The 15-year outcomes of high-dose-rate brachytherapy for radical dose escalation in patients with prostate cancer—A benchmark for high-tech external beam radiotherapy alone?

PurposeDose escalation using high-dose-rate brachytherapy (HDR-BT) is an established treatment method for prostate cancer. First, long-term results were previously published (specific Kiel method). This study aims to evaluate 10-/15-year outcomes of Kiel Protocol 1 (1986–1992).Methods and MaterialsConformal external beam radiotherapy (EBRT) was delivered to the pelvis (50 Gy per conventional fractionation) along with an HDR boost to the prostate amounting to a combined biologic equivalent dose in 2 Gy per fraction of 117.25 Gy (α/β = 3). The HDR-BT was performed in two fractions of 15 Gy to the peripheral zone of McNeal. The EBRT-clinical target volume covered the full pelvis. The analyzed cohort totaled 122 patients. The reported end points were overall/cancer-specific survival, local recurrence/distant metastasis rates, and biochemical (BC) control rates according to American Society for Therapeutic Radiology and Oncology/Phoenix definitions. All end points were calculated using the Kaplan–Meier method and the log-rank test in univariate analyses.ResultsThe mean follow-up time was 116.8 months. The 5-, 10-, and 15-year survival rates were 81%, 62.1%, and 45% for overall survival; 92.1%, 83.1%, and 75.3% for cancer-specific survival; 92.5%, 91.4%, and 83.9% for local recurrence–free survival; and 83.8%, 81.2%, and 69.8% for distant metastasis–free survival, respectively. American Society for Therapeutic Radiology and Oncology–defined BC tumor control rates at 5, 10, and 15 years were 81.1%, 74%, and 67.8%, respectively. According to Phoenix, the BC control rates at 5, 10, and 15 years were 77.8%, 69%, and 63.6%, respectively.ConclusionsThe long-term results for the combination of HDR-BT and EBRT continue to show excellent results, providing high equivalent dose in 2 Gy per fraction and high disease control rates. These outcomes were reproducible for the extended follow-up period ranging up to 21.9 years.     

An integrated system for clinical treatment verification of HDR prostate brachytherapy combining source tracking with pretreatment imaging

PurposeHigh-dose-rate (HDR) prostate brachytherapy treatment is usually delivered in one or a few large dose fractions. Poor execution of a planned treatment could have significant clinical impact, as high doses are delivered in seconds, and mistakes in an individual fraction cannot be easily rectified. Given that most potential errors in HDR brachytherapy ultimately lead to a geographical miss, a more direct approach to verification of correct treatment delivery is to directly monitor the position of the source throughout the treatment. In this work, we report on the clinical implementation of our treatment verification system that uniquely combines the 2D source-tracking capability with 2D pretreatment imaging, using a single flat panel detector (FPD).Methods and MaterialsThe clinical brachytherapy treatment couch was modified to allow integration of the FPD into the couch. This enabled the patient to be set up in the brachytherapy bunker in a position that closely matched that at treatment planning imaging. An anteroposterior image was acquired of the patient immediately before treatment delivery and was assessed by the Radiation Oncologist online, to reestablish the positions of the catheters relative to the prostate. Assessment of catheter positions was performed in the left-right and superior-inferior directions along the entire catheter length and throughout the treatment volume. Source tracking was then performed during treatment delivery, and the measured position of the source dwells were directly compared to the treatment plan for verification.ResultsThe treatment verification system was integrated into the clinical environment without significant change to workflow. Two patient cases are presented in this work to provide clinical examples of this system, which is now in routine use for all patient treatments in our clinic. The catheter positions were visualized relative to the prostate, immediately before treatment delivery. For one of the patient cases presented in this work, they agreed with the treatment plan on average by 1.5 mm and were identifiable as a predominantly inferior shift. The source tracking was performed during treatment delivery, and for the same case, the mean deviation from the planned dwell positions was 1.9 mm (max = 4.9 mm) for 280 positions across all catheters.ConclusionWe have implemented our noninvasive treatment verification system based on an FPD in the clinical environment. The device is integrated into a patient treatment couch, and the process is now included in the routine clinical treatment procedure with minor impact on workflow. The system which combines both 2D pretreatment imaging and HDR 2D source tracking provides a range of information that can be used for comprehensive treatment verification. The system has the potential to meaningfully improve safety standards by allowing widespread adoption of routine treatment verification in HDR brachytherapy.     

In vivo diode dosimetry vs. computerized tomography and digitally reconstructed radiographs for critical organ dose calculation in high-dose-rate brachytherapy of cervical cancer

Purpose

To investigate the correlation between the dose predicted by the treatment planning system using digitally reconstructed radiographs or three-dimensional (3D)-reconstructed CT images and the dose measured by semiconductor detectors, under clinical conditions of high-dose-rate brachytherapy of the cervix uteri.

Patients and methods

Thirty-two intracavitary brachytherapy applications were performed for 12 patients with cancer of the cervix uteri. The prescribed dose to Point A was 7 Gy. Dose was calculated for both International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal points based on digitally reconstructed radiographs and for 3D CT images-based volumetric calculation of the bladder and rectum. In vivo diode dosimetry was performed for the bladder and rectum.

Results

The ICRU reference point and the volumes of 1, 2, and 5 cm³ received 3.6 ± 0.9, 5.6 ± 2.0, 5.1 ± 1.7, 4.3 ± 1.4 and 5.0 ± 1.2, 5.3 ± 1.3, 4.9 ± 1.1, and 4.2 ± 0.9 Gy for the bladder and rectum, respectively. The ratio of the 1 cm³ and the ICRU reference point dose to the diode dose was 1.8 ± 0.7 and 1.2 ± 0.5 for the bladder and 1.9 ± 0.6 and 1.7 ± 0.5 for the rectum, respectively.

Conclusions

3D image-based dose calculation is the most accurate and reliable method to evaluate the dose given to critical organs. In vivo diode dosimetry is an important method of quality assurance, but clinical decisions should be made based on 3D-reconstructed CT image calculations.     

Implementation of high-dose-rate brachytherapy for prostatic carcinoma in an unshielded operating room facility

PurposeThe purpose of the study was to describe our approach towards safe delivery of single-fraction high-dose-rate (HDR) brachytherapy (BT) boost in patients with prostate cancer in the setting of an unshielded operating room (OR).Methods and MaterialsA total of 95 patients received 15 Gy HDR BT boost. The procedure involved transrectal ultrasound–based catheter insertion and planning in the OR, after which the patient was moved to a shielded treatment room for radiation. This required three vital components: (1) an OR table capable of transporting the patient in lithotomy position, (2) robust motion management checks to ensure reproducibility of prostate and catheter positions in the treatment room before radiation delivery, (3) remote monitoring of patient vitals while under anesthesia, during the radiation. Initial viability of this approach was confirmed by assessing acute toxicities using the Common Terminology Criteria for Adverse Events v4.0 and American Urologic Association symptom scores.ResultsWe found good stability in prostate and catheter position, with less than 1 mm shifts in each direction due to patient transfer. The median baseline American Urologic Association score was 7 (3–11), which increased to 12 (7–17) at 4 weeks and 9 (5–14) at 3 months (p = 0.003). Common Terminology Criteria for Adverse Events ≥ grade 2 genitourinary and gastrointestinal toxicities were experienced by 7% and 0% patients, respectively, at 3 months posttreatment completion.ConclusionsSingle-fraction HDR prostate BT can be delivered safely in an unshielded OR facility with a distant shielded treatment room using rigorous motion management checks and supplementary procedural equipment.     

A surrogate urethra for real-time planning of high-dose-rate prostate brachytherapy

PurposeThis study characterizes prostatic urethra cross-section to develop a surrogate urethra for accurate prediction of urethral dose during real-time high-dose-rate prostate brachytherapy.Materials and MethodsArchived preoperative transrectal ultrasound images from 100 patients receiving low-dose-rate prostate brachytherapy were used to characterize the prostatic urethra, contoured on ultrasound using aerated gel. Consensus contours, defined using majority vote, described commonalities in cross-sectional shape across patients. Potential simplified surrogates were defined and evaluated against the true urethra. The best performing surrogate, a circle of varying size (CS) was retrospectively contoured on 85 high-dose-rate prostate brachytherapy treatment plans. Dose to this recommended surrogate was compared with urethral doses estimated by the standard 6 mm circle surrogate.ResultsClear variation in urethral cross-sectional shape was observed along its length and between patients. The standard circle surrogate had low predictive sensitivity (61.1%) compared with true urethra because of underrepresentation of the verumontanum midgland. The CS best represented the true urethra across all validation metrics (dice: 0.73, precision: 67.0%, sensitivity: 83.2%, conformity: 0.78). Retrospective evaluation of planned doses using the CS surrogate resulted in significant differences in all reported urethral dose parameters compared with the standard circle, with the exception of D_100%. The urethral dose limit (115%) was exceeded in 40% of patients for the CS surrogate.ConclusionsThe proposed CS surrogate, consisting of circles of varying diameter, is simple yet better represents the true urethra compared with the standard 6 mm circle. Higher urethral doses were predicted using CS, and the improved accuracy of CS may offer increased predictive power for urethral toxicity, a subject of future work.     

Dosimetric evaluation of MRI-to-ultrasound automated image registration algorithms for prostate brachytherapy

PurposeIdentifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively.Methods and MaterialsTen patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D₉₀, D_mean, V₁₅₀, and V₂₀₀ to the prostate and DIL were reported. For urethra and rectum, D₁₀ and V₈₀ were reported.ResultsSignificant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans.ConclusionThe dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D₉₀ and D_mean. A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy.     

Clinical evaluation of an MRI-to-ultrasound deformable image registration algorithm for prostate brachytherapy

Purpose

Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy (HDR-BT) treatment planning is challenging. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study evaluates the efficacy of an in-house software for MRI-to-TRUS DIL registration (MR2US) and compares its results to rigid and B-Spline deformable registration.

Dose perturbation due to catheter materials in high-dose-rate interstitial 192Ir brachytherapy

PurposeCatheters made of either metal or plastic are currently used in brachytherapy treatment to insert radiative sources into patients. However, the radiation dose perturbations due to catheter attenuation are not taken into account in treatment planning. The purpose of this work is to quantify the effects of catheter composition on dose distribution and study their impacts on the overall treatment with high-dose-rate ¹⁹²Ir sources.Methods and MaterialsDose perturbations are first studied in a simplified case consisting of two parallel catheters. The catheter wall is either composed of stainless steel or polyoxymethylene. The attenuations are studied as the distance between the two catheters is varied from 5 to 30 mm. Dose perturbations resulting from irradiation are evaluated with a Monte Carlo GEANT4 dose calculation algorithm. The dose differences are further investigated with seven typical high-dose-rate prostate treatment plans involving 17 catheters.ResultsThe dose differences compared with water in the simplified case reach −4.3 ± 0.1% for stainless steel and 1.7 ± 0.5% for polyoxymethylene at 10 mm above the source when the catheters are separated by a distance of 5 mm. Dose perturbations are reduced in real treatment plans because of the contributions of the many dwell positions. Stainless steel and polyoxymethylene catheters induce on an average a dose difference of −1.3 ± 0.3% and 0.1 ± 0.2%, respectively in the target.ConclusionsThe dose differences reported in this work do not warrant any changes in the clinical procedures.     

Assessment of a source position checking tool for the quality assurance of transfer tubes used in HDR 192Ir brachytherapy treatments

PurposeThe determination of source positions before treatment is an essential part of the quality assurance (QA) associated with high dose rate brachytherapy treatments. The purpose of this study was to design and commission a tool to allow the quantification of source positions across multiple transfer tube types.Methods and MaterialsA bespoke flexi-adapter jig, three transfer tube adapters, and a film piercing pointer were designed and built for source position QA across three transfer tube types—the standard, 6 French, and gynae transfer tubes. The jig was calibrated against a manufacturer source position check tool, and intratube and intertube source position variations investigated across a total of 40 transfer tubes, using strips of Gafchromic film irradiated at multiple positions 20 mm apart with a microSelectron V3 afterloader (Elekta, Holland). The performance of the jig in localizing the nominal dwell positions relative to the manufacturer check tool was assessed. Associated expanded uncertainties were quantified in line with the International Organization for Standardization Guidelines.ResultsThe mean expanded uncertainty associated with the use of the jig was 0.4 ± 0.0 mm (k = 1). The performance of the jig was 0.3 ± 0.0 mm, while the intratube and intertube source positional variations were observed to be within ±1.0 mm across most transfer tubes.ConclusionsA bespoke flexi-adapter jig capable of allowing source position measurements to be carried out on various transfer tube types has been designed. Measurement results highlight the need for routine QA of all transfer tubes in clinical use.     

Workflow and efficiency in MRI-based high-dose-rate brachytherapy for cervical cancer in a high-volume brachytherapy center

PurposeWe report the clinical workflow and time required for MRI-based image-guided brachytherapy (MR-IGBT) of cervical cancer patients in a high-volume brachytherapy center with 10 years of experiences to provide a practical guideline for implementing MR-IGBT into clinical use.Methods and MaterialsWe recorded the time and workflow of each procedure step within the 40 consecutive ring and tandem applicator fractions of MR-IGBT by our multidisciplinary team. We divided the entire procedure into four sections based on where the procedure was performed: (1) applicator insertion under sedation, (2) MR imaging, (3) planning, and (4) treatment delivery. In addition, we compared the current procedure time to the initial procedure time when first implementing MR-IGBT in 2007–2008 via a retrospective review.ResultsMean total procedure time was 149.3 min (SD 17.9, ranges 112–178). The multidisciplinary team included an anesthesia team, radiologist, radiation oncologist, nurses, radiation therapists, MRI technicians, dosimetrists, and physicists. The mean procedure time and ranges for each section (min) were as follows: (1) 56.2 (28.0–103.0), (2) 31.0 (19.0–70.0), (3) 44.3 (21.0–104.0), and (4) 17.8 (9.0–34.0). Under current setting, the combined mean procedure time for MR imaging and planning was 63.2 min. In comparison, the same procedure took 137.7 min in 2007–2008 period, which was significantly longer than the current workflow (p < 0.001).ConclusionsA skilled and dedicated multidisciplinary team is required for an efficient clinical workflow and delivery of MR-IGBT. Over the years, we have improved efficiency with clinical experience and continuous efforts in staff education.     

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer

PurposeHigh dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer.Methods and MaterialsForty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition.ResultsWith a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities.ConclusionFifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease.     

The impact of rectal/bladder filling and applicator positioning on in vivo rectal dosimetry in vaginal cuff brachytherapy using an enhanced therapy setting

PurposeThe impact of rectal filling and bladder volume on in vivo rectal dosimetry (IVD) in vaginal cuff brachytherapy (VCBT) is unknown. The purpose of this study was to compare rectal doses from IVD with those calculated from treatment planning and to identify influencing factors.Materials and MethodsWe collected data of 80 VCBT sessions, four for each of 20 patients. Each was retrospectively compared with doses determined by the treatment planning system. Factors potentially predicting the IVD rectum dose were analyzed.ResultsFor a series of 80 brachytherapy applications, the calculated mean dose to the rectum was 2.52 Gy. The mean difference between all calculated and measured doses for the 80 applications with five probe positions each was 0.09 Gy (p = 0.952) proving high overall accordance between IVD and calculated doses at the rectum. The mean volume of the rectum was 119 ± 57 cm³. The rectal volume was not statistically significantly associated with the IVD or the calculated rectum doses. At the third and fourth rectal probe position in craniocaudal ordering, increased filling of the urinary bladder resulted in decreased measured and calculated doses (p < 0.05 for both). A rectum pointing position of the applicator significantly increased the maximum rectum dose compared with a bladder-oriented position (p < 0.05).ConclusionsIVD provided valuable data for rectal exposure in VCBT. Increased bladder filling and vaginal applicator positioning off the rectum elicited related with less rectal radiation exposure, whereas rectal filling did not. Further confirmation including assessment of IVD in bladder is pending to define optimal dosimetric conditions in VCBT.     

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.     

Prostate-specific antigen bounce after high-dose-rate prostate brachytherapy and hypofractionated external beam radiotherapy

PurposeTo report the frequency, timing, and magnitude of prostate-specific antigen (PSA) bounce (PB) in patients who received high-dose-rate (HDR) brachytherapy (HDRB) plus hypofractionated external beam radiation therapy (HypoRT) and to assess a possible correlation between PB and biochemical failure (BF).Methods and MaterialsPatients with intermediate-risk prostate cancer received 10 Gy single-fraction ¹⁹²Ir HDRB followed by 50 Gy in 20 daily fractions of HypoRT without androgen deprivation therapy. All patients had a minimum 2-year followup. The PB was defined as PSA elevation higher than 0.2 ng/mL from previous measurement with subsequent drop to pre-bounce level. The BF was defined as PSA nadir + 2 ng/mL.ResultsA total of 114 patients treated between 2001 and 2009 were eligible for analysis. At a median followup of 66 months, the PB was found in 45 (39%) patients with a median time to bounce of 16 months (range, 3–76 months). The median time to PSA normalization after a PB was 9 months (range, 2–40 months). The median magnitude of PB was 0.45 ng/mL (range, 0.2–6.62). The BF occurred in 12 (10.5%) patients of whom three had a PB. Median time to BF was 52.5 months. Four patients (3.5%) in the PB group fit the criteria for BF.ConclusionsThe PB is common after HDRB and HypoRT and can occur up to 76 months after treatment. It can rarely fit the criteria for BF. The time to PB is shorter than the time to BF. There is a lower incidence of BF in patients with a PB. An acknowledgment of this phenomenon should be made when interpreting PSA results during followup to prevent unnecessary interventions.