The purpose of this study is to characterize the dosimetric properties and accuracy of a novel treatment platform (Edge radiosurgery system) for localizing and treating patients with frameless, image‐guided stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various components of the system, such as a comprehensive assessment of the dosimetric properties of the flattening filter‐free (FFF) beams for both high definition (HD120) MLC and conical cone‐based treatment, positioning accuracy and beam attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test, and integrated end‐to‐end accuracy tests, have been performed. The end‐to‐end test of the system was performed by CT imaging a phantom and registering hidden targets on the treatment couch to determine the localization accuracy of the optical surface monitoring system (OSMS), cone‐beam CT (CBCT), and MV imaging systems, as well as the radiation isocenter targeting accuracy. The deviations between the percent depth‐dose curves acquired on the new linac‐based system (Edge), and the previously published machine with FFF beams (TrueBeam) beyond Dmax were within 1.0% for both energies. The maximum deviation of output factors between the Edge and TrueBeam was 1.6%. The optimized dosimetric leaf gap values, which were fitted using Eclipse dose calculations and measurements based on representative spine radiosurgery plans, were 0.700 mm and 1.000 mm, respectively. For the conical cones, 6X FFF has sharper penumbra ranging from 1.2−1.8 mm (80%‐20%) and 1.9−3.8 mm (90%‐10%) relative to 10X FFF, which has 1.2−2.2 mm and 2.3−5.1 mm, respectively. The relative attenuation measurements of the couch for PA, PA (rails‐in), oblique, oblique (rails‐out), oblique (rails‐in) were: −2.0%, −2.5%, −15.6%, −2.5%, −5.0% for 6X FFF and −1.4%, −1.5%, −12.2%, −2.5%, −5.0% for 10X FFF, respectively, with a slight decrease in attenuation versus field size. The systematic deviation between the OSMS and CBCT was −0.4±0.2 mm, 0.1±0.3 mm, and 0.0±0.1 mm in the vertical, longitudinal, and lateral directions. The mean values and standard deviations of the average deviation and maximum deviation of the daily Winston‐Lutz tests over three months are 0.20±0.03 mm and 0.66±0.18 mm, respectively. Initial testing of this novel system demonstrates the technology to be highly accurate and suitable for frameless, linac‐based SRS and SBRT treatment.PACS number: 87.56.J‐

The safety of oncolytic adenovirus-mediated suicide and interleukin-12 ( IL 12 ) gene therapy was evaluated in metastatic pancreatic cancer patients. In this phase I study, a replication-competent adenovirus (Ad5-yCD/ mut TK SR39 rep -hIL-12) expressing yCD/ mut TK SR39 (yeast cytidine deaminase/mutant S39R HSV-1 thymidine kinase) and human IL-12 ( IL 12 ) was injected into tumors of 12 subjects with metastatic pancreatic cancer (T2N0M1-T4N1M1) at escalating doses (1 × 10 11 , 3 × 10 11 , or 1 × 10 12 viral particles). Subjects received 5-fluorocytosine (5-FC) therapy for 7 days followed by chemotherapy (FOLFIRINOX or gemcitabine/albumin-bound paclitaxel) starting 21 days after adenovirus injection. The study endpoint was toxicity through day 21. Experimental endpoints included measurements of serum IL 12 , interferon gamma (IFNG), and CXCL10 to assess immune system activation. Peripheral blood mononuclear cells and proliferation markers were analyzed by flow cytometry. Twelve patients received Ad5-yCD/ mut TK SR39 rep -hIL-12 and oral 5-FC. Approximately 94% of the 121 adverse events observed were grade 1/2 requiring no medical intervention. Ad5-yCD/ mut TK SR39 rep -hIL-12 DNA was detected in the blood of two patients. Elevated serum IL 12 , IFNG, and CXCL10 levels were detected in 42%, 75%, and 92% of subjects, respectively. Analysis of immune cell populations indicated activation after Ad5-yCD/ mut TK SR39 rep -hIL-12 administration. The median survival of patients in the third cohort is 18.1 (range, 3.5–20.0) months. The study maximum tolerated dose (MTD) was not reached.

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Ledipasvir‐sofosbuvir, a once‐a‐day, oral combination pill, was approved in 2014 for the treatment of chronic hepatitis C infection. Initial trials did not comment on nephrotoxicity; however, recent data suggest a risk of acute kidney injury (AKI) with the use of the medication. We assessed the rates of AKI in patients undergoing ledipasvir‐sofosbuvir in a large, urban tertiary care center. This single‐center retrospective observation study included all patients undergoing therapy from October 1, 2014, to October 1, 2015. Rates of AKI, defined by more than a 0.3 mg/dL increase in serum creatinine level, were calculated. Patients were followed 12 weeks after therapy to assess for sustained viral response as well as to assess for improvement of AKI after completion of therapy, defined by less than 0.2 mg/dL above baseline serum creatinine. In total, 197 patients were included in the final analysis who had completed ledipasvir‐sofosbuvir therapy and completed laboratory values. Among the patients treated, 38 (19%) had AKI during therapy. An additional 4 (2%) had AKI at the end of therapy. Of the 38 patients who experienced AKI, 20 (53%) had improvement in serum creatinine to less than 0.2 mg/dL above their baseline. When comparing for chronic kidney disease (CKD) stage, those with CKD I or II experienced AKI 17% of the time compared with 47% of the time in CKD III or worse (P = 0.005). Conclusion: AKI was seen in nearly one‐fifth of our patients, and patients with CKD stage III or worse are at increased risk. Although ledipasvir‐sofosbuvir is generally safe in the general population, close monitoring of renal function is recommended.