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Quantitative longitudinal mapping of radiation-treated prostate cancer using MR fingerprinting with radial acquisition and subspace reconstruction

Yu, Victoria Y; Otazo, Ricardo; Wu, Can; Subashi, Ergys; Baumann, Manuel; Koken, Peter; Doneva, Mariya; Mazurkewitz, Peter; Shasha, Daniel; Zelefsky, Michael; Cervino, Laura; Cohen, Ouri
MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the acquisition. Iterative reconstruction with the subspace model and additional regularization of the signal representation in the subspace is performed to minimize the number of spokes and maintain matching quality and SNR. Reconstruction accuracy was assessed using the ISMRM NIST phantom. In-vivo validation was performed on two healthy subjects and two prostate cancer patients undergoing radiation therapy. The longitudinal repeatability was quantified using the concordance correlation coefficient (CCC) in one of the healthy subjects by repeated scans over 1 year. One prostate cancer patient was scanned at three time points, before initiating therapy and following brachytherapy and external beam radiation. Changes in the T1/T2 maps obtained with the proposed method were quantified. The prostate, peripheral and transitional zones, and visible dominant lesion were delineated for each study, and the statistics and distribution of the quantitative mapping values were analyzed. Significant image quality improvements compared with standard reconstruction methods were obtained with the proposed subspace reconstruction method. A notable decrease in the spread of the T1/T2 values without biasing the estimated mean values was observed with the subspace reconstruction and agreed with reported literature values. The subspace reconstruction enabled visualization of small differences in T1/T2 values in the tumor region within the peripheral zone. Longitudinal imaging of a volunteer subject yielded CCC of 0.89 for MRF T1, and 0.81 for MRF T2 in the prostate gland. Longitudinal imaging of the prostate patient confirmed the feasibility of capturing radiation treatment related changes. This work is a proof-of-concept for a high resolution and fast quantitative mapping using golden-angle radial MRF combined with a subspace reconstruction technique for longitudinal treatment response assessment in subjects undergoing radiation treatment.
PMID: 37015305
ISSN: 1873-5894
CID: 5529722

Deep learning-based dominant index lesion segmentation for MR-guided radiation therapy of prostate cancer

Simeth, Josiah; Jiang, Jue; Nosov, Anton; Wibmer, Andreas; Zelefsky, Michael; Tyagi, Neelam; Veeraraghavan, Harini
BACKGROUND:Dose escalation radiotherapy enables increased control of prostate cancer (PCa) but requires segmentation of dominant index lesions (DIL). This motivates the development of automated methods for fast, accurate, and consistent segmentation of PCa DIL. PURPOSE/OBJECTIVE:To construct and validate a model for deep-learning-based automatic segmentation of PCa DIL defined by Gleason score (GS) ≥3+4 from MR images applied to MR-guided radiation therapy. Validate generalizability of constructed models across scanner and acquisition differences. METHODS:Five deep-learning networks were evaluated on apparent diffusion coefficient (ADC) MRI from 500 lesions in 365 patients arising from internal training Dataset 1 (156 lesions in 125 patients, 1.5Tesla GE MR with endorectal coil), testing using Dataset 1 (35 lesions in 26 patients), external ProstateX Dataset 2 (299 lesions in 204 patients, 3Tesla Siemens MR), and internal inter-rater Dataset 3 (10 lesions in 10 patients, 3Tesla Philips MR). The five networks include: multiple resolution residually connected network (MRRN) and MRRN regularized in training with deep supervision implemented into the last convolutional block (MRRN-DS), Unet, Unet++, ResUnet, and fast panoptic segmentation (FPSnet) as well as fast panoptic segmentation with smoothed labels (FPSnet-SL). Models were evaluated by volumetric DIL segmentation accuracy using Dice similarity coefficient (DSC) and the balanced F1 measure of detection accuracy, as a function of lesion aggressiveness and size (Dataset 1 and 2), and accuracy with respect to two-raters (on Dataset 3). Upon acceptance for publication segmentation models will be made available in an open-source GitHub repository. RESULTS:In general, MRRN-DS more accurately segmented tumors than other methods on the testing datasets. MRRN-DS significantly outperformed ResUnet in Dataset2 (DSC of 0.54 vs. 0.44, p < 0.001) and the Unet++ in Dataset3 (DSC of 0.45 vs. p = 0.04). FPSnet-SL was similarly accurate as MRRN-DS in Dataset2 (p = 0.30), but MRRN-DS significantly outperformed FPSnet and FPSnet-SL in both Dataset1 (0.60 vs. 0.51 [p = 0.01] and 0.54 [p = 0.049] respectively) and Dataset3 (0.45 vs. 0.06 [p = 0.002] and 0.24 [p = 0.004] respectively). Finally, MRRN-DS produced slightly higher agreement with experienced radiologist than two radiologists in Dataset 3 (DSC of 0.45 vs. 0.41). CONCLUSIONS:MRRN-DS was generalizable to different MR testing datasets acquired using different scanners. It produced slightly higher agreement with an experienced radiologist than that between two radiologists. Finally, MRRN-DS more accurately segmented aggressive lesions, which are generally candidates for radiative dose ablation.
PMID: 36856092
ISSN: 2473-4209
CID: 5529712

A Multicenter Prospective Trial of Electronic Skin Surface Brachytherapy for Keratinocyte Carcinoma: Early Cosmesis, Quality of Life, and Adverse Events

Kuo, Alyce M; Lee, Erica H; Rossi, Anthony M; Nehal, Kishwer S; Cordova, Miguel A; Steckler, Alexa M; Lian, Ming; Cohen, Gil'ad; Zhang, Zhigang; Zelefsky, Michael J; Kasper, Michael E; Barker, Christopher A
PURPOSE:Keratinocyte carcinomas are amenable to many treatments, including radiation therapy (RT). Electronic skin surface brachytherapy (ESSB) enables the precise delivery of radiation without radioisotopes. In this prospective multicenter clinical trial, we characterized early outcomes of ESSB prospectively through both patient- and clinician-reported measures. To corroborate the cosmesis observations, we also assessed patient-reported quality of life (QoL) and adverse events. METHODS AND MATERIALS:keratinocyte carcinoma were treated with ESSB. At 2-, 6-, and 12-weeks post-treatment, cosmesis from ESSB was assessed by both the patient and a clinician study investigator as either "good," "fair," or "bad." The Skindex-16 and the Skin Cancer Index (SCI) were used to assess patient QoL before and after treatment. Adverse events were assessed using the Common Toxicity Criteria for Adverse Events, version 4.0. RESULTS:Cosmesis and QoL were collected at 97% (99/102) of possible patient follow-up times. By 12 weeks post-treatment, 93.9% (31/33) of patient-reported and 96.9% (31/32) of clinician-reported cosmesis outcomes were "good." Compared with baseline, total Skindex-16 score significantly deteriorated at 2 weeks post-treatment (10.5 vs 24.5, P <.001), but significantly improved at 6 weeks (10.5 vs 4.7, P = .014) and 12 weeks (10.5 vs 2.1, P = .001) post-treatment. The total SCI score significantly improved from baseline to 6 weeks (78.4 vs 89.0, P = .001) post-treatment. The most frequent adverse events were radiation dermatitis, skin pain, and pruritus. All adverse events resolved to Grade ≤1 by 12 weeks post-treatment. CONCLUSIONS:This prospective, multicenter study demonstrated that ESSB is associated with a high rate of "good" early patient-reported cosmesis and increasing QoL and satisfaction with time. Validated assessments demonstrated a significant improvement in quality of life and resolution of moderate early adverse events by 6 to 12 weeks after treatment and corroborate the observation of favorable cosmesis.
PMID: 36586493
ISSN: 1879-355x
CID: 5529702

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study

Corkum, Mark T; Buyyounouski, Mark K; Chang, Albert J; Chung, Hans T; Chung, Peter; Cox, Brett W; Crook, Juanita M; Davis, Brian J; Frank, Steven J; Henriquez, Ivan; Horwitz, Eric M; Hoskin, Peter; Hsu, I-Chow; Keyes, Mira; King, Martin T; Kollmeier, Marisa A; Krauss, Daniel J; Kukielka, Andrzej M; Morton, Gerard; Orio, Peter F; Pieters, Bradley R; Potters, Louis; Rossi, Peter J; Showalter, Timothy N; Solanki, Abhishek A; Song, Daniel; Vanneste, Ben; Vigneault, Eric; Wojcieszek, Piotr A; Zelefsky, Michael J; Kamrava, Mitchell
BACKGROUND AND PURPOSE:Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS:International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS:Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION:Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.
PMID: 37059334
ISSN: 1879-0887
CID: 5529742

Identification of incidental brain tumors in prostate cancer patients via PSMA PET/CT

McLaughlin, Lily A; Yildirim, Onur; Rosenblum, Marc K; Imber, Brandon S; Haseltine, Justin M; Zelefsky, Michael J; Schöder, Heiko; Morris, Michael J; Rafelson, William M; Krebs, Simone; Moss, Nelson S
PURPOSE/OBJECTIVE:Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in the setting of biochemical recurrence. METHODS:F-piflufolastat) PET/CT imaging at an NCI-designated Comprehensive Cancer Center from 1/2018 to 12/2022. Imaging reports and clinical courses were reviewed to identify brain lesions and describe clinical and pathologic features. RESULTS:Two-thousand seven hundred and sixty-three patients underwent 3363 PSMA PET/CT scans in the absence of neurologic symptoms. Forty-four brain lesions were identified, including 33 PSMA-avid lesions: 10 intraparenchymal metastases (30%), 4 dural-based metastases (12%), 16 meningiomas (48%), 2 pituitary macroadenomas (6%), and 1 epidermal inclusion cyst (3%) (incidences of 0.36, 0.14, 0.58, 0.07, and 0.04%). The mean parenchymal metastasis diameter and mean SUVmax were 1.99 cm (95%CI:1.25-2.73) and 4.49 (95%CI:2.41-6.57), respectively. At the time of parenchymal brain metastasis detection, 57% of patients had no concurrent extracranial disease, 14% had localized prostate disease only, and 29% had extracranial metastases. Seven of 8 patients with parenchymal brain metastases remain alive at a median 8.8 months follow-up. CONCLUSION/CONCLUSIONS:Prostate cancer brain metastases are rare, especially in the absence of widespread metastatic disease. Nevertheless, incidentally detected brain foci of PSMA uptake may represent previously unknown prostate cancer metastases, even in small lesions and in the absence of systemic disease.
PMID: 37247180
ISSN: 1573-7373
CID: 5529772

Local Failure after Prostate SBRT Predominantly Occurs in the PI-RADS 4 or 5 Dominant Intraprostatic Lesion

Gorovets, Daniel; Wibmer, Andreas G; Moore, Assaf; Lobaugh, Stephanie; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean; Zelefsky, Michael J
BACKGROUND:A positive post-treatment prostate biopsy following definitive radiotherapy carries significant prognostic implications. OBJECTIVE:To determine whether local recurrences after prostate stereotactic body radiation therapy (SBRT) are associated with the presence of and occur more commonly within the region of a PI-RADS 4 or 5 dominant intra-prostatic lesion (DIL) identified on pre-treatment multi-parametric magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS/METHODS:247 patients with localized prostate cancer treated with SBRT at our institution from 2009-2018 underwent post-treatment biopsies (median time to biopsy: 2.2 years) to evaluate local control. INTERVENTIONS/METHODS:Prostate SBRT (median 40 Gy in 5 fractions). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:MRIs were read by a single diagnostic radiologist blinded to other patient characteristics and treatment outcomes. The DIL presence, size, location, and extent were then analyzed to determine associations with the post-treatment biopsy outcomes. RESULTS AND LIMITATIONS/CONCLUSIONS:Among patients who underwent post-treatment biopsies, 39/247 (15.8%) were positive for Gleason-gradable prostate adenocarcinoma, of which 35/39 (90%) had a DIL initially present and 29/39 (74.4%) had a positive biopsy within the DIL. Factors independently associated with post-treatment biopsy outcomes included the presence of a DIL (OR 6.95; p = 0.001), radiographic T3 disease (OR 5.23, p < 0.001), SBRT dose ≥40 Gy (OR 0.26, p = 0.003), and use of androgen deprivation therapy (ADT; OR 0.28, p = 0.027). Among patients with a DIL (N = 149), the only factors associated with post-treatment biopsy outcomes included ≥50% percent cores positive (OR 2.4, p = 0.037), radiographic T3 disease (OR 4.04, p = 0.001), SBRT dose ≥40 Gy (OR 0.22, p < 0.001), and use of ADT (OR 0.21, p = 0.014). CONCLUSIONS:Our results suggest that men with PI-RADS 4 or 5 DILs have a higher risk of local recurrence after prostate SBRT and that most recurrences are located within the DIL. PATIENT SUMMARY/RESULTS:We found the presence of a dominant tumor on pre-treatment MRI was strongly associated with residual cancer within the prostate after SBRT and that most recurrences were within the dominant tumor.
PMID: 35307323
ISSN: 2588-9311
CID: 5529622

SBRT focal dose intensification using an MR-Linac adaptive planning for intermediate-risk prostate cancer: An analysis of the dosimetric impact of intra-fractional organ changes

Brennan, Victoria Sarah; Burleson, Sarah; Kostrzewa, Caroline; Godoy Scripes, Paola; Subashi, Ergys; Zhang, Zhigang; Tyagi, Neelam; Zelefsky, Michael J
INTRODUCTION:Using an magnetic resonance linear accelerator (MR-Linac) may improve the precision of visible tumor boosting with ultra-hypofractionation by accounting for daily positional changes in the target and organs at risk (OAR). PATIENTS AND METHODS:Fifteen patients with prostate cancer and an MR-detected dominant lesion were treated on the MR-Linac with stereotactic body radiation (SBRT) to 40 Gy in 5 fractions, boosting the gross tumor volume (GTV) to 45 Gy with daily adaptive planning. Imaging was acquired again after initial planning (verification scan), and immediately after treatment (post-treatment scan). Prior to beam-on, additional adjustments were made on the verification scan. Contours were retrospectively adjusted on verification and post-treatment scans, and the daily plan recalculated on these scans to estimate the true dose delivered. RESULTS:The median prostate D95% for plan 1, 2 and 3 was 40.3 Gy, 40.5 Gy and 40.3 Gy and DIL D95% was 45.7 Gy, 45.2 Gy and 44.6 Gy, respectively. Bladder filling was associated with reduced GTV coverage (p = 0.03, plan 1 vs 2) and prostate coverage (p = 0.03, plan 2 vs 3). The D0.035 cc constraint was exceeded on verification and post-treatment plans in 24 % and 33 % of fractions for the urethra, 31 % and 45 % for the bladder, and 35 % and 25 % for the rectum, respectively. CONCLUSION:MR-Linac guided, daily adaptive SBRT with focal boosting of the GTV yields acceptable planned and delivered dosimetry. Adaptive planning with a MR-Linac may reliably deliver the prescribed dose to the intended tumor target.
PMID: 36549340
ISSN: 1879-0887
CID: 5529692

Assessment of Patients With Prostate Cancer and Their Understanding of the International Prostate Symptom Score Questionnaire

Gewanter, Richard M; Sandhu, Jaspreet S; Tin, Amy L; Gross, Jeffrey P; Mazzarella, Kathleen; Urban, Joanne; Elsebai, Natalia; Hopkins, Margaret F; Vickers, Andrew J; Zelefsky, Michael J
PURPOSE/UNASSIGNED:The International Prostate Symptom Score (IPSS) is a widely used tool for evaluating patient-reported lower urinary tract symptoms. In this study, we assessed patients with prostate cancer and their understanding of IPSS questions. METHODS AND MATERIALS/UNASSIGNED:Consecutive patients with prostate cancer (N = 144) self-completed an online IPSS questionnaire within 1 week before their visit at our radiation oncology clinic. At the visit, a nurse reviewed each IPSS question to ensure the patient understood it and then verified the patient's answer. Preverified and nurse-verified scores were recorded and analyzed for discrepancies. RESULTS/UNASSIGNED:Complete concordance between preverified and nurse-verified responses to individual IPSS questions existed for 70 men (49%). In terms of overall IPSS score, 61 men (42%) had a lower or improved IPSS after nurse verification, and 9 men (6%) had a higher or worse IPSS. Before verification, patients overstated their symptoms of frequency, intermittency, and incomplete emptying. As a result of the nurse verification, 4 of 7 patients with IPSS in the severe range (20-35) were recategorized to the moderate range (8-19). Sixteen percent of patients whose preverified IPSS were in the moderate range were recategorized after nurse verification to the mild range (0-7). Treatment option eligibility changed for 10% of patients after nurse verification. CONCLUSIONS/UNASSIGNED:Patients frequently misunderstand the IPSS questionnaire, leading them to respond in ways that do not accurately reflect their symptoms. Clinicians should verify patient understanding of the IPSS questions, particularly when using the score to determine eligibility for treatments.
PMID: 37213479
ISSN: 2452-1094
CID: 5529762

Quality Metric to Assess Adequacy of Hydrogel Rectal Spacer Placement for Prostate Radiation Therapy and Association of Metric Score With Rectal Toxicity Outcomes

Grossman, Craig E; Folkert, Michael R; Lobaugh, Stephanie; Desai, Neil B; Kollmeier, Marisa A; Gorovets, Daniel; McBride, Sean M; Timmerman, Robert D; Zhang, Zhigang; Zelefsky, Michael J
PURPOSE/UNASSIGNED:Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS/UNASSIGNED:A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated. RESULTS/UNASSIGNED: = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity. CONCLUSIONS/UNASSIGNED:We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT.
PMID: 37213478
ISSN: 2452-1094
CID: 5529752

Introduction [Editorial]

Zelefsky, Michael
PMID: 36529598
ISSN: 1873-1449
CID: 5529682