Dimos Baltas

3-D conformal HDR brachytherapy as monotherapy for localized prostate cancer. A pilot study.

Purpose:Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning.Patients and Methods:Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) ≤ 10 ng/ml, Gleason score ≤ 7 and clinical stage ≤ T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT® was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (Dref) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D90, D10 urethra, and D10 rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales.Results:Median D90 was 106% of Dref (range: 93–115%), median D10 urethra 159% of Dref (range: 127–192%), and median D10 rectum 55% of Dref (range: 35–68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred.Conclusion:3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.Ziel:Pilotstudie zur Evaluation der Praktikabilität, Akuttoxizität und konformalen Qualität der konformalen dreidimensionalen (3-D) High-Dose-Rate-(HDR-)Brachytherapie als Monotherapie beim lokal begrenzten Prostatakarzinom unter Einsatz intraoperativer Real-Time-Planung.Patienten und Methodik:Zwischen 05/2002 und 05/2003 wurden 52 Patienten mit einem Prostatakarzinom, PSA-Wert (prostataspezifisches Antigen) ≤ 10 ng/ml, Gleason-Score ≤ 7 und klinischem Stadium ≤ T2a behandelt. Der mediane PSA-Wert betrug 6,4 ng/ml und der mediane Gleason-Score 5. 24/52 Patienten waren im Stadium T1c und 28/52 im Stadium T2a. Für die TRUS-gesteuerte (transrektaler Ultraschall) transperineale Implantation von flexiblen Plastiknadeln in die Prostata kam das Real-Time- HDR-Planungssystem SWIFT® zum Einsatz. Nach der Implantation wurde ein CT-basiertes 3-D-Postplanning durchgeführt. Alle Patienten erhielten ein Implantat für vier Fraktionen HDR-Brachytherapie in 48 h mit einer Referenzdosis (Dref) von 9,5 Gy bis zu einer Gesamtdosis von 38,0 Gy. Dosis-Volumen-Histogramme (DVH) wurden analysiert, um die konformale Qualität der Implantate mit Berechnung der D90, D10 Urethra und D10 Rektum zu bestimmen. Akuttoxizitäten wurden unter Verwendung der CTC-Skalen (Common Toxicity Criteria) evaluiert.Ergebnisse:Die mediane D90 betrug 106% von Dref (Range: 93–115%), die mediane D10 Urethra 159% von Dref (Range: 127–192%), die mediane D10 Rektum 55% von Dref (Range: 35–68%). Die mediane Nachbeobachtungszeit beträgt gegenwärtig 8 Monate. Bei 2/52 Patienten wurden akute urogenitale Grad-3-Toxizitäten beobachtet. Gastrointestinale Toxizitäten > Grad 1 traten nicht auf.Schlussfolgerung:Die konformale 3-D-HDR-Brachytherapie als Monotherapie unter Einsatz intraoperativer Real-Time-Planung erweist sich als praktikable und hochkonformale Behandlung mit minimalen akuten Nebenwirkungen beim lokal begrenzten Prostatakarzinom. Eine längere Nachbeobachtungszeit ist zur Beurteilung von Spättoxizitäten und biochemischer Kontrolle notwendig.

Review of clinical brachytherapy uncertainties: Analysis guidelines of GEC-ESTRO and the AAPM

Background and purpose A substantial reduction of uncertainties in clinical brachytherapy should result in improved outcome in terms of increased local control and reduced side effects. Types of uncertainties have to be identified, grouped, and quantified. Methods A detailed literature review was performed to identify uncertainty components and their relative importance to the combined overall uncertainty. Results Very few components (e.g., source strength and afterloader timer) are independent of clinical disease site and location of administered dose. While the influence of medium on dose calculation can be substantial for low energy sources or non-deeply seated implants, the influence of medium is of minor importance for high-energy sources in the pelvic region. The level of uncertainties due to target, organ, applicator, and/or source movement in relation to the geometry assumed for treatment planning is highly dependent on fractionation and the level of image guided adaptive treatment. Most studies to date report the results in a manner that allows no direct reproduction and further comparison with other studies. Often, no distinction is made between variations, uncertainties, and errors or mistakes. The literature review facilitated the drafting of recommendations for uniform uncertainty reporting in clinical BT, which are also provided. The recommended comprehensive uncertainty investigations are key to obtain a general impression of uncertainties, and may help to identify elements of the brachytherapy treatment process that need improvement in terms of diminishing their dosimetric uncertainties. It is recommended to present data on the analyzed parameters (distance shifts, volume changes, source or applicator position, etc.), and also their influence on absorbed dose for clinically-relevant dose parameters (e.g., target parameters such as D90 or OAR doses). Publications on brachytherapy should include a statement of total dose uncertainty for the entire treatment course, taking into account the fractionation schedule and level of image guidance for adaptation. Conclusions This report on brachytherapy clinical uncertainties represents a working project developed by the Brachytherapy Physics Quality Assurances System (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this report has been reviewed and approved by the American Association of Physicists in Medicine.

A multiobjective gradient-based dose optimization algorithm for external beam conformal radiotherapy

A multiobjective gradient-based algorithm has been developed for the purpose of dose distribution optimization in external beam conformal radiotherapy. This algorithm is based on the concept of gathering the values of all objectives into a single value. The weighting factors of the composite objective values are varied in different steps, allowing the reconstruction of the trade-off surfaces (three or more objectives) or curves (two objectives) which define the boundary between the feasible and non-feasible domain regions. The analysis of these curves allows the decision-maker to select the solution that best fits the clinical goals. In contrast to all the other algorithms, our method provides not a single solution but a sample of solutions representing all possible clinical importance factors (weights) for the objectives used. The application of this algorithm to two test cases shows that a correct selection for the importance factors to multiply the individual objectives in the global objective value is not trivial and that the location and shape of the boundary region between the feasible and non-feasible solution regions are case dependent. Provided that the individual objective functions are analytically differentiable and that the number of objectives is the range of two to three, the computation times are acceptable for clinical use. Furthermore, the optimization for a unique combination of importance factors within the aggregate objective function is performed in less than 1 min.

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.

3-D Conformal HDR Brachytherapy as Monotherapy for Localized Prostate Cancer

Purpose:Pilot study to evaluate feasibility, acute toxicity and conformal quality of three-dimensional (3-D) conformal high-dose- rate (HDR) brachytherapy as monotherapy for localized prostate cancer using intraoperative real-time planning.Patients and Methods:Between 05/2002 and 05/2003, 52 patients with prostate cancer, prostate-specific antigen (PSA) ≤ 10 ng/ml, Gleason score ≤ 7 and clinical stage ≤ T2a were treated. Median PSA was 6.4 ng/ml and median Gleason score 5. 24/52 patients had stage T1c and 28/52 stage T2a. For transrectal ultrasound-(TRUS-)guided transperineal implantation of flexible plastic needles into the prostate, the real-time HDR planning system SWIFT® was used. After implantation, CT-based 3-D postplanning was performed. All patients received one implant for four fractions of HDR brachytherapy in 48 h using a reference dose (Dref) of 9.5 Gy to a total dose of 38.0 Gy. Dose-volume histograms (DVHs) were analyzed to evaluate the conformal quality of each implant using D90, D10 urethra, and D10 rectum. Acute toxicity was evaluated using the CTC (Common Toxicity Criteria) scales.Results:Median D90 was 106% of Dref (range: 93–115%), median D10 urethra 159% of Dref (range: 127–192%), and median D10 rectum 55% of Dref (range: 35–68%). Median follow-up is currently 8 months. In 2/52 patients acute grade 3 genitourinary toxicity was observed. No gastrointestinal toxicity > grade 1 occurred.Conclusion:3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.Ziel:Pilotstudie zur Evaluation der Praktikabilität, Akuttoxizität und konformalen Qualität der konformalen dreidimensionalen (3-D) High-Dose-Rate-(HDR-)Brachytherapie als Monotherapie beim lokal begrenzten Prostatakarzinom unter Einsatz intraoperativer Real-Time-Planung.Patienten und Methodik:Zwischen 05/2002 und 05/2003 wurden 52 Patienten mit einem Prostatakarzinom, PSA-Wert (prostataspezifisches Antigen) ≤ 10 ng/ml, Gleason-Score ≤ 7 und klinischem Stadium ≤ T2a behandelt. Der mediane PSA-Wert betrug 6,4 ng/ml und der mediane Gleason-Score 5. 24/52 Patienten waren im Stadium T1c und 28/52 im Stadium T2a. Für die TRUS-gesteuerte (transrektaler Ultraschall) transperineale Implantation von flexiblen Plastiknadeln in die Prostata kam das Real-Time- HDR-Planungssystem SWIFT® zum Einsatz. Nach der Implantation wurde ein CT-basiertes 3-D-Postplanning durchgeführt. Alle Patienten erhielten ein Implantat für vier Fraktionen HDR-Brachytherapie in 48 h mit einer Referenzdosis (Dref) von 9,5 Gy bis zu einer Gesamtdosis von 38,0 Gy. Dosis-Volumen-Histogramme (DVH) wurden analysiert, um die konformale Qualität der Implantate mit Berechnung der D90, D10 Urethra und D10 Rektum zu bestimmen. Akuttoxizitäten wurden unter Verwendung der CTC-Skalen (Common Toxicity Criteria) evaluiert.Ergebnisse:Die mediane D90 betrug 106% von Dref (Range: 93–115%), die mediane D10 Urethra 159% von Dref (Range: 127–192%), die mediane D10 Rektum 55% von Dref (Range: 35–68%). Die mediane Nachbeobachtungszeit beträgt gegenwärtig 8 Monate. Bei 2/52 Patienten wurden akute urogenitale Grad-3-Toxizitäten beobachtet. Gastrointestinale Toxizitäten > Grad 1 traten nicht auf.Schlussfolgerung:Die konformale 3-D-HDR-Brachytherapie als Monotherapie unter Einsatz intraoperativer Real-Time-Planung erweist sich als praktikable und hochkonformale Behandlung mit minimalen akuten Nebenwirkungen beim lokal begrenzten Prostatakarzinom. Eine längere Nachbeobachtungszeit ist zur Beurteilung von Spättoxizitäten und biochemischer Kontrolle notwendig.

Multiobjective Evolutionary optimization of the number of beams, their orientations and weights for intensity-modulated radiation therapy

We propose a hybrid multiobjective (MO) evolutionary optimization algorithm (MOEA) for intensity-modulated radiotherapy inverse planning and apply it to optimize the number of incident beams, their orientations and intensity profiles. The algorithm produces a set of efficient solutions, which represent different clinical trade-offs and contains information such as variety of dose distributions and dose-volume histograms. No importance factors are required and solutions can be obtained in regions not accessible by conventional weighted sum approaches. The application of the algorithm using a test case, a prostate and a head and neck tumour case is shown. The results are compared with MO inverse planning using a gradient-based optimization algorithm.

Anatomy-based three-dimensional dose optimization in brachytherapy using multiobjective genetic algorithms.

In conventional dose optimization algorithms, in brachytherapy, multiple objectives are expressed in terms of an aggregating function which combines individual objective values into a single utility value, making the problem single objective, prior to optimization. A multiobjective genetic algorithm (MOGA) was developed for dose optimization based on an a posteriori approach, leaving the decision-making process to a planner and offering a representative trade-off surface of the various objectives. The MOGA provides a flexible search engine which provides the maximum of information for a decision maker. Tests performed with various treatment plans in brachytherapy have shown that MOGA gives solutions which are superior to those of traditional dose optimization algorithms. Objectives were proposed in terms of the COIN distribution and differential volume histograms, taking into account patient anatomy in the optimization process.

CT-Based Interstitial HDR Brachytherapy

Purpose: Development, application and evaluation of a CT-guided implantation technique and a fully CT-based treatment planning procedure for brachytherapy. Methods and Materials: A brachytherapy procedure based on CT-guided implantation technique and CT-based treatment planning has been developed and clinical evaluated. For this purpose a software system (PROMETHEUS) for the 3D reconstruction of brachytherapy catheters and patient anatomy using only CT scans has been developed. An interface for the Nucletron PLATO BPS treatment planning system for optimization and calculation of dose distribution has been devised. The planning target volume(s) are defined as sets of points using contouring tools and are used for optimization of the 3D dose distribution. Dose-volume histogram based analysis of the dose distribution (COIN analysis) enables a clinically realistic evaluation of the brachytherapy application to be made. The CT-guided implantation of catheters and the CT-based treatment planning procedure has been performed for interstitial brachytherapy and for different tumor sites in 197 patients between 1996 and 1997. Results: The accuracy of the CT reconstruction was tested using first a quality assurance phantom and second, a simulated interstitial implant of 12 needles. These were compared with the results of reconstruction using radiographs. Both methods gave comparable results with regard to accuracy, but the CT based reconstruction was faster. Clinical feasibility was proved in pre-irradiated recurrences of brain tumors, in pretreated recurrences or metastatic disease, and in breast carcinomas. The tumor volumes treated were in the range 5.1 to 2,741 cm3. Analysis of implant quality showed a slightly significant lower COIN value for the bone implants, but no differences with respect to the planning target volume. Conclusions: The Offenbach system, incorporating the PROMETHEUS software for interstitial HDR brachytherapy has proved to be extremely valuable in routine clinical practice for many tumor sites. Our CT-guided implantation technique together with a fully CT-based planning system has enabled conformal brachytherapy treatment to become routine.Ziel: Entwicklung, Anwendung und Evaluierung einer CT-gesteuerten Implantationstechnik und einer vollständig CT-gestützten Behandlungsplanung für Brachytherapie. Material und Methoden: Es wurde ein Brachytherapieverfahren, basierend auf einer CT-gesteuerten Implantationstechnik und CT-gestützter Bestrahlungsplanung, entwickelt und klinisch evaluiert. Für diese Zielsetzung wurde ein Softwaresystem (PROMETHEUS) zur 3D-Rekonstruktion der Applikatoren und der individuellen anatomischen Verhältnisse unter ausschließlicher Verwendung von CT-Schnittbildern entwickelt. Hierzu wurde ein Interface für das Nucletron-PLATO-BPS-Planungssystem zur Optimierung und Berechnung der Dosisverteilung realisiert. Das Zielvolumen (PTV) wird definiert und zur Optimierung der dreidimensionalen Dosisverteilung verwendet. Die Analyse der Dosisverteilung mittels Dosisvolumenhistogrammen (COIN) ermöglicht eine klinische Bewertung des Brachytherapieverfahrens. Die CT-gesteuerte Katheterimplantation und die CT-gestützte Bestrahlungsplanung zur Behandlung unterschiedlicher Tumoren in verschiedenen anatomischen Regionen wurden bei 197 Patienten in dem Zeitraum 1996 bis 1997 durchgeführt. Ergebnisse: Die Genauigkeit der CT-Rekonstruktion wurde mit Hilfe eines Brachytherapie-QA-Phantoms und eines Implantats mit zwölf Nadeln überprüft. Die Ergebnisse wurden mit denen der konventionellen Rekonstruktion aus Röntgenaufnahmen verglichen. Beide Methoden ergaben vergleichbare Ergebnisse in Hinblick auf die Rekonstruktionsgenauigkeit. Die CT-gestützte Rekonstruktion war jedoch schneller. In der klinischen Anwendung wurden Tumorvolumina zwischen 5,1 und 2 741 cm3 behandelt. Die Auswertung der Bestrahlungspläne ergab einen geringfügig signifikant geringeren COIN-Wert für die Knochenimplantate, aber keine Unterschiede hinsichtlich des Tumorvolumens. Schlußfolgerung: Die entwickelte Offenbacher Methode hat sich in der klinischen Routine zur Durchführung einer CT-gestützten Brachytherapie in unterschiedlichen Tumorlokalisationen bewährt. Unsere CT-gesteuerte Implantationstechnik zusammen mit dem CT-gestützten Planungssystem ermöglicht uns eine konformale Brachytherapiebehandlung.

Multiobjective inverse planning for intensity modulated radiotherapy with constraint-free gradient-based optimization algorithms

We consider the behaviour of the limited memory L-BFGS algorithm as a representative constraint-free gradient-based algorithm which is used for multiobjective (MO) dose optimization for intensity modulated radiotherapy (IMRT). Using a parameter transformation, the positivity constraint problem of negative beam fluences is entirely eliminated: a feature which to date has not been fully understood by all investigators. We analyse the global convergence properties of L-BFGS by searching for the existence and the influence of possible local minima. With a fast simulated annealing (FSA) algorithm we examine whether the L-BFGS solutions are globally Pareto optimal. The three examples used in our analysis are a brain tumour, a prostate tumour and a test case with a C-shaped PTV. In 1% of the optimizations global convergence is violated. A simple mechanism practically eliminates the influence of this failure and the obtained solutions are globally optimal. A single-objective dose optimization requires less than 4 s for 5400 parameters and 40000 sampling points. The elimination of the problem of negative beam fluences and the high computational speed permit constraint-free gradient-based optimization algorithms to be used for MO dose optimization. In this situation, a representative spectrum of possible solutions is obtained which contains information such as the trade-off between the objectives and range of dose values. Using simple decision making tools the best of all the possible solutions can be chosen. We perform an MO dose optimization for the three examples and compare the spectra of solutions, firstly using recommended critical dose values for the organs at risk and secondly, setting these dose values to zero.

A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy

Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives.