Evaluating outcomes and toxicities for a newly implemented MRI-based brachytherapy program for cervical cancer.

OBJECTIVE: We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. METHODS: A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85-95 Gyα/ß=10 Gy in 2 implants each delivering 2 fractions. RESULTS: Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9-39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3-118.8) and HR-CTV D90 of 89 Gy (IQR 86.1-90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9-88.0), 65.9 Gy (IQR 59.6-71.2), 65.1 Gy (IQR 57.7-69.6), and 55 Gy (IQR 48.9-60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. CONCLUSION: MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease.

Variability in prostate cancer detection among radiologists and urologists using MRI fusion biopsy.

Objectives: The aim of this study is to evaluate the impact of radiologist and urologist variability on detection of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) with magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion prostate biopsies. Patients and methods: The Prospective Loyola University MRI (PLUM) Prostate Biopsy Cohort (January 2015 to December 2020) was used to identify men receiving their first MRI and MRI/TRUS fusion biopsy for suspected PCa. Clinical, MRI and biopsy data were stratified by radiologist and urologist to evaluate variation in Prostate Imaging-Reporting and Data System (PI-RADS) grading, lesion number and cancer detection. Multivariable logistic regression (MVR) models and area under the curve (AUC) comparisons assessed the relative impact of individual radiologists and urologists. Results: A total of 865 patients (469 biopsy-naïve) were included across 5 urologists and 10 radiologists. Radiologists varied with grading 15.4% to 44.8% of patients with MRI lesions as PI-RADS 3. PCa detection varied significantly by radiologist, from 34.5% to 66.7% (p = 0.003) for PCa and 17.2% to 50% (p = 0.001) for csPCa. Urologists' PCa diagnosis rates varied between 29.2% and 55.8% (p = 0.013) and between 24.6% and 39.8% (p = 0.36) for csPCa. After adjustment for case-mix on MVR, a fourfold to fivefold difference in PCa detection was observed between the highest-performing and lowest-performing radiologist (OR 0.22, 95%CI 0.10-0.47, p < 0.001). MVR demonstrated improved AUC for any PCa and csPCa detection when controlling for radiologist variation (p = 0.017 and p = 0.038), but controlling for urologist was not significant (p = 0.22 and p = 0.086). Any PCa detection (OR 1.64, 95%CI 1.06-2.55, p = 0.03) and csPCa detection (OR 1.57, 95%CI 1.00-2.48, p = 0.05) improved over time (2018-2020 vs. 2015-2017). Conclusions: Variability among radiologists in PI-RADS grading is a key area for quality improvement significantly impacting the detection of PCa and csPCa. Variability for performance of MRI-TRUS fusion prostate biopsies exists by urologist but with less impact on overall detection of csPCa.

MRI versus non-MRI diagnostic pathways before radical prostatectomy: Impact on nerve-sparing, positive surgical margins, and biochemical recurrence.

PURPOSE: Magnetic resonance imaging (MRI) prior to biopsy has improved detection of clinically significant prostate cancer (CaP), but its impact on surgical outcomes is less well established. We compared MRI vs. non-MRI diagnostic pathways among patients receiving radical prostatectomy (RP) for impact on surgical outcomes. MATERIALS AND METHODS: Men diagnosed with CaP and receiving RP at Loyola University Medical Center (2014-2021) were categorized into MRI or non-MRI diagnostic pathways based on receipt of MRI before prostate biopsy. Primary outcomes of interest included positive surgical margin (PSM) rates, the performance of bilateral nerve-sparing, and biochemical recurrence (BCR). Multivariable logistic regression models, Kaplan-Meier curves, and Cox proportional hazards regression were employed. RESULTS: Of 609 patients, 281 (46.1%) were in the MRI and 328 (53.9%) in the non-MRI groups. MRI patients had similar PSA, biopsy grade group (GG) distribution, RP GG, pT stage, and RP CaP volume compared to non-MRI patients. PSM rates were not statistically different for the MRI vs. non-MRI groups (22.8% vs. 26.8%, P = 0.25). Bilateral nerve-sparing rates were higher for the MRI vs. non-MRI groups (OR 1.95 (95%CI 1.32-2.88), P = 0.001). The MRI group demonstrated improved BCR (HR 0.64 (95%CI 0.41-0.99), P = 0.04) after adjustment for age, PSA, RP GG, pT, pN, and PSM status. On meta-analysis, a 5.2% PSM reduction was observed but high heterogeneity for use of nerve-sparing. CONCLUSIONS: An MRI-based diagnostic approach selected patients for RP with a small reduction in PSM rates, greater utilization of bilateral nerve-sparing, and improved cancer control by BCR compared to a non-MRI approach even after adjustment for known prognostic factors.

MRI vs Transrectal Ultrasound to Estimate Prostate Volume and PSAD: Impact on Prostate Cancer Detection.

OBJECTIVES: To compare multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) to estimate prostate volume and prostate specific antigen density (PSAD) as well as subsequent impact on prostate cancer (PCa) detection. METHODS: Patients referred for mpMRI prior to mpMRI-TRUS fusion-guided prostate biopsy between 2015 and 2020 were identified. Volume and calculated PSAD by mpMRI and TRUS were compared. Associations with presence of any PCa and clinically significant PCa (csPCa; Gleason ≥3 + 4) were evaluated using linear regression (interaction by volume quartile), logistic regression, and receiver operating characteristics. RESULTS: Among 640 men, TRUS underestimated prostate volume relative to mpMRI (median 49.2cc vs. 54.1cc) with 8% lower volume per cc up to 77.5cc (First-third quartile) and 39% lower volume per additional cc above 77.5cc (fourth quartile). For men undergoing radical prostatectomy, mpMRI had a higher correlation coefficient relative to TRUS (0.913 vs 0.878) when compared to surgical pathology. mpMRI PSAD had slightly higher odds vs TRUS PSAD for detecting any PCa (OR 2.94 and OR 2.78, both P <.001) or csPCa (OR 4.20 and OR 4.02, both P <.001). AUC improvements were of borderline significance for mpMRI vs. TRUS PSAD for any PCa (0.689 vs 0.675, P = .05) and not significant for csPCa (0.732 vs 0.722, P = .20). PSAD was not associated with PCa detection for prostates ≥77.5cc. CONCLUSION: TRUS underestimates prostate volume relative to mpMRI. PSAD based on mpMRI may be better associated with detection of PCa compared to TRUS, but utility of PSAD may be limited for larger prostates.

A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

A concurrent, deep learning-based computer-aided detection system for prostate multiparametric MRI: a performance study involving experienced and less-experienced radiologists.

OBJECTIVES: To evaluate the effect of a deep learning-based computer-aided diagnosis (DL-CAD) system on experienced and less-experienced radiologists in reading prostate mpMRI. METHODS: In this retrospective, multi-reader multi-case study, a consecutive set of 184 patients examined between 01/2018 and 08/2019 were enrolled. Ground truth was combined targeted and 12-core systematic transrectal ultrasound-guided biopsy. Four radiologists, two experienced and two less-experienced, evaluated each case twice, once without (DL-CAD-) and once assisted by DL-CAD (DL-CAD+). ROC analysis, sensitivities, specificities, PPV and NPV were calculated to compare the diagnostic accuracy for the diagnosis of prostate cancer (PCa) between the two groups (DL-CAD- vs. DL-CAD+). Spearman's correlation coefficients were evaluated to assess the relationship between PI-RADS category and Gleason score (GS). Also, the median reading times were compared for the two reading groups. RESULTS: In total, 172 patients were included in the final analysis. With DL-CAD assistance, the overall AUC of the less-experienced radiologists increased significantly from 0.66 to 0.80 (p = 0.001; cutoff ISUP GG ≥ 1) and from 0.68 to 0.80 (p = 0.002; cutoff ISUP GG ≥ 2). Experienced radiologists showed an AUC increase from 0.81 to 0.86 (p = 0.146; cutoff ISUP GG ≥ 1) and from 0.81 to 0.84 (p = 0.433; cutoff ISUP GG ≥ 2). Furthermore, the correlation between PI-RADS category and GS improved significantly in the DL-CAD + group (0.45 vs. 0.57; p = 0.03), while the median reading time was reduced from 157 to 150 s (p = 0.023). CONCLUSIONS: DL-CAD assistance increased the mean detection performance, with the most significant benefit for the less-experienced radiologist; with the help of DL-CAD less-experienced radiologists reached performances comparable to that of experienced radiologists. KEY POINTS: • DL-CAD used as a concurrent reading aid helps radiologists to distinguish between benign and cancerous lesions in prostate MRI. • With the help of DL-CAD, less-experienced radiologists may achieve detection performances comparable to that of experienced radiologists. • DL-CAD assistance increases the correlation between PI-RADS category and cancer grade.

Risk of prostate cancer for men with prior negative biopsies undergoing magnetic resonance imaging compared with biopsy-naive men: A prospective evaluation of the PLUM cohort.

BACKGROUND: Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models. RESULTS: Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%). CONCLUSIONS: Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed. LAY SUMMARY: Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies.

Systematic versus Targeted Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy among Men with Visible Lesions.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-guided biopsy may improve prostate cancer (PCa) detection and reduce grade misclassification. We compared PCa detection rates on systematic, magnetic resonance imaging-targeted, and combined biopsy with evaluation of important subgroups. MATERIALS AND METHODS: Men with clinical suspicion of harboring PCa from 2 institutions with visible Prostate Imaging-Reporting and Data System (PI-RADSTMv2) lesions receiving mpMRI-US fusion-guided prostate biopsy were included (2015-2020). Detection of PCa was categorized by grade group (GG). Clinically-significant PCa (csPCa) was defined as ≥GG2. Patients were stratified by biopsy setting and PI-RADS. RESULTS: Of 1,236 patients (647 biopsy-naïve) included, 626 (50.6%) harbored PCa and 412 (33.3%) had csPCa on combined biopsy. Detection of csPCa was 27.9% vs 23.3% (+4.6%) and GG1 PCa was 11.3% vs 17.8% (-6.5%) for targeted vs systematic cores. Benefit in csPCa detection was higher in the prior negative than biopsy-naïve setting (+7.8% [p <0.0001] vs +1.7% [p=0.3]) while reduction in GG1 PCa detection remained similar (-5.6% [p=0.0002] vs -7.3% [p=0.0001]). Targeted biopsy showed increased csPCa detection for PI-RADS 5, decrease in GG1 for PI-RADS 3, and both for PI-RADS 4 relative to systematic biopsy. Combined biopsy detected more csPCa (+10.0%) and slightly fewer GG1 PCa (-0.5%) compared to systematic alone. Upgrading to ≥GG2 by targeted biopsy occurred in 9.8% with no cancer and 23.6% with GG1 on systematic biopsy. CONCLUSIONS: Combined biopsy doubled the benefit of targeted biopsy alone in detection of csPCa without increasing GG1 PCa diagnoses relative to systematic biopsy. Utility of targeted biopsy was higher in the prior negative biopsy cohort, but advantages of combined biopsy were maintained regardless of biopsy history.

Computed tomography versus magnetic resonance imaging in high-dose-rate prostate brachytherapy planning: The impact on patient-reported health-related quality of life.

PURPOSE: High-dose-rate (HDR) prostate brachytherapy uses volumetric imaging for treatment planning. Our institution transitioned from computed tomography (CT)-based planning to MRI-based planning with the hypothesis that improved visualization could reduce treatment-related toxicity. This study aimed to compare the patient-reported health-related quality of life (hrQOL) and physician-graded toxicity outcomes of CT-based and MRI-based HDR prostate brachytherapy. METHODS: From 2016 to 2019, 122 patients with low- or intermediate-risk prostate cancer were treated with HDR brachytherapy as monotherapy. Patients underwent CT only or CT and MRI imaging for treatment planning and were grouped per treatment planning imaging modality. Patient-reported hrQOL in the genitourinary (GU), gastrointestinal (GI), and sexual domains was assessed using International Prostate Symptom Score and Expanded Prostate Cancer Index Composite Short Form-26 questionnaires. Baseline characteristics, changes in hrQOL scores, and physician-graded toxicities were compared between groups. RESULTS: The median follow-up was 18 months. Patient-reported GU, GI, and sexual scores worsened after treatment but returned toward baseline over time. The CT cohort had a lower baseline mean International Prostate Symptom Score (5.8 vs. 7.8, p = 0.03). The other patient-reported GU and GI scores did not differ between groups. Overall, sexual scores were similar between the CT and MRI cohorts (p = 0.08) but favored the MRI cohort at later follow-up with a smaller decrease in Expanded Prostate Cancer Index Composite Short Form-26 sexual score from baseline at 18 months (4.9 vs. 19.8, p = 0.05). Maximum physician-graded GU, GI, and sexual toxicity rates of grade ≥2 were 68%, 3%, and 53%, respectively, with no difference between the cohorts (p = 0.31). CONCLUSION: Our study shows that CT- and MRI-based HDR brachytherapy results in similar rates of GU and GI toxicity. MRI-based planning may result in improved erectile function recovery compared with CT-based planning.

Noninvasive Monitoring of Allogeneic Stem Cell Delivery with Dual-Modality Imaging-Visible Microcapsules in a Rabbit Model of Peripheral Arterial Disease.

Stem cell therapies, although promising for treating peripheral arterial disease (PAD), often suffer from low engraftment rates and the inability to confirm the delivery success and track cell distribution and engraftment. Stem cell microencapsulation combined with imaging contrast agents may provide a means to simultaneously enhance cell survival and enable cell tracking with noninvasive imaging. Here, we have evaluated a novel MRI- and X-ray-visible microcapsule formulation for allogeneic mesenchymal stem cell (MSC) delivery and tracking in a large animal model. Bone marrow-derived MSCs from male New Zealand White rabbits were encapsulated using a modified cell encapsulation method to incorporate a dual-modality imaging contrast agent, perfluorooctyl bromide (PFOB). PFOB microcapsules (PFOBCaps) were then transplanted into the medial thigh of normal or PAD female rabbits. In vitro MSC viability remained high (79 ± 5% at 4 weeks of postencapsulation), and as few as two and ten PFOBCaps could be detected in phantoms using clinical C-arm CT and 19F MRI, respectively. Successful injections of PFOBCaps in the medial thigh of normal (n = 15) and PAD (n = 16) rabbits were demonstrated on C-arm CT at 1-14 days of postinjection. Using 19F MRI, transplanted PFOBCaps were clearly identified as "hot spots" and showed one-to-one correspondence to the radiopacities on C-arm CT. Concordance of 19F MRI and C-arm CT locations of PFOBCaps with postmortem locations was high (95%). Immunohistological analysis revealed high MSC survival in PFOBCaps (>56%) two weeks after transplantation while naked MSCs were no longer viable beyond three days after delivery. These findings demonstrate that PFOBCaps could maintain cell viability even in the ischemic tissue and provide a means to monitor cell delivery and track engraftment using clinical noninvasive imaging systems.

Quantitative CT and 19F-MRI tracking of perfluorinated encapsulated mesenchymal stem cells to assess graft immunorejection.

OBJECTIVES: Peripheral artery disease (PAD) affects 12-14% of the world population, and many are not eligible for conventional treatment. For these patients, microencapsulated stem cells (SCs) offer a novel means to transplant mismatched therapeutic SCs to prevent graft immunorejection. Using c-arm CT and 19F-MRI for serial evaluation of dual X-ray/MR-visible SC microcapsules (XMRCaps) in a non-immunosuppressed rabbit PAD model, we explore quantitative evaluation of capsule integrity as a surrogate of transplanted cell fate. MATERIALS AND METHODS: XMRCaps were produced by impregnating 12% perfluorooctylbromine (PFOB) with rabbit or human SCs (AlloSC and XenoSC, respectively). Volume and 19F concentration measurements of XMRCaps were assessed both in phantoms and in vivo, at days 1, 8 and 15 after intramuscular administration in rabbits (n = 10), by 3D segmenting the injection sites and referencing to standards with known concentrations. RESULTS: XMRCap volumes and concentrations showed good agreement between CT and MRI both in vitro and in vivo in XenoSC rabbits. Injected capsules showed small variations over time and were similar between AlloSC and XenoSC rabbits. Histological staining revealed high cell viability and intact capsules 2 weeks after administration. CONCLUSIONS: Quantitative and non-invasive tracking XMRCaps using CT and 19F-MRI may be useful to assess graft immunorejection after SC transplantation.

Can MRI-only replace MRI-CT planning with a titanium tandem and ovoid applicator?

PURPOSE/OBJECTIVE(S): To evaluate dosimetric differences between MRI-only and MRI-CT planning with a titanium tandem and ovoid applicator to determine if all imaging and planning goals can be achieved with MRI only. MATERIALS/METHODS: We evaluated 10 patients who underwent MRI-CT-based cervical brachytherapy with a titanium tandem and ovoid applicator. High-risk clinical target volume and organs at risk were contoured on the 3D T2 MRI, which were transferred to the co-registered CT, where the applicator was identified. Retrospectively, three planners independently delineated the applicator on the axial 3D T2 MRI while blinded to the CT. Identical dwell position times in the delivered plan were loaded. Dose-volume histogram parameters were compared to the previously delivered MRI-CT plan. RESULTS: There were no significant differences in dose to D90 or D98 of the high-risk clinical target volume with MRI vs. MRI-CT planning. MRI vs. MRI-CT planning resulted in mean D0.1cc bladder of 8.8 ± 3.4 Gy vs. 8.5 ± 3.2 Gy (p = 0.29) and D2cc bladder of 6.2 ± 1.4 Gy vs. 6.0 ± 1.4 Gy (p = 0.33), respectively. Mean D0.1cc rectum was 5.7 ± 1.2 Gy vs. 5.3 ± 1.2 Gy (p = 0.03) and D2cc rectum 4.0 ± 0.8 Gy vs. 4.2 ± 1.0 Gy (p = 0.18), respectively. Mean D0.1cc sigmoid was 5.2 ± 1.3 Gy vs. 5.4 ± 1.6 Gy (p = 0.23) and D2cc sigmoid 3.9 ± 1.0 Gy vs. 4.0 ± 1.1 Gy (p = 0.18), respectively. CONCLUSION: There were no clinically significant dosimetric differences between the MRI and MRI-CT plans. This study demonstrates that cervical brachytherapy with a titanium applicator can be planned with MRI alone, which is now our clinical standard.

Providing MR Imaging for Cervical Cancer Brachytherapy: Lessons for Radiologists.

Brachytherapy (BT), the use of a locally placed or implanted radioactive source for treatment of an adjacent tumor, is an important component in the treatment of patients with both early- and advanced-stage cervical cancer and is increasingly part of the standard treatment protocol. When it is feasible, many radiation oncologists choose to include a magnetic resonance (MR) imaging examination for planning BT treatment (ie, an MR imaging examination after placement of the applicator but before radiation dosing). MR imaging provides excellent soft-tissue contrast and allows radiation oncologists to individualize the radiation dose to the target volume and minimize the dose to adjacent organs that are at risk for radiation damage. However, traditionally, the radiology department has not performed imaging studies for planning, and the requirements are different compared with those of standard diagnostic imaging. In addition, many applicators are available for use in BT treatment of cervical cancer, and each must considered separately to determine MR safety and to define the best imaging parameters. Starting and supporting a robust gynecologic BT program includes implementing imaging protocols that are helpful to both radiation oncologists and diagnostic radiologists. By becoming more familiar with this treatment modality and the logistics of imaging patients undergoing BT, radiologists can provide imaging support for colleagues in the radiation oncology department and better care for patients. ©RSNA, 2018.

Simultaneous tumor and surrogate motion tracking with dynamic MRI for radiation therapy planning.

Respiration-induced tumor motion is a major obstacle for achieving high-precision radiotherapy of cancers in the thoracic and abdominal regions. Surrogate-based estimation and tracking methods are commonly used in radiotherapy, but with limited understanding of quantified correlation to tumor motion. In this study, we propose a method to simultaneously track the lung tumor and external surrogates to evaluate their spatial correlation in a quantitative way using dynamic MRI, which allows real-time acquisition without ionizing radiation exposure. To capture the lung and whole tumor, four MRI-compatible fiducials are placed on the patient's chest and upper abdomen. Two different types of acquisitions are performed in the sagittal orientation including multi-slice 2D cine MRIs to reconstruct 4D-MRI and two-slice 2D cine MRIs to simultaneously track the tumor and fiducials. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and groupwise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in the 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model of the fiducials to their segmentations on the 2D cine MRIs. We tested our method on ten lung cancer patients. Using a correlation analysis, the 3D tumor trajectory demonstrates a noticeable phase mismatch and significant cycle-to-cycle motion variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from the fiducials at different locations.

Reduction of MRI signal distortion from titanium intracavitary brachytherapy applicator by optimizing pulse sequence parameters.

PURPOSE: To demonstrate that optimized pulse sequence parameters for a T2-weighted (T2w) fast spin echo acquisition reduced artifacts from a titanium brachytherapy applicator compared to conventional sequence parameters. METHODS AND MATERIALS: Following Institutional Review Board approval and informed consent, seven patients were successfully imaged with both standard sagittal T2w fast spin echo parameters (voxel size of 0.98 × 0.78 × 4.0 mm3; readout bandwidth of 200 Hz/px; repetition time of 2800 ms; echo time of 91 ms; echo train length of 15; 36 slices; and imaging time of 3:16 min) and an additional optimized T2w sequence (voxel size of 0.98 × 0.98 × 4.0 mm3; readout bandwidth of 500 Hz/px; repetition time of 3610 ms; echo time of 91 ms; echo train length of 25; 18-36 slices; and imaging time of 1:15-2:30 min), which had demonstrated artifact reduction in prior phantom work. Visualized intracavitary tandem was hand-segmented by two of the authors. Three body imaging radiologists assessed image quality and intraobserver agreement scores were analyzed. RESULTS: The average segmented volume of the intracavitary applicator significantly (p < 0.05) decreased with the experimental pulse sequence parameters as compared to the standard pulse sequence. Comparison of experimental and standard T2w sequence qualitative scores for each reviewer showed no significant differences between the two techniques. CONCLUSIONS: This study demonstrated that pulse sequence parameter optimization can significantly reduce distortion artifact from titanium applicators while maintaining image quality and reasonable imaging times.

Early outcomes and impact of a hybrid IC/IS applicator for a new MRI-based cervical brachytherapy program.

PURPOSE: The purpose of this study was to report early outcomes and assess the learning curve in a new MRI-based cervical brachytherapy program. METHODS: We accrued 33 patients prospectively, and only patients with ≥3 months' followup (n = 27) were assessed for disease control and toxicity. Eras were defined as first half and second half for the intracavitary (IC)-only era (n = 13 each), and the intracavitary/interstitial (IC/IS) era was separated by difference in applicator availability (n = 7). Dose to 90% of the high-risk clinical target volume (D90 HR-CTV) and minimum dose to the maximally irradiated 2 cubic centimeters (D2cc) to organs at risk were used to assess dosimetry. Statistics were performed with t tests and Kaplan-Meier method. RESULTS: Median followup was 14.7 months. Median treatment duration was 50.5 vs. 57 days for patients treated with external beam radiation therapy at our institution vs. an outside institution (p = 0.03). One-year local control, noncervical pelvic control, distant metastasis-free rate, and overall survival were 84.0%, 96.0%, 78.5%, and 91.3%, respectively. When comparing the first half and second half eras of IC only, there were no differences in median D90 HR-CTV or D2cc of the bladder, rectum, or sigmoid. Comparing the entire IC era to the IC/IS era, median D90 HR-CTV trended higher from 88.0 Gy to 92.9 Gy (p = 0.11). D2cc rectum decreased from 69.3 Gy to 62.6 Gy (p = 0.01), and D2cc bladder trended lower from 87.5 Gy to 83.6 Gy (p = 0.09). CONCLUSIONS: There was no significant difference between the first half and second half eras with IC-only MRI-based brachytherapy. Incorporation of an IC/IS applicator generated the greatest dosimetric improvement. Early results of the MRI-based brachytherapy program are favorable.

Evaluation of lung tumor motion management in radiation therapy with dynamic MRI.

Surrogate-based tumor motion estimation and tracing methods are commonly used in radiotherapy despite the lack of continuous real time 3D tumor and surrogate data. In this study, we propose a method to simultaneously track the tumor and external surrogates with dynamic MRI, which allows us to evaluate their reproducible correlation. Four MRI-compatible fiducials are placed on the patient's chest and upper abdomen, and multi-slice 2D cine MRIs are acquired to capture the lung and whole tumor, followed by two-slice 2D cine MRIs to simultaneously track the tumor and fiducials, all in sagittal orientation. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and group-wise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model to the fiducial segmentations on the 2D cine MRIs. We tested our method on five lung cancer patients. Internal target volume from 4D-CT showed average sensitivity of 86.5% compared to the actual tumor motion for 5 min. 3D tumor motion correlated with the external surrogate signal, but showed a noticeable phase mismatch. The 3D tumor trajectory showed significant cycle-to-cycle variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from fiducials at different locations.

How one institution overcame the challenges to start an MRI-based brachytherapy program for cervical cancer.

PURPOSE: Adaptive magnetic resonance imaging (MRI)-based brachytherapy results in improved local control and decreased high-grade toxicities compared to historical controls. Incorporating MRI into the workflow of a department can be a major challenge when initiating an MRI-based brachytherapy program. This project aims to describe the goals, challenges, and solutions when initiating an MRI-based cervical cancer brachytherapy program at our institution. MATERIAL AND METHODS: We describe the 6-month multi-disciplinary planning phase to initiate an MRI-based brachytherapy program. We describe the specific challenges that were encountered prior to treating our first patient. RESULTS: We describe the solutions that were realized and executed to solve the challenges that we faced to establish our MRI-based brachytherapy program. We emphasize detailed coordination of care, planning, and communication to make the workflow feasible. We detail the imaging and radiation physics solutions to safely deliver MRI-based brachytherapy. The focus of these efforts is always on the delivery of optimal, state of the art patient care and treatment delivery within the context of our available institutional resources. CONCLUSIONS: Previous publications have supported a transition to MRI-based brachytherapy, and this can be safely and efficiently accomplished as described in this manuscript.

Spectral characterization of tissues in high spectral and spatial resolution MR images: Implications for a classification-based synthetic CT algorithm.

PURPOSE: To characterize the spectral parameters of tissues with high spectral and spatial resolution magnetic resonance images to be used as a foundation for a classification-based synthetic CT algorithm. METHODS: A phantom was constructed consisting of a section of fresh beef leg with bone embedded in 1% agarose gel. The high spectral and spatial (HiSS) resolution MR imaging sequence used had 1.0 mm in-plane resolution and 11.1 Hz spectral resolution. This sequence was used to image the phantom and one patient. Post-processing was performed off-line with IDL and included Fourier transformation of the time-domain data, labeling of fat and water peaks, and fitting the magnitude spectra with Lorentzian functions. Images of the peak height and peak integral of both the water and fat resonances were generated and analyzed. Several regions-of-interest (ROIs) were identified in phantom: bone marrow, cortical bone, adipose tissue, muscle, agar gel, and air; in the patient, no agar gel was present but an ROI of saline in the bladder was analyzed. All spectra were normalized by the noise within each voxel; thus, all parameters are reported in terms of signal-to-noise (SNR). The distributions of tissue spectral parameters were analyzed and scatterplots generated. Water peak height in cortical bone was compared to air using a nonparametric t-test. Composition of the various ROIs in terms of water, fat, or fat and water was also reported. RESULTS: In phantom, the scatterplot of peak height (water versus fat) showed good separation of bone marrow and adipose tissue. Water versus fat integral scatterplot showed better separation of muscle and cortical bone than the peak height scatterplot. In the patient data, the distributions of water and fat peak heights were similar to that in phantom, with more overlap of bone marrow and cortical bone than observed in phantom. The relationship between bone marrow and cortical bone for peak integral was better separated than those of peak heights in the patient data. For both the phantom and patient, there was a significant amount of overlap in spectral parameters of cortical bone versus air. CONCLUSION: These results show promising results for utilizing HiSS imaging in a classification-based synthetic CT algorithm. Cortical bone and air overlap was expected due to the short T2* of bone; reducing early echo times would improve the SNR in bone and image data from these early echoes could help differentiate these tissue types. Further studies need to be done with the goal of better separation of air and bone, and to extend the concept to volumetric imaging before it can be clinically applied.

Point A vs. HR-CTV D90 in MRI-based cervical brachytherapy of small and large lesions.

PURPOSE: To evaluate the dosimetric benefits of MRI-based brachytherapy in small and large high-risk clinical target volume (HR-CTV) in cervical cancer. METHODS AND MATERIALS: Twenty-eight fractions obtained from sixteen cervical cancer patients treated with MRI-based high-dose-rate brachytherapy with standard tandem and ovoid applicators were used; original fractions were optimized to HR-CTV D90. Fractions were separated based on the median volume into small and large (HR-CTV <25 cm3 or >25 cm3) lesion groups. Retrospective plans prescribed to Point A were created for each fraction. D0.1 cc, D2 cc, and International Commission of Radiation Unit and Measurements (ICRU) points were used to compare Point A vs. HR-CTV D90 plans for bladder, rectum, and sigmoid. RESULTS: In the small lesion group, Point A plans vs. HR-CTV D90 plans had significantly higher D0.1 cc, D2 cc, and ICRU points for bladder, rectum, and sigmoid (p < 0.05). In the large lesion group, there was no significant difference between Point A and HR-CTV D90 plans for D0.1 cc, D2 cc, and ICRU points to the organs at risk (OARs). CONCLUSIONS: The dosimetric advantages to OARs offered by MRI-based brachytherapy with prescription to HR-CTV D90 compared to Point A is most distinct for patients with smaller HR-CTV (<25 cm3). This study demonstrates sufficient tumor coverage with lower doses to OARs in HR-CTV D90 vs. Point A plans in the small lesion group. These improvements were not seen in the large lesion group, indicating a lesser dosimetric advantage of HR-CTV D90 compared to Point A planning when the cervical lesion is >25 cm3. Incorporation of interstitial needles for patients with larger HR-CTV is likely the best method to decrease dose to OARs and improve tumor coverage.