Nawaid Usmani

The 2015 CUA-CUOG Guidelines for the management of castration-resistant prostate cancer (CRPC)

Agents that have shown improvements in survival in mCRPC now include abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223. Bone supportive agents and palliative radiation continue to play an important role in the overall management of mCRPC. Given the complexity, variety and importance of optimizing the use of these agents, a multidisciplinary team approach is highly recommended.

A treatment planning study comparing helical tomotherapy with intensity-modulated radiotherapy for the treatment of anal cancer

PURPOSE A planning study to compare helical tomotherapy (HT) and intensity-modulated radiotherapy (IMRT) for the treatment of anal canal cancer. MATERIALS AND METHODS Sixteen (8 males and 8 females) patients with anal cancer previously treated radically were identified. HT and IMRT plans were generated and dosimetric comparisons of the plans were performed. The planning goals were to deliver 54Gy to the tumor (PTV(54Gy)) and 48Gy to the nodes at risk (PTV(Node)) in 30 fractions. RESULTS PTVs: HT plans were more homogeneous for both men and women. Male patients: HT vs. IMRT: D(max): 55.87+/-0.58 vs. 59.17+/-3.24 (p=0.036); D(min): 52.91+/-0.36 vs. 44.09+/-6.84 (p=0.012); female patients: HT vs. IMRT: D(max): 56.14+/-0.71 vs. 59.47+/-0.81 (p=0.012); D(min): 52.36+/-0.87 vs. 50.97+/-1.42 (p=0.028). OARs: In general, HT plans delivered a lower dose to the peritoneal cavity, external genitalia and the bladder and IMRT plans resulted in greater sparing of the pelvic bones (iliac crest/femur) for both men and women. Iliac crest/femur: the difference was significant only for the mean V10Gy of iliac crest in women (p< or =0.012). External genitalia: HT plans achieved better sparing in women compared to men (p< or =0.046). For men, the mean doses were 18.96+/-3.17 and 15.72+/-3.21 for the HT and IMRT plan, respectively (p< or =0.017). Skin: both techniques achieved comparable sparing of the non-target skin (p=NS). CONCLUSIONS HT and IMRT techniques achieved comparable target dose coverage and organ sparing, whereas HT plans were more homogeneous for both men and women.

Time course of prostatic edema post permanent seed implant determined by magnetic resonance imaging

PURPOSE To quantify the time course of postimplant prostatic edema magnitude and spatial isotropy using serial magnetic resonance imaging (MRI). METHODS AND MATERIALS Forty patients with histologic diagnosis of prostate cancer received an iodine-125 seed implant (Day 0) and consented to 1.5-T MRI on Days -1, 0, 14, and 28. Seeds of strength 0.39mCi were placed in a modified peripheral loading pattern to deliver 145Gy to the target volume. MR images consisted of 3-4mm thick axial slices with no gap. The image sets were anonymized and randomized to minimize contouring bias, then contoured by a single radiation oncologist. Contours were reoriented about their center of mass to align the prostate long axis with the superior-inferior (S-I) direction; prostate volumes and dimensions in the left-right (L-R), anterior-posterior (A-P), and S-I directions through the center of mass were calculated. RESULTS The average relative edema volume was 1.18±0.14 (1standard deviation) on Day 0 and 1.01±0.15 on Day 30. Between Days 0 and 30, the edema resolved linearly with time on average. Average relative edema dimensions on Day 0 in the L-R, A-P, and S-I directions were 1.01±0.07, 1.11±0.09, and 1.08±0.13, respectively. CONCLUSIONS As measured using MRI, the average edema magnitude for our study population was ∼20% on Day 0 and resolved linearly with time to ∼0% on Day 30. The edema exhibited spatial anisotropy, the prostate expanding on Day 0 by ∼10% in each of the A-P and S-I directions and by ∼0% in the L-R direction.

The Prediction of Radiotherapy Toxicity Using Single Nucleotide Polymorphism−Based Models: A Step Toward Prevention

Radiotherapy is a mainstay of cancer treatment, used in either a curative or palliative manner to treat approximately 50% of patients with cancer. Normal tissue toxicity limits the doses used in standard radiation therapy protocols and impedes improvements in radiotherapy efficacy. Damage to surrounding normal tissues can produce reactions ranging from bothersome symptoms that negatively affect quality of life to severe life-threatening complications. Improved ways of predicting, before treatment, the risk for development of normal tissue toxicity may allow for more personalized treatment and reduce the incidence and severity of late effects. There is increasing recognition that the cause of normal tissue toxicity is multifactorial and includes genetic factors in addition to radiation dose and volume of exposure, underlying comorbidities, age, concomitant chemotherapy or hormonal therapy, and use of other medications. An understanding of the specific genetic risk factors for normal tissue response to radiation has the potential to enhance our ability to predict adverse outcomes at the treatment-planning stage. Therefore, the field of radiogenomics has focused upon the identification of genetic variants associated with normal tissue toxicity resulting from radiotherapy. Innovative analytic methods are being applied to the discovery of risk variants and development of integrative predictive models that build on traditional normal tissue complication probability models by incorporating genetic information. Results from initial studies provide promising evidence that genetic-based risk models could play an important role in the implementation of precision medicine for radiation oncology through enhancing the ability to predict normal tissue reactions and thereby improve cancer treatment.

Can Images Obtained With High Field Strength Magnetic Resonance Imaging Reduce Contouring Variability of the Prostate

PURPOSE The objective of this study is to determine whether there is less contouring variability of the prostate using higher-strength magnetic resonance images (MRI) compared with standard MRI and computed tomography (CT). METHODS AND MATERIALS Forty patients treated with prostate brachytherapy were accrued to a prospective study that included the acquisition of 1.5-T MR and CT images at specified time points. A subset of 10 patients had additional 3.0-T MR images acquired at the same time as their 1.5-T MR scans. Images from each of these patients were contoured by 5 radiation oncologists, with a random subset of patients repeated to quantify intraobserver contouring variability. To minimize bias in contouring the prostate, the image sets were placed in folders in a random order with all identifiers removed from the images. RESULTS Although there was less interobserver contouring variability in the overall prostate volumes in 1.5-T MRI compared with 3.0-T MRI (p < 0.01), there was no significant differences in contouring variability in the different regions of the prostate between 1.5-T MRI and 3.0-T MRI. MRI demonstrated significantly less interobserver contouring variability in both 1.5-T and 3.0-T compared with CT in overall prostate volumes (p < 0.01, p = 0.01), with the greatest benefits being appreciated in the base of the prostate. Overall, there was less intraobserver contouring variability than interobserver contouring variability for all of the measurements analyzed. CONCLUSIONS Use of 3.0-T MRI does not demonstrate a significant improvement in contouring variability compared with 1.5-T MRI, although both magnetic strengths demonstrated less contouring variability compared with CT.

A Two-Body Rigid/Flexible Model of Needle Steering Dynamics in Soft Tissue

Robotics-assisted needle steering can enhance targeting accuracy in percutaneous interventions. This paper presents a novel dynamical model for robotically controlled needle steering. This is the first model that predicts both needle shape and tip position in soft tissue, and accepts needle insertion velocity, needle 180° axial rotation, and needle base force/torque as inputs. A hybrid formulation of needle steering dynamics in soft tissue is presented, which considers the needle as a two-body rigid/flexible coupled system composed of a moving, discrete, and rigid part attached to a vibrating compliant part that is subject to external excitation forces. The former is the carrier representing the surgeons hand or the needle inserting robot, while the latter is a beam modeling the continuous deflection of the needle inside tissue. A novel time-delayed tissue model and a fracture mechanics-based model are developed to model the tissue reaction forces and cutting force at the needle tip, respectively. Experiments are performed on synthetic and ex vivo animal tissues to identify the model parameters and validate the needle steering model. The maximum error of the 2-D model in predicting the needle tip position in the insertion plane was 1.59 mm in the case of no axial rotation and 0.74 mm with axial rotation.

A mechanics-based model for simulation and control of flexible needle insertion in soft tissue

In needle-based medical procedures, beveled-tip flexible needles are steered inside soft tissue with the aim of reaching pre-defined target locations. The efficiency of needle-based interventions depends on accurate control of the needle tip. This paper presents a comprehensive mechanics-based model for simulation of planar needle insertion in soft tissue. The proposed model for needle deflection is based on beam theory, works in real-time, and accepts the insertion velocity as an input that can later be used as a control command for needle steering. The model takes into account the effects of tissue deformation, needle-tissue friction, tissue cutting force, and needle bevel angle on needle deflection. Using a robot that inserts a flexible needle into a phantom tissue, various experiments are conducted to separately identify different subsets of the model parameters. The validity of the proposed model is verified by comparing the simulation results to the empirical data. The results demonstrate the accuracy of the proposed model in predicting the needle tip deflection for different insertion velocities.

Comparison of prostate volume, shape, and contouring variability determined from preimplant magnetic resonance and transrectal ultrasound images.

PURPOSE To compare preimplant prostate contours and contouring variability between magnetic resonance (MR) and transrectal ultrasound images. METHODS AND MATERIALS Twenty-three patients were imaged using ultrasound (US) and MR before permanent brachytherapy treatment. Images were anonymized, randomized, and duplicated, and the prostate was independently delineated by five radiation oncologists. Contours were compared in terms of volume, dimensions, posterior rectal indentation, and observer variability. The Jaccard index quantified spatial overlap between contours from duplicated images. RESULTS The mean US/MR volume ratio was 0.99±0.08 (p=0.5). The width, height, and length ratios for the prostate were 0.98±0.06 (p=0.09), 0.99±0.08 (p=0.4), and 1.05±0.14 (p=0.1). Rectal indentation was larger on US by 0.18mL (p=0.01) and correlated with prostate volume (p<0.01). MR and US interobserver variability in volume were similar at 3.5±1.7 and 3.3±1.9mL (p=0.6). Intraobserver variability was smaller on US at 1.4±1.1mL compared with MR at 2.4±2.2mL (p=0.01). Local intraobserver variability was lower on US at the midgland slice (p<0.01) but lower on MR at the base (p<0.01) and apex (p<0.01) slices. CONCLUSIONS US is comparable to MR for preimplant prostate delineation, with no significant difference in volume and dimensions. Rectal indentation because of the transrectal ultrasound probe was measurable, although the effects were small. Intraobserver variability was lower on US for the prostate volume but was lower on MR locally at the base and apex. However, the difference was not observed for the interobserver variability, which was similar between MR and US.

Multiactuator Haptic Feedback on the Wrist for Needle Steering Guidance in Brachytherapy

Brachytherapy is a cancer treatment procedure where long needles are inserted toward an inner body target in order to deliver radioactive seeds that treat the cancer cells. Controlling the trajectory of the needle is very challenging as it deviates from a straight path during insertion. In this letter, we present the pilot study of usefulness of a wristband with haptic feedback designed to help surgeons guide the needle toward a desired destination. The wristband embeds eight miniature actuators distributed around the wrist. The actuators are controlled to generate different haptic stimuli, each of which informs the user about a necessary needle steering manoeuvre. We describe the design of the wristband and its evaluation in two distinct user studies. In the first study, we evaluate how accurately users can identify the vibration patterns. In the second study, we focus on how the user responds to these patterns while performing needle insertion into tissue in an environment with high cognitive visual load. The reported average success rate in identifying the haptic pattern and the success rate in performing the correct action during needle insertion are 86% and 72%, respectively. These results suggest that the device could work in tandem with a needle steering algorithm to help surgeons achieve high quality implants and develop needle steering skills.

Ultrasound-Guided Model Predictive Control of Needle Steering in Biological Tissue

In needle-based medical procedures, beveled tip flexible needles are steered inside soft tissue to reach the desired target locations. In this paper, we have developed an autonomous image-guided needle steering system that enhances targeting accuracy in needle insertion while minimizing tissue trauma. The system has three main components. First is a novel mechanics-based needle steering model that predicts needle deflection and accepts needle tip rotation as an input for needle steering. The second is a needle tip tracking system that determines needle deflection from the ultrasound images. The needle steering model employs the estimated needle deflection at the present time to predict needle tip trajectory in the future steps. The third component is a nonlinear model predictive controller (NMPC) that steers the needle inside the tissue by rotating the needle beveled tip. The MPC controller calculates control decisions based on iterative optimization of the predictions of the needle steering model. To validate the proposed ultrasound-guided needle steering system, needle insertion experiments in biological tissue phantoms are performed in two cases–with and without obstacle. The results demonstrate that our needle steering strategy guides the needle to the desired targets with the maximum error of 2.85mm.