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Low-Dose-Rate Brachytherapy Combined With Ultrahypofractionated Radiation Therapy for Clinically Localized, Intermediate-Risk Prostate Cancer: Results From a Prospective Trial

Kollmeier, Marisa A; McBride, Sean; Varghese, Melissa; Debonis, Dylan; Zhang, Zhigang; Cohen, Gilad; Damato, Antonio L; Mychalczak, Borys; Gewanter, Richard; Zelefsky, Michael J
PURPOSE:To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer. METHODS AND MATERIALS:This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (prescription dose, 100 Gy), followed 1 month later with ultrahypofractionated stereotactic RT (25 Gy in 5 fractions) to the prostate and seminal vesicles. The primary endpoint was the rate of grade 2+ genitourinary toxicity at 12 months using Common Terminology Criteria for Adverse Events v 4.0. Secondary endpoints included patient-reported quality-of-life metrics (International Prostate Scoring System [IPSS], International Index of Erectile Function, and Expanded Prostate Cancer Index Composite-bowel). Biochemical failure was defined as prostate-specific antigen nadir +2 ng/mL. Posttreatment biopsies were performed at between 24 and 36 months; median follow-up was 36 months. RESULTS:The rate of grade 2 urinary toxicity at 12 months was 25% with no grade 3 urinary toxicity noted. Mean IPSS at baseline and 12 and 24 months was 5, 10, and 6.2, respectively. Mean change in IPSS from baseline at 12 months was +5.5 (interquartile range, 1-9.75) and +1.05 (interquartile range, -3 to 3.25) at 24 months. Grade 2 bowel toxicity was 5% at 12 months with no grade 3 bowel toxicity noted. Mean Expanded Prostate Cancer Index Composite-bowel domain scores at baseline and 12 months were 92.8 and 90.3, respectively. Of patients who were potent (International Index of Erectile Function ≥21) at baseline, 75% remained potent at 12 months. Of 40 patients, 28 underwent posttreatment prostate biopsy (PPB), which was negative (n = 20) or demonstrated severe treatment effect (n = 8). No patient had a positive PPB or developed biochemical failure during the follow-up period. One patient without a PPB developed osseous metastases at 18 months posttreatment in the absence of biochemical failure. CONCLUSION:Low-dose-rate brachytherapy in combination with ultrahypofractionated stereotactic RT was safe and effective for intermediate-risk prostate cancer in early results of this trial.
PMID: 32505609
ISSN: 1879-355x
CID: 5529432

Role of Androgen-Deprivation Therapy Remains Uncertain for Intermediate-Risk Patients When Using Dose-Escalated Radiotherapy [Comment]

Kollmeier, Marisa A; McBride, Sean; Gorovets, Daniel; Zelefsky, Michael J
PMID: 32997577
ISSN: 1527-7755
CID: 5529452

Strict bladder filling and rectal emptying during prostate SBRT: Does it make a dosimetric or clinical difference?

Byun, David J; Gorovets, Daniel J; Jacobs, Lauren M; Happersett, Laura; Zhang, Pengpeng; Pei, Xin; Burleson, Sarah; Zhang, Zhigang; Hunt, Margie; McBride, Sean; Kollmeier, Marisa A; Zelefsky, Michael J
BACKGROUND:To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. METHODS:Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. RESULTS:Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = - 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (- 3.6 ± 9.6%; P < 0.01) and D2cc (- 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (- 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. CONCLUSIONS:Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.
PMCID:7565753
PMID: 33066781
ISSN: 1748-717x
CID: 5275082

Clinical experience and workflow challenges with magnetic resonance-only radiation therapy simulation and planning for prostate cancer

Tyagi, Neelam; Zelefsky, Michael J; Wibmer, Andreas; Zakian, Kristen; Burleson, Sarah; Happersett, Laura; Halkola, Aleksi; Kadbi, Mo; Hunt, Margie
BACKGROUND AND PURPOSE/OBJECTIVE:Magnetic Resonance (MR)-only planning has been implemented clinically for radiotherapy of prostate cancer. However, fewer studies exist regarding the overall success rate of MR-only workflows. We report on successes and challenges of implementing MR-only workflows for prostate. MATERIALS AND METHODS/METHODS:A total of 585 patients with prostate cancer underwent an MR-only simulation and planning between 06/2016-06/2018. MR simulation included images for contouring, synthetic-CT generation and fiducial identification. Workflow interruptions occurred that required a backup CT, a re-simulation or an update to our current quality assurance (QA) process. The challenges were prospectively evaluated and classified into syn-CT generation, motion/artifacts in the MRs, fiducial QA and bowel preparation guidelines. RESULTS:MR-only simulation was successful in 544 (93.2 %) patients. . In seventeen patients (2.9%), reconstruction of synthetic-CT failed due to patient size, femur angulation, or failure to determine the body contour. Twenty-four patients (4.1%) underwent a repeat/backup CT scan because of artifacts on the MR such as image blur due to patient motion or biopsy/surgical artifacts that hampered identification of the implanted fiducial markers. In patients requiring large coverage due to nodal involvement, inhomogeneity artifacts were resolved by using a two-stack acquisition and adaptive inhomogeneity correction. Bowel preparation guidelines were modified to address frequent rectum/gas issues due to longer MR scan time. CONCLUSIONS:MR-only simulation has been successfully implemented for a majority of patients in the clinic. However, MR-CT or CT-only pathway may still be needed for patients where MR-only solution fails or patients with MR contraindications.
PMCID:7598055
PMID: 33134566
ISSN: 2405-6316
CID: 5529472

To Radiate or Not to Radiate-The Challenges of Pelvic Reirradiation

Kamran, Sophia C; Zelefsky, Michael; Nguyen, Paul L; Lawton, Colleen A F
Patients who receive pelvic radiation are at risk for both local recurrences of their primary malignancy or for the development of a new malignancy in the irradiated pelvic structures. The management of postirradiation pelvic tumor is complicated and can be associated with both poor prognosis and significant morbidity. Historically, reirradiation within the pelvis was never entertained as part of treatment management due to concern for severe toxicity and exceeding of normal-tissue tolerances. However, it may play a role with modern techniques and careful patient selection. The following case and accompanying expert opinions demonstrate some of the key considerations for pelvic reirradiation as a treatment option.
PMID: 32503789
ISSN: 1532-9461
CID: 5529422

11C-Choline PET/CT in Recurrent Prostate Cancer: Retrospective Analysis in a Large U.S. Patient Series

Michaud, Laure; Touijer, Karim A; Mauguen, Audrey; Zelefsky, Michael J; Morris, Michael J; Lyashschenko, Serge K; Durack, Jeremy C; Humm, John L; Weber, Wolfgang A; Schöder, Heiko
Our purpose was to evaluate the performance of 11C-choline PET/CT in detecting biochemically recurrent prostate cancer (PCa) in a large non-European cohort (in the context of emerging evidence for prostate-specific membrane antigen PET in this setting) and to map patterns of PCa recurrence. Methods: We retrospectively analyzed 11C-choline PET/CT scans from 287 patients who were enrolled in an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean, 3.43 ng/mL; median, 0.94 ng/mL; range, 0.15-89.91 ng/mL) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP) (79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy, and 70 had a persistent PSA elevation after receiving initial treatment (69 after RP, 1 after radiotherapy). The level of suspicion for recurrence on 11C-choline PET/CT was scored (0, negative; 1, equivocal; 2, positive) by 2 readers. The correlation between 11C-choline PET/CT positivity and initial treatment, Gleason score, National Comprehensive Cancer Network stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map 11C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the 2 readers deemed 66% of the 11C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with a PSA of less than 0.5 ng/mL, 56% of patients with a PSA of 0.5-0.99 ng/mL, 70% of patients with a PSA of 1.0-1.99 ng/mL, and 90% of patients with a PSA of at least 2.0 ng/mL scored either 1 or 2 on 11C-choline PET/CT scans. When considering scores of 2 only, 11C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA < 0.5 ng/mL, 0.5-0.99 ng/mL, 1.0-1.99 ng/mL, and ≥ 2.0 ng/mL). In multivariate analysis, only PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had 11C-choline-positive suspected recurrences outside the initial treatment field. Conclusion:
PMCID:7262219
PMID: 31862801
ISSN: 1535-5667
CID: 5529382

VA-Radiation Oncology Quality Surveillance Program

Hagan, Michael; Kapoor, Rishabh; Michalski, Jeff; Sandler, Howard; Movsas, Benjamin; Chetty, Indrin; Lally, Brian; Rengan, Ramesh; Robinson, Cliff; Rimner, Andreas; Simone, Charles; Timmerman, Robert; Zelefsky, Michael; DeMarco, John; Hamstra, Daniel; Lawton, Colleen; Potters, Louis; Valicenti, Richard; Mutic, Sasa; Bosch, Walter; Abraham, Christopher; Caruthers, Douglas; Brame, Ryan; Palta, Jatinder R; Sleeman, William; Nalluri, Joseph
PURPOSE:We sought to develop a quality surveillance program for approximately 15,000 US veterans treated at the 40 radiation oncology facilities at the Veterans Affairs (VA) hospitals each year. METHODS AND MATERIALS:State-of-the-art technologies were used with the goal to improve clinical outcomes while providing the best possible care to veterans. To measure quality of care and service rendered to veterans, the Veterans Health Administration established the VA Radiation Oncology Quality Surveillance program. The program carries forward the American College of Radiology Quality Research in Radiation Oncology project methodology of assessing the wide variation in practice pattern and quality of care in radiation therapy by developing clinical quality measures (QM) used as quality indices. These QM data provide feedback to physicians by identifying areas for improvement in the process of care and identifying the adoption of evidence-based recommendations for radiation therapy. RESULTS:Disease-site expert panels organized by the American Society for Radiation Oncology (ASTRO) defined quality measures and established scoring criteria for prostate cancer (intermediate and high risk), non-small cell lung cancer (IIIA/B stage), and small cell lung cancer (limited stage) case presentations. Data elements for 1567 patients from the 40 VA radiation oncology practices were abstracted from the electronic medical records and treatment management and planning systems. Overall, the 1567 assessed cases passed 82.4% of all QM. Pass rates for QM for the 773 lung and 794 prostate cases were 78.0% and 87.2%, respectively. Marked variations, however, were noted in the pass rates for QM when tumor site, clinical pathway, or performing centers were separately examined. CONCLUSIONS:The peer-review protected VA-Radiation Oncology Surveillance program based on clinical quality measures allows providers to compare their clinical practice to peers and to make meaningful adjustments in their personal patterns of care unobtrusively.
PMID: 31983560
ISSN: 1879-355x
CID: 5529392

Prognostic Value of Pretreatment MRI in Patients With Prostate Cancer Treated With Radiation Therapy: A Systematic Review and Meta-Analysis

Woo, Sungmin; Han, Sangwon; Kim, Tae-Hyung; Suh, Chong Hyun; Westphalen, Antonio C; Hricak, Hedvig; Zelefsky, Michael J; Vargas, Hebert Alberto
PMCID:7499902
PMID: 31799874
ISSN: 1546-3141
CID: 5452562

Clinical Outcomes of Combined Prostate- and Metastasis-Directed Radiation Therapy for the Treatment of De Novo Oligometastatic Prostate Cancer

Imber, Brandon S; Varghese, Melissa; Goldman, Debra A; Zhang, Zhigang; Gewanter, Richard; Marciscano, Ariel E; Mychalczak, Borys; Gorovets, Daniel; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J
PURPOSE/OBJECTIVE:The Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial reported overall survival benefits for prostate-directed radiation therapy (PDRT) in low-burden metastatic prostate cancer. Oligometastasis-directed radiation therapy (ORT) improves androgen deprivation therapy (ADT)-free and progression-free survivals. Comprehensive PDRT + ORT to all detectable metastases may offer benefit for de novo oligometastatic prostate cancer (DNOPC) and is under prospective study; given few available benchmarks, we reviewed our institutional experience. METHODS AND MATERIALS/METHODS:Forty-seven patients with DNOPC with predominantly M1b disease received neoadjuvant, concurrent, and adjuvant ADT plus PDRT + ORT to 1 to 6 oligometastases. Gross pelvic (N1) nodes were not considered oligometastases unless focally targeted without broader nodal coverage. Outcomes were analyzed from radiation therapy (RT) start using Kaplan-Meier, competing risks, and Cox regression. Median follow-up was 27 (95% confidence interval, 16-42) months. RESULTS:= .025). Overall, 23 (49%) patients were trialed off ADT; 16 (70%) had testosterone recovery (>150 ng/dL) and, of these, 5 had subsequent PSA rise and restarted ADT 2 to 21 months postrecovery. The remaining 11 were maintained off ADT without BCR. Median noncastrate duration was 8 months; 7 patients had normalized testosterone for >1 year. CONCLUSIONS:A comprehensive, radiotherapeutic-based treatment strategy has favorable clinical outcomes and can produce prolonged noncastrate remissions in a subset with DNOPC.
PMCID:7718501
PMID: 33305082
ISSN: 2452-1094
CID: 5529482

Higher SBRT Dose Levels for Localized Prostate Cancer Are Associated with Improved Post-treatment Biopsy Outcomes [Meeting Abstract]

Zelefsky, M. J.; Pinitpatcharalert, A.; Goldman, D. A.; Kollmeier, M. A.; Hopkins, M.; McBride, S.; Gorovets, D., Jr.; Happersett, L.; Zhang, Z.
ISI:000582521503096
ISSN: 0360-3016
CID: 5531252