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PURPOSE: Accurate localization of the lumpectomy cavity during accelerated partial breast radiation (APBR) is essential for daily setup to ensure the prescribed dose encompasses the target and avoids unnecessary irradiation to surrounding normal tissues. Three-dimensional ultrasound (3D-US) allows direct visualization of the lumpectomy cavity without additional radiation exposure. The purpose of this study was to evaluate the feasibility of 3D-US in daily target localization for APBR. MATERIALS AND METHODS: Forty-seven patients with stage I breast cancer who underwent breast conserving surgery were treated with a 2-week course of APBR. Patients with visible lumpectomy cavities on high quality 3D-US images were included in this analysis. Prior to each treatment, X-ray and 3D-US images were acquired and compared to images from simulation to confirm accurate position and determine shifts. Volume change of the lumpectomy cavity was determined daily with 3D-US. RESULTS: A total of 118 images of each modality from 12 eligible patients were analyzed. The average change in cavity volume was 7.8% (range, -24.1% to 14.4%) on 3D-US from simulation to the end-of-treatment. Based on 3D-US, significantly larger shifts were necessary compared to portal films in all three dimensions: anterior/posterior (p = 7E-11), left/right (p = 0.002), and superior/inferior (p = 0.004). CONCLUSION: Given that the lumpectomy cavity is not directly visible via X-ray images, accurate positioning may not be fully achieved by X-ray images. Therefore, when the lumpectomy cavity is visible on US, 3D-US can be considered as an alternative to X-ray imaging during daily positioning for selected patients treated with APBR, thus avoiding additional exposure to ionizing radiation.

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PURPOSE: Transperineal ultrasound (TPUS) allows for continuous imaging of the prostate gland, but the accuracy of TPUS has not been rigorously studied. We determined the feasibility of prostate imaging with TPUS and subsequently compared prostate localization with TPUS and computed tomography (CT). METHODS AND MATERIALS: We completed 2 sequential evaluations of TPUS. The feasibility study included 15 men with localized prostate cancer and tested if TPUS adequately imaged the prostate. Image qualities of the prostate and adjacent normal structures were measured. The subsequent study included 17 men who at the time of initial radiation treatment planning and in 3 subsequent sessions had CT and TPUS imaging performed and compared. RESULTS: Feasibility of TPUS was confirmed in the first trial. After expected hardware and software modifications were completed, TPUS provided near complete edge definition of the prostate in the final 5 patients in the feasibility trial. The second study allowed for the comparison of 30 image sets. The differences between TPUS and CT in each direction (mean + standard deviation) were found to be 0.06 ± 2.86 mm (anteroposterior), 0.49 ± 3.49 mm (superoinferior), and 0.63 ± 3.27 mm (left-right), with no significant difference between the 2 modalities (all P > .32). The Euclidean distance variance using the 2 techniques was 5.25 ± 1.79 mm, which was significantly different. CONCLUSIONS: TPUS provides good imaging of the prostate gland. We noted excellent correlation in gland localization when TPUS is compared with CT scans when comparing routine 3-dimensional positional data. Euclidean distance variation suggests the potential that summation of small errors may in fact lead to significant differences in actual gland positional certainty. The reported difference is within the range of standard planning target volume expansion however requires additional evaluation.

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Although IFN-γ is required for resolution of Listeria monocytogenes infection, the identities of the IFN-γ-responsive cells that initiate the process remain unclear. We addressed this question using novel mice with conditional loss of IFN-γR (IFNGR1). Itgax-cre(+)Ifngr1(f/f) mice with selective IFN-γ unresponsiveness in CD8α(+) dendritic cells displayed increased susceptibility to infection. This phenotype was due to the inability of IFN-γ-unresponsive CD8α(+) dendritic cells to produce the initial burst of IL-12 induced by IFN-γ from TNF-α-activated NK/NKT cells. The defect in early IL-12 production resulted in increased IL-4 production that established a myeloid cell environment favoring Listeria growth. Neutralization of IL-4 restored Listeria resistance in Itgax-cre(+)Ifngr1(f/f) mice. We also found that Itgax-cre(+)Ifngr1(f/f) mice survived infection with low-dose Listeria as the result of a second wave of IL-12 produced by Ly6C(hi) monocytes. Thus, an IFN-γ-driven cascade involving CD8α(+) dendritic cells and NK/NKT cells induces the rapid production of IL-12 that initiates the anti-Listeria response.

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Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/ß) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN's actions. However, the specific cells affected by IFN-α/ß and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/ß receptor 1) in dendritic cells (DCs; Itgax-Cre(+)Ifnar1(f/f) mice) cannot reject highly immunogenic tumor cells and that CD8α(+) DCs from these mice display defects in antigen cross-presentation to CD8(+) T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α(+) DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.

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