A simulated comparison of lung tumor target verification using stereoscopic tomosynthesis or radiography.

PURPOSE: Mobile lung tumors are increasingly being treated with ablative radiotherapy, for which precise motion management is essential. In-room stereoscopic radiography systems are able to guide ablative radiotherapy for stationary cranial lesions but not optimally for lung tumors unless fiducial markers are inserted. We propose augmenting stereoscopic radiographic systems with multiple small x-ray sources to provide the capability of imaging with stereoscopic, single frame tomosynthesis. METHODS: In single frame tomosynthesis, nine x-ray sources are placed in a 3 × 3 configuration and energized simultaneously. The beams from these sources are collimated so that they converge on the tumor and then diverge to illuminate nine non-overlapping sectors on the detector. These nine sector images are averaged together and filtered to create the tomosynthesis effect. Single frame tomosynthesis is intended to be an alternative imaging mode for existing stereoscopic systems with a field of view that is three times smaller and a temporal resolution equal to the frame rate of the detector. We simulated stereoscopic tomosynthesis and radiography using Monte Carlo techniques on 60 patients with early-stage lung cancer from the NSCLC-Radiomics dataset. Two board-certified radiation oncologists reviewed these simulated images and rated them on a 4-point scale (1: tumor not visible; 2: tumor visible but inadequate for motion management; 3: tumor visible and adequate for motion management; 4: tumor visibility excellent). Each tumor was independently presented four times (two viewing angles from radiography and two viewing angles from tomosynthesis) in a blinded fashion over two reading sessions. RESULTS: The fraction of tumors that were rated as adequate or excellent for motion management (scores 3 or 4) from at least one viewing angle was 53% using radiography and 90% using tomosynthesis. From both viewing angles, the corresponding fractions were 7% for radiography and 48% for tomosynthesis. Readers agreed exactly on 62% of images and within 1 point on 98% of images. The acquisition technique was estimated to be 75 mAs at 120 kVp per treatment fraction assuming one verification image per breath, approximately one order of magnitude less than a standard dose cone beam CT. CONCLUSIONS: Stereoscopic tomosynthesis may provide a noninvasive, low dose, intrafraction motion verification technique for lung tumors treated by ablative radiotherapy. The system architecture is compatible with real-time video capture at 30 frames per second. Simulations suggest that most, but not all, lung tumors can be adequately visualized from at least one viewing angle.

Dose Sculpting Intensity Modulated Radiation Therapy for Vertebral Body Sparing in Children With Neuroblastoma.

PURPOSE: To assess the effect of dose sculpting intensity modulated radiation therapy on vertebral body growth in children with neuroblastoma. METHODS AND MATERIALS: From 2000 to 2011, 88 children with neuroblastoma underwent radiation at the authors' institution. Children with paravertebral tumors with at least 3 years of evaluable posttreatment imaging were included, and children who underwent spine reirradiation before follow-up were excluded. If vertebral bodies could not be spared, these "target" vertebral bodies were treated to at least 18 Gy. Thoracic and lumbar vertebral bodies were assessed separately. Dose data for target, spared, and internal control vertebral bodies were extracted. Multivariate generalized estimating equation modeling was used to assess the effect of dose and other clinical factors on vertebral body growth. RESULTS: A total of 34 patients (20 boys, 14 girls) met study criteria. Median age at start of radiation was 4.3 years; all but 1 had prior high-dose chemotherapy with stem cell rescue. Mean growth rates of target, spared, and control vertebral bodies (cm/body/y) were, respectively, 0.027, 0.032, and 0.044 in thoracic spine and 0.033, 0.055, and 0.083 in lumbar spine. On multivariate generalized estimating equation analysis, higher dose, older treatment age, male gender, and thoracic spine location were significantly associated with decreased vertebral body growth (P<.0001, P<.0001, P=.007, and P<.0001, respectively). Dose and spine location were significant in a 3-way interaction model (P<.0001). CONCLUSIONS: Vertebral bodies spared by intensity modulated radiation therapy grew faster than target vertebrae. Regardless of intent to spare or target, multivariate analysis confirms that lower dose results in significantly increased growth rate. This technique should be investigated prospectively.

Real-time tomosynthesis for radiation therapy guidance.

PURPOSE: Fluoroscopy has been a tool of choice for monitoring treatments or interventions because of its extremely fast imaging times. However, the contrast obtained in fluoroscopy may be insufficient for certain clinical applications. In stereotactic ablative radiation therapy of the lung, fluoroscopy often lacks sufficient contrast for gating treatment. The purpose of this work is to describe and assess a real-time tomosynthesis design that can produce sufficient contrast for guidance of lung tumor treatment within a small field of view. METHODS: Previous tomosynthesis designs in radiation oncology have temporal resolution on the order of seconds. The proposed system design uses parallel acquisition of multiple frames by simultaneously illuminating the field of view with multiple sources, enabling a temporal resolution of up to 30 frames per second. For a small field of view, a single flat-panel detector could be used if different sectors of the detector are assigned to specific sources. Simulated images were generated by forward projection of existing clinical datasets. The authors varied the number of tubes and the power of each tube in order to determine the impact on tumor visualization. RESULTS: Visualization of the tumor was much clearer in tomosynthesis than in fluoroscopy. Contrast generally improved with the number of sources used, and a minimum of four sources should be used. The high contrast of the lung allows very low system power, and in most cases, less than 1 mA was needed. More power is required in the lateral direction than the AP direction. CONCLUSIONS: The proposed system produces images adequate for real-time guidance of radiation therapy. The additional hardware requirements are modest, and the system is capable of imaging at high frame rates and low dose. Further development, including a prototype system and a dosimetry study, is needed to further evaluate the feasibility of this device for radiation therapy guidance.

A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration.

To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways whose knockdown dramatically enhances cellular migration. Some of these pathways share features of epithelial-to-mesenchymal transition (EMT), and together they implicate key regulators of transcription, cellular signaling, and metabolism, as well as novel modulators of cellular trafficking, such as DLG5. In delineating downstream pathways mediating these migration phenotypes, we observed universal activation of ERKs and a profound dependence on their RSK effectors. Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration induced by knockdown of all 31 genes, suggesting that convergence of diverse migratory pathways on this kinase may provide a therapeutic opportunity in disorders of cell migration, including cancer metastasis.