Patterns of failure of diffuse large B­cell lymphoma patients after involved-site radiotherapy.

PURPOSE: Radiotherapy (RT) in combination with chemoimmunotherapy is highly efficient in the treatment of diffuse large B­cell lymphoma (DLBCL). This retrospective analysis evaluated the efficacy of the treatment volume and the dose concept of involved-site RT (ISRT). PATIENTS AND METHODS: We identified 60 histologically confirmed stage I-IV DLBCL patients treated with multimodal cytotoxic chemoimmunotherapy and followed by consolidative ISRT from 2005-2015. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate analyses were performed by log-rank test and Mann-Whitney U­test. RESULTS: After initial chemoimmunotherapy (mostly R­CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 19 (36%) patients achieved complete response (CR), 34 (64%) partial response (PR) or less. Excluded were 7 (12%) patients with progressive disease after chemoimmunotherapy. All patients underwent ISRT with a dose of 40 Gy. After a median follow-up of 44 months, 79% of the patients remained disease free, while 21% presented with failure, progressive systemic disease, or death. All patients who achieved CR after chemoimmunotherapy remained in CR. Of the patients achieving PR after chemotherapy only 2 failed at the initial site within the ISRT volume. No marginal relapse was observed. Ann Arbor clinical stage I/II showed significantly improved PFS compared to stage III/IV (93% vs 65%; p ≤ 0.021). International Prognostic Index (IPI) score of 0 or 1 compared to 2-5 has been associated with significantly increased PFS (100% vs 70%; p ≤ 0.031). Postchemoimmunotherapy status of CR compared to PR was associated with significantly increased PFS (100% vs 68%; p ≤ 0.004) and OS (100% vs 82%; p ≤ 0.026). Only 3 of 53 patients developed grade II late side effects, whereas grade III or IV side effects have not been observed. CONCLUSION: These data suggest that a reduction of the RT treatment volume from involved-field (IF) to involved-site (IS) is sufficient because no marginal failures occurred. The concept of IS will likely reduce the risk for late sequelae of RT.

Nicotinic acid has anti-atherogenic and anti-inflammatory properties on advanced atherosclerotic lesions independent of its lipid-modifying capabilities.

Inflammation contributes to atherosclerotic plaque initiation and progression. Recent studies suggest that nicotinic acid has anti-inflammatory effects independent of its lipid-modifying capabilities. We assessed the hypothesis that administration of nicotinic acid to older apolipoprotein E (apoE)-deficient mice with established lesions will reduce lesion size and plaque inflammation independent of its lipid-modifying effects. Therefore nicotinic acid was administered to 27-week-old apo E-deficient mice exhibiting advanced atherosclerotic lesions within the innominate artery. After 27 weeks of treatment both animal groups had no significant changes in plasma lipid levels. Mice treated with nicotinic acid (n = 22) demonstrated a 30% reduction in total lesion area compared with controls (n = 20). Furthermore, they revealed a more stable plaque composition with an increase in fibrous cap thickness and a reduction in the size of the necrotic core. Immunohistochemistry demonstrated a reduced accumulation of macrophages and a reduced expression of vascular cell adhesion molecule-1 and tissue factor. Additionally, administration of nicotinic acid significantly reduced tumor necrosis factor alpha expression in the thoracic aorta as demonstrated by real-time PCR. In conclusion, these data suggest that long-term administration of nicotinic acid has anti-atherogenic and anti-inflammatory properties on advanced atherosclerotic lesions, which are independent of its lipid-modifying actions.