PurposeAtelectasis (AT), or collapsed lung, is frequently associated with central lung tumors. We investigated the variation of atelectasis volumes during radiation therapy and analyzed the effect of AT volume changes on the reproducibility of the primary tumor (PT) position.Methods and materialsTwelve patients with lung cancer who had AT and 10 patients without AT underwent repeated 4-dimensional fan beam computed tomography (CT) scans during radiation therapy per protocols that were approved by the institutional review board. Interfraction volume changes of AT and PT were correlated with PT displacements relative to bony anatomy using both a bounding box (BB) method and change in center of mass (COM). Linear regression modeling was used to determine whether PT and AT volume changes were independently associated with PT displacement. PT displacement was compared between patients with and without AT.ResultsThe mean initial AT volume on the planning CT was 189 cm3 (37-513 cm3), and the mean PT volume was 93 cm3 (12-176 cm3). During radiation therapy, AT and PT volumes decreased on average 136.7 cm3 (20-369 cm3) for AT and 40 cm3 (−7 to 131 cm3) for PT. Eighty-three percent of patients with AT had at least one unidirectional PT shift that was greater than 0.5 cm outside of the initial BB during treatment. In patients with AT, the maximum PT COM shift was ≥0.5 cm in all patients and >1 cm in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently associated with PT displacement (P < .01), and the correlation was smaller with COM (R2 = 0.58) compared with the BB method (R2 = 0.80). The median root mean squared PT displacement with the BB method was significantly less for patients without AT (0.45 cm) compared with those with AT (0.8cm, P = .002).ConclusionsChanges in AT and PT volumes during radiation treatment were significantly associated with PT displacements that often exceeded standard setup margins. Repeated 3-dimensional imaging is recommended in patients with AT to evaluate for PT displacements during treatment.

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Increasing attention is drawn to the contributions of abnormalities in both innate and acquired immune responses to the pathogenesis of autoimmune diseases, such as type 1 diabetes (T1D). Dendritic cells (DC) are critical immune cells linking innate and acquired immune responses and previous studies in NOD mice suggest abnormalities in these cells. To address DC dysregulation we examined kinetic global gene expression in NOD and B6 GM-CSF/IL-4-induced bone marrow-derived DC following lipopolysaccharide (LPS)-stimulation. We identified expression differences in over 300 genes including a cluster of 16 interferon (IFN-alpha/beta) target genes overexpressed in NOD DC. Mechanistically, heightened IFN-alpha/beta responses were not due to increased production of this cytokine, IFN-gamma priming or increased Syk kinase activity. We found, however, heightened responses to IFN-alpha/beta in NOD versus B6 as demonstrated by increased type 1 IFN target gene expression, for example, IRF-7, in NOD DC and macrophages. Analysis of multiple congenic strains demonstrated that the Idd5 susceptibility region largely governed heightened IFN-alpha responses. Of interest, heightened IFN-alpha/beta response in NOD mice was not confined to hematopoietic cells but was also seen in the pancreas and beta cells. Compounding the IFN-alpha response defect, NOD mice harbor significantly more PDC in spleen in comparison to B6 and produce four- to sixfold more IFN-alpha when stimulated with CpG. Finally, treatment of NOD mice with IFN-alpha inducing agents, for example, high-dose poly I:C accelerates diabetes in both female and male mice. The abnormalities in the IFN-alpha/beta axis appear to play a significant role in T1D pathogenesis.

Purpose: Atelectasis (AT), or collapsed lung, is frequently associated with central lung tumors. We investigated the variation of atelectasis volumes during radiation therapy and analyzed the effect of AT volume changes on the reproducibility of the primary tumor (PT) position. Methods and materials: Twelve patients with lung cancer who had AT and 10 patients without AT underwent repeated 4-dimensional fan beam computed tomography (CT) scans during radiation therapy per protocols that were approved by the institutional review board. Interfraction volume changes of AT and PT were correlated with PT displacements relative to bony anatomy using both a bounding box (BB) method and change in center of mass (COM). Linear regression modeling was used to determine whether PT and AT volume changes were independently associated with PT displacement. PT displacement was compared between patients with and without AT. Results: The mean initial AT volume on the planning CT was 189 cm 3 (37-513 cm 3 ), and the mean PT volume was 93 cm 3 (12-176 cm 3 ). During radiation therapy, AT and PT volumes decreased on average 136.7 cm 3 (20-369 cm 3 ) for AT and 40 cm 3 (À7 to 131 cm 3 ) for PT. Eighty-three percent of patients with AT had at least one unidirectional PT shift that was greater than 0.5 cm outside of the initial BB during treatment. In patients with AT, the maximum PT COM shift was !0.5 cm in all patients and >1 cm in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently associated with PT displacement (P < .01), and the correlation was smaller with COM (R 2 Z 0.58) compared with the BB method (R 2 Z 0.80). The median root mean squared PT displacement with the BB method was significantly less for patients without AT (0.45 cm) compared with those with AT (0.8cm, P Z .002).

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