Purpose To quantify the multi-institutional and multi-observer variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT), and its dosimetric impacts, as the first step of a RTOG effort to establish a breast cancer atlas. Methods and Materials Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, and chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative patients with breast cancer. Inter-observer differences in structure delineation were quantified with regard to volume, distance between centers of mass, percent overlap, and average surface distance. The mean, median and standard deviation for these quantities were calculated for all possible combinations. To asses the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated. Results The variability in contouring the targets and OARs between the institutions/observers was substantial. The structure overlaps were as low as 10% and the volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries as well as approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These inter-observer differences result in substantial variations in dosimetric planning for breast RT. Conclusions The differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of IMRT/IGRT.

Historically, heart dose from left-sided breast radiotherapy has been associated with a risk of cardiac injury. Data suggests that there is not a threshold for the deleterious effects from radiation on the heart. Over the past several years, advances in radiation delivery techniques have reduced cardiac morbidity due to treatment. Deep inspiration breath hold (DIBH) is a technique that takes advantage of a more favorable position of the heart during inspiration to minimize heart doses over a course of radiation therapy. In the accompanying review article, we outline several methods used to deliver treatment with DIBH, quantify the benefits of DIBH treatment, discuss considerations for patient selection, and identify challenges associated with DIBH techniques.

To proliferate, the parasitic protozoan undergoes binary fission in a unidirectional manner along the cell's longitudinal axis from the cell anterior toward the cell posterior. This unusual mode of cell division is controlled by a regulatory pathway composed of two evolutionarily conserved protein kinases, Polo-like kinase and Aurora B kinase, and three trypanosome-specific proteins, CIF1, CIF2, and CIF3, which act in concert at the cytokinesis initiation site located at the distal tip of the newly assembled flagellum attachment zone (FAZ). However, additional regulators that function in this cytokinesis signaling cascade remain to be identified and characterized. Using proximity biotinylation, co-immunofluorescence microscopy, and co-immunoprecipitation, we identified 52 CIF1-associated proteins and validated six CIF1-interacting proteins, including the putative protein phosphatase KPP1, the katanin p80 subunit KAT80, the cleavage furrow-localized proteins KLIF and FRW1, and the FAZ tip-localized proteins FAZ20 and FPRC. Further analyses of the functional interplay between CIF1 and its associated proteins revealed a requirement of CIF1 for localization of a set of CIF1-associated proteins, an interdependence between KPP1 and CIF1, and an essential role of katanin in the completion of cleavage furrow ingression. Together, these results suggest that CIF1 acts as a master regulator of cytokinesis in by recruiting a cohort of cytokinesis regulatory proteins to the cytokinesis initiation site.

To evaluate the performance of the first clinical real-time motion tracking and compensation system using multileaf collimator (MLC) and jaws during helical tomotherapy delivery. Methods: Appropriate mechanical and dosimetry tests were performed on the first clinical real-time motion tracking system (Synchrony on Radixact, Accuray Inc) recently installed in our institution. kV radiography dose was measured by CTDIw using a pencil chamber. Changes of beam characteristics with jaw offset and MLC leaf shift were evaluated. Various dosimeters and phantoms including A1SL ion chamber (Standard Imaging), Gafchromic EBT3 films (Ashland), TomoPhantom (Med Cal), ArcCheck (Sun Nuclear), Delta4 (ScandiDos), with fiducial or high contrast inserts, placed on two dynamical motion platforms (CIRS dynamic motion-CIRS, Hexamotion-ScandiDos), were used to assess the dosimetric accuracy of the available Synchrony modalities: fiducial tracking with nonrespiratory motion (FNR), fiducial tracking with respiratory modeling (FR), and fiducial free (e.g., lung tumor tracking) with respiratory modeling (FFR). Motion detection accuracy of a tracking target, defined as the difference between the predicted and instructed target positions, was evaluated with the root mean square (RMS). The dose accuracy of motion compensation was evaluated by verifying the dose output constancy and by comparing measured and planned (predicted) three-dimensional (3D) dose distributions based on gamma analysis. Results: The measured CTDIw for a single radiograph with a 120 kVp and 1.6 mAs protocol was 0.084 mGy, implying a low imaging dose of 8.4 mGy for a typical Synchrony motion tracking fraction with 100 radiographs. The dosimetric effect of the jaw swing or MLC leaf shift was minimal on depth dose (<0.5%) and was <2% on both beam profile width and output for typical motions. The motion detection accuracies, that is, RMS, were 0.84, 1.13, and 0.48 mm for FNR, FR, and FFR, respectively, well within the 1.5 mm recommended tolerance. Dose constancy with Synchrony was found to be within 2%. The gamma passing rates of 3D dose measurements for a variety of Synchrony plans were well within the acceptable level. Conclusions: The motion tracking and compensation using kV radiography, MLC shifting, and jaw swing during helical tomotherapy delivery was tested to be mechanically and dosimetrically accurate for clinical use.

Background and Purpose To demonstrate and examine the ability of a newly developed software tool to estimate and analyze consensus contours from manually created contours by expert radiation oncologists. Material and Methods Several statistical methods and a graphical user interface were developed. For evaluation purposes, we used three breast cancer CT scans from the RTOG Breast Cancer Atlas Project. Specific structures were contoured before and after the experts’ consensus panel meeting. Differences in the contours were evaluated qualitatively and quantitatively by the consensus software tool. Estimates of consensus contours were analyzed for the different structures and Dice similarity and Dice-Jaccard coefficients were used for comparative evaluation. Results Based on kappa statistics, highest levels of agreement were seen in the left breast, lumpectomy, and heart. Significant improvements between pre- and post-consensus contours were seen in delineation of the chestwall and breasts while significant variations were noticed in the supraclavicular and internal mammary nodes. Dice calculations for all pre-consensus STAPLE estimations and final consensus panel structures reached 0.80 or greater for the heart, left/right breast, case-A lumpectomy, and chestwall. Conclusions Using the consensus software tool incorporating STAPLE estimates provided the ability to create contours similar to the ones generated by expert physicians.