Interobserver variation in postimplant computed tomography contouring affects quality assessment of prostate brachytherapy

PURPOSE: Permanent seed implants are accepted treatment of early stage prostate cancer. Implant quality is assessed by post implant CT-based dosimetry but prostate contours on CT images are obscured by metallic seed artefact and edema. Outcome depends on implant quality, but perceived implant quality depends on accurate prostate contouring. This study documents inter observer variation in prostate contouring on post implant CT scans. METHODS AND MATERIALS: Ten patients had implant dosimetry calculated on 4 copies of the post implant CT scan. Prostate contours from MRI-CT fusion were the gold standard for prostate edge identification. CTs were contoured by an experienced prostate brachytherapist matching CT images to the pre implant TRUS, and by 2 GU radiation oncologists experienced in conformal radiotherapy planning. Dosimetry was compared to that obtained using MRI-CT fusion in terms of D90 and V100. RESULTS: Contours and dosimetry were not reproducible among the 3 observers. The V100's of the experienced brachytherapist differed from that of MRI-CT fusion by a mean of 2.4% compared to 9.1% and 4.4% for observers 1 and 2, and the D90 by a mean of 9.3 Gy compared to 30.3 and 14.4 Gy for observers 1 and 2. CONCLUSIONS: Quality assessment of prostate brachytherapy based on 1 month post implant CT is difficult. This may obscure the dose-response relationship in brachytherapy as well as create problems for quality assurance in multicentre trials evaluating brachytherapy against standard modalities. Whenever possible, MRI-CT fusion should be employed to verify prostate contours post implant.     

Impact of oedema on implant geometry and dosimetry for temporary high dose rate brachytherapy of the prostate

The optimal timing of dosimetry for permanent seed prostatic implants remains contentious given the half life of post-implant oedema resolution. The aim of this study was to establish whether prostatic oedematous change over the duration of a temporary high dose rate (HDR) interstitial brachytherapy (BR) boost would result in significant needle displacement, and whether this change in geometry would influence dosimetry. Two CT scans, one for dosimetric purposes on the day of the implant and the second just prior to implant removal, were obtained for four patients receiving transperineal interstitial prostate brachytherapy. The relative changes in cross-sectional dimensions of the implants were calculated by establishing the change in mean radial distance (MRD) of the needle positions from the geometric centre of the implant for each patient's pair of CT studies. The treatment plan, as calculated from the first CT scan, was used in the second set of CT images to allow a comparison of dose distribution. The percentage change in MRD over the duration of the temporary implants ranged from -1.91% to 1.95%. The maximum change in estimated volume was 3.94%. Dosimetric changes were negligible. In the four cases studied, the degree of oedematous change and consequent displacement of flexiguide needle positions was negligible and did not impact on the dosimetry. The rate and direction of oedematous change can be extremely variable but on the basis of the four cases studied and the results of a larger recent study, it might not be necessary to re-image patients for dosimetric purposes over the duration of a fractionated HDR BT boost to the prostate where flexiguide needles are utilized. Nevertheless, further investigation with larger patient numbers is required.     

Feasibility of an MRI-only workflow for postimplant dosimetry of low-dose-rate prostate brachytherapy: Transition from phantoms to patients

PurposeThe lack of positive contrast from brachytherapy seeds in conventional MR images remains a major challenge toward an MRI-only workflow for postimplant dosimetry of low-dose-rate brachytherapy. In this work, the feasibility of our recently proposed MRI-only workflow in clinically relevant scenarios is investigated and the necessary modifications in image acquisition and processing pipeline are proposed for transition to the clinic.Methods and MaterialsFour prostate phantoms with a total of 321 I-125 implanted dummy seeds and three patients with a total of 168 implanted seeds were scanned using a gradient echo sequence on 1.5 T and 3T MR scanners. Quantitative susceptibility mapping (QSM) was performed for seed visualization. Before QSM, the seed-induced distortion correction was performed followed by edge enhancement. Seed localization was performed using spatial clustering algorithms and was compared with CT. In addition, feasibility of the proposed method on detection of prostatic calcifications was studied.ResultsThe proposed susceptibility-based algorithm generated consistent positive contrast for the seeds in phantoms and patients. All the 321 seeds in the four phantoms were correctly identified; the MR-derived seeds centroids agreed well with CT-derived positions (average error = 0.5 ± 0.3 mm). The proposed algorithm for seed visualization was found to be orientation invariant. In patient cases, all seeds were visualized and correctly localized (average error = 1.2 ± 0.9 mm); no significant differences between dose volume histogram parameters were found. Prostatic calcifications were depicted with negative contrast on QSM and spatially agreed with CT.ConclusionsThe proposed MRI-based approach has great potential to replace the current CT-based practices. Additional patient studies are necessary to further optimize and validate the workflow.     

Preliminary study of correction of original metal artifacts due to I-125 seeds in postimplant dosimetry for prostate permanent implant brachytherapy

Purpose

We investigated a subtraction-based reprojection approach to reduce CT metal artifacts due to I-125 seeds and evaluated the clinical implications in postimplant dosimetry for prostate permanent implant brachytherapy.

Materials and Methods

The raw projection data were used to reduce metal artifacts due to I-125 seeds. CT images of the metal parts only were separated from the original CT images by setting the threshold for pixel value to that of the I-125 seeds. Using these images, sinograms of CT images with and without seeds were obtained by inverse Radon transform (iRT), and the sinogram of the metal image was subtracted from that of the original image. Finally, the image was reconstructed using the sinogram by Radon transform (RT). This technique was applied to a prostate phantom and to a patient undergoing prostate permanent implant brachytherapy.

Results

Metal artifacts from I-125 seeds were reduced in both the phantom and patient studies. This technique decreased the density of the inner region of seeds but enhanced the density of the seed edge, thereby facilitating the identification of seed number, orientation, and location.

Conclusion

This method reduces metal artifacts from I-125 seeds, and has potential for decreasing the time required for and improving the accuracy of postimplant dosimetry.     

Interfractional fluctuation of rectal dose in high dose rate brachytherapy for prostate cancer

Purpose The aim of the study was to explore the cause of the difference in the maximal rectal dose between the first and second high dose rate (HDR) brachytherapy applications by comparing the thickness of the anterior rectal wall. Materials and methods The rectal dose and the thickness of the anterior rectal wall were analyzed in 26 patients with prostate cancer. After undergoing external beam radiation treatment with a total isocenter dose of 50 Gy, they were treated with HDR brachytherapy of 7.5 Gy/fraction, two fractions daily. The interval between the first HDR brachytherapy session and the second was 5 h. The rectal doses were directly surveyed during irradiation of the HDR brachytherapy. Thickening of the anterior rectal wall was measured at the same level by axial computed tomography scans obtained before the first and second HDR brachytherapy applications. Results The maximal surveyed rectal doses during the first and second HDR brachytherapy applications were 188 ± 51 cGy and 220 ± 35 cGy, respectively (P < 0.01). The fluctuation ratio exceeded 1 in each case. The thickness of the anterior rectal wall before the first and second HDR brachytherapy applications was 18.78 ± 4.34 mm and 14.95 ± 4.09 mm (P < 0.01), respectively. The fluctuation difference exceeded 0 in each case. Conclusion The different rectal dose is attributable to thinning of the anterior rectal wall. The total rectal dose is within the range of doses at risk of exerting a toxic effect on the rectum.     

Preliminary study of correction of original metal artifacts due to 1-125 seeds in postimplant dosimetry for prostate permanent implant brachytherapy

Purpose We investigated a subtraction-based reprojection approach to reduce CT metal artifacts due to I-125 seeds and evaluated the clinical implications in postimplant dosimetry for prostate permanent implant brachytherapy. Materials and Methods The raw projection data were used to reduce metal artifacts due to I-125 seeds. CT images of the metal parts only were separated from the original CT images by setting the threshold for pixel value to that of the I-125 seeds. Using these images, sinograms of CT images with and without seeds were obtained by inverse Radon transform (iRT), and the sinogram of the metal image was subtracted from that of the original image. Finally, the image was reconstructed using the sinogram by Radon transform (RT). This technique was applied to a prostate phantom and to a patient undergoing prostate permanent implant brachytherapy. Results Metal artifacts from I-125 seeds were reduced in both the phantom and patient studies. This technique decreased the density of the inner region of seeds but enhanced the density of the seed edge, thereby facilitating the identification of seed number, orientation, and location. Conclusion This method reduces metal artifacts from I-125 seeds, and has potential for decreasing the time required for and improving the accuracy of postimplant dosimetry. This study was partly supported by a Grant-in-Aid for Scientific Research (Grant No. 177908826807) of the Japan Society for the Promotion of Science (JSPS).     

Radiation protection and dosimetry issues for patients with prostate cancer after I-125 low-dose-rate brachytherapy permanent implant

PurposeThe aim of this work was to analyze the exposure rates measured in the proximity of patients who underwent prostate low-dose-rate brachytherapy with I-125 implant. Effective doses to relatives and to population were computed to estimate the time to reach radioprotection dose constraints.Methods and MaterialsMeasurements were obtained from 180 patients, whereas the body mass index was calculated and reported for 77 patients. The day after the implant, $\dot{K}$ measurements were conducted at various skin distances and positions and converted to effective doses. A theoretical model was developed to estimate effective doses from total implanted activity. The latter was approximated with a 10-mL vial inside the patient.ResultsThe $\dot{K}$ measurements showed a low correlation with the total implanted activity, albeit an increasing trend of $\dot{K}$ was observed on increasing the activity. A stronger correlation was found between body mass index and $\dot{K}$ measurements.The effective dose to population is in general lower than dose constraints as well as the effective doses to relatives, with the exception of children and pregnant women, who command special precautions. We report differences between the experimental model– and theoretical model–based dose evaluation together with their comparison with previous studies found in literature.ConclusionsBased on the $\dot{K}$ measurements and the results of the present analysis, it is possible to provide the patient with radiation safety instructions specifically tailored to his relatives’ habits and working environment.     

Biologically effective dose and definitive radiation treatment for localized prostate cancer

Background and purpose

It is not clear if prolongation of definitive external radiation therapy for prostate cancer has an effect on biochemical failure. The aim of this work was to evaluate whether the biologically effective dose (BED), and in particular the duration of radiotherapy, intended as overall treatment time, has an effect on biochemical failure rates and to develop a nomogram useful to predict the 6-year probability of biochemical failure.

Patients and methods

A total of 670 patients with T1–3 N0 prostate cancer were treated with external beam definitive radiotherapy, to a total dose of 72–79.2 Gy in 40–44 fractions. The computed BED values were treated with restricted cubic splines. Variables were checked for colinearity using Spearman’s test. The Kaplan–Meier method was used to calculate freedom from biochemical relapse (FFBR) rates. The Cox regression analysis was used to identify prognostic factors of biochemical relapse in the final most performing model and to create a nomogram. Concordance probability estimate and calibration methods were used to validate the nomogram.

Results

Neoadjuvant and concomitant androgen deprivation was administered to 475 patients (70?%). The median follow-up was 80 months (range 20–129 months). Overall, the 6-year FFBR rate was 88.3?%. BED values were associated with higher biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy treatment were independent variables of biochemical failure.

Conclusion

A prolongation of RT (lower BED values) is associated with an increased risk of biochemical failure. The nomogram may be helpful in decision making for the individual patient.     

An investigation into the use of polymer gel dosimetry in low dose rate brachytherapy

An investigation has been carried out into the properties of the BANG polymer gel and its use in the dosimetry of low dose rate brachytherapy. It was discovered that the response of the gel was reproducible and linear to 10 Gy. The gel was found to be tissue equivalent with a response independent of energy to within experimental accuracy (standard error of measurement +/- 5%). The slope of the calibration curve was found to increase from 0.28 +/- 0.01 s-1 Gy-1 to 0.50 +/- 0.02 s-1 Gy-1 for an increase in monomer concentration from 6 to 9%. Absorbed dose distributions for a straight applicator containing 36 137Cs sources were measured using the gel and the results compared with measurements made with thermoluminescent dosemeters (TLDs) and calculated values. Good agreement was found for the relative measurements. The root mean square residual percentage errors were 3%, 1% and 4% for the gel and the two groups of TLDs, respectively. There were some significant differences in absolute values of absorbed dose in the gel, possibly owing to the effects of oxygen. Measurements of a complex gynaecological insert were also made and compared with isodose curves from a planning system (Helax TMS), and in areas unaffected by oxygen diffusion the isodose levels from 100 to 50% agreed to within less than 0.5 mm.     

External radiotherapy and permanent prostate brachytherapy in patients with localized prostate cancer

We examined the difference in prostate-specific antigen (PSA)-freedom from recurrence (FFR) in patients with localized prostate cancer treated with permanent prostate brachytherapy (PPB) alone or external radiotherapy combined with PPB (RT-PPB). A total of 1476 patients with prostate cancer (T1/T2) were treated with PPB by following the American Brachytherapy Society criteria. Patient self-selection and preference allowed for an overlap of treatment methodologies and risk factors. Monotherapy consisted of 125I or 103Pd. RT-PPB consisted of RT followed by PPB. PSA-FFR was based on a published modification of the American Society for Therapeutic Radiology and Oncology definition. Cox regression analysis was performed to assess the role of Gleason sum, pretreatment PSA value, clinical stage, RT-PPB, the addition of hormones, and the minimum dose covering 90% of the prostate volume (D90 dose). Monotherapy was used for 1016 patients (79%), and RT-PPB was used for 281 patients (21%), with an overall 6-year PSA-FFR of 83.2% (median follow-up of 34.7 months; range, 6-91 months). Multivariate Cox regression analysis to predict PSA-FFR identified the following highly significant variables: pretreatment PSA value, Gleason sum, and the addition of hormones. When the D90% (D90 dose relative to the prescribed dose) was included as a variable, Cox regression identified only the following significant variables: D90%, pretreatment PSA, and Gleason sum. Cox regression failed to identify an improvement in PSA-FFR with RT-PPB or the addition of hormones. Although these conclusions question the role for RT-PPB, only a comparative trial will be able to answer this question definitively.     

Parallel imaging compressed sensing for accelerated imaging and improved signal-to-noise ratio in MRI-based postimplant dosimetry of prostate brachytherapy

PurposeTo investigate the feasibility of using parallel imaging compressed sensing (PICS) to reduce scan time and improve signal-to-noise ratio (SNR) in MRI-based postimplant dosimetry of prostate brachytherapy.Methods and MaterialsTen patients underwent low-dose-rate prostate brachytherapy with radioactive seeds stranded with positive magnetic resonance-signal seed markers and were scanned on a Siemens 1.5T Aera. MRI comprised a fully balanced steady-state free precession sequence with two 18-channel external pelvic array coils with and without a rigid two-channel endorectal coil. The fully sampled data sets were retrospectively subsampled with increasing acceleration factors and reconstructed with parallel imaging and compressed sensing algorithms. The images were assessed in a blinded reader study by board-certified care providers. Rating scores were compared for statistically significant differences between reconstruction types.ResultsImages reconstructed from subsampling up to an acceleration factor of 4 with PICS demonstrated consistently sufficient quality for dosimetry with no apparent loss of SNR, anatomy depiction, or seed/marker conspicuity when compared to the fully sampled images. Images obtained with acceleration factors of 5 or 6 revealed reduced spatial resolution and seed marker contrast. Nevertheless, the reader study revealed that images obtained with an acceleration factor of up to 5 and reconstructed with PICS were adequate-to-good for postimplant dosimetry.ConclusionsCombined parallel imaging and compressed sensing can substantially reduce scan time in fully balanced steady-state free precession imaging of the prostate while maintaining adequate-to-good image quality for postimplant dosimetry. The saved scan time can be used for multiple signal averages and improved SNR, potentially obviating the need for an endorectal coil in MRI-based postimplant dosimetry.     

Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement

PURPOSEThe purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer.METHODS AND MATERIALSThe American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life.RESULTSLDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure.CONCLUSIONSLDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.     

In vivo dosimetry with semiconductors in medium dose rate (MDR) brachytherapy for cervical cancer

Purpose

This study was performed to evaluate the role of in vivo dosimetry with semiconductor detectors in gynaecological medium dose rate brachytherapy, and to compare the actual doses delivered to organs at risk (as measured using in vivo dosimetry) with those calculated during treatment planning.

Materials and methods

Doses to the rectum and bladder were measured in a group of patients with cervical carcinoma using semiconductor detectors and compared to the doses calculated using a treatment planning system. 36 applications of brachytherapy at dose rates of 1.8–2.3 Gy/h were performed in the patients.

Results

The mean differences between the measured and calculated doses were 3 % for the rectum and 11 % for the bladder.

Conclusions

The main reason for the differences between the measured and calculated doses was patient movement. To reduce the risk of large errors in the dose delivered, in vivo dosimetry should be performed in addition to treatment planning system computations.     

Integrating external beam and prostate seed implant dosimetry for intermediate and high-risk prostate cancer using biologically effective dose: Impact of image registration technique

PURPOSECombining external beam radiation therapy (EBRT) and prostate seed implant (PSI) is efficacious in treating intermediate- and high-risk prostate cancer at the cost of increased genitourinary toxicity. Accurate combined dosimetry remains elusive due to lack of registration between treatment plans and different biological effect. The current work proposes a method to convert physical dose to biological effective dose (BED) and spatially register the dose distributions for more accurate combined dosimetry.METHODS AND MATERIALSA PSI phantom was CT scanned with and without seeds under rigid and deformed transformations. The resulting CTs were registered using image-based rigid registration (RI), fiducial-based rigid registration (RF), or b-spline deformable image registration (DIR) to determine which was most accurate. Physical EBRT and PSI dose distributions from a sample of 91 previously-treated combined-modality prostate cancer patients were converted to BED and registered using RI, RF, and DIR. Forty-eight (48) previously-treated patients whose PSI occurred before EBRT were included as a “control” group due to inherent registration. Dose-volume histogram (DVH) parameters were compared for RI, RF, DIR, DICOM, and scalar addition of DVH parameters using ANOVA or independent Student's t tests (α = 0.05).RESULTSIn the phantom study, DIR was the most accurate registration algorithm, especially in the case of deformation. In the patient study, dosimetry from RI was significantly different than the other registration algorithms, including the control group. Dosimetry from RF and DIR were not significantly different from the control group or each other.CONCLUSIONSCombined dosimetry with BED and image registration is feasible. Future work will utilize this method to correlate dosimetry with clinical outcomes.     

Biological effective dose for comparison and combination of external beam and low-dose rate interstitial brachytherapy prostate cancer treatment plans.

We report a methodology for comparing and combining dose information from external beam radiotherapy (EBRT) and interstitial brachytherapy (IB) components of prostate cancer treatment using the biological effective dose (BED). On a prototype early-stage prostate cancer patient treated with EBRT and low-dose rate I-125 brachytherapy, a 3-dimensional dose distribution was calculated for each of the EBRT and IB portions of treatment. For each component of treatment, the BED was calculated on a point-by-point basis to produce a BED distribution. These individual BED distributions could then be summed for combined therapies. BED dose-volume histograms (DVHs) of the prostate, urethra, rectum, and bladder were produced and compared for various combinations of EBRT and IB. Transformation to BED enabled computation of the relative contribution of each modality to the prostate dose, as the relative weighting of EBRT and IB was varied. The BED-DVHs of the prostate and urethra demonstrated dramatically increased inhomogeneity with the introduction of even a small component of IB. However, increasing the IB portion relative to the EBRT component resulted in lower dose to the surrounding normal structures, as evidenced by the BED-DVHs of the bladder and rectum. Conformal EBRT and low-dose rate IB conventional dose distributions were successfully transformed to the common "language" of BED distributions for comparison and for merging prostate cancer radiation treatment plans. The results of this analysis can assist physicians in quantitatively determining the best combination and weighting of radiation treatment modalities for individual patients.     

A PC program for estimating organ dose and effective dose values in computed tomography

Dose values in CT are specified by the manufacturers for all CT systems and operating conditions in phantoms. It is not trivial, however, to derive dose values in patients from this information. Therefore, we have developed a PC-based program which calculates organ dose and effective dose values for arbitrary scan parameters and anatomical ranges. Values for primary radiation are derived from measurements or manufacturer specifications; values for scattered radiation are derived from Monte Carlo calculations tabulated for standard anthropomorphic phantoms. Based on these values, organ doses can be computed by the program for arbitrary scan protocols in conventional and in spiral CT. Effective dose values are also provided, both with ICRP 26 and ICRP 60 tissue-weighting coefficients. Results for several standard CT protocols are presented in tabular form in this paper. In addition, potential for dose reduction is demonstrated, for example, in spiral CT and in quantitative CT. Providing realistic patient dose estimates for arbitrary CT protocols is relevant both for the physician and the patient, and it is particularly useful for educational and training purposes. The program, called WinDose, is now in use at the Erlangen University hospitals (Germany) as an information tool for radiologists and patients. Further extensions are planned. Received: 9 March 1998; Revision received: 4 June 1998; Accepted: 4 November 1998