Transarterial chemoembolization (TACE) using lipiodol‐based regimens, including the administration of an anticancer‐in‐oil emulsion followed by embolic agents, is widely used in the treatment of ...hepatocellular carcinoma (HCC). This approach has been supported by meta‐analyses of randomized, controlled trials (RCTs) performed more than a decade ago. We performed a systematic review to understand current efficacy and safety data of lipiodol TACE in treatment of HCC. A search of the literature published between January 1, 1980 and June 30, 2013 was performed using MEDLINE and EMBASE databases. All potentially relevant publications were reviewed and articles were selected based on predefined inclusion and exclusion criteria. Of a total of 1,564 articles reviewed, 101 articles, including a total of 10,108 patients treated with lipiodol TACE, were selected for the efficacy analysis. Objective response rate was 52.5% (95% confidence interval CI: 43.6‐61.5). Overall survival (OS) was 70.3% at 1 year, 51.8% at 2 years, 40.4% at 3 years, and 32.4% at 5 years. Median OS was 19.4 months (95% CI: 16.2‐22.6). A total of 217 articles presenting precise description on numbers of adverse events (AEs) were selected for the safety review: In these studies, a total of 21,461 AEs were reported in 15,351 patients. Liver enzyme abnormalities were the most commonly observed AE, followed by the symptoms associated with postembolization syndrome. Overall mortality rate was 0.6% and the most common cause of death was related to acute liver insufficiency. Conclusions: In a systematic literature review, survival figures of HCC patients undergoing lipiodol TACE appear to be in line with those reported in previous RCTs, and no new or unexpected safety concerns were identified. (Hepatology 2016;64:106–116)
Pancreatic ductal adenocarcinoma (PDAC) is resistant to T-cell–mediated immunotherapy. We engineered T cells to transiently express a messenger RNA encoding a chimeric antigen receptor (CAR) specific ...for mesothelin, a protein that is overexpressed by PDAC cells. We performed a phase I study to evaluate the safety and efficacy of adoptive cell therapy with autologous mesothelin-specific CAR T cells (CARTmeso cells) in 6 patients with chemotherapy-refractory metastatic PDAC. Patients were given intravenous CARTmeso cells 3 times weekly for 3 weeks. None of the patients developed cytokine release syndrome or neurologic symptoms and there were no dose-limiting toxicities. Disease stabilized in 2 patients, with progression-free survival times of 3.8 and 5.4 months. We used 18F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography imaging to monitor the metabolic active volume (MAV) of individual tumor lesions. The total MAV remained stable in 3 patients and decreased by 69.2% in 1 patient with biopsy-proven mesothelin expression; in this patient, all liver lesions had a complete reduction in FDG uptake at 1 month compared with baseline, although there was no effect on the primary PDAC. Transient CAR expression was detected in patients’ blood after infusion and led to expansion of new immunoglobulin G proteins. Our results provide evidence for the potential antitumor activity of messenger RNA CARTmeso cells, as well as PDAC resistance to the immune response.
Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and ...meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014 .
This phase I study investigated the safety and activity of lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin (CART-meso) in patients with ...malignant pleural mesothelioma, ovarian carcinoma, and pancreatic ductal adenocarcinoma. Fifteen patients with chemotherapy-refractory cancer (n = 5 per indication) were treated with a single CART-meso cell infusion. CART-meso cells were engineered by lentiviral transduction with a construct composed of the anti-mesothelin single-chain variable fragment derived from the mouse monoclonal antibody SS1 fused to intracellular signaling domains of 4-1BB and CD3zeta. Patients received 1–3 × 107 or 1–3 × 108 CART-meso cells/m2 with or without 1.5 g/m2 cyclophosphamide. Lentiviral-transduced CART-meso cells were well tolerated; one dose-limiting toxicity (grade 4, sepsis) occurred at 1–3 × 107/m2 CART-meso without cyclophosphamide. The best overall response was stable disease (11/15 patients). CART-meso cells expanded in the blood and reached peak levels by days 6–14 but persisted transiently. Cyclophosphamide pre-treatment enhanced CART-meso expansion but did not improve persistence beyond 28 days. CART-meso DNA was detected in 7/10 tumor biopsies. Human anti-chimeric antibodies (HACA) were detected in the blood of 8/14 patients. CART-meso cells were well tolerated and expanded in the blood of all patients but showed limited clinical activity. Studies evaluating a fully human anti-mesothelin CAR are ongoing.
Haas et al. studied lentiviral-transduced chimeric antigen receptor (CAR)-modified T cells recognizing mesothelin in patients with solid cancers, including mesothelioma, ovarian cancer, and pancreatic cancer. They show that mesothelin-specific CAR T cells are well tolerated when administered systemically but produce limited clinical activity. Although a cyclophosphamide preconditioning regimen improved CAR T cell expansion in patients, it did not prolong their persistence in the blood. Their findings provide the framework for subsequent studies testing next generation CAR T cells targeting mesothelin in solid tumors.
Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of ...terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.
With increasing incidence of renal mass, it is important to make a pretreatment differentiation between benign renal mass and malignant tumor. We aimed to develop a deep learning model that ...distinguishes benign renal tumors from renal cell carcinoma (RCC) by applying a residual convolutional neural network (ResNet) on routine MR imaging.
Preoperative MR images (T2-weighted and T1-postcontrast sequences) of 1,162 renal lesions definitely diagnosed on pathology or imaging in a multicenter cohort were divided into training, validation, and test sets (70:20:10 split). An ensemble model based on ResNet was built combining clinical variables and T1C and T2WI MR images using a bagging classifier to predict renal tumor pathology. Final model performance was compared with expert interpretation and the most optimized radiomics model.
Among the 1,162 renal lesions, 655 were malignant and 507 were benign. Compared with a baseline zero rule algorithm, the ensemble deep learning model had a statistically significant higher test accuracy (0.70 vs. 0.56,
= 0.004). Compared with all experts averaged, the ensemble deep learning model had higher test accuracy (0.70 vs. 0.60,
= 0.053), sensitivity (0.92 vs. 0.80,
= 0.017), and specificity (0.41 vs. 0.35,
= 0.450). Compared with the radiomics model, the ensemble deep learning model had higher test accuracy (0.70 vs. 0.62,
= 0.081), sensitivity (0.92 vs. 0.79,
= 0.012), and specificity (0.41 vs. 0.39,
= 0.770).
Deep learning can noninvasively distinguish benign renal tumors from RCC using conventional MR imaging in a multi-institutional dataset with good accuracy, sensitivity, and specificity comparable with experts and radiomics.
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