Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

Quantification of Tumor Oxygenation Based on FMISO PET: Influence of Location and Oxygen Level of the Well-Oxygenated Reference Region.

Tumor hypoxia may play a fundamental role in determining the radiotherapy outcome for several cancer types. Functional imaging with hypoxia specific radiotracers offers a way to visualize and quantify regions of increased radioresistance, which may benefit from dose escalation strategies. Conversion of the uptake in positron emission tomography (PET) images into oxygenation maps offers a way to quantitatively characterize the microenvironment. However, normalization of the uptake with respect to a well-oxygenated reference volume (WOV), which should be properly selected, is necessary when using conversion functions. This study aims at assessing the sensitivity of quantifying tumor oxygenation based on 18F-fluoromisonidazole (FMISO) PET with respect to the choice of the location and the oxygenation level of the WOV in head and neck cancer patients. WOVs varying not only in shape and location but also with respect to the assigned pO2 level were considered. pO2 values other than the standard 60 mmHg were selected according to the specific tissue type included in the volume. For comparison, the volume which would be considered as hypoxic based on a tissue-to-muscle ratio equal to 1.4 was also delineated, as conventionally done in clinical practice. Hypoxia mapping strategies are found highly sensitive to selection of the location of well-oxygenated region, but also on its assigned oxygenation level, which is crucial for hypoxia-guided adaptive dose escalation strategies.

Stereotactic body radiotherapy (SBRT) in recurrent or oligometastatic pancreatic cancer : A toxicity review of simultaneous integrated protection (SIP) versus conventional SBRT.

BACKGROUND: Stereotactic body radiotherapy (SBRT) in pancreatic cancer can be limited by its proximity to organs at risk (OAR). In this analysis, we evaluated the toxicity and efficacy of two different treatment approaches in patients with locally recurrent or oligometastatic pancreatic cancer. MATERIALS AND METHODS: According to the prescription method, patients were divided in two cohorts (C1 and C2). The planning target volume (PTV) was created through a 4 mm expansion of the internal target volume. In C2, a subvolume was additionally created, a simultaneous integrated protection (SIP), which is the overlap of the PTV with the planning risk volume of an OAR to which we prescribed a reduced dose. RESULTS: In all, 18 patients were treated (7 with local recurrences, 9 for oligometastases, 2 for both). Twelve of 23 lesions were treated without SIP (C1) and 11 with SIP (C2). The median follow-up was 12.8 months. Median overall survival (OS) was 13.2 (95% confidence interval [CI] 9.8-14.6) months. The OS rates at 6 and 12 months were 87 and 58%, respectively. Freedom from local progression for combined cohorts at 6 and 12 months was 93 and 67% (95% CI 15-36), respectively. Local control was not statistically different between the two groups. One patient in C2 experienced grade ≥3 acute toxicities and 1 patient in C1 experienced a grade ≥3 late toxicity. CONCLUSION: The SIP approach is a useful prescription method for abdominal SBRT with a favorable toxicity profile which does not compromise local control and overall survival despite dose sacrifices in small subvolumes.

Evaluating the impact of a rigid and a deformable registration method of pre-treatment images for hypoxia-based dose painting.

PURPOSE: To assess the impact of rigid and deformable image registration methods (RIR, DIR) on the outcome of a hypoxia-based dose painting strategy. MATERIALS AND METHODS: Thirty head and neck cancer patients were imaged with [18F]FMISO-PET/CT before radiotherapy. [18F]FMISO-PET/CT images were registered to the planning-CT by RIR or DIR. The [18F]FMISO uptake was converted into oxygen partial pressure (pO2) maps. Hypoxic Target Volumes were contoured on pO2 maps for the deformed (HTVdef) and non-deformed (HTV) cases. A dose escalation strategy by contours, aiming at 95 % tumour control probability (TCP), was applied. HTVs were characterised based on geometry-related metrics, the underlying pO2 distribution, and the dose boost level. A dosimetric and radiobiological evaluation of selected treatment plans made considering RIR and DIR was performed. Moreover, the TCP of the RIR dose distribution was evaluated when considering the deformed [18F]FMISO-PET image as an indicator of the actual target radiosensitivity to determine the potential impact of an unalignment. RESULTS: Statistically significant differences were found between HTV and HTVdef for volume-based metrics and underlying pO2 distribution. Eight out of nine treatment plans for HTV and HTVdef showed differences on the level 10 %/3 mm on a gamma analysis. The TCP difference, however, between RIR and the case when the RIR dose distribution was used with the deformed radiosensitivity map was below 2 pp. CONCLUSIONS: Although the choice of the CTplan-to-PET registration method pre-treatment impacts the HTV localisation and morphology and the corresponding dose distribution, it negligibly affects the TCP in the proposed dose escalation strategy by contours.

On the use of HDR 60Co source with the MammoSite radiation therapy system.

This work summarizes Monte Carlo results in order to evaluate the potential of using HDR 60Co sources in accelerated partial breast irradiation (APBI) with the MammoSite applicator. Simulations have been performed using the MCNP5 Monte Carlo Code, in simple geometries comprised of two concentric spheres; the internal consisting of selected concentrations, C, of a radiographic contrast solution in water (Omnipaque 300) to simulate the MammoSite balloon and the external consisting of water to simulate surrounding tissue. The magnitude of the perturbation of delivered dose due to the radiographic contrast medium used in the MammoSite applicator is calculated. At the very close vicinity of the balloon surface, a dose build-up region is observed, which leads to a dose overestimation by the treatment planning system (TPS) which depends on Omnipaque 300 solution concentration (and is in order of 2.3%, 3.0%, and 4.5%, respectively, at 1 mm away from the balloon - water interface, for C=10%, 15%, and 20%). However, dose overestimation by the TPS is minimal for points lying at the prescription distance (d=1 cm) or beyond, for all simulated concentrations and radii of MammoSite balloon. An analytical estimation of the integral dose outside the CTV in the simple geometries simulated shows that dose to the breast for MammoSite applications is expected to be comparable using HDR 60Co and 192Ir sources, and higher than that for 169Yb. The higher enegies of 60Co sources result to approximately twice radiation protection requirements as compared to 169Ir sources. However, they allow for more accurate dosimetry calculation with currently used treatment planning algorithms for 60Co sources, compared to 169Ir.

Radiation transmission data for radionuclides and materials relevant to brachytherapy facility shielding.

To address the limited availability of radiation shielding data for brachytherapy as well as some disparity in existing data, Monte Carlo simulation was used to generate radiation transmission data for 60Co, 137CS, 198Au, 192Ir 169Yb, 170Tm, 131Cs, 125I, and 103pd photons through concrete, stainless steel, lead, as well as lead glass and baryte concrete. Results accounting for the oblique incidence of radiation to the barrier, spectral variation with barrier thickness, and broad beam conditions in a realistic geometry are compared to corresponding data in the literature in terms of the half value layer (HVL) and tenth value layer (TVL) indices. It is also shown that radiation shielding calculations using HVL or TVL values could overestimate or underestimate the barrier thickness required to achieve a certain reduction in radiation transmission. This questions the use of HVL or TVL indices instead of the actual transmission data. Therefore, a three-parameter model is fitted to results of this work to facilitate accurate and simple radiation shielding calculations.

Significance of the impact of motion compensation on the variability of PET image features.

In lung cancer, quantification by positron emission tomography/computed tomography (PET/CT) imaging presents challenges due to respiratory movement. Our primary aim was to study the impact of motion compensation implied by retrospectively gated (4D)-PET/CT on the variability of PET quantitative parameters. Its significance was evaluated by comparison with the variability due to (i) the voxel size in image reconstruction and (ii) the voxel size in image post-resampling. The method employed for feature extraction was chosen based on the analysis of (i) the effect of discretization of the standardized uptake value (SUV) on complementarity between texture features (TF) and conventional indices, (ii) the impact of the segmentation method on the variability of image features, and (iii) the variability of image features across the time-frame of 4D-PET. Thirty-one PET-features were involved. Three SUV discretization methods were applied: a constant width (SUV resolution) of the resampling bin (method RW), a constant number of bins (method RN) and RN on the image obtained after histogram equalization (method EqRN). The segmentation approaches evaluated were 40[Formula: see text] of SUVmax and the contrast oriented algorithm (COA). Parameters derived from 4D-PET images were compared with values derived from the PET image obtained for (i) the static protocol used in our clinical routine (3D) and (ii) the 3D image post-resampled to the voxel size of the 4D image and PET image derived after modifying the reconstruction of the 3D image to comprise the voxel size of the 4D image. Results showed that TF complementarity with conventional indices was sensitive to the SUV discretization method. In the comparison of COA and 40[Formula: see text] contours, despite the values not being interchangeable, all image features showed strong linear correlations (r > 0.91, [Formula: see text]). Across the time-frames of 4D-PET, all image features followed a normal distribution in most patients. For our patient cohort, the compensation of tumor motion did not have a significant impact on the quantitative PET parameters. The variability of PET parameters due to voxel size in image reconstruction was more significant than variability due to voxel size in image post-resampling. In conclusion, most of the parameters (apart from the contrast of neighborhood matrix) were robust to the motion compensation implied by 4D-PET/CT. The impact on parameter variability due to the voxel size in image reconstruction and in image post-resampling could not be assumed to be equivalent.

On the use of high dose rate 192Ir and 169Yb sources with the MammoSite radiation therapy system.

Ample literature exists on the dose overestimation by commercially available treatment planning systems in MammoSite applications using high dose rate 192Ir sources for partial breast brachytherapy as monotherapy, due to their inability to predict the dose reduction caused by the radiographic contrast solution in the balloon catheter. In this work Monte Carlo simulation is used to verify the dose rate reduction in a balloon breast applicator which does not vary significantly with distance and it is 1.2% at the prescription distance for the reference simulated geometry of 10% diluted radiographic contrast media and 2.5 cm balloon radius. Based on these findings and the minimal hardening of the initially emitted photon spectrum for 192Ir, a simple analytical method is proposed and shown capable for correcting dosimetry planning in clinical applications. Simulations are also performed to assess the corresponding dose reduction in applications of balloon breast applicators using high dose rate 169Yb sources that have recently become available. Results yield a far more significant and distance dependent dose reduction for 169Yb (on the order of 20% at the prescription distance for the abovementioned reference simulation geometry). This dose reduction cannot be accounted for using simple analytical methods as for 192Ir due to the significant hardening of the initially emitted 169Yb photons within the diluted radiographic contrast media. Combined with results of previous works regarding the effect of altered scatter conditions (relative to treatment planning system assumptions) on breast treatment planning accuracy, which is more pronounced for 169Yb relative to 192Ir, these findings call for the amendment of dose treatment planning systems before using 169Yb high dose rate sources in balloon breast applicators.

High Dose Rate Brachytherapy as Monotherapy for Localised Prostate Cancer: Review of the Current Status.

The aim of this article is to review and present the published data on high dose rate (HDR) brachytherapy as monotherapy in the treatment of localised prostate cancer. A search and review of the literature was carried out on PubMed and MedLine using the medical subject headings 'high-dose-rate, brachytherapy, prostate cancer, monotherapy' as search terms. The search yielded more than 100 articles and abstracts published between 2000 and 2016. Only original clinical data on HDR monotherapy reporting oncological outcomes were included. When more than one series from the same institution were identified, the most recent one encompassing the largest patient number was considered for analysis. For citation crosscheck, the ISI web of science database was used employing the same search terms. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control and toxicity scores. Fifteen articles comprising 3546 patients reported clinical outcome and toxicity, with follow-up ranging from median 1.4 to 8.0 years. A variety of dose and fractionation schedules were described, including 19.0 Gy as a single fraction to 54.0 Gy in nine fractions. Biochemical control rates ranged from 66 to 100% in low-risk, 63 to 98% in intermediate-risk and 81-93% in high-risk patients. Late grade 3 genitourinary and gastrointestinal toxicity was 0-16% and 0-2%, respectively. The reported potency preservation rates ranged from 60 to 90%. In conclusion, high biochemical control and low complication rates are reported with HDR monotherapy. It is a safe and effective local treatment modality for organ-confined prostate cancer with reproducible high-quality dosimetry.

A dosimetric comparison of 169Yb and 192Ir for HDR brachytherapy of the breast, accounting for the effect of finite patient dimensions and tissue inhomogeneities.

Monte Carlo simulation dosimetry is used to compare 169Yb to 192Ir for breast high dose rate (HDR) brachytherapy applications using multiple catheter implants. Results for bare point sources show that while 169Yb delivers a greater dose rate per unit air kerma strength at the radial distance range of interest to brachytherapy in homogeneous water phantoms, it suffers a greater dose rate deficit in missing scatter conditions relative to 192Ir. As a result of these two opposing factors, in the scatter conditions defined by the presence of the lung and the finite patient dimensions in breast brachytherapy the dose distributions calculated in a patient equivalent mathematical phantom by Monte Carlo simulations for the same implant of either 169Yb or 1921r commercially available sources are found comparable. Dose volume histogram results support that 169Yb could be at least as effective as 192Ir delivering the same dose to the lung and slightly reduced dose to the breast skin. The current treatment planning systems' approach of employing dosimetry data precalculated in a homogeneous water phantom of given shape and dimensions, however, is shown to notably overestimate the delivered dose distribution for 169Yb. Especially at the skin and the lung, the treatment planning system dose overestimation is on the order of 15%-30%. These findings do not undermine the potential of 169Yb HDR sources for breast brachytherapy relative to the most commonly used 192Ir HDR sources. They imply, however, that there could be a need for the amendment of dose calculation algorithms employed in clinical treatment planning of particular brachytherapy applications, especially for intermediate photon energy sources such as 169Yb.

Comparison of radiation shielding requirements for HDR brachytherapy using 169Yb and 192Ir sources.

169Yb has received a renewed focus lately as an alternative to 192Ir sources for high dose rate (HDR) brachytherapy. Following the results of a recent work by our group which proved 169Yb to be a good candidate for HDR prostate brachytherapy, this work seeks to quantify the radiation shielding requirements for 169Yb HDR brachytherapy applications in comparison to the corresponding requirements for the current 192Ir HDR brachytherapy standard. Monte Carlo simulation (MC) is used to obtain 169Yb and 192Ir broad beam transmission data through lead and concrete. Results are fitted to an analytical equation which can be used to readily calculate the barrier thickness required to achieve a given dose rate reduction. Shielding requirements for a HDR brachytherapy treatment room facility are presented as a function of distance, occupancy, dose limit, and facility workload, using analytical calculations for both 169Yb and 192Ir HDR sources. The barrier thickness required for 169Yb is lower than that for 192Ir by a factor of 4-5 for lead and 1.5-2 for concrete. Regarding 169Yb HDR brachytherapy applications, the lead shielding requirements do not exceed 15 mm, even in highly conservative case scenarios. This allows for the construction of a lead door in most cases, thus avoiding the construction of a space consuming, specially designed maze. The effects of source structure, attenuation by the patient, and scatter conditions within an actual treatment room on the above-noted findings are also discussed using corresponding MC simulation results.

Polymer gel dosimetry for the TG-43 dosimetric characterization of a new 125I interstitial brachytherapy seed.

In this work, a polymer gel-magnetic resonance (MR) imaging method is employed for the dosimetric characterization of a new 125I low dose rate seed (IsoSeed model I25.S17). Two vials filled with PABIG gel were prepared in-house and one new seed as well as one commercially available 125I seed of similar dose rate and well-known dosimetric parameters (IsoSeed model I25.S06) were positioned in each vial. Both seeds in each vial were MR scanned simultaneously on days 11 and 26 after implantation. The data obtained from the known seed in each vial are used to calibrate the gel dose response which, for the prolonged irradiation duration necessitated by the investigated dose rates, depends on the overall irradiation time. Data for this study are presented according to the AAPM TG-43 dosimetric formalism. Polymer gel results concerning the new seed are compared to corresponding, published dosimetric results obtained, for the purpose of the new seed clinical implementation, by our group using the established methods of Monte Carlo (MC) simulation and thermo-luminescence dosimetry (TLD). Polymer gel dosimetry yields an average dose rate constant value of lambda = (0.921 +/- 0.031) cGy h(-1) U(-1) relative to (MC)lambda = (0.929 +/- 0.014) cGy h(-1) U(-1), (TLD)lambda = (0.951 +/- 0.044) cGy h(-1) U(-1) and the average value of Lambda = (0.940 +/- 0.051) cGy h(-1) U(-1) proposed for the clinical implementation of the new seed. Results for radial dose function, g(L)(r), and anisotropy function, F(r, theta), also agree with corresponding MC calculations within experimental uncertainties which are smaller for the polymer gel method compared to TLD. It is concluded that the proposed polymer gel-magnetic resonance imaging methodology could be used at least as a supplement to the established techniques for the dosimetric characterization of new low energy and low dose rate interstitial brachytherapy seeds.

Radiological evaluation of the metal-bone interface of a porous tantalum monoblock acetabular component.

Between January 1998 and December 1998, 82 consecutive patients (86 hips) underwent total hip arthroplasty using a trabecular metal monoblock acetabular component. All patients had a clinical and radiological follow-up evaluation at six, 12 and 24 weeks, 12 months, and then annually thereafter. On the initial post-operative radiograph 25 hips had a gap between the outer surface of the component and the acetabular host bed which ranged from 1 to 5 mm. All patients were followed up clinically and radiologically for a mean of 7.3 years (7 to 7.5). The 25 hips with the 1 to 5 mm gaps were studied for component migration at two years using the Einzel-Bild-Roentgen-Analyse (EBRA) digital measurement method. At 24 weeks all the post-operative gaps were filled with bone and no acetabular component had migrated. The radiographic outcome of all 86 components showed no radiolucent lines and no evidence of lysis. No acetabular implant was revised. There were no dislocations or other complications. The bridging of the interface gaps (up to 5 mm) by the trabecular metal monoblock acetabular component indicates the strong osteoconductive, and possibly osteoinductive, properties of trabecular metal.

A dosimetric comparison of 169Yb versus 192Ir for HDR prostate brachytherapy.

For the purpose of evaluating the use of 169Yb for prostate High Dose Rate brachytherapy (HDR), a hypothetical 169Yb source is assumed with the exact same design of the new microSelectron source replacing the 192Ir active core by pure 169Yb 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 (SWIFT), which features an inverse treatment planning option based on a multiobjective dose optimization engine. The quality of prostate HDR brachytherapy using the real 192Ir and hypothetical 169Yb 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, 169Yb proves at least equivalent to 192Ir irrespective of prostate volume. This has to be evaluated in view of the shielding requirements for the 169Yb energies that are minimal relative to that for 192Ir.

Monte Carlo and thermoluminescence dosimetry of the new IsoSeed model I25.S17 125I interstitial brachytherapy seed.

Monte Carlo simulation and experimental thermoluminescence dosimetry were utilized for the dosimetric characterization of the new IsoSeed model I25.S17 125I interstitial brachytherapy seed. The new seed design is similar to that of the selectSeed and 6711 seeds, with the exception of its molybdenum marker. Full dosimetric data are presented following the recommendations in the Update of the AAPM Task Group 43 report (TG-43U1). A difference of 3.3% was found between Monte Carlo dose rate constant results calculated by air kerma strengths from simulations using a point detector and a detector resembling the solid angle subtended to the seed by the Wide Angle Free Air Chamber (WAFAC) in the primary standard calibration geometry. Following the TG-43U1 recommendations, an average value of lambdaMC = (0.929 +/- 0.014) cGy h(-1) U(-1) was adopted for the new seed. This value was then averaged with the measured value of lambdaEXP = (0.951 +/- 0.044) cGy h(-1) U(-1) to yield the proposed dose rate constant for the new seed that is equal to lambda = (0.940 +/- 0.051) cGy h(-1) U(-1). The Monte Carlo calculated radial dose function and two-dimensional (2-D) anisotropy function results for the new seed were found in agreement with experimental results to within statistical uncertainty of repeated measurements. Monte Carlo simulations were also performed for 125I seeds of similar geometry and dimensions for the purpose of comparison. The new seed presents dosimetric characteristics that are very similar to that of the selectSeed. In comparison to the most extensively studied Amersham 6711 seed, the new one presents similar dosimetric characteristics with a slightly reduced dose rate constant (1.5%).

In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir high-dose-rate brachytherapy using CT-based planning for the treatment of prostate cancer.

PURPOSE: To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. METHODS AND MATERIALS: A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. RESULTS: The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. CONCLUSIONS: Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

A conformal index (COIN) to evaluate implant quality and dose specification in brachytherapy.

PURPOSE: To propose a new index (COIN) that can be easily understood and computed to assess high dose rate (HDR) brachytherapy interstitial implant quality and dose specification and is an improvement on existing indexes. METHODS AND MATERIALS: The COIN index is based on an extension of dose-volume histograms and employs an analogous concept to that of cost-benefit analysis, which has already been applied to quality-of-life assessments for two alternative treatment protocols. The COIN index calculation methodology is shown for two cases: with and without critical structures. An analysis is given of dose distributions for two planning treatment volumes (PTV) of simple geometrical shape, applying both the rules of the Paris system and that of the "Offenbach" system. 40 patients who have received interstitial implants form the clinical material. With current HDR brachytherapy technology both for dose delivery, using remote afterloaders, and for three-dimensional (3D) treatment planning, it is now possible to relatively easily plan conformal brachytherapy treatments that would have been impossible with manual afterloading techniques and two-dimensional (2D) treatment planning. RESULTS: Examples of the use of the COIN index are presented for experimental and clinical data. CONCLUSIONS: The results show that COIN is a useful and practical index to improve the quality of treatment of interstitial brachytherapy implants. Further work will be undertaken with a larger population of implanted cancer patients and a subdivision of the results by treatment site.

Reconstruction and navigation system for intraoperative brachytherapy using the flab technique for colorectal tumor bed irradiation.

PURPOSE: To present the development of a new navigation and reconstruction system based on an electromagnetic free-hand tracker and on CT imaging for treatment planning of intraoperative high-dose-rate brachytherapy (IORT-HDRB) in the sacral region. Our aim is to improve accuracy and to enable individualized treatment planning and dose documentation to be performed for IORT-HDRB using a flab technique. METHODS AND MATERIALS: The material consists of an electromagnetic 3D tracker system, a PC workstation with Microsoft Windows NT 4.0 operating system, and a recognition program for continuous speech. In addition, we designed an external reference system constructed of titanium and Perspex, which is positioned in the pelvis, and a special digitizer pen for reconstruction of the flab geometry. The flab design incorporates a series of silicon 10-mm-diameter spherical pellets. Measurements were made with a pelvic phantom in order to study the accuracy of the system. The reconstruction results are stored and can be exported via network or floppy to our different treatment planning systems. RESULTS: Our results for the reconstruction of a flab with six catheters and a total of 100 spherical pellets give mean errors in the range (2.5 +/- 0.6) mm to (3.5 +/- 0.8) mm depending on the positions of the pelvic phantom and transmitter relative to the operation table. These errors are calculated by comparing the reconstruction results of our system with those using a CT-based reconstruction of the flab geometry. For the accuracy of the navigation system for the pelvic phantom, we obtained mean errors in the range (2.2 +/- 0.7) mm to (3. 1 +/- 1.0) mm. CONCLUSIONS: The new system we have developed enables navigation and reconstruction within the surgical environment with a clinically acceptable level of accuracy. It offers the possibility of individualized treatment planning and effective documentation of the 3D dose distribution in IORT-HDRB using a flab technique.

Comparison of calibration procedures for 192Ir high-dose-rate brachytherapy sources.

PURPOSE: To compare the efficacy of different calibration procedures for 192Ir high-dose-rate (HDR) brachytherapy sources and to determine their suitability in clinical practice. In addition the manufacturer's calibration is compared with our experimental measurements so that the accuracy of the source strength on the manufacturer certificate which is supplied with each new 192Ir source can be accessed. METHODS AND MATERIALS: We compared three types of calibration system: well-type chambers (HDR-1000 and SDS), cylindrical phantom, and plate phantom. The total number of measurements we obtained was 365. The number of sources used for the calibration procedure comparison was 20 and the number used for comparison with the manufacturer's calibration was 46. This study was made during the period 1989-1997. Also, Physikalisch-Technische Bundesanstalt (PTB) calibrated one of our sources using their PTB protocol so that the results could be compared with our own. RESULTS: The sensitivity of each system on scattering from the room walls was studied. It was found that different minimum lateral distances from the walls were required for the different systems tested: 15 cm and 25 cm for the well-type chambers, 75 cm for the cylindrical phantom, and 13 cm for the plate phantom. The minimum thickness required to reach phantom scattering saturation for the plate phantom setup is 24 cm. The influence of the applicator material used in the calibration setup was found to be 1.7% for the stainless steel dosimetry applicator compared to the plastic 5F applicator. The accuracy of source positioning within the applicator can lead to dosimetric errors of +/-1.2% for the radial distance of 8.0 cm used with both solid phantoms. The change in the response for both well-type chambers was only 0.1% for changes in the source position within +/-7.5 mm around the response peak. Good agreement was found between all dosimetry systems included in our study. Taking the HDR-1000 well-type chamber results as a reference, we observed percentage root mean square (RMS) values of 0.11% for the SDS well-type chamber, 0.44% for the cylindrical, and 0.60% for the plate phantom setup. A comparison of our results using the cylindrical phantom with those of the manufacturer showed a percentage RMS value of 3.3% with a percentage fractional error range of -13.0% to +6.0%. The comparison of our calibration results with those of PTB gave deviations less than 0.4% for all systems. CONCLUSIONS: Our results have shown that with careful use of all calibration system protocols an accurate determination of source strength can be obtained. However, the manufacturer's calibration is not accurate enough on its own, and it should be mandatory for clinics to always measure the source strength of newly delivered 192Ir brachytherapy sources. The influence of the applicator material, metal or plastic, should always be taken into account.

Analysis of late effects data using dose-response models: application to human skin telangiectasia data.

The clinical data for skin telangiectasia from previous prospective studies at the Radiotherapy Department in Gothenborg are reanalyzed using two dose-response models - the general formulations of the well known linear-quadratic (LQ) and NSD isoeffect models. Assuming that essentially no repopulation appears in the vessel endothelium for overall treatment times up to 68 days, the alpha/beta-value of 2.75 Gy is obtained for the LQ-model. The time factor is found not to be significant by the NSD-model for the treatment times used (less than or equal to 68 days) at the 95% level of confidence. The estimated value of the exponent of the number of fractions, A, is 0.321. The obtained values of the alpha/beta-ratio and of A show high sensitivity of the vessel endothelium to changes in the dose per fraction. Our results show that within the interval of the number of fractions used, 10-35 fractions, the NSD-model gives predictions comparable to those of the LQ-model. For number of fractions smaller than 5, a high discrepancy occurs between the two models, the NSD-model predicting higher values of the isoeffective total dose. The maximal deviation between the models appears for N = 1; 25% and 27% at the 5 and 50% level of effect, respectively. For large N and especially at low effect probabilities the NSD-model again predicts higher isoeffective doses: the dose predicted by the NSD-model for a regimen with 40 fractions and for 5% probability of telangiectasia is 7.5%, higher than that predicted by the LQ-model. Based on the estimated dose-response curves, considering the telangiectasia as the decisive late tissue effect, the requirement for the combined uncertainty in the dose delivery is estimated between 3 and 4.5%.