Natasa Milickovic

High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

PURPOSE To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. METHODS AND MATERIALS Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. RESULTS The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. CONCLUSION Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

4D analysis of influence of patient movement and anatomy alteration on the quality of 3D U/S-based prostate HDR brachytherapy treatment delivery.

PURPOSE Modern HDR brachytherapy treatment for prostate cancer based on the 3D ultrasound (U/S) plays increasingly important role. The purpose of this study is to investigate possible patient movement and anatomy alteration between the clinical image set acquisition, made after the needle implantation, and the patient irradiation and their influence on the quality of treatment. METHODS The authors used 3D U/S image sets and the corresponding treatment plans based on a 4D-treatment planning procedure: plans of 25 patients are obtained right after the needle implantation (clinical plan is based on this 3D image set) and just before and after the treatment delivery. The authors notice the slight decrease of treatment quality with increase of time gap between the clinical image set acquisition and the patient irradiation. 4D analysis of dose-volume-histograms (DVHs) for prostate: CTV1 = PTV, and urethra, rectum, and bladder as organs at risk (OARs) and conformity index (COIN) is presented, demonstrating the effect of prostate, OARs, and needles displacement. RESULTS The authors show that in the case that the patient body movement/anatomy alteration takes place, this results in modification of DVHs and radiobiological parameters, hence the plan quality. The observed average displacement of needles (1 mm) and of prostate (0.57 mm) is quite small as compared with the average displacement noted in several other reports [A. A. Martinez et al., Int. J. Radiat. Oncol., Biol., Phys. 49(1), 61-69 (2001); S. J. Damore et al., Int. J. Radiat. Oncol., Biol., Phys. 46(5), 1205-1211 (2000); P. J. Hoskin et al., Radiotherm. Oncol. 68(3), 285-288 (2003); E. Mullokandov et al., Int. J. Radiat. Oncol., Biol., Phys. 58(4), 1063-1071 (2004)] in the literature. CONCLUSIONS Although the decrease of quality of dosimetric and radiobiological parameters occurs, this does not cause clinically unacceptable changes to the 3D dose distribution, according to our clinical protocol.

Radiobiological evaluation of the influence of dwell time modulation restriction in HIPO optimized HDR prostate brachytherapy implants.

Purpose One of the issues that a planner is often facing in HDR brachytherapy is the selective existence of high dose volumes around some few dominating dwell positions. If there is no information available about its necessity (e.g. location of a GTV), then it is reasonable to investigate whether this can be avoided. This effect can be eliminated by limiting the free modulation of the dwell times. HIPO, an inverse treatment plan optimization algorithm, offers this option. In treatment plan optimization there are various methods that try to regularize the variation of dose non-uniformity using purely dosimetric measures. However, although these methods can help in finding a good dose distribution they do not provide any information regarding the expected treatment outcome as described by radiobiology based indices. Material and methods The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO and modulation restriction (MR) has been compared to alternative plans with HIPO and free modulation (without MR). All common dose-volume indices for the prostate and the organs at risk have been considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by calculating the response probabilities of the tumors and organs-at-risk (OARs) involved in these prostate cancer cases. The radiobiological models used are the Poisson and the relative seriality models. Furthermore, the complication-free tumor control probability, P+ and the biologically effective uniform dose (D¯¯) were used for treatment plan evaluation and comparison. Results Our results demonstrate that HIPO with a modulation restriction value of 0.1-0.2 delivers high quality plans which are practically equivalent to those achieved with free modulation regarding the clinically used dosimetric indices. In the comparison, many of the dosimetric and radiobiological indices showed significantly different results. The modulation restricted clinical plans demonstrated a lower total dwell time by a mean of 1.4% that was proved to be statistically significant (p = 0.002). The HIPO with MR treatment plans produced a higher P+ by 0.5%, which stemmed from a better sparing of the OARs by 1.0%. Conclusions Both the dosimetric and radiobiological comparison shows that the modulation restricted optimization gives on average similar results with the optimization without modulation restriction in the examined clinical cases. Concluding, based on our results, it appears that the applied dwell time regularization technique is expected to introduce a minor improvement in the effectiveness of the optimized HDR dose distributions.

High dose rate brachytherapy as monotherapy for localised prostate cancer: a hypofractionated two-implant approach in 351 consecutive patients

BackgroundTo report the clinical outcome of high dose rate brachytherapy as sole treatment for clinically localised prostate cancer.MethodsBetween March 2004 and January 2008, a total of 351 consecutive patients with clinically localised prostate cancer were treated with transrectal ultrasound guided high dose rate brachytherapy. The prescribed dose was 38.0 Gy in four fractions (two implants of two fractions each of 9.5 Gy with an interval of 14 days between the implants) delivered to an intraoperative transrectal ultrasound real-time defined planning treatment volume. Biochemical failure was defined according to the Phoenix Consensus and toxicity evaluated using the Common Toxicity Criteria for Adverse Events version 3.ResultsThe median follow-up time was 59.3 months. The 36 and 60 month biochemical control and metastasis-free survival rates were respectively 98%, 94% and 99%, 98%. Toxicity was scored per event with 4.8% acute Grade 3 genitourinary and no acute Grade 3 gastrointestinal toxicity. Late Grade 3 genitourinary and gastrointestinal toxicity were respectively 3.4% and 1.4%. No instances of Grade 4 or greater acute or late adverse events were reported.ConclusionsOur results confirm high dose rate brachytherapy as safe and effective monotherapy for clinically organ-confined prostate cancer.

A dosimetric comparison of versus for HDR prostate brachytherapy

For the purpose of evaluating the use of Yb169 for prostate High Dose Rate brachytherapy (HDR), a hypothetical Yb169 source is assumed with the exact same design of the new microSelectron source replacing the Ir192 active core by pure Yb169 metal. Monte Carlo simulation is employed for the full dosimetric characterization of both sources and results are compared following the AAPM TG-43 dosimetric formalism. Monte Carlo calculated dosimetry results are incorporated in a commercially available treatment planning system (SWIFTTM), which features an inverse treatment planning option based on a multiobjective dose optimization engine. The quality of prostate HDR brachytherapy using the real Ir192 and hypothetical Yb169 source is compared in a comprehensive analysis of different prostate implants in terms of the multiobjective dose optimization solutions as well as treatment quality indices such as Dose Volume Histograms (DVH) and the Conformal Index (COIN). Given that scattering overcompensates for absorption in intermediate photon energies and distances in the range of interest to prostate HDR brachytherapy, Yb169 proves at least equivalent to Ir192 irrespective of prostate volume. This has to be evaluated in view of the shielding requirements for the Yb169 energies that are minimal relative to that for Ir192.

Comparison of Evolutionary and Deterministic Multiobjective Algorithms for Dose Optimization in Brachytherapy

We compare two multiobjective evolutionary algorithms, with deterministic gradient based optimization methods for the dose optimization problem in high-dose rate (HDR) brachytherapy. The optimization considers up to 300 parameters. The objectives are expressed in terms of statistical parameters, from dose distributions. These parameters are approximated from dose values from a small number of points. For these objectives it is known that the deterministic algorithms converge to the global Pareto front. The evolutionary algorithms produce only local Pareto-optimal fronts. The performance of the multiobjective evolutionary algorithms is improved if a small part of the population is initialized with solutions from deterministic algorithms. An explanation is that only a very small part of the search space is close to the global Pareto front. We estimate the performance of the algorithms in some cases in terms of probability compared to a random optimum search method.

Application of Multiobjective Evolutionary Algorithms for Dose Optimization Problems in Brachytherapy

In High Dose Rate (HDR) brachytherapy the conventional dose optimization algorithms consider the multiple objectives in form of an aggregate function which combines individual objectives into a single utility value. As a result, the optimization problem becomes single objective, prior to optimization. Up to 300 parameters must be optimized satisfying objectives which are often competing. We use multiobjective dose optimization methods where the objectives are expressed in terms of quantities derived from dose-volume histograms or in terms of statistical parameters of dose distributions from a small number of sampling points. For the last approach we compare the optimization results of evolutionary multiobjective algorithms with deterministic optimization methods. The deterministic algorithms are very efficient and produce the best results. The performance of the multiobjective evolutionary algorithms is improved if a small part of the population is initialized by deterministic algorithms.

Hypofractionated accelerated computed tomography–guided interstitial high-dose-rate brachytherapy for liver malignancies

PURPOSE To report our results of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the local treatment of inoperable primary and secondary liver malignancies. METHODS AND MATERIALS Between 2000 and 2009, 31 patients underwent a total of 42 BRT procedures for 36 hepatic lesions exceeding 4 cm and located adjacent to the liver hilum and bile duct bifurcation. The median tumor volume was 99 cm(3) (range, 46-1348 cm(3)). The median age was 64 years (range, 27-85 years). The HDR-BRT delivered a median total physical dose of 13.0 Gy (range, 7.0-32.0 Gy) in twice daily fractions of median 7.0 Gy (range, 4.0-10.0 Gy) in 14 patients and in once daily fractions of median 8.0 Gy (range, 7.0-14.0 Gy) in 17 patients. RESULTS The median followup was 13.3 months with an overall survival rate of 66% at 1 year. The local control rate for patients with metastatic lesions was 79%, 59%, and 59%, and for the subgroup with primary hepatic tumors 88%, 50%, and 50% at 1, 2, and 3 years, respectively. Severe side effects occurred in 4.7% of BRT procedures with no treatment-related deaths. CONCLUSIONS Our results confirm CT-guided interstitial HDR-BRT to be a safe procedure for the local treatment of inoperable liver malignancies unsuitable for thermal ablation.

Effect of using different U/S probe Standoff materials in image geometry for interventional procedures: the example of prostate.

Purpose This study investigates the distortion of geometry of catheters and anatomy in acquired U/S images, caused by utilizing various stand-off materials for covering a transrectal bi-planar ultrasound probe in HDR and LDR prostate brachytherapy, biopsy and other interventional procedures. Furthermore, an evaluation of currently established water-bath based quality assurance (QA) procedures is presented. Material and methods Image acquisitions of an ultrasound QA setup were carried out at 5 MHz and 7 MHz. The U/S probe was covered by EA 4015 Silicone Standoff kit, or UA0059 Endocavity balloon filled either with water or one of the following: 40 ml of Endosgel®, Instillagel®, Ultraschall gel or Space OAR™ gel. The differences between images were recorded. Consequently, the dosimetric impact of the observed image distortion was investigated, using a tissue equivalent ultrasound prostate phantom – Model number 053 (CIRS Inc., Norfolk, VA, USA). Results By using the EA 4015 Silicone Standoff kit in normal water with sound speed of 1525 m/s, a 3 mm needle shift was observed. The expansion of objects appeared in radial direction. The shift deforms also the PTV (prostate in our case) and other organs at risk (OARs) in the same way leading to overestimation of volume and underestimation of the dose. On the other hand, Instillagel® and Space OAR™ “shrinks” objects in an ultrasound image for 0.65 mm and 0.40 mm, respectively. Conclusions The use of EA 4015 Silicone Standoff kit for image acquisition, leads to erroneous contouring of PTV and OARs and reconstruction and placement of catheters, which results to incorrect dose calculation during prostate brachytherapy. Moreover, the reliability of QA procedures lies mostly in the right temperature of the water used for accurate simulation of real conditions of transrectal ultrasound imaging.

Application of multiobjective genetic algorithms in anatomy based dose optimization in brachytherapy and its comparation with deterministic algorithms

In high dose rate (HDR) brachytherapy the conventional dose optimization algorithms consider the multiple objectives in the form of an aggregate function which combines individual objectives into a single utility value. As a result, the optimization problem becomes a single objective, prior to optimization. Up to 300 parameters must be optimized, satisfying objectives which are often competing. We use multiobjective dose optimization methods where the objectives are expressed in terms of quantities derived from dose-volume histograms or in terms of statistical parameters of dose distributions from a small number of sampling points. For the last approach we compare the optimization results of evolutionary multiobjective algorithms with deterministic optimization methods. The deterministic algorithms are very efficient and produce the best results, but they also have certain limitations. The performance of the multiobjective evolutionary algorithms is improved if a small part of the population is initialized by deterministic algorithms.