I-Chow Hsu

American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy.

PURPOSE A well-established body of literature supports the use of high-dose-rate (HDR) brachytherapy as definitive treatment for localized prostate cancer. Most of the articles describe HDR as a boost with adjuvant external beam radiation, but there is a growing experience with HDR monotherapy. METHODS AND MATERIALS The American Brachytherapy Society has convened a group of expert practitioners and physicists to develop guidelines for the use of HDR in the management of prostate cancer. This involved an extensive literature review and input from an expert panel. RESULTS Despite a wide variation in doses and fractionation reported, HDR brachytherapy provides biochemical control rates of 85-100%, 81-100%, and 43-93% for low-, intermediate-, and high-risk prostate cancers, respectively. Severe toxicity is rare, with most authors reporting less than 5% Grade 3 or higher toxicity. Careful attention to patient evaluation for appropriate patient selection, meticulous technique, treatment planning, and delivery are essential for successful treatment. CONCLUSION The clinical outcomes for HDR are excellent, with high rates of biochemical control, even for high-risk disease, with low morbidity. HDR monotherapy, both for primary treatment and salvage, are promising treatment modalities.

Needle insertion and radioactive seed implantation in human tissues: simulation and sensitivity analysis

To facilitate training and planning for medical procedures such as prostate brachytherapy, we are developing an interactive simulation of needle insertion and radioactive seed implantation in soft tissues. We describe a new 2D dynamic FEM model based on a reduced set of scalar parameters such as needle friction, sharpness, and velocity, where the mesh is updated to maintain element boundaries along the needle shaft and the effects of needle tip and frictional forces are simulated. The computational complexity of our model grows linearly with the number of elements in the mesh and achieves 24 frames per second for 1250 triangular elements on a 750 MHz PC. We use the simulator to characterize the sensitivity of seed placement error to physician-controlled and biological parameters. Results indicate that seed placement error is highly sensitive to physician-controlled parameters such as needle position, sharpness, and friction, and less sensitive to patient-specific parameters such as tissue stiffness and compressibility.

Phase II Trial of Combined High-Dose-Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Preliminary Results of RTOG 0321

PURPOSE To estimate the rate of late Grade 3 or greater genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) after treatment with external beam radiotherapy and prostate high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALS Each participating institution submitted computed tomography-based HDR brachytherapy dosimetry data electronically for credentialing and for each study patient. Patients with locally confined Stage T1c-T3b prostate cancer were eligible for the present study. All patients were treated with 45 Gy in 25 fractions using external beam radiotherapy and one HDR implant delivering 19 Gy in two fractions. All AEs were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Late GU/GI AEs were defined as those occurring >9 months from the start of the protocol treatment, in patients with ≥18 months of potential follow-up. RESULTS A total of 129 patients from 14 institutions were enrolled in the present study. Of the 129 patients, 125 were eligible, and AE data were available for 112 patients at analysis. The pretreatment characteristics of the patients were as follows: Stage T1c-T2c, 91%; Stage T3a-T3b, 9%; prostate-specific antigen level ≤10 ng/mL, 70%; prostate-specific antigen level >10 but ≤20 ng/mL, 30%; and Gleason score 2-6, 10%; Gleason score 7, 72%; and Gleason score 8-10, 18%. At a median follow-up of 29.6 months, three acute and four late Grade 3 GU/GI AEs were reported. The estimated rate of late Grade 3-5 GU and GI AEs at 18 months was 2.56%. CONCLUSION This is the first prospective, multi-institutional trial of computed tomography-based HDR brachytherapy and external beam radiotherapy. The technique and doses used in the present study resulted in acceptable levels of AEs.

Stereotactic Body Radiotherapy as Monotherapy or Post–External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response

PURPOSE High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. PATIENTS AND METHODS To date, 38 patients have been treated with SBRT at the University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy × 4 fractions), and 18 were treated with SBRT boost (9.5 Gy × 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. RESULTS SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). CONCLUSIONS Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.

Sensorless planning for medical needle insertion procedures

Medical procedures such as seed implantation, biopsies, and treatment injections require inserting a needle tip to a specific target location inside the human body. This is difficult because (1) needle insertion causes soft tissues to displace and deform, and (2) it is often difficult or impossible to obtain precise imaging data during insertion. We are developing a sensorless planning system for needle insertion that incorporates numerical optimization with a soft tissue simulation based on a dynamic FEM formulation that models the effects of needle tip and frictional forces using a 2D mesh. In this paper we describe a sensorless planning algorithm for radioactive seed implantation that computes needle insertion offsets that compensate for tissue deformations. We apply the method to seed implantation during permanent seed prostate brachytherapy to minimize seed placement error in simulation without relying on real-time imaging.

INVERSE PLANNING FOR INTERSTITIAL GYNECOLOGIC TEMPLATE BRACHYTHERAPY: TRULY ANATOMY-BASED PLANNING

PURPOSE Commercially available optimization schemes generally result in an undesirable dose distribution, because of the particular shapes of tumors extending laterally from the tandem. Dose distribution is therefore manually obtained by adjusting relative dwell time values until an acceptable solution is found. The objective of this work is to present the clinical application of an inverse planning dose optimization tool for the automatic determination of source dwell time values in the treatment of interstitial gynecologic templates. METHODS AND MATERIALS In cases where the tumor extends beyond the range of the tandem-ovoid applicator, catheters as well as the tandem are inserted into the paravaginal and parametrial region in an attempt to cover the tumor volume. CT scans of these patients are then used for CT-based dose planning. Dose distribution is obtained manually by varying the relative dwell times until adequate dose coverage is achieved. This manual planning is performed by an experienced physician. In parallel, our in-house inverse planning based on simulated annealing is used to automatically determine which of all possible dwell positions will become active and to calculate the dwell time values needed to fulfill dose constraints applied to the tumor volume and to each organ at risk. To compare the results of these planning methods, dose-volume histograms and isodose distributions were generated for the target and each organ at risk. RESULTS This procedure has been applied for the dose planning of 12 consecutive interstitial gynecologic templates cases. For all cases, once the anatomy was contoured, the routine of inverse planning based on simulated annealing found the solution to the dose constraints within 1 min of CPU time. In comparison, manual planning took more than 45 min. The inverse planning-generated plans showed improved protection to organs at risk for the same coverage compared to manual planning. CONCLUSION This inverse planning tool reduced the planning time significantly and produced improved plans with reduced dose to the organs at risk. Furthermore, the inverse planning approach improves the physicians control over treatment. The focus becomes the physicians prescription to the target and his or her compromise due to dose to normal structures.

Salvage HDR Brachytherapy for Recurrent Prostate Cancer After Previous Definitive Radiation Therapy: 5-Year Outcomes

PURPOSE Evaluate efficacy and toxicity of salvage high-dose-rate brachytherapy (HDRB) for locally recurrent prostate cancer after definitive radiation therapy (RT). METHODS AND MATERIALS We retrospectively analyzed 52 consecutively accrued patients undergoing salvage HDRB between 1998 and 2009 for locally recurrent prostate cancer after previous definitive RT. After pathologic confirmation of locally recurrent disease, patients received 36 Gy in 6 fractions. Twenty-four patients received neoadjuvant hormonal therapy before salvage, and no patients received adjuvant hormonal therapy. Determination of biochemical failure after salvage HDRB was based on the Phoenix definition. Overall survival (OS) and bF distributions were calculated using the Kaplan-Meier method. Univariate analyses were performed to identify predictors of biochemical control. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities, based on Common Terminology Criteria for Adverse Events (version 4), were documented. RESULTS Median follow-up after salvage HDRB was 59.6 months. The 5-year OS estimate was 92% (95% confidence interval [CI]: 80%-97%) with median survival not yet reached. Five-year biochemical control after salvage was 51% (95% CI: 34%-66%). Median PSA nadir postsalvage was 0.1 (range: 0-7.2) reached at a median of 10.2 months after completing HDRB. As for complications, acute and late grade 3 GU toxicities were observed in only 2% and 2%, respectively. No grade 2 or higher acute GI events and 4% grade 2 GI late events were observed. On univariate analysis, disease-free interval after initial definitive RT (P=.07), percent of positive cores at the time of diagnosis (P=.08), interval from first recurrence to salvage HDRB (P=.09), and pre-HDRB prostate-specific antigen (P=.07) were each of borderline significance in predicting biochemical control after salvage HDRB. CONCLUSIONS Prostate HDRB is an effective salvage modality with relatively few long-term toxicities. We provide potential predictors of biochemical control for prostate salvage HDRB.

Measurement of craniocaudal catheter displacement between fractions in computed tomography-based high dose rate brachytherapy of prostate cancer.

The objective of the present work was to measure the craniocaudal displacement of catheters occurring between consecutive fractions of transrectal ultrasound (TRUS)‐guided high dose rate (HDR) prostate brachytherapy. Ten consecutive patients were treated with 2 fractions of 9.5‐Gy TRUS‐guided HDR brachytherapy, with dental putty being used for the fixation of catheters. For each patient, a computed tomography (CT) scan with 3‐mm slice thickness was acquired before each of the 2 fractions. Two different references were used to measure the catheter displacement between fractions: the ischial bone as a bony marker (BM) and the center of two gold markers (COGM) implanted in the prostate. Catheter displacement was calculated by multiplying the thickness of the CT slice by the difference in number of CT slices between the reference slice and the slice containing the tip of a catheter. The average magnitude of caudal catheter displacement was 2.7 mm (range: −6.0 mm to 13.5 mm) for the BM method and 5.4 mm (range: −3.75 mm to 18.0 mm) for the COGM method. The measurement data obtained from the BM and COGM methods verified that prostate movement and catheter displacement both occurred independently between fractions. The most anterior and medial two catheters (catheter positions 8 and 12) had the greatest tendency to be displaced in the caudal direction because they were located at the most distant position from the fulcrum, making them susceptible to rotation of the dental putty in the lateral plane because of the movement of the patients’ legs between fractions. In conclusion, the combination of the BM and COGM methods can demonstrate prostate and catheter movement relative to the BM between fractions. Our technique found a pattern of catheter displacement. Based on that finding, further improvement of our results may be possible by modification of our current technique. PACS number: 87.53.Jw

Normal tissue dosimetric comparison between hdr prostate implant boost and conformal external beam radiotherapy boost: potential for dose escalation

PURPOSE To compare the dose and volume of bladder and rectum treated using high-dose-rate (HDR) prostate implant boost versus conformal external beam radiotherapy boost, and to use the dose-volume information to perform a critical volume tolerance (CVT) analysis and then estimate the potential for further dose escalation using HDR brachytherapy boost. METHODS AND MATERIALS Using CT scan data collected before and after patients underwent HDR prostate implant, a 7-field conformal prostate-only external beam treatment plan and HDR brachytherapy treatment plan were constructed for each patient. Doses to the normal structures were calculated. Dose-volume histograms (DVH) were plotted for comparison of the two techniques. Wilcoxon signed rank test was performed at four dose levels to compare the dose to normal structures between the two treatment techniques. The acute and late effects of HDR brachytherapy were calculated based on the linear-quadratic (LQ) model. CVT analyses were performed to calculate the potential dose gain (PDG) using HDR brachytherapy boost. RESULTS The volume of bladder and rectum receiving high dose was significantly less from implant boost. On the average, 0.19 cc of the bladder received 100% of the brachytherapy prescription dose, compared with 5.1 cc of the bladder receiving 100% of the prescription dose in the 7-field conformal external beam radiotherapy boost. Similarly, 0.25 cc of the rectum received 100% of the dose with the implant boost, as compared to 2.9 cc in the conformal external beam treatment. The implant also delivered higher doses inside the prostate volume. On average, 47% of the prostate received > or =150% of the prescription dose. The CVT analysis revealed a range of PDG using the HDR brachytherapy boost which depended on the following variables: critical volume (CV), critical volume tolerance dose (CVTD), number of HDR fractions (N), and the dose of external beam radiotherapy (XRT) delivered with brachytherapy boost. The PDG varied from -3.45% to 10.53% for tumor with an alpha-beta ratio of 10 and 7.14% to 64.6% for tumor with an alpha-beta ratio of 1.5 based on the parameters used for calculation in this study. CONCLUSIONS HDR brachytherapy can provide better sparing of rectum and bladder while delivering a higher dose to the prostate. Even with the increased late effects of high dose per fraction, there is still a potential for dose escalation beyond external radiotherapy limits using HDR brachytherapy.

Sensorless Motion Planning for Medical Needle Insertion in Deformable Tissues

Minimally invasive medical procedures such as biopsies, anesthesia drug injections, and brachytherapy cancer treatments require inserting a needle to a specific target inside soft tissues. This is difficult because needle insertion displaces and deforms the surrounding soft tissues causing the target to move during the procedure. To facilitate physician training and preoperative planning for these procedures, we develop a needle insertion motion planning system based on an interactive simulation of needle insertion in deformable tissues and numerical optimization to reduce placement error. We describe a 2-D physically based, dynamic simulation of needle insertion that uses a finite-element model of deformable soft tissues and models needle cutting and frictional forces along the needle shaft. The simulation offers guarantees on simulation stability for mesh modifications and achieves interactive, real-time performance on a standard PC. Using texture mapping, the simulation provides visualization comparable to ultrasound images that the physician would see during the procedure. We use the simulation as a component of a sensorless planning algorithm that uses numerical optimization to compute needle insertion offsets that compensate for tissue deformations. We apply the method to radioactive seed implantation during permanent seed prostate brachytherapy to minimize seed placement error.