have an increased risk for specific SPCs; drinking alcohol did not alter the effect of radiotherapy. Smoking significantly increased mortality risk reducing the protective effect of radiotherapy treatment.

Role of hormonal therapy in the management of intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation.

PURPOSE: To study the impact of hormonal therapy (HTx) on intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation. METHODS AND MATERIALS: Patients with Stage T1b-T3bN0 prostate cancer, and Gleason score > or = 7 or prostate-specific antigen (PSA) level >10 ng/mL were treated with seed implantation with or without HTx. Their disease was defined as intermediate risk (PSA 10-20, Gleason score 7, or Stage T2b) or high risk (two or more intermediate criteria, or PSA >20 ng/mL, Gleason score 8-10, or Stage T2c-T3). The median follow-up for 201 eligible patients was 42 months (range 18-110). Biochemical failure was defined as a rising PSA >1.0 ng/mL. Pretreatment disease characteristics, implant dose, and HTx were evaluated using univariate and multivariate analyses. RESULTS: HTx significantly improved 5-year actuarial freedom from biochemical failure rate, 79% vs. 54% without HTx. In addition, high-dose, PSA < or = 15 ng/mL, intermediate risk, and Stage T2a or lower significantly improved outcome in the univariate analyses. HTx was the most significant predictor of 5-year actuarial freedom from biochemical failure (p <0.0001) in a multivariate analysis. The best outcome was in the intermediate-risk patients treated with a high implant dose and HTx, resulting in a 4-year actuarial freedom from biochemical failure rate of 94%. CONCLUSION: In this retrospective review, HTx improved outcome in intermediate- to high-risk prostate cancer patients treated with brachytherapy. HTx was the most important prognostic factor in the univariate and multivariate analyses.

Prognostic significance of race on biochemical control in patients with localized prostate cancer treated with permanent brachytherapy: multivariate and matched-pair analyses.

PURPOSE: To compare PSA relapse-free survival (PSA-RFS) between African-American (AA) and white American (WA) males treated with permanent prostate brachytherapy (PPB) for clinically localized prostate cancer. METHODS AND MATERIALS: One thousand eighty-one consecutive patients, including 246 African-Americans, underwent PPB with 103Pd or 125I, alone or with external beam radiation therapy between September 1992 and September 1999. Computer-generated matching was performed to create two identical cohorts of WA and AA males, based on the use of neoadjuvant androgen ablation (NAAD), pretreatment PSA, and Gleason score. Presenting characteristics were used to define risk groups, as follows: Low risk had PSA 10 or Gleason score >or=7, and high risk had PSA >10 and Gleason score >or=7. PSA-RFS was calculated using the Kattan modification of the ASTRO definition, and the log-rank test was used to compare Kaplan-Meier PSA-RFS curves. Univariate and multivariate analyses were performed to determine predictors of PSA-RFS. RESULTS: Overall, univariate analysis revealed that AA males at presentation had lower disease stage (p = 0.01), had lower Gleason scores (p = 0.017), were younger (p = 0.001), and were more likely to receive NAAD (p = 0.001) than their WA counterparts. There were no differences in pretreatment PSA, isotope selection, use of external beam radiation therapy, median follow-up, or risk group classification between AA and WA males. Pretreatment PSA and Gleason score were significant predictors of PSA-RFS in multivariate analysis, and race was not significant. There was no significant difference between the 5-year PSA-RFS for AA males (84.0%) and the matched cohort of WA males (81.2%) (p = 0.384). Race was not a predictor of 5-year PSA-RFS among patients treated with or without NAAD and within low-, intermediate-, and high-risk groups. CONCLUSION: Race is not an independent predictor of 5-year PSA-RFS in patients with localized prostate cancer treated with PPB. This result is consistent with other studies that also show that race does not contribute to differences in outcome after definitive therapies for localized prostate cancer.

Regionally specific effects of BDNF on oligodendrocytes.

To define the effects of neurotrophins on oligodendrocytes, we monitored NGF, BDNF and NT-3 actions on basal forebrain (BF) and cortical populations. NGF, BDNF and NT-3 applied to BF oligodendrocytes elicited increases in expression of myelin basic protein (MBP) and enhanced the numbers of MBP+ cells, without affecting total cell numbers. In the cortex, however, while NGF and NT-3 influenced MBP expression, BDNF was without effect. To explore this apparent regional difference in BDNF action, we compared expression of the neurotrophin receptors trkA, trkB and trkC. While BF cells expressed all three trks, cortical cells did not express the full-length BDNF receptor, trkB. Interestingly, in no case was any receptor expressed by all oligodendrocytes, indicating that oligodendrocytes may be heterogeneous within a brain region. The data suggest that BF oligodendrocytes are influenced by BDNF to express MBP and are distinct in this ability from cortical cells.