Histopathological Features of MRI-Invisible Regions of Prostate Cancer Lesions.

BACKGROUND: Previous studies have reported tumor volume underestimation with multiparametric (mp)MRI in prostate cancer diagnosis. PURPOSE: To investigate why some parts of lesions are not visible on mpMRI by comparing their histopathology features to those of visible regions. STUDY TYPE: Retrospective. POPULATION: Thirty-four patients with biopsy-proven prostate cancer scheduled for prostatectomy (median 68.7 years). FIELD STRENGTH/SEQUENCE: T2 -weighted, diffusion-weighted imaging, T2 mapping, and dynamic contrast-enhanced MRI on two 3T systems and one 1.5T system. ASSESSMENT: Two readers delineated suspicious lesions on mpMRI. A pathologist delineated the lesions on histopathology. A patient-customized mold enabled the registration of histopathology and MRI. On histopathology we identified mpMRI visible and invisible lesions. Subsequently, within the visible lesions we identified regions that were visible and regions that were invisible on mpMRI. For each lesion and region the following characteristics were determined: size, location, International Society of Urological Pathology (ISUP) grade, and Gleason subpatterns (density [dense/intermediate], tumor morphology [homogeneous/heterogeneous], cribriform growth [yes/no]). STATISTICAL TESTS: With generalized linear mixed-effect modeling we investigated which features explain why a lesion or a region was invisible on MRI. We compared imaging values (T2 , ADC, and Ktrans ) for these features with one-way analysis of variance (ANOVA). RESULTS: Small, anterior, and ISUP grade 1-2 lesions (n = 34) were missed more frequent than large, posterior, ISUP grade ≥ 3 lesions (n = 35). Invisible regions on mpMRI had lower tumor density, heterogeneous tumor morphology, and were located in the transition zone. Both T2 and ADC values were higher in "intermediate" compared with "dense" regions (P = 0.002 and < 0.001) and in regions with heterogeneous compared with homogeneous morphology (P < 0.001 and 0.03). Ktrans was not significantly different (P = 0.24 and 0.99). DATA CONCLUSION: Regions of prostate cancer lesions that are invisible on mpMRI have different histopathology features than visible regions. This may have implications for monitoring during active surveillance and focal treatment strategies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1235-1246.

In vivo dosimetry with an inorganic scintillation detector during multi-channel vaginal cylinder pulsed dose-rate brachytherapy: Dosimetry for pulsed dose-rate brachytherapy.

Background and purpose: In vivo dosimetry is not standard in brachytherapy and some errors go undetected. The aim of this study was to evaluate the accuracy of multi-channel vaginal cylinder pulsed dose-rate brachytherapy using in vivo dosimetry. Materials and methods: In vivo dosimetry data was collected during the years 2019-2022 for 22 patients (32 fractions) receiving multi-channel cylinder pulsed dose-rate brachytherapy. An inorganic scintillation detector was inserted in a cylinder channel. Each fraction was analysed as independent data sets. In vivo dosimetry-based source-tracking was used to determine the relative source-to-detector position. Measured dose was compared to planned and re-calculated source-tracking based doses. Assuming no change in organ and applicator geometry throughout treatment, the planned and source-tracking based dose distributions were compared in select volumes via γ-index analysis and dose-volume-histograms. Results: The mean ± SD planned vs. measured dose deviations in the first pulse were 0.8 ± 5.9 %. In 31/32 fractions the deviation was within the combined in vivo dosimetry uncertainty (averaging 9.7 %, k = 2) and planning dose calculation uncertainty (1.6 %, k = 2). The dwell-position offsets were < 2 mm for 88 % of channels, with the largest being 5.1 mm (4.0 mm uncertainty, k = 2). 3 %/2 mm γ pass-rates averaged 97.0 % (clinical target volume (CTV)), 100.0 % (rectum), 99.9 % (bladder). The mean ± SD deviation was -1. 1  ± 2.9 % for CTV D98, and -0.2 ± 0.9 % and -1.2 ± 2.5 %, for bladder and rectum D2cm3 respectively, indicating good agreement between intended and delivered dose. Conclusions: In vivo dosimetry verified accurate and stable dose delivery in multi-channel vaginal cylinder based pulsed dose-rate brachytherapy.

3D dose reconstruction based on in vivo dosimetry for determining the dosimetric impact of geometric variations in high-dose-rate prostate brachytherapy.

INTRODUCTION: In vivo dosimetry (IVD) can be used for source tracking (ST), i.e., estimating source positions, during brachytherapy. The aim of this study was to exploit IVD-based ST to perform 3D dose reconstruction for high-dose-rate prostate brachytherapy and to evaluate the robustness of the treatments against observed geometric variations. MATERIALS AND METHODS: Twenty-three fractions of high-dose-rate prostate brachytherapy were analysed. The treatment planning was based on MRI. Time-resolved IVD was performed using a fibre-coupled scintillator. ST was retrospectively performed using the IVD measurements. The ST identified 2D positional shifts of each treatment catheter and thereby inferred updated source positions. For each fraction, the dose was recalculated based on the source-tracked catheter positions and compared with the original plan dose using differences in dose volume histogram indices. RESULTS: Of 352 treatment catheters, 344 had shifts of less than 5 mm. Shifts between 5 and 10 mm were observed for 3 catheters, and shifts greater than 10 mm for 2 catheters. The ST failed for 3 catheters. The maximum relative difference in clinical target volume (prostate + 3 mm isotropic margin) D90% was 5%. In one fraction, the bladder D2cm3 dose increased by 18% (1.4 Gy) due to a single source position being inside the bladder rather than nearby as planned. The max increase in urethra dose was 1.5 Gy (15%). CONCLUSION: IVD-based 3D dose reconstruction for high-dose-rate prostate brachytherapy is feasible. The dosimetric impact of the observed catheter shifts was limited. Dose reconstruction can therefore aid in determining the dosimetric impact of geometric variations and errors in brachytherapy.

Intensity profile based measurement of prostate gold markers influence on 1.5 and 3T diffusion-weighted MR images.

BACKGROUND AND PURPOSE: In this study the influence of fiducial markers (FMs) on diffusion-weighted (DW) magnetic resonance images was investigated by measuring the intensity variations due to the artefact from the FM image reconstruction. MATERIAL AND METHODS: DW- and reference T1W images were acquired of an Agar-gel phantom containing two fixed cylindrical FMs, with a 1.5- and 3T MR scanner. The center of gravity (CoG) positions of the manually segmented FM artefacts (FMA) and the size of FMAs in x-, y- and z direction were measured in the two corresponding image sets, based on the intensity changes caused by the FM reconstruction. Also, a similarity measure, the Dice similarity coefficient (DSC), of the segmented FMAs in the two image sets was calculated. RESULTS: The mean shift of the CoG of the manually segmented FMAs in the phase encoding (PE) and the two orthogonal directions, respectively, was: 1.5T/3T; 0.3 ± 0.1/0.5 ± 0.3 cm and 1.5T/3T; 0.1 ± 0.1/0.1 ± 0.1 cm. The largest shift was observed in the 3T DW images for FMs aligned with the long axis orthogonal to the PE direction (0.9 ± 0.1 cm). The mean size of the FMA in the PE- and the two orthogonal directions, respectively, was: 1.5T/3T; 1.7 ± 0.5/1.3 ± 0.1 cm, and 1.5T/3T; 0.9 ± 0.3/1.0 ± 0.2 cm. The mean DSC value of the segmented artefact volumes in the DW- vs. T1W images were 21% and 5% for the 1.5- and 3.0T MR scanner, respectively. CONCLUSIONS: This study has shown that both the size and displacement of the FMAs increase in the PE direction on DW images. The larger shifts were observed for FMs positioned with the long axis orthogonal to the PE direction. Measurements obtained for different b-values gave consistent results.

Accuracy of an in vivo dosimetry-based source tracking method for afterloading brachytherapy - A phantom study.

PURPOSE: To report on the accuracy of an in vivo dosimetry (IVD)-based source tracking (ST) method for high dose rate (HDR) prostate brachytherapy (BT). METHODS: The ST was performed on a needle-by-needle basis. A least square fit of the expected to the measured dose rate was performed using the active dwell positions in the given needle. Two fitting parameters were used to determine the position of each needle relative to the IVD detector: radial (away or toward the detector) and longitudinal (along the axis of the treatment needle). The accuracy of the ST was assessed in a phantom where the geometries of five HDR prostate BT treatments previously treated at our clinic were reproduced. For each of the five treatment geometries, one irradiation was performed with the detector placed in the middle of the implant. Furthermore, four additional irradiations were performed for one of the geometries where the detector was retracted caudally in four steps of 10-15 mm and up to 12 mm inferior of the most inferior active dwell position, which represented the prostate apex. The time resolved dose measurements were retrieved at a rate of 20 Hz using a detector based on an Al2 O3 :C radioluminescence crystal, which was placed inside a standard BT needle. Individual calibrations of the detector were performed prior to each of the nine irradiations. RESULTS: Source tracking could be applied in all needles across all nine irradiations. For irradiations with the detector located in the middle region of the implant (a total of 89 needles), the mean ± standard deviation (SD, k = 1) accuracy was -0.01 mm ± 0.38 mm and 0.30 mm ± 0.38 mm in the radial and longitudinal directions, respectively. Caudal retraction of the detector did not lead to reduced accuracy as long as the detector was located superior to the most inferior active dwell positions in all needles. However, reduced accuracy was observed for detector positions inferior to the most inferior active dwell positions which corresponded to detector positions in and inferior to the prostate apex region. Detector positions in the prostate apex and 12 mm inferior to the prostate resulted in mean ± SD (k = 1) ST accuracy of 0.7 mm ± 1 mm and 2.8 mm ± 1.6 mm, respectively, in radial direction, and -1.7 mm ± 1 mm and -2.1 mm ± 1.1 mm, respectively, in longitudinal direction. The largest deviations for the configurations with those detector positions were 2.6 and 5.4 mm, respectively, in the radial direction and -3.5 and -3.8 mm, respectively, in the longitudinal direction. CONCLUSION: This phantom study demonstrates that ST based on IVD during prostate BT is adequately accurate for clinical use. The ST yields submillimeter accuracy on needle positions as long as the IVD detector is positioned superior to at least one active dwell position in all needles. Locations of the detector inferior to the prostate apex result in decreased ST accuracy while detector locations in the apex region and above are advantageous for clinical applications.

Characterization of combined intracavitary/interstitial brachytherapy including oblique needles in locally advanced cervix cancer.

PURPOSE: To characterize and report on dosimetric outcomes of image guided adaptive brachytherapy (IGABT) using intracavitary and interstitial (IC/IS) applicators including oblique needles (O-needles) in locally advanced cervical cancer (LACC). METHODS AND MATERIALS: Twenty LACC patients treated with radio-chemotherapy and offered IC/IS-IGABT including O-needles were analyzed. An in-house 3D-printed vaginal template was used to steer the needles parallel and obliquely in relation to the tandem, supplemented with free-hand needles if needed. Implant characteristics and loading patterns were analyzed. Using the equivalent dose in 2Gy-fractions (EQD2) concept, cumulative (EBRT+BT) V85, V75, V60Gy, targets/OARs doses and high dose volumes (150%, 200% and 300% (100% = 85 Gy EQD210)) were evaluated. RESULTS: Median(range) tumor width at diagnosis was 5.5(3.6; 7.5)cm; CTVHR volume was 45(23; 136)cm3 with maximum distance from tandem to CTVHR border of 3.4(2.5; 4.8)cm. T-stage distribution was IIB/III/IVA in 6(30%)/9(45%)/5(25%) of patients. At BT, 13(65%) patients had distal parametrial/pelvic wall infiltration. Median(range) number of needles per patient was 11(8-18). Average distribution of intrauterine, vaginal and interstitial dwell times were 31%, 25% and 44%, respectively. Median(range) dwell-time per dwell position was 11(2-127)% of average point-A based standard loading. Median V85Gy/V150%/V200%/V300% were 85(38; 171)/41(21; 93)/22(12; 41)/7(4; 19) cm3; CTVHR D90% was 93(83; 97)Gy EQD210; bladder/rectum/sigmoid/bowel D2cm3 were 78(64; 104)/65(52; 76)/59(53; 69)/61(47; 76)Gy EQD23. CONCLUSIONS: The use of O-needles in patients with large and/or unfavorable tumors resulted in excellent target coverage and OARs sparing. Intrauterine and vaginal loadings were reduced compared to standard loading and almost half of the loading was shifted into IS needles. This was achieved with gentle loading in the majority of dwell positions.

Needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer evaluated by repeated MRI.

PURPOSE: To quantify needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer and propose a threshold for needle migration. METHODS AND MATERIALS: Twenty-four high-risk prostate cancer patients treated with an HDR boost of 2 × 8.5 Gy were included. Patients received an MRI for planning (MRI1), before (MRI2), and after treatment (MRI3). Time from needle insertion to MRI3 was ∼3 hours. Needle migration was evaluated from coregistered images: MRI1-MRI2 and MRI1-MRI3. Dose volume histogram parameters from the treatment plan based on MRI1 were related to parameters based on needle positions in MRI2 or MRI3. Regression was used to model the average needle migration per implant and change in D90 clinical target volume, CTVprostate+3mm. The model fit was used for estimating the dosimetric impact in equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy. RESULTS: Needle migration was on average 2.2 ± 1.8 mm SD from MRI1-MRI2 and 5.0 ± 3.0 mm SD from MRI1-MRI3. D90 CTVprostate+3mm was robust toward average needle migration ≤3 mm, whereas for migration >3 mm D90 decreased by 4.5% per mm. A 3 mm of needle migration resulted in a decrease of 0.9, 1.7, 2.3, 4.8, and 7.6 equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy, respectively. CONCLUSIONS: Substantial needle migration in high-dose-rate brachytherapy occurs frequently in 1-3 hours following needle insertion. A 3-mm threshold of needle migration is proposed, but 2 mm may be considered for dose levels ≥15 Gy.

Time-resolved in vivo dosimetry for source tracking in brachytherapy.

PURPOSE: The purpose of this article is to demonstrate that brachytherapy source tracking can be realized with in vivo dosimetry. This concept could enable real-time treatment monitoring. METHODS: In vivo dosimetry was incorporated in the clinical routine during high-dose-rate prostate brachytherapy at Aarhus University Hospital. The dosimetry was performed with a radioluminescent crystal positioned in a dedicated brachytherapy needle in the prostate. The dose rate was recorded every 50-100 ms during treatment and analyzed retrospectively. The measured total delivered dose and dose rates for each dwell position with dwell times >0.7 s were compared with expected values. Furthermore, the distance between the source and dosimeter, which was derived from the measured dose rates, was compared with expected values. The measured dose rate pattern in each needle was used to determine the most likely position of the needle relative to the dosimeter. RESULTS: In total, 305 needles and 3239 dwell positions were analyzed based on 20 treatments. The measured total doses differed from the expected values by -4.7 ± 8.4% (1SD) with range (-17% to 12%). It was possible to determine needle shifts for 304 out of 305 needles. The mean radial needle shift between imaging and treatment was 0.2 ± 1.1 mm (1SD), and the mean longitudinal shift was 0.3 ± 2.0 mm (1SD). CONCLUSION: Time-resolved in vivo dosimetry can be used to provide geometric information about the treatment progression of afterloading brachytherapy. This information may provide a clear indication of errors and uncertainties during a treatment and, therefore, enables real-time treatment monitoring.

Dosimetric impact of contouring and needle reconstruction uncertainties in US-, CT- and MRI-based high-dose-rate prostate brachytherapy treatment planning.

BACKGROUND AND PURPOSE: The purpose was to evaluate the dosimetric impact of target contouring and needle reconstruction uncertainties in an US-, CT- and MRI-based HDR prostate BT treatment planning. MATERIAL AND METHODS: US, CT, and MR images were acquired post-needle insertion in 22 HDR-BT procedures for 11 consecutive patients. Dose plans were simulated for an US-, CT- and MRI-based HDR-BT treatment planning procedure. Planning uncertainties in US- and CT-based plans were evaluated using MRI-based planning as reference. Target (CTVProstate) was re-contoured on MRI. Dose results were expressed in total equivalent dose given in 2Gy fractionation dose for EBRT (46Gy) plus 2 HDR-BT fractions. RESULTS: Uncertainties in US- and CT-based planning caused the planned CTVProstate-D90% to decrease with a mean of 2.9±5.0Gy (p=0.03) and 2.9±2.9Gy (p=0.001), respectively. The intra-observer contouring variation on MRI resulted in a mean variation of 1.6±1.5Gy in CTVProstate-D90%. Reconstruction uncertainties on US resulted in a dose variation of±3Gy to the urethra, whereas data for CT were not available for this. CONCLUSIONS: Uncertainties related to contouring and reconstruction in US- and CT-based HDR-BT treatment plans resulted in a systematic overestimation of the prescribed target dose. Inter-modality uncertainties (US and CT versus MR) were larger than MR intra-observer uncertainties.

Learning curve of MRI-based planning for high-dose-rate brachytherapy for prostate cancer.

PURPOSE: To evaluate introduction of MRI-based high-dose-rate brachytherapy (HDRBT), including procedure times, dose-volume parameters, and perioperative morbidity. METHODS AND MATERIALS: Study included 42 high-risk prostate cancer patients enrolled in a clinical protocol, offering external beam radiotherapy + two HDRBT 8.5 Gy boosts. Time was recorded for initiation of anesthesia (A), fixation of needle implant (B), end of MR imaging (C), plan approval (D), and end of HDRBT delivery (E). We defined time A-E as total procedure time, A-B as operating room time, B-C as MRI procedure time, C-D as treatment planning time, and D to E as treatment delivery time. Dose-volume parameters were retrieved from the dose planning system. Results from the first 21 patients were compared with the last 21 patients. RESULTS: Total procedure time, operating room time, MRI procedure time, and treatment planning time decreased significantly from average 7.6 to 5.3 hours (p < 0.01), 3.6 to 2.4 hours (p < 0.01), 1.6 to 0.8 hours (p < 0.01), and 2.0 to 1.3 hours (p < 0.01), respectively. HDRBT delivery time remained unchanged at 0.5 hours. Clinical target volume prostate+3mmD90 fulfilled planning aim in 92% of procedures and increased significantly from average 8.3 to 9.0 Gy (p < 0.01). Urethral D0.1 cm(3) and rectal D2 cm(3) fulfilled planning aim in 78% and 95% of procedures, respectively, and did not change significantly. Hematuria occurred in (95%), hematoma (80%), moderate to strong pain (35%), and urinary retention (5%) of procedures. CONCLUSIONS: After introduction of MRI-based HDRBT, procedure times were significantly reduced. D90 Clinical target volumeprostate+3mm fulfilled constraints in most patients and improved over time, but not at expense of an increased urethral or rectal dose.

The influence of a rectal ultrasound probe on the separation between prostate and rectum in high-dose-rate brachytherapy.

PURPOSE: The aim of this study was to compare the distance between prostate and rectum as well as rectal dose-volume histogram (DVH) parameters for high-dose-rate (HDR) prostate brachytherapy (BT) with and without a transrectal ultrasound (US) probe in place during delivery. METHODS AND MATERIALS: The study included 20 patients with high-risk prostate cancer treated consecutively with combined external beam radiotherapy (EBRT) and MRI-based HDR-BT. The MRI-based HDR-BT dose plan and prostate gland contour were transferred to the US images after rigid MRI/US coregistration, followed by delineation of the rectum on US images acquired with a transrectal US probe. The prostate-rectum separation was estimated at the apex, reference, and base plane on the US (with rectal probe) and MR images (without rectal probe). Rectal DVH parameters for EBRT + HDR-BT given in equivalent 2 Gy fractionation doses were estimated and compared for US-based and MRI-based HDR-BT dose planning. RESULTS: The median (and range) prostate-rectum separation increased on MR images (without rectal probe) as compared with on US images (with rectal probe) by 10 mm (-5, 18) at the base, 1 mm (-2, 3) at the reference and decreased at the apex by 2 mm (-5, 11). The rectal D5.0cm3, D2.0cm3, and D0.1cm3 decreased by a median of 4 Gy (-1, 10), 4 Gy (-2, 13), and 7 Gy (-4, 26), respectively. CONCLUSIONS: MRI-based HDR-BT without a rectal US probe in place as compared with US-based BT with the probe in place demonstrated a significant increase in the prostate-rectum separation, with a potential of reducing rectal dose.

Re-distribution of brachytherapy dose using a differential dose prescription adapted to risk of local failure in low-risk prostate cancer patients.

BACKGROUND AND PURPOSE: We investigated the application of a differential target- and dose prescription concept for low-dose-rate prostate brachytherapy (LDR-BT), involving a re-distribution of dose according to risk of local failure and treatment-related morbidity. MATERIAL AND METHODS: Our study included 15 patients. Multi-parametric MRI was acquired prior to LDR-BT for gross tumor volume (GTV) delineation. Trans-rectal ultrasound (US) images were acquired during LDR-BT for prostate gland- (CTV(Prostate)) and organs at risk delineation. The GTV contour was transferred to US images after US/MRI registration. An intermediate-risk target volume (CTV(Prostate)) and a high-risk target volume (CTV(HR)=GTV+5 mm margin) were defined. Two virtual dose plans were made: Plan(risk-adapt) consisted of a de-escalated dose of minimum 125 Gy to the CTV(Prostate) and an escalated dose to 145-250 Gy to the CTV(HR); Plan(ref) included the standard clinical dose of minimum 145 Gy to the CTV(Prostate). Dose-volume-histogram (DVH) parameters were expressed in equivalent 2 Gy fractionation doses. RESULTS: The median D(90%) to the GTV and CTV(HR) significantly increased by 44 Gy and 17 Gy, respectively when comparing Plan(risk-adapt) to Plan(ref). The median D(10%) and D(30%) to the urethra significantly decreased by 9 Gy and 11 Gy, respectively and for bladder neck by 18 Gy and 15 Gy, respectively. The median rectal D(2.0cm(3)) had a significant decrease of 4 Gy, while the median rectal D(0.1cm(3)) showed an increase of 1 Gy. CONCLUSIONS: Our risk adaptive target- and dose prescription concept of prescribing a lower dose to the whole gland and an escalated dose to the GTV using LDR-BT seed planning was technically feasible and resulted in a significant dose-reduction to urethra and bladder neck.