Ralph Brasacchio

Is there a favorable subset of patients with prostate cancer who develop oligometastases

OBJECTIVE To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.

In vivo motion and force measurement of surgical needle intervention during prostate brachytherapy

In this paper, we present needle insertion forces and motion trajectories measured during actual brachytherapy needle insertion while implanting radioactive seeds in the prostate glands of 20 different patients. The needle motion was captured using ultrasound images and a 6 degree-of-freedom electromagnetic-based position sensor. Needle velocity was computed from the position information and the corresponding time stamps. From in vivo data we found the maximum needle insertion forces to be about 15.6 and 8.9N for 17gauge (1.47mm) and 18gauge (1.27mm) needles, respectively. Part of this difference in insertion forces is due to the needle size difference (17G and 18G) and the other part is due to the difference in tissue properties that are specific to the individual patient. Some transverse forces were observed, which are attributed to several factors such as tissue heterogeneity, organ movement, human factors in surgery, and the interaction between the template and the needle. However, theses insertion forces are significantly responsible for needle deviation from the desired trajectory and target movement. Therefore, a proper selection of needle and modulated velocity (translational and rotational) may reduce the tissue deformation and target movement by reducing insertion forces and thereby improve the seed delivery accuracy. The knowledge gleaned from this study promises to be useful for not only designing mechanical/robotic systems but also developing a predictive deformation model of the prostate and real-time adaptive controlling of the needle.

Intraoperative optimized inverse planning for prostate brachytherapy: early experience

PURPOSE To demonstrate the feasibility of an intraoperative inverse planning technique with advanced optimization for prostate seed implantation. METHODS AND MATERIALS We have implemented a method for optimized inverse planning of prostate seed implantation in the operating room (OR), based on the genetic algorithm (GA) driven Prostate Implant Planning Engine for Radiotherapy (PIPER). An integrated treatment planning system was deployed, which includes real-time ultrasound image acquisition, treatment volume segmentation, GA optimization, real-time decision making and sensitivity analysis, isodose and DVH evaluation, and virtual reality navigation and surgical guidance. Ten consecutive patients previously scheduled for implantation were included in the series. RESULTS The feasibility of the technique was established by careful monitoring of each step in the OR and comparison with conventional preplanned implants. The median elapsed time for complete image capture, segmentation, GA optimization, and plan evaluation was 4, 10, 2.2, and 2 min, respectively. The dosimetric quality of the OR-based plan was shown to be equivalent to the corresponding preplan. CONCLUSION An intraoperative optimized inverse planning technique was developed for prostate brachytherapy. The feasibility of the method was demonstrated through an early clinical experience.

Robot-Assisted prostate brachytherapy

In contemporary brachytherapy procedures, needle placement at the desired target is challenging due to a variety of reasons. A robot-assisted brachytherapy system can improve the needle placement and seed delivery resulting in enhanced patient care. In this paper we present a 16 DOF (degrees-of-freedom) robotic system (9DOF positioning module and 7 DOF surgery module) developed and fabricated for prostate brachytherapy. Techniques to reduce needle deflection and target movement have been incorporated after verifying with extensive experiments. Provisions for needle motion and force feedback have been included into the system for improving the robot control and seed delivery. Preliminary experimental results reveal that the prototype system is quite accurate (sub-millimeter) in placing brachytherapy needles.

Autotransplantation for relapsed or refractory Hodgkin's disease : long-term follow-up and analysis of prognostic factors

Seventy consecutive patients with refractory or relapsed Hodgkin’s disease who received high-dose chemotherapy followed by autologous stem cell rescue were analyzed to identify clinically relevant predictors of long-term event-free survival. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine and cyclophosphamide (BEAC). The 5-year Kaplan–Meier event-free survival (EFS) for the entire cohort was 32% (95% confidence interval; 18–45%) with a median follow-up of 3.6 years (range 7 months–7.6 years). The most significant predictor of improved survival was the presence of minimal disease (defined as all areas ⩽2 cm) at the time of transplant: the 5 years EFS was 46 vs 10% for patients with bulky disease (P = 0.0002). Other independent predictors identified by step-wise regression analysis included the presence of non-refractory disease and the administration of post-transplant involved-field radiotherapy (XRT). Treatment-related mortality occurred in 13 of 70 patients: nine patients (13%) died within the first 100 days, mainly from cardiopulmonary toxicity. However, only one of 24 patients (4%) transplanted during the last 4.5 years died from early treatment-related complications. While high-dose therapy followed by autotransplantation led to long-term EFS of 50% for patients with favorable prognostic factors, a substantial proportion of patients relapsed, indicating that new therapeutic strategies are needed.

AUTOMATED TREATMENT PLANNING ENGINE FOR PROSTATE SEED IMPLANT BRACHYTHERAPY

PURPOSE To develop a computer-intelligent planning engine for automated treatment planning and optimization of ultrasound- and template-guided prostate seed implants. METHODS AND MATERIALS The genetic algorithm was modified to reflect the 2D nature of the implantation template. A multi-objective decision scheme was used to rank competing solutions, taking into account dose uniformity and conformity to the planning target volume (PTV), dose-sparing of the urethra and the rectum, and the sensitivity of the resulting dosimetry to seed misplacement. Optimized treatment plans were evaluated using selected dosimetric quantifiers, dose-volume histogram (DVH), and sensitivity analysis based on simulated seed placement errors. These dosimetric planning components were integrated into the Prostate Implant Planning Engine for Radiotherapy (PIPER). RESULTS PIPER has been used to produce a variety of plans for prostate seed implants. In general, maximization of the minimum peripheral dose (mPD) for given implanted total source strength tended to produce peripherally weighted seed patterns. Minimization of the urethral dose further reduced the loading in the central region of the PTV. Isodose conformity to the PTV was achieved when the set of objectives did not reflect seed positioning uncertainties; the corresponding optimal plan generally required fewer seeds and higher source strength per seed compared to the manual planning experience. When seed placement uncertainties were introduced into the set of treatment planning objectives, the optimal plan tended to reach a compromise between the preplanned outcome and the likelihood of retaining the preferred outcome after implantation. The reduction in the volatility of such seed configurations optimized under uncertainty was verified by sensitivity studies. CONCLUSION An automated treatment planning engine incorporating real-time sensitivity analysis was found to be a useful tool in dosimetric planning for prostate brachytherapy.

Robotic system for prostate brachytherapy.

In contemporary brachytherapy procedures, needle placement at the desired target is challenging for a variety of reasons. A robot-assisted brachytherapy system can potentially improve needle placement and seed delivery, resulting in enhanced therapeutic outcome. In this paper we present a robotic system with 16 degrees of freedom (DOF) (9 DOF for the positioning module and 7 DOF for the surgery module) that has been developed and fabricated for prostate brachytherapy. Strategies to reduce needle deflection and target movement were incorporated after extensive experimental validation. Provision for needle motion and force feedback was included in the system to improve robot control and seed delivery. Preliminary experimental results reveal that the prototype system is sufficiently accurate in placing brachytherapy needles.

Evaluation of robotic needle insertion in conjunction with in vivo manual insertion in the operating room

Precise interstitial intervention is quite challenging because of several reasons. Researchers have reported in vitro needle insertion forces encountered while steering through soft tissue and soft material phantoms. Hardly any in vivo force measurement data is available in the literature. In this paper, we present needle insertion forces and torques measured during actual brachytherapy procedure in the operating room (OR). We highlight human factors involved in the surgical needle intervention during prostate seed implant (PSI) procedures. We believe that some of the issues can be eliminated or reduced using a robotic system. We have also presented in vitro data during robotic needle insertion into animal soft tissue phantoms and compared with manual insertions.

Automatic localization of implanted seeds from post-implant CT images.

An automatic localization method of implanted seeds from a series of post-implant computed tomography (CT) images is described in this paper. Post-implant CT studies were obtained for patients who underwent prostate brachytherapy. Bright areas were segmented using binary thresholding in each CT slice, and geometrical information on these areas was collected. Large areas (possibly containing two connected seeds) were split into smaller ones by geometry-based filtering in each slice. The area connectivity along the longitudinal direction was analysed using a geometry-based connection search algorithm executed on every area slice by slice, so that the connected areas were combined into one object. The weighted centroid of each object was taken as the seed position. This method was tested on a seed-containing prostate phantom as well as using CT studies from patients. Statistical analysis demonstrates that it can achieve above 99% detection rate with reliable localization accuracy and high speed. It is reliable and convenient for localizing implanted seeds on CT and can be used to assist post-implant dosimetry for prostate brachytherapy.

Needle insertion force estimation model using procedure-specific and patient-specific criteria.

Placement accuracy of different types of surgical needles in soft biological tissues depends on a variety of factors. The needles used for prostate brachytherapy procedures are typically about 200 mm in length and 1.27-1.47 mm in diameter. These needles are prone to deflection and thereby depositing the seeds at a location other than the planned one. Thus tumorous tissues may not receive the planned dose whereas the critical organs may be over-dosed. A significant amount of needle deflection and target movement is related to some procedure-specific criteria and some patient-specific criteria. In this paper we have developed needle insertion force models taking both procedure-specific criteria and patient-specific criteria. These statistical models can be used to estimate the force that the needle will experience during insertion and thereby control the needle to reduce the needle deflection and enhance seed delivery accuracy