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Background Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biological activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase II trial were to determine safety and efficacy of cilengitide when combined with radiation and temozolomide for newly diagnosed glioblastoma (GBM) and to select a dose for comparative clinical testing. Methods A total of 112 patients were accrued. Eighteen patients received standard RT+TMZ with cilengitide in a safety run-in phase followed by a randomized phase II with ninety-four patients assigned to either 500 or 2000 mg dose groups. The trial was designed to estimate overall survival benefit when compared with the NABTT internal historical control or the published EORTC 26981 data. Results Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for those receiving the 500 mg dose, 20.8 months for those receiving the 2000mg dose, 30 months for patients with methylated MGMT promoters and 17.4 months for unmethylated patients. For patients ages 70 and younger, the median survival and survival at 24 months was superior to that observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27% (p=0.008) respectively). Conclusions Cilengitide is well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with GBM regardless of MGMT status. From an efficacy and safety standpoint, future trials of this agent in this population should utilize the 2000 mg dose.

On‐board magnetic resonance (MR) image guidance during radiation therapy offers the potential for more accurate treatment delivery. To utilize the real‐time image information, a crucial prerequisite is the ability to successfully segment and track regions of interest (ROI). The purpose of this work is to evaluate the performance of different segmentation algorithms using motion images (4 frames per second) acquired using a MR image‐guided radiotherapy (MR‐IGRT) system. Manual contours of the kidney, bladder, duodenum, and a liver tumor by an experienced radiation oncologist were used as the ground truth for performance evaluation. Besides the manual segmentation, images were automatically segmented using thresholding, fuzzy k‐means (FKM), k‐harmonic means (KHM), and reaction‐diffusion level set evolution (RD‐LSE) algorithms, as well as the tissue tracking algorithm provided by the ViewRay treatment planning and delivery system (VR‐TPDS). The performance of the five algorithms was evaluated quantitatively by comparing with the manual segmentation using the Dice coefficient and target registration error (TRE) measured as the distance between the centroid of the manual ROI and the centroid of the automatically segmented ROI. All methods were able to successfully segment the bladder and the kidney, but only FKM, KHM, and VR‐TPDS were able to segment the liver tumor and the duodenum. The performance of the thresholding, FKM, KHM, and RD‐LSE algorithms degraded as the local image contrast decreased, whereas the performance of the VP‐TPDS method was nearly independent of local image contrast due to the reference registration algorithm. For segmenting high‐contrast images (i.e., kidney), the thresholding method provided the best speed (<1 ms) with a satisfying accuracy (Dice=0.95). When the image contrast was low, the VR‐TPDS method had the best automatic contour. Results suggest an image quality determination procedure before segmentation and a combination of different methods for optimal segmentation with the on‐board MR‐IGRT system.PACS number(s): 87.57.nm, 87.57.N‐, 87.61.Tg

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Purpose:18 F-fluorodeoxyglucose (FDG) positron emission tomographye(PET)/computed tomography (CT) imaging is used for staging and treatment planning of patients with anal cancer. Quantitative pre-and posttreatment metrics that are predictive of recurrence are unknown. We evaluated the association between pre-and posttreatment FDG-PET/CT parameters and outcomes for patients with squamous cell carcinoma of the anus (SCCA). Methods and materials: The records of 110 patients treated between 2003 and 2013 with definitive radiation therapy for SCCA were reviewed under an institutional review boardeapproved protocol. The median radiation therapy dose was 50.4 Gy (range, 35-60 Gy). Concurrent chemotherapy was administered for 109 of 110 patients and generally consisted of 5-fluorouracil and mitomycin C (n Z 94). All patients underwent pretreatment FDG-PET/CT and 101 of 110 underwent posttreatment FDG-PET/CT 3 months after completion of radiation therapy. The maximum standard uptake value (SUV max ) was analyzed, in addition to multiple patient and treatment factors, by univariate and multivariate Cox regression for correlation with local recurrence (LR) and overall survival (OS). Results: The median follow-up was 28.6 months. LR occurred in 1 of 15 (6.7%), 5 of 47 (10.6%), and 6 of 48 (12.5%) patients with stage I, II, and III disease, respectively. On univariate analysis, a significant association was observed between reduced LR and posttreatment SUV max <6.1 (P Z .0095) and between increased OS and posttreatment SUV max <6.1 (P Z .0086). On multivariate analysis, a significant association was observed between reduced LR and posttreatment SUV max <6.1 (P Z .0013) and the use of intensity modulated radiation therapy (P < .001). A

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Purpose: Bowel toxicity can be difficult to manage in the treatment of abdominal cancers. The bowel experiences large motion during treatment, causing it to enter high‐dose regions. Real‐time MR imaging during radiotherapy allows for potential visualization and dosimetric avoidance of the bowel during treatment. To investigate the feasibility of real‐time ‘bowel‐gated’ treatment using onboard MRI, we assessed two bowel‐tracking algorithms on 32 cine imagesets acquired with the ViewRay hybrid MR‐ radiotherapy unit. Methods: The Viewray(TM) System, which is an integrated 0.35T MR‐Co‐60 system that is pending 510k approval, was used to acquire 32 cine image sets in 5 patients under an IRB‐approved trial. Each imageset was acquired in 2D (coronal or sagittal orientation) for an average duration of 0.5‐2.5 minutes at a frame rate of 4 frames/s. The initial position of the bowel was manually contoured on the first image frame. Two algorithms were evaluated in tracking bowel from its initial position throughout its motion for the duration of the cine set ‐ a normalized cross‐ correlation (NCC) algorithm, and a weighted NCC (WNCC) algorithm. To assess the tracking feasibility and accuracy of these two methods, the initial contour was virtually shifted with the tracked motion and displayed on tracked cine images. The agreement between the shifted contour and the border of the bowel was manually inspected and noted for each frame. Results: Both algorithms successfully tracked 31/32 cases in 100% of frames. The WNCC algorithm outperformed the NCC algorithm in speed, with a mean processing speed of .007s versus .013s, respectively, and captured a greater range of motion in all cases. Conclusions: The demonstrated feasibility of bowel tracking on cine MR imagesets indicates its potential successful use in real‐time bowel tracking and gated radiotherapy. While both algorithms performed well, the WNCC algorithm was superior in processing speed and sensitivity to bowel motion.

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