Purpose
To assess catheter reconstruction and error detection performance of an afterloader (Elekta Brachytherapy, Veenendaal, The Netherlands) equipped with electromagnetic (EM) tracking ...capabilities.
Materials/Methods
The Flexitron research unit used was equipped with a special check cable integrating an EM sensor (NDI Aurora V3) that enables tracking and reconstruction capability. The reconstructions of a 24‐cm long catheter were performed using two methods: continuous fixed‐speed check cable backward stepping (at 1, 2.5, 5, 10, 25 and 50 cm/s) and stepping through each dwell position every 1 mm. The ability of the system to differentiate between two closely located (parallel) catheters was investigated by connecting catheters to the afterloader and moving it from its axis with an increment of 1 mm. A robotic arm (Meca500, Mecademic, Montreal) with an accuracy of 0.01 mm was used to move the catheter between each reconstruction. Reconstructions were obtained with a locally weighted scatterplot smoothing algorithm. To quantify the reconstruction accuracy, distances between two catheters were computed along the reconstruction track with a 5 mm step. The reconstructions of curve catheter paths were assessed through parallel and perpendicular phantom configuration to the EM field generator. Indexer length and lateral errors were simulated and a ROC analysis was made.
Results
Using a 50 cm/s check cable speed does not allow for accurate reconstructions. A slower check cable speed results in better reconstruction performance and smaller standard deviations. At 1 cm/s, a catheter can be shifted laterally down to 1 mm and all paths can be uniquely identified. The optimum operating distance from the field generator (50 to 300 mm) resulted in a lower absolute mean deviation from the expected value (0.2 ± 0.1 mm) versus being positioned on the edge of the electromagnetic sensitive detection volume (0.6 ±0.3 mm). The reconstructions of curved catheters with a check cable speed under 5 cm/s gave a 0.8 mm ±0.3 mm error, or better. All indexer and lateral shifts of 1 mm were detected with a check cable speed of 2.5 cm/s or lower.
Conclusions
The EM‐equipped Flexitron afterloader is able to track and reconstruct catheters with high accuracy. A speed under 5 cm/s is recommended for straight and curved catheter reconstructions. It allows catheter identification down to 1 mm inter‐catheter distance shift. The check cable can also be used to detect common shift errors.
Background
Complex intracavity and interstitial (IC/IS) applicators, such as the Venezia applicator, can improve the HR‐CTV coverage while adequately protecting organs at risk in the treatment of ...cervical cancer with high‐dose‐rate (HDR) brachytherapy. Although the Venezia applicator offers more choice for catheter selection, commercially available catheter and dose optimization algorithms are still missing for complex applicators. Moreover, studies on catheter and dose optimization for IC/IS implants in the treatment of cervical cancer are still limited.
Purpose
This work aims to combine a GPU‐based multi‐criteria optimization (gMCO) algorithm with a sparse catheter (SC) optimization algorithm for the Venezia applicator.
Methods
Fifty‐eight cervical cancer patients who received 28 Gy in 4 fx of HDR brachytherapy with the Venezia applicator (combination to external beam radiation therapy) are retrospectively revisited. The modelization of the applicator is done by virtually reconstructing all the IS catheters passing through the ring. Template catheters are reconstructed using an in‐house python script. To perform simultaneous MCO and SC optimization (SC+MCO), the objective function includes aggregated dose objectives in a weighted sum and a group sparsity term that individually penalizes the contribution of IS catheters. Plans generated with the SC+MCO algorithm are compared with plans generated with MCO using clinical catheters (CC+MCO) and the clinical plans (CP). The EMBRACE II soft constraints (planning aims) and hard constraints (limits for prescribed dose) are used as plan evaluation criteria.
Results
CC+MCO gives the most important gain with an increase up to 20.7% in meeting all EMBRACE II soft constraints compared with CP. The SC+MCO algorithm (adding catheter optimization to MCO) provides a second order increase (up to 12.1% with total acceptance rate of 60.3% or 35/58) in the acceptance rate versus CC+MCO (total increase of 32.8% vs. CP). Acceptance rate in EMBRACE II hard constraints is 98.3% (57/58) for both CC+MCO and SC+MCO versus 91.4% (53/58) for CP. The median SC+MCO optimization time is 11 s to generate a total of 5000 Pareto‐optimal plans with different catheter configurations (position and number) for each fraction.
Conclusions
Simultaneous catheter and MCO optimization is clinically feasible for HDR cervical cancer brachytherapy using the Venezia applicator. Clinical catheter configurations could be improved and/or the catheter number could be reduced without decreasing plan quality using SC+MCO compared with the CP.
Purpose
To evaluate the performance of an electromagnetic (EM)‐tracked scintillation dosimeter in detecting source positional errors of IVD in HDR brachytherapy treatment.
Materials and Methods
Two ...different scintillator dosimeter prototypes were coupled to 5 degrees‐of‐freedom (DOF) EM sensors read by an Aurora V3 system. The scintillators used were a 0.3 × 0.4 × 0.4 mm3 ZnSe:O and a BCF‐60 plastic scintillator of 0.5 mm diameter and 2.0 mm in length (Saint‐Gobain Crystals). The sensors were placed at the dosimeter's tip at 20.0 mm from the scintillator. The EM sampling rate was 40/s while the scintillator signal was sampled at 100 000/s using two photomultiplier tubes from Hamamatsu (series H10722) connected to a data acquisition board. A high‐pass filter and a low‐pass filter were used to separate the light signal into two different channels. All measurements were performed with an afterloader unit (Flexitron‐Elekta AB, Sweden) in full‐scattered (TG43) conditions. EM tracking was further used to provide distance/angle‐dependent energy correction for the ZnSe:O inorganic scintillator. For the error detection part, lateral shifts of 0.5 to 3 mm were induced by moving the source away from its planned position. Indexer length (longitudinal) errors between 0.5 to 10 mm were also introduced. The measured dose rate difference was converted to a shift distance, with and without using the positional information from the EM sensor.
Results
The inorganic scintillator had both a signal‐to‐noise‐ratio (SNR) and signal‐to‐background‐ratio (SBR) close to 70 times higher than those of the plastic scintillator. The mean absolute difference from the dose measurement to the dose calculated with TG‐43U1 was 1.5% ±0.7%. The mean absolute error for BCF‐60 detector was 1.7% ±1.2%$\pm 1.2\%$ when compared to TG‐43 calculations formalism. With the inorganic scintillator and EM tracking, a maximum area under the curve (AUC) gain of 24.0% was obtained for a 0.5‐mm lateral shift when using the EMT data with the ZnSe:O. Lower AUC gains were obtained for a 3‐mm lateral shifts with both scintillators. For the plastic scintillator, the highest gain from using EM tracking information occurred for a 0.5‐mm lateral shift at 20 mm from the source. The maximal gain (17.4%) for longitudinal errors was found at the smallest shifts (0.5 mm).
Conclusions
This work demonstrates that integrating EM tracking to in vivo scintillation dosimeters enables the detection of smaller shifts, by decreasing the dosimeter positioning uncertainty. It also serves to perform position‐dependent energy correction for the inorganic scintillator,providing better SNR and SBR, allowing detection of errors at greater distances from the source.
To report the outcomes of our high-dose-rate brachytherapy (HDR-BT) boost experience in localized prostate cancer treated with different combinations of radiation doses and fractionation.
Between ...1999 and 2011, 832 patients were treated with different regimens of external beam radiotherapy (EBRT) and HDR-BT. These regimens were converted into three biologically effective dose (BED) groups. The biochemical failure-free survival (BFFS), reported with the phoenix definition and prostate-specific antigen (PSA) >0.2ng/ml at 5-year, genitourinary (GU) and gastrointestinal (GI) toxicities were compared between the groups.
The 5-, 10-year BFFS for the entire cohort were 94.6% and 92.5%, for overall survival (OS) 96.1% and 80.3% and for prostate cancer-specific survival (PCSS) 99.5% and 97.8%. The percentage of patients with a 5-year PSA level <0.2ng/ml was 68.6%, 78.7% and 86.7% in the BED group of <250, 250–260 and >260Gy (p=0.005) while the 5-year BFFS rates according to phoenix definition were 97.3%, 94.3% and 94.9% for BED group <250, 250–260 and >260Gy (p=0.453). On multivariate logistic regression, patients in the BED>260Gy group were significantly more likely to remain free from 5-year PSA values ≥0.2ng/mL compared with those in the BED<250Gy group (OR: 0.350, p=0.011). Grade≥3 acute GU toxicity was reported in 2 patients (4.7%) for BED>260Gy while grade≥3 late GU toxicity was reported in 6 (1.7%) and 9 (4.9%) patients for 250–260Gy and >260Gy BED groups.
The increase in BED with the hypofractionated regimens correlates with an improvement in biochemical control with of urinary toxicity. This increase in urinary toxicity is small and clinically acceptable.
Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to ...investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission.
The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants.
Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0–61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio OR 0·79, 95·1% CI 0·61–1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57–0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001).
In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended.
The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.
•Boost to DIL with permanent seed prostate implant shows a trend toward improvement of biochemical control in intermediate risk cancer patient.•Our data support previous studies which demonstrated no ...increased toxicity with DIL boost technique in LDR brachytherapy.•This study presents the largest population with intermediate risk prostate cancer patient treated with DIL technique and low dose brachytherapy in the literature.
To compare bDFS and toxicity outcomes in a population of intermediate risk prostate cancer patients treated using I-125 LDR brachytherapy with or without DIL boost based on multiple core biopsy maps.
Between January 2005 and December 2013, all our intermediate risk prostate cancer patients treated with LDR I-125 brachytherapy were reviewed. All patients were given 144 Gy to the prostate. A pathologic DIL distribution (defined by sextant biopsy) was contoured prospectively prior to planning, to be covered by the 150% isodose line. Of the 165 patients treated, 55 received a DIL boost. Patients completed prospectively the IPSS questionnaire, a sexual and bowel function questionnaire. Gastro-intestinal toxicities were graded according to CTCAE v4.03. A patient was considered to have erectile dysfunction if he was unable to achieve erection to perform intercourse. BDFS was determined according to the Phoenix consensus definitions.
The median follow-up was 78 months. The estimated 7-year bDFS rate was 96% (95% CI, 74–99%) in the DIL group versus 89% (95% CI, 79–94%) in the control group (p = 0.188). There was no difference between groups in urinary, gastro-intestinal or sexual toxicities up to 5 years of follow-up. There was no difference in urinary obstruction with catheterization between DIL versus control groups (3,6 vs 2,8 %, p = 1.00). Only 1 patient in the DIL group had ≥grade 3 toxicity (TURP) and none in the control group.
Boost to DIL defined by sextant biopsy with permanent seed prostate implant shows a trend toward improvement of biochemical control in intermediate risk prostate cancer patient without increasing toxicity.
Ultrasound-based planning for high-dose-rate prostate brachytherapy is commonly used in the clinic, mainly because it offers fast real-time image-guided capability at a relatively low cost. The main ...difficulty with US planning is the catheter reconstruction due to artefacts (from multiple catheters) and echogenicity. Electromagnetic tracking (EMT) system offers a fast and accurate solution for automatic reconstruction of catheters using the EMT technology. In this study, the commissioning and performance evaluation of the new real-time prostate high-dose-rate brachytherapy investigational system from Philips Disease Management Solutions integrating EMT was performed before its clinical integration.
The Philips' clinical investigational system includes a treatment planning software (TPS) that was commissioned based on AAPM TG53 and TG56 recommendations for the use of TPS in brachytherapy. First, the CIRS - model 045A - QA phantom was used to evaluate the ultrasound (US) image quality and 3D image handling. Distances, volumes, and dimensions of the structures inside the phantom were measured and compared to the actual values. The calibration reproducibility and accuracy of the electromagnetic (EM) sensor used to track the US probe (rotation and translation) were performed using a specifically designed QA tool mounted on the probe and immersed in a salted water tank. This was performed for 3 different B&K 8848 US probes to evaluate the sensitivity of EM calibration to the probe geometric properties (manufacturing process). The new TPS performance was compared to that in OncentraBrachy (OcB) V4.5.5 (Elekta) using 30 clinical cases as part of a retrospective study. Following the system commissioning, clinical workflows were explored; tests were performed with the brachytherapy team on phantoms and finally implemented in the clinic.
US image quality evaluation showed a mean difference with actual dimensions (lengths, widths and distances) of 0.4 mm (±0.3 mm) and mean difference in volume sizes of 0.2 cc (±0.2 cc). Then, the calibration of the US-to-EM coordinate system was performed for 3 different probes. For each probe, 3 measurements were acquired for every position of the calibration tool and measurements were repeated 3 times for a total of 27 measurements per probe per plane. The error was slightly higher in transverse mode compared to sagittal mode with mean values of 0.6 ± 0.2 mm and 0.3 ± 0.1 mm respectively. 30 clinical cases were used to compare the new TPS performance to OcB (IPSA). Optimized plans obtained with both systems were all clinically acceptable, but the plans from the Philips system have slightly higher V150% values, V200% values and dose to organs at risk. In the case of organs at risk, plans could have been manually modified to reduce the dose. Philips' system had a larger number of active dwell positions and longer treatment times.
The first clinical version of Philips' system was proven to be stable, accurate and precise. The fully integrated EM tracking technology opens the way for automated catheter reconstruction and on-the-fly dynamical replanning.
To validate the Advanced Collapsed cone Engine (ACE) dose calculation engine of Oncentra Brachy (OcB) treatment planning system using an (192)Ir source.
Two levels of validation were performed, ...conformant to the model-based dose calculation algorithm commissioning guidelines of American Association of Physicists in Medicine TG-186 report. Level 1 uses all-water phantoms, and the validation is against TG-43 methodology. Level 2 uses real-patient cases, and the validation is against Monte Carlo (MC) simulations. For each case, the ACE and TG-43 calculations were performed in the OcB treatment planning system. ALGEBRA MC system was used to perform MC simulations.
In Level 1, the ray effect depends on both accuracy mode and the number of dwell positions. The volume fraction with dose error ≥2% quickly reduces from 23% (13%) for a single dwell to 3% (2%) for eight dwell positions in the standard (high) accuracy mode. In Level 2, the 10% and higher isodose lines were observed overlapping between ACE (both standard and high-resolution modes) and MC. Major clinical indices (V100, V150, V200, D90, D50, and D2cc) were investigated and validated by MC. For example, among the Level 2 cases, the maximum deviation in V100 of ACE from MC is 2.75% but up to ~10% for TG-43. Similarly, the maximum deviation in D90 is 0.14 Gy between ACE and MC but up to 0.24 Gy for TG-43.
ACE demonstrated good agreement with MC in most clinically relevant regions in the cases tested. Departure from MC is significant for specific situations but limited to low-dose (<10% isodose) regions.
To use quantities measurable during in vivo dosimetry to build unique channel identifiers, that enable detection of brachytherapy errors.
Treatment plan of 360 patients with prostate cancer who ...underwent high-dose-rate brachytherapy (range, 16-25 catheters; mean, 17) were used. A single point virtual dosimeter was placed at multiple positions within the treatment geometry, and the source-dosimeter distance and dwell time were determined for each dwell position in each catheter. These values were compared across all catheters, dwell position by dwell position, simulating a treatment delivery. A catheter was considered uniquely identified if, for a given dwell position, no other catheters had the same measured values. The minimum number of dwell positions needed to identify a specific catheter and the optimal dosimeter location uniquely were determined. The radial (r) and vertical (z) dimensions of the source-dosimeter distance were also examined for their utility in discriminating catheters.
Using a virtual dosimeter with no uncertainties, all catheters were identified in 359 of the 360 cases with 9 dwell position measurements. When only the dwell time were measured, all catheters were uniquely identified after 1 dwell position. With a 2-mm spatial accuracy (r,z), all catheters were identified in 94% of the plans. Simultaneous measurement of source-dosimeter distance and dwell time ensured full catheter identification in all plans ranging from 2 to 6 dwell positions. The number of dwell positions needed to uniquely identify all catheters was lower when the distance from the implant center was higher.
The most efficient fingerprinting approach involved combining source-dosimeter distance (i.e., source tracking) and dwell time. The further the dosimeter is placed from the center of the implant the better it can uniquely identify catheters.
The purpose of this study was to evaluate whether the dose to bladder neck (BN) is a predictor of acute and late urinary toxicity after high-dose-rate brachytherapy (HDRB) boost for prostate cancer.
...Between 2014 and 2016, patients with prostate cancer treated at our institution with external beam radiation therapy and 15 Gy single-fraction HDRB boost for intermediate- and high-risk disease according to D'Amico definition were reviewed. Intraoperative CT scan-based inverse planning and ultrasound-based inverse planning were performed in 173 and 136 patients, respectively. The following structures were prospectively contoured: prostate, urethra, rectum, bladder, and the BN defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. Dose to the BN was reported only, no constraint was applied. Acute and late urinary toxicity were assessed using the International Prostate Symptom Score (IPSS) and the Common Terminology Criteria for Adverse Events v.4.0. Clinical and dosimetry factors associated with urinary toxicity were analyzed using generalized linear models.
A total of 309 patients with median age of 71 years (range 50-89) were included. Median followup was 25 months (range 0-39 months). Using D'Amico definition, 71% of the patients had intermediate-risk disease, whereas 29% had high-risk disease. The mean pretreatment prostate-specific antigen value was 9.65 ng/mL. The mean pretreatment, after 6 weeks and over 6 months IPSSs were 8.34, 12.14, and 10.02, respectively. Urinary obstruction was reported in 14 cases (4.5%). Pretreatment IPSS (p = 0.003) and prostate volume (p = 0.024) were significantly associated with acute and late urinary toxicity. The dose for the most exposed 2 cc (D
) of BN was not correlated with acute (p = 0.798) or late urinary toxicity (p = 0.859). BN D
was not correlated with urinary obstruction (p = 0.272), but bladder V
was (p = 0.021).
High pretreatment IPSS, large prostate volume and bladder V
were the only predictors of acute and late urinary toxicity after HDRB boost in our study. Although BN D
was associated with acute and late urinary toxicity after low-dose-rate brachytherapy, no correlation was found after HDRB. A prospective study comparing dose to the BN in HDRB monotherapy would validate the impact of BN dose on acute and late urinary toxicity.
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