Faculty Bibliography

PURPOSE/UNASSIGNED:Rectal spacers have gained popularity as a dose-sparing material for prostate cancer radiation therapy (RT). However, the procedure can be associated with unintended rectal wall infiltration (RWI) of the spacer gel. We therefore classified RWI severity as a function of depth and explored its association with rectal toxicity using a data set from prostate cancer patients treated with RT on a prospective randomized clinical trial (RCT). METHODS AND MATERIALS/UNASSIGNED:Postimplant T2-weighted magnetic resonance images of 149 subjects randomized to the hydrogel spacer arm of a published multicenter RCT were assessed for the presence and depth of RWI. All implants were assigned a score of 0 (no rectal wall signal changes), 1 (rectal wall edema/signal change), 2 (partial RWI), or 3 (full-thickness RWI); RWI was defined as a score of 2 or 3. Correlations were made between RWI score and physician-reported procedure, acute, and late rectal toxicity. RESULTS/UNASSIGNED:= .85) rectal toxicity incidence or grade was detected between RWI categories; none of the 6 men with a RWI score of 3 developed late rectal toxicity by 15 months. CONCLUSIONS/UNASSIGNED:Based on data from an RCT, RWI did not contribute to increased rectal toxicity prior and up to 15 months after conventional prostate cancer RT.

PURPOSE/UNASSIGNED:Multiparametric magnetic resonance imaging (MRI) is known to provide predictors for malignancy and treatment outcome. The inclusion of these datasets in workflows for online adaptive planning remains under investigation. We demonstrate the feasibility of longitudinal relaxometry in online MR-guided adaptive stereotactic body radiotherapy (SBRT) to the prostate and dominant intra-prostatic lesion (DIL). METHODS/UNASSIGNED:Fifty patients with intermediate-risk prostate cancer were included in the study. The clinical target volume (CTV) was defined as the prostate gland plus 1 cm of seminal vesicles. The gross tumor volume (GTV) was defined as the DIL identified on multiparametric MRI. Online adaptive radiotherapy was delivered in a 1.5 T MR-Linac using a prescription of 800 cGy/900 cGy × 5 fractions to the CTV + 3 mm/GTV + 2 mm. Relaxometry and diffusion-weighted imaging were implemented using clinically available sequences. Test-retest measurements were performed in eight patients, at each treatment fraction. Bias and uncertainty in relaxometry measurements were also assessed using a reference phantom. RESULTS/UNASSIGNED:The bias in longitudinal/transverse relaxation times was negligible while uncertainty was within 3 %. Test-retest measurements demonstrate that bias/uncertainty in patient T1 and T2 were comparable to bias/uncertainty estimated in the phantom. Mean T1 and T2 relaxation were significantly different between the prostate and DIL. The correlation between T1, T2, and diffusion was significant in the DIL, but not in the prostate. During treatment, mean T1 in the DIL approaches mean T1 in the prostate. CONCLUSIONS/UNASSIGNED:Longitudinal relaxometry for online MR-guided adaptive SBRT is feasible in a high-field MR-Linac and may provide complementary information for target delineation and response assessment.

BACKGROUND:Ultrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer. OBJECTIVE:To report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer. DESIGN, SETTING AND PARTICIPANTS/METHODS:Between 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:The primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure. RESULTS AND LIMITATIONS/CONCLUSIONS:The median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5-40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity. CONCLUSIONS:SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment. PATIENT SUMMARY/RESULTS:We investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity. This trial is registered on ClinicalTrials.gov as NCT00911118.

PURPOSE/OBJECTIVE:The use of magnetic resonance imaging (MRI) in radiotherapy planning is becoming more widespread, particularly with the emergence of MRI-guided radiotherapy systems. Existing guidelines for defining the prostate bed clinical target volume (CTV) show considerable heterogeneity. This study aimed to establish baseline interobserver variability (IOV) for prostate bed CTV contouring on MRI, develop international consensus guidelines, and evaluate its effect on IOV. METHODS AND MATERIALS/METHODS:Participants delineated the CTV on 3 MRI scans, obtained from the Elekta Unity MR-Linac, as per their normal practice. Radiation oncologist contours were visually examined for discrepancies, and interobserver comparisons were evaluated against simultaneous truth and performance level estimation (STAPLE) contours using overlap metrics (Dice similarity coefficient and Cohen's kappa), distance metrics (mean distance to agreement and Hausdorff distance), and volume measurements. A literature review of postradical prostatectomy local recurrence patterns was performed and presented alongside IOV results to the participants. Consensus guidelines were collectively constructed, and IOV assessment was repeated using these guidelines. RESULTS:Sixteen radiation oncologists' contours were included in the final analysis. Visual evaluation demonstrated significant differences in the superior, inferior, and anterior borders. Baseline IOV assessment indicated moderate agreement for the overlap metrics while volume and distance metrics demonstrated greater variability. Consensus for optimal prostate bed CTV boundaries was established during a virtual meeting. After guideline development, a decrease in IOV was observed. The maximum volume ratio decreased from 4.7 to 3.1 and volume coefficient of variation reduced from 40% to 34%. The mean Dice similarity coefficient rose from 0.72 to 0.75 and the mean distance to agreement decreased from 3.63 to 2.95 mm. CONCLUSIONS:Interobserver variability in prostate bed contouring exists among international genitourinary experts, although this is lower than previously reported. Consensus guidelines for MRI-based prostate bed contouring have been developed, and this has resulted in an improvement in contouring concordance. However, IOV persists and strategies such as an education program, development of a contouring atlas, and further refinement of the guidelines may lead to additional improvements.

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.

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.

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.

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.

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.

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.