The use of MRI deformable image registration for CT-based brachytherapy in locally advanced cervical cancer.

PURPOSE: Incorporation of MRI into image-based brachytherapy (IBBT) is limited by logistics, reimbursement, and workflow demands. Our goal is to determine if deformable image registration (DIR) using a preimplantation MRI is feasible to construct a high-risk target volume during IBBT. METHODS AND MATERIALS: From 2010 to 2013, 20 patients were treated with high-dose-rate IBBT for cervical cancer. A preimplantation MRI was fused to the planning CT, and DIR was performed using MIM v6.1. The gross tumor volume (GTV) and high-risk clinical target volume were contoured on the MRI (HR-CTV MRI), and a separate high-risk clinical target volume was made from the deformable image registration of the preimplantation MRI to the planning CT (HR-CTV'). The treated target volume from the planning CT without the DIR or fusion (HR-CTV BT) was compared with the HR-CTV'. The geometric means of the GTV, HR-CTV MRI, HR-CTV', and HR-CTV BT were analyzed. Statistical analysis using Wilcoxon rank and analysis of variance were performed. RESULTS: There was a significant larger difference between the GTV and the HR-CTV MRI, HR-CTV', and HR-CTV BT (p < 0.0001). There was also a significant difference between the HR-CTV MRI vs. the HR-CTV BT (p < 0.040). There was no significant difference between the HR-CTV MRI and HR-CTV'. DIR was advantageous in the setting of residual disease pre-IBBT. CONCLUSIONS: DIR is feasible to define an HR-CTV for MRI-guided, CT IBBT. The HR-CTV MRI predicted a smaller treatment volume in comparison with the HR-CTV BT. DIR is limited by patient anatomy and is most beneficial in patients with gross disease.

Women at increased risk for cardiac toxicity following chemoradiation therapy for esophageal carcinoma.

PURPOSE: The purpose of this study was to identify factors associated with cardiac toxicity in patients treated with chemoradiation therapy (CRT) for esophageal carcinoma. METHODS AND MATERIALS: One hundred twenty-seven patients with adenocarcinoma or squamous cell carcinoma of the esophagus treated from July 2002 to June 2011 at 2 academic institutions with preoperative or definitive CRT were retrospectively reviewed. Association of cardiac toxicity with a number of variables was investigated, including heart disease, cardiac bypass and angioplasty, diabetes, insulin use, smoking, chemotherapy regimen, and tumor location. T test assessed risk of cardiac toxicity secondary to age. Dose volume histograms (DVH) were evaluated for percentage of heart volume receiving >20, 30, 40, and 50 Gy (V20-V50). The Fisher exact test analyzed for an association between dose volume parameters and cardiac toxicity. RESULTS: Patient population included 100 men and 27 women with a mean age of 64 years. Median follow-up was 12.7 months (range, 0.3-99.6 months). Any cardiac toxicity occurred in 28 patients, the majority of which were pericardial effusion (23/28). Odds ratio for toxicity in women was 4.15 (95% confidence interval [CI], 1.63-10.50; P = .0017) and time to cardiac toxicity by sex was significant (P = .0003). Patients above the median cutoff for V20, V30, and V40 had increased odds of developing cardiac toxicity (P = .03, .008, .002). There was 4.0 increased odds of developing cardiac toxicity with V40 >57% (95% CI, 1.5-10.3, P = .002). On multivariable logistic regression analysis, sex was the only variable associated with any cardiac toxicity and pericardial effusion (P = .0016, P = .0038). None of the other investigated variables were associated with increased risk of cardiac toxicity. CONCLUSIONS: Female patients and dose greater than the median for V20-V40 were associated with the development of cardiac toxicity, specifically pericardial effusion. These data suggest exercising increased care when designing radiation fields in women undergoing CRT for esophageal carcinoma, as pericardial effusion may be a long-term complication.

IFN-gamma negatively regulates CpG-induced IL-10 in bone marrow-derived dendritic cells.

Dendritic cells (DCs) are important players in the regulation of Th1- and Th2-dominated immune responses. In these studies we showed that IFN-gamma, the key mediator of Th1 immunity, actively suppressed the production of IL-10 in murine DCs when activated with LPS or CpG. Our analysis revealed that both LPS and CpG induced IL-10 and IL-12 production but that the presence of IFN-gamma, in a dose-dependent manner, suppressed the production of IL-10 while enhancing that of IL-12. The observed inhibition of IL-10 production was independent of IL-12. Experiments performed with STAT-1 knockout mice demonstrated that the primary production of IL-12 induced by CpG was STAT-1 dependent, whereas the production of IL-10 was not. This finding was confirmed by the observation that CpG-induced IL-12 production could be inhibited by anti-IFN-beta Abs, whereas CpG-induced IL-10 production could not be inhibited. These data also demonstrated that the inhibitory effect of IFN-gamma on IL-10 expression was STAT-1 dependent and transcriptionally regulated. Thus, DCs respond to CpG by producing proinflammatory and anti-inflammatory cytokines such as IL-12 and IL-10, respectively, and IFN-gamma acts to not only enhance IL-12 but also to inhibit IL-10 production. The current data demonstrate a novel pathway for IFN-gamma-mediated immunoregulation and suggest that IFN-gamma-dependent suppression of IL-10 production by DCs may be involved in the antagonism between Th1 and Th2 patterns of immune reactivity.