Prognostic Value of CT Radiomic Features in Resectable Pancreatic Ductal Adenocarcinoma.

In this work, we assess the reproducibility and prognostic value of CT-derived radiomic features for resectable pancreatic ductal adenocarcinoma (PDAC). Two radiologists contoured tumour regions on pre-operative CT of two cohorts from two institutions undergoing curative-intent surgical resection for PDAC. The first (n = 30) and second cohorts (n = 68) were used for training and validation of proposed prognostic model for overall survival (OS), respectively. Radiomic features were extracted using PyRadiomics library and those with weak inter-reader reproducibility were excluded. Through Cox regression models, significant features were identified in the training cohort and retested in the validation cohort. Significant features were then fused via Cox regression to build a single radiomic signature in the training cohort, which was validated across readers in the validation cohort. Two radiomic features derived from Sum Entropy and Cluster Tendency features were both robust to inter-reader reproducibility and prognostic of OS across cohorts and readers. The radiomic signature showed prognostic value for OS in the validation cohort with hazard ratios of 1.56 (P = 0.005) and 1.35 (P = 0.022), for the first and second reader, respectively. CT-based radiomic features were shown to be prognostic in patients with resectable PDAC. These features may help stratify patients for neoadjuvant or alternative therapies.

Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study.

PURPOSE: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). METHODS AND MATERIALS: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. RESULTS: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. CONCLUSIONS: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.

MRI-guided transurethral ultrasound therapy of the prostate gland using real-time thermal mapping: initial studies.

OBJECTIVE: To confirm the correlation between planning and thermal injury of the prostate as determined by magnetic resonance imaging (MRI) and histology in canine and humans treated with transurethral ultrasound. MATERIAL AND METHODS: Canine studies: 2 sets of in vivo studies were performed under general anesthesia in 1.5 T clinical MRI. Nine dogs were treated using single transducer; 8 dogs were treated using urethral applicator with multiple transducers. Rectal cooling was maintained. After initial imaging, a target boundary was selected and high-intensity ultrasound energy delivered. The spatial temperature distribution was measured continuously every 5 seconds with MR thermometry using the proton-resonant frequency shift method. The goal was to achieve 55 °C at the target boundary. After treatment, the prostate was harvested and fixed with adjoining tissue, including rectum. Temperature maps, anatomical images, and histologic sections were registered to each other and compared. Human studies: To date, 5 patients with localized prostate cancer have been treated immediately before radical prostatectomy. Approximately 30% of the gland volume was targeted. RESULTS: A continuous pattern of thermal coagulation was successfully achieved within the target region, with an average spatial precision of 1-2 mm. Radical prostatectomy was routine, with an uncomplicated postoperative course in all patients. The correlation between anatomical, thermal, and histologic images was ≤3 mm. Treatment time was <30 minutes. No thermal damage to rectal tissue was observed. CONCLUSIONS: Thermal ablation within the prescribed target of the prostate has been successfully demonstrated in canine studies. The treatment is also feasible in humans.

Analysis of factors important for transurethral ultrasound prostate heating using MR temperature feedback.

The feasibility of using MR thermometry for temperature feedback to control a transurethral ultrasound heating applicator with planar transducers was investigated. The sensitivity of a temperature-based feedback algorithm to spatial (control point area, slice thickness, angular alignment) and non-spatial (imaging time, temperature uncertainty) parameters was evaluated through numerical simulations. The angular alignment of the control point with the ultrasound beam was an important parameter affecting the average spatial error in heat delivery. The other spatial parameters were less influential, thus providing an opportunity to reduce spatial resolution for increased SNR in the MR imaging. The update time was the most important non-spatial parameter determining the performance of the control algorithm. Combined non-spatial and spatial parameters achieved acceptable performance with a voxel size of 3 mm x 3 mm, a 10 mm slice thickness and a 5 s update time. Temperature uncertainty of up to 2 degrees C had little effect on the performance of the control algorithm but did reduce the average error slightly due to a systematic, noise-induced overestimation of the boundary temperature. These simulations imply that MR thermometry performed on clinical 1.5 T imaging systems is of sufficient quality for use as thermal feedback for conformal prostate thermal therapy with transurethral ultrasound heating applicators incorporating planar transducers.

Method for MRI-guided conformal thermal therapy of prostate with planar transurethral ultrasound heating applicators.

A method for conformal prostate thermal therapy using transurethral ultrasound heating applicators incorporating planar transducers is described. The capability to shape heating patterns to the geometry of the prostate gland from a single element in a multi-element heating applicator was evaluated using Bioheat transfer modelling. Eleven prostate geometries were obtained from patients who underwent MR imaging of the prostate gland prior to radical prostatectomy. Results indicate that ultrasound heating applicators incorporating multi-frequency planar transducers (4 x 20 mm, f = 4.7 MHz, 9.7 MHz) are capable of shaping thermal damage patterns to the geometry of individual prostates. A temperature feedback control algorithm has been developed to control the frequency, rotation rate and applied power level from transurethral heating applicators based on measurements of the boundary temperature during heating. The discrepancy between the thermal damage boundary and the target boundary was less than 5 mm, and the transition distance between coagulation and normal tissue was less than 1 cm. Treatment times for large prostate volumes were less than 50 min, and perfusion did not have significant impact on the control algorithm. Rectal cooling will play an important role in reducing undesired heating near the rectal wall. Experimental validation of the simulations in a tissue-mimicking gel phantom demonstrated good agreement between the predicted and generated patterns of thermal damage.

Interstitial microwave thermal therapy for prostate cancer.

Thermal therapy is used to kill tumors by heating them to temperatures >50 degrees C for an extended period of time. Cell death results from thermal coagulation. The energy sources available for this approach include radiofrequency electrodes, microwave antennas, laser fiberoptics, and ultrasound transducers. Each of these modalities has the potential to be delivered in a minimally invasive manner, and many theoretical and experimental investigations of these devices have been performed. This review describes current knowledge of interstitial microwave thermal therapy for prostate cancer. Examples are given from an ongoing trial in patients who have recurrent or persistent disease following radiation therapy. Future directions for pretreatment planning and real-time monitoring and control are discussed. These techniques have the potential to optimize treatments on a patient-specific basis and will be instrumental in planned future trials of this therapy as first line for prostate cancer.