Publications by authors named "Amar U Kishan"

128 Publications

Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis.

Lancet Oncol 2021 03;22(3):402-410

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Background: The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer.

Methods: For this meta-analysis, we searched PubMed for all trials in localised or biochemically recurrent prostate cancer published between Jan 1, 1970, and Jan 15, 2020. Eligible trials had to be randomised, therapeutic, reporting overall survival and at least one intermediate clinical endpoint, and with a sample size of at least 70 participants. Trials of metastatic disease were excluded. Intermediate clinical endpoints included biochemical failure, local failure, distant metastases, biochemical failure-free survival, progression-free survival, and metastasis-free survival. Candidacy for surrogacy was assessed using the second condition of the meta-analytical approach (ie, correlation of the treatment effect of the intermediate clinical endpoint and overall survival), using R weighted by the inverse variance of the log intermediate clinical endpoint hazard ratio. The intermediate clinical endpoint was deemed to be a surrogate for overall survival if R was 0·7 or greater.

Findings: 75 trials (53 631 patients) were included in our analysis. Median follow-up was 9·1 years (IQR 5·7-10·6). Biochemical failure (R 0·38 [95% CI 0·11-0·64]), biochemical failure-free survival (R 0·12 [0·0030-0·33]), biochemical failure and clinical failure (R 0·28 [0·0045-0·65]), and local failure (R 0·085 [0·00-0·37]) correlated poorly with overall survival. Progression-free survival (R 0·46 [95% CI 0·22-0·67]) showed moderate correlation with overall survival, and metastasis-free survival (R 0·78 [0·59-0·89]) correlated strongly.

Interpretation: Intermediate clinical endpoints based on biochemical and local failure did not meet the second condition of the meta-analytical approach and are not surrogate endpoints for overall survival in localised prostate cancer. Our findings validate metastasis-free survival as the only identified surrogate endpoint for overall survival to date.

Funding: Prostate Cancer Foundation and National Institutes of Health.
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http://dx.doi.org/10.1016/S1470-2045(20)30730-0DOI Listing
March 2021

Use and Impact of Positron Emission Tomography/Computed Tomography Prior to Salvage Radiation Therapy in Men with Biochemical Recurrence After Radical Prostatectomy: A Scoping Review.

Eur Urol Oncol 2021 Feb 23. Epub 2021 Feb 23.

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address:

Context: The use, common findings, and impact of modern molecular positron emission tomography (PET)/computed tomography (CT) imaging prior to salvage radiation therapy (RT) in men with biochemical recurrence after radical prostatectomy (RP) have not been evaluated comprehensively.

Objective: We performed a scoping systematic review of the literature assessing detection rates, detection patterns, changes in management, as well as changes in patient outcome resulting from molecular PET/CT imaging using three molecular tracers: F-fluciclovine, Ga prostate-specific membrane antigen (PSMA)-11, and F-DCFPyL.

Evidence Acquisition: A computerized bibliographic search of the Medline/PubMed database was carried out from inception to October 1, 2020. We included published reports and abstracts evaluating the utility of Fluciclovine, Ga-PSMA-11, and F-DCFPyL PET in the detection of recurrent disease in the post-RP, pre-salvage RT setting. Outcomes of interest were extracted and tabulated, and existing evidence was synthesized qualitatively.

Evidence Synthesis: A total of 45 studies were included in our qualitative synthesis. Detection rates were high across most studies, and there was often a clear relationship between prostate-specific antigen (PSA) level and positive imaging findings. Though limited randomized data are available, there appears to be increased sensitivity with the use of PSMA ligands compared with fluciclovine at low PSA values. Most studies have shown that only one-third to one-half of patients with detected lesions have lesions in the prostatic fossa alone. Management changes occur in nearly 50% of patients undergoing molecular imaging, and biochemical response in patients who undergo molecular PET-based RT planning appears to be statistically superior to the response in patients who undergo conventional imaging -based RT planning alone. High biochemical responses from molecular PET-based salvage RT, ranging from 45% to 94%, did not appear to come at the expense of increased genitourinary or gastrointestinal toxicity. The presence or absence of avid lesions appears to be a strong prognostic factor.

Conclusions: Molecular PET/CT imaging in the post-RP, pre-salvage RT setting often triggers management changes that result from detecting lesions in locations not typically included in consensus-driven postoperative RT fields. Ongoing trials will assess the benefit of PSMA PET in guiding salvage RT following RP and determine its impact on long-term outcomes.

Patient Summary: We reviewed and reported detection rates, detection patterns, and changes in management resulting from molecular positron emission tomography/computed tomography imaging in men with biochemically recurrent prostate cancer following radical prostatectomy. Prior to the receipt of salvage radiation therapy, molecular tracers targeting prostate-specific membrane antigen appear to be especially sensitive at identifying the place where prostate cancer has come back after surgery, which can help radiation oncologists better target the recurrent disease and potentially improve the rates of cure from prostate cancer in this setting. Future studies will determine whether these imaging tools will change cure rates and side effects, but early results are promising.
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http://dx.doi.org/10.1016/j.euo.2021.01.007DOI Listing
February 2021

Identifying the Best Candidates for Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as the Primary Staging Approach Among Men with High-risk Prostate Cancer and Negative Conventional Imaging.

Eur Urol Oncol 2021 Feb 15. Epub 2021 Feb 15.

Department of Radiation Oncology, UCLA Medical Center, Los Angeles, CA, USA. Electronic address:

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. On multivariable analysis, Gleason grade group (GG) and percent positive core (PPC) on systematic biopsy significantly predict overall upstaging (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.33-3.45; p =  0.002; and OR 1.03, 95% CI 1.01-1.04; p <  0.001). Overall upstaging was significantly more frequent among men with GG 5 disease (33.0% vs. 17.6%; p =  0.0097) and PPC ≥50% (33.0% vs 15.0%; p =  0.0020). We constructed a nomogram that predicts overall upstaging using initial prostate-specific antigen, PPC, GG, and cT stage, with coefficients estimated from a standard logistic regression model (using maximum likelihood estimation). It is internally validated with a tenfold cross-validated area under the receiver operating characteristic curve estimated at 0.74 (95% CI 0.67-0.82). In our cohort, 90% of patients who had a nomogram-estimated risk below the cutoff of 22% for overall upstaging could have been spared PSMA PET/CT as our model correctly predicted no upstaging. In other words, the predictive model only missed 10% of patients who would otherwise have benefitted from PSMA PET/CT. PATIENT SUMMARY: We analyzed predictors of overall upstaging (lymph node or/and metastasis) by prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) from conventional imaging in men with high-risk prostate cancer undergoing initial staging deemed free of disease in the lymph nodes and distant metastasis by conventional imaging techniques. We found that the pathologic grade and disease burden in a prostate biopsy are associated with upstaging. We also developed a tool that predicts the probability of upstaging according to an individual patient's characteristics. Our study may help in defining patient groups who are most likely to benefit from the addition of a PSMA PET/CT scan.
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http://dx.doi.org/10.1016/j.euo.2021.01.006DOI Listing
February 2021

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients.

Int J Radiat Oncol Biol Phys 2021 Jan 23. Epub 2021 Jan 23.

Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California. Electronic address:

Purpose: To explore the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in high-risk prostate cancer (HRPCa) in a consortium of 7 institutional phase 2 trials and prospective registries.

Methods And Materials: Individual patient data were pooled for 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework. Fine and Gray competing risk and Cox proportional hazards regression models were developed to assess the association between time to BCR and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade ≥2 genitourinary and gastrointestinal and the following a priori-specified variables: age, dose per fraction, ADT use, and nodal radiation therapy.

Results: Median follow-up was 49.5 months. Seventy-two percent of patients received ADT, with a median duration of 9 months, and 19% received elective nodal radiation therapy. Estimated 4-year BCRFS and DMFS rates were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%). The crude incidences of late grade ≥3 genitourinary and gastrointestinal toxicity were 2.3% and 0.9%.

Conclusions: These data support a favorable toxicity and efficacy profile for SBRT for HRPCa. Further prospective studies are needed to evaluate the optimal dose and target volume in the context of SBRT for HRPCa.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.016DOI Listing
January 2021

Adaptive Radiation Therapy (ART) Strategies and Technical Considerations: A State of the ART Review From NRG Oncology.

Int J Radiat Oncol Biol Phys 2021 Mar 24;109(4):1054-1075. Epub 2020 Oct 24.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida.

The integration of adaptive radiation therapy (ART), or modifying the treatment plan during the treatment course, is becoming more widely available in clinical practice. ART offers strong potential for minimizing treatment-related toxicity while escalating or de-escalating target doses based on the dose to organs at risk. Yet, ART workflows add complexity into the radiation therapy planning and delivery process that may introduce additional uncertainties. This work sought to review presently available ART workflows and technological considerations such as image quality, deformable image registration, and dose accumulation. Quality assurance considerations for ART components and minimum recommendations are described. Personnel and workflow efficiency recommendations are provided, as is a summary of currently available clinical evidence supporting the implementation of ART. Finally, to guide future clinical trial protocols, an example ART physician directive and a physics template following standard NRG Oncology protocol is provided.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.021DOI Listing
March 2021

A Practical Guide for Navigating the Design, Build, and Clinical Integration of Electronic Patient-Reported Outcomes in the Radiation Oncology Department.

Pract Radiat Oncol 2021 Jan 15. Epub 2021 Jan 15.

Department of Radiation Oncology, University of California, Los Angeles, California.

The development and integration of electronic patient-reported outcomes (ePROs) into the radiation oncology clinic workflow provide novel opportunities, accompanied by unique design considerations and implementation challenges. The processes required for implementation of ePROs are entirely distinct from standard paper-based surveys, with the majority of time devoted to conception and design before initiating questionnaire build, detailed workflow process mapping including development of new workflows, comprehensive communication of the vision between providers and the information technology team, and quality assurance. Based on our experience with implementation of ePROs in our radiation oncology department, we developed a stepwise framework for approaching ePRO conceptual design, build, workflow integration, and the electronic health record interface. Here, we provide a guide for the numerous considerations, decision points, and solutions associated with the implementation of ePROs in the radiation oncology department setting. Although various ePRO tools and electronic health record capabilities impose different requirements, opportunities, and limitations, the conceptual processes and many of the electronic build considerations are broadly applicable.
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http://dx.doi.org/10.1016/j.prro.2020.12.007DOI Listing
January 2021

The Mutational Landscape of Metastatic Castration-sensitive Prostate Cancer: The Spectrum Theory Revisited.

Eur Urol 2021 Jan 5. Epub 2021 Jan 5.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Emerging data suggest that metastasis is a spectrum of disease burden rather than a binary state, and local therapies, such as radiation, might improve outcomes in oligometastasis. However, current definitions of oligometastasis are solely numerical.

Objective: To characterize the somatic mutational landscape across the disease spectrum of metastatic castration-sensitive prostate cancer (mCSPC) to elucidate a biological definition of oligometastatic CSPC.

Design, Setting, And Participants: This was a retrospective study of men with mCSPC who underwent clinical-grade sequencing of their tumors (269 primary tumor, 25 metastatic sites). Patients were classified as having biochemically recurrent (ie, micrometastatic), metachronous oligometastatic (≤5 lesions), metachronous polymetastatic (>5 lesions), or de novo metastatic (metastasis at diagnosis) disease.

Outcome Measurements And Statistical Analysis: We measured the frequency of driver mutations across metastatic classifications and the genomic associations with radiographic progression-free survival (rPFS) and time to castrate-resistant prostate cancer (CRPC).

Results And Limitations: The frequency of driver mutations in TP53 (p =  0.01), WNT (p =  0.08), and cell cycle (p =  0.04) genes increased across the mCSPC spectrum. TP53 mutation was associated with shorter rPFS (26.7 vs 48.6 mo; p =  0.002), and time to CRPC (95.6 vs 155.8 mo; p =  0.02) in men with oligometastasis, and identified men with polymetastasis with better rPFS (TP53 wild-type, 42.7 mo; TP53 mutated, 18.5 mo; p =  0.01). Mutations in TP53 (incidence rate ratio [IRR] 1.45; p =  0.004) and DNA double-strand break repair (IRR 1.61; p <  0.001) were associated with a higher number of metastases. Mutations in TP53 were also independently associated with shorter rPFS (hazard ratio [HR] 1.59; p =  0.03) and the development of CRPC (HR 1.71; p =  0.01) on multivariable analysis. This study was limited by its retrospective nature, sample size, and the use of commercially available sequencing platforms, resulting in a limited predefined set of genes examined.

Conclusions: Somatic mutational profiles reveal a spectrum of metastatic biology that helps in redefining oligometastasis beyond a simple binary state of lesion enumeration.

Patient Summary: Oligometastatic prostate cancer is typically defined as less than three to five metastatic lesions and evidence suggests that using radiation or surgery to treat these sites improves clinical outcomes. As of now, treatment decisions for oligometastasis are solely defined according to the number of lesions. However, this study suggests that tumor mutational profiles can provide a biological definition of oligometastasis and complement currently used numerical definitions.
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http://dx.doi.org/10.1016/j.eururo.2020.12.040DOI Listing
January 2021

Update from PSMA-SRT Trial NCT03582774: A Randomized Phase 3 Imaging Trial of Prostate-specific Membrane Antigen Positron Emission Tomography for Salvage Radiation Therapy for Prostate Cancer Recurrence Powered for Clinical Outcome.

Eur Urol Focus 2021 Mar 30;7(2):238-240. Epub 2020 Dec 30.

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA; Institute of Urologic Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Physics and Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

The purpose of this randomized trial is to evaluate the success rate of salvage radiation therapy for recurrence of prostate cancer after radical prostatectomy, with and without planning based on prostate-specific membrane antigen positron emission tomography/computed tomography. Enrollment has been completed and patients are being followed for 5yr.
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http://dx.doi.org/10.1016/j.euf.2020.12.009DOI Listing
March 2021

MR-Guided Radiotherapy for Prostate Cancer.

Front Oncol 2020 9;10:616291. Epub 2020 Dec 9.

Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, London, United Kingdom.

External beam radiotherapy remains the primary treatment modality for localized prostate cancer. The radiobiology of prostate carcinoma lends itself to hypofractionation, with recent studies showing good outcomes with shorter treatment schedules. However, the ability to accurately deliver hypofractionated treatment is limited by current image-guided techniques. Magnetic resonance imaging is the main diagnostic tool for localized prostate cancer and its use in the therapeutic setting offers anatomical information to improve organ delineation. MR-guided radiotherapy, with daily re-planning, has shown early promise in the accurate delivery of radiotherapy. In this article, we discuss the shortcomings of current image-guidance strategies and the potential benefits and limitations of MR-guided treatment for prostate cancer. We also recount present experiences of MR-linac workflow and the opportunities afforded by this technology.
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http://dx.doi.org/10.3389/fonc.2020.616291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757637PMC
December 2020

A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER).

Eur Urol 2020 Dec 10. Epub 2020 Dec 10.

Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address:

Context: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.

Objective: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.

Evidence Acquisition: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.

Evidence Synthesis: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.

Conclusions: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.

Patient Summary: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
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http://dx.doi.org/10.1016/j.eururo.2020.11.010DOI Listing
December 2020

The Impact of F-DCFPyL PET-CT Imaging on Initial Staging, Radiation, and Systemic Therapy Treatment Recommendations for Veterans With Aggressive Prostate Cancer.

Adv Radiat Oncol 2020 Nov-Dec;5(6):1364-1369. Epub 2020 Sep 9.

Imaging Service, VA Greater Los Angeles Healthcare System, Los Angeles, California.

Purpose: Our purpose was to study the effect of 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (F-DCFPyL) positron emission tomography (PET)-computed tomography (CT) on staging/treatment recommendations of previously untreated prostate cancer. We report here results of a prospective single center single arm imaging trial within Veterans Affairs (Greater Los Angeles): the frequency of patients upstaged to M1 disease (primary endpoint) and the frequency of patients with change in treatment recommendations (secondary endpoint). This is the first report of prostate-specific membrane antigen PET-CT exclusive to U.S. veterans.

Methods And Materials: Veterans with Gleason ≥4 + 3, clinical stage ≥T2c, or prostate-specific antigen >10 ng/mL were eligible. Patients underwent conventional imaging (Tc-methyl diphosphonate bone scan or F-NaF PET-CT; and pelvic CT or pelvic magnetic resonance imaging) in addition to F-DCFPyL PET-CT. The effect of F-DCFPyL PET-CT on treatment change was determined by applying prespecified treatment recommendations based on National Comprehensive Cancer Network guidelines and modern clinical practice.

Results: One hundred patients underwent F-DCFPyL PET-CT. Nineteen out of 84 (23%) patients initially thought to be nonmetastatic were upstaged to M1; 8/16 (50%) patients initially thought to have M1 disease were downstaged to M0. In total, 39/100 (39%) had a change in prespecified treatment recommendations, including change of radiation therapy volume/dose in 39/100 (39%) and starting abiraterone in 22/100 (22%).

Conclusions: Incorporation of F-DCFPyL PET-CT into the initial conventional imaging workup for prostate cancer can substantially affect staging/treatment recommendations.
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http://dx.doi.org/10.1016/j.adro.2020.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718503PMC
September 2020

Clinical Development and Evaluation of Megavoltage Topogram for Fast Patient Alignment on Helical Tomotherapy.

Adv Radiat Oncol 2020 Nov-Dec;5(6):1334-1341. Epub 2020 Jun 17.

Department of Radiation Oncology, UCLA School of Medicine, Los Angeles, California.

Purpose: To develop and evaluate a fast patient localization tool using megavoltage (MV)-topogram on helical tomotherapy.

Methods And Materials: Eighty-one MV-topogram pairs for 18 pelvis patients undergoing radiation were acquired weekly under an institutional review board-approved clinical trial. The MV-topogram imaging protocol requires 2 orthogonal acquisitions at static gantry angles of 0 degrees and 90 degrees for a programed scan length. A MATLAB based in-house software was developed to reconstruct the MV-topograms offline. Reference images (digitally reconstructed topograms, digitally reconstructed topograms) were generated using the planning computed tomography and tomotherapy geometry. The MV-topogram based alignment was determined by registering the MV-topograms to the digitally reconstructed topogram using bony landmark on commercial MIM software. The daily shifts in 3 translational directions determined from MV-topograms were compared with the megavoltage computed tomography (MVCT) based patient shifts. Linear-regression and two one-sided tests equivalence tests were performed to investigate the relation and equivalence between the 2 techniques. Seventy-eight MV-topogram pairs for 19 head and neck patients were included to validate the finding.

Results: The magnitudes of alignment differences of (MVCT - MV-topogram) (and standard deviations) were -0.3 ± 2.1, -0.8 ± 2.4, and 1.6 ± 1.7 mm for pelvis and 0.6 ± 1.2, 0.8 ± 4.2, 1.6 ± 2.6 mm for head and neck; the linear-regression coefficients between 2 imaging techniques were 1.18, 1.10, 0.94, and 0.86, 0.63, 0.38 in the lateral, longitudinal, vertical directions for pelvis and head and neck, respectively. The acquisition time for a pair of MV-topograms was up to 12.7 times less than MVCT scans (coarse scan mode) while covering longer longitudinal length.

Conclusions: MV-topograms showed equivalent clinical performance to the standard MVCT with significantly less acquisition time for pelvis and H&N patients. The MV-topogram can be used as an alternative or complimentary tool for bony landmark-based patient alignment on tomotherapy.
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http://dx.doi.org/10.1016/j.adro.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718556PMC
June 2020

A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer.

Eur Urol 2021 Mar 5;79(3):374-383. Epub 2020 Dec 5.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Context: Molecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.

Objective: To perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).

Evidence Acquisition: The review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446-52) and American Urology Association (AUA) criteria.

Evidence Synthesis: In total, 42 studies and 30407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n=12141), prospective registries (n=17053), and prospective and post hoc randomized trial analyses (n=1213). In 32 studies (n=12600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n=8543). GC use changed the management in active surveillance (number needed to test [NNT]=9) and postprostatectomy (NNT=1.5-4) settings in five studies (n=4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.

Conclusions: Consistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.

Patient Summary: In this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.
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http://dx.doi.org/10.1016/j.eururo.2020.11.021DOI Listing
March 2021

Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy.

Cancers (Basel) 2020 Dec 2;12(12). Epub 2020 Dec 2.

Department of Radiation Oncology, University of California, Los Angeles, CA 90095, USA.

Prostate cancer (PCa) is the most common noncutaneous solid organ malignancy among men worldwide. Radiation therapy is a standard of care treatment option that has historically been delivered in the form of small daily doses of radiation over the span of multiple weeks. PCa appears to have a unique sensitivity to higher doses of radiation per fraction, rendering it susceptible to abbreviated forms of treatment. Stereotactic body radiation therapy (SBRT) and high-dose-rate brachytherapy (HDRBT) are both modern radiation modalities that allow the precise delivery of ablative doses of radiation to the prostate while maximally sparing sensitive surrounding normal structures. In this review, we highlight the evidence regarding the radiobiology, oncological outcomes, toxicity and dose/fractionation schemes of SBRT and HDRBT monotherapy in men with low-and intermediate-risk PCa.
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http://dx.doi.org/10.3390/cancers12123606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761604PMC
December 2020

Factors Influencing Noncompletion of Radiation Therapy Among Men With Localized Prostate Cancer.

Int J Radiat Oncol Biol Phys 2021 Apr 1;109(5):1279-1285. Epub 2020 Dec 1.

Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida; Office of Community Outreach and Engagement, Sylvester Comprehensive Cancer Center, Miami, Florida. Electronic address:

Purpose: Treatment noncompletion may occur with radiation therapy (RT), especially with protracted treatment courses such as RT for prostate cancer, and may affect the efficacy of RT. For men with localized prostate cancer managed with primary RT, we evaluated associations between rates of treatment noncompletion and RT fractionation schedules.

Methods And Materials: The National Cancer Database identified men diagnosed from 2004 to 2014 treated with primary RT. Patients receiving 180 cGy/fraction or 200 cGy/fraction were defined as having completed radiation therapy if they received ≥41 fractions of 180 cGy/fraction or ≥37 fractions of 200 cGy/fraction. Stereotactic body radiation therapy (SBRT) was defined as 5 to 8 fractions of 600 to 800 cGy/fraction. Odds ratios compared rates of treatment noncompletion, adjusting for sociodemographic covariates. A propensity-adjusted multivariable Cox regression assessed the association between treatment completion and overall survival.

Results: Of 157,657 patients, 95.7% (n = 150,847) received conventional fractionation and 4.3% (n = 6810) received SBRT. Rates of noncompletion were 12.5% (n = 18,803) among patients who received conventional fractionation and 1.9% (n = 131) among patients who received SBRT (odds ratio [OR] versus conventional, 0.21; 95% confidence interval [CI], 0.18-0.26; P < .001). The rate of noncompletion among 25,727 African American patients was 12.8%, compared with 11.8% among 126,199 white patients (OR, 1.14; 95% CI, 1.09-1.19; P < .001). In a subgroup analysis, the disparity in noncompletion persisted for conventional fractionation (13.2% vs 12.3%, respectively; OR, 1.09; 95% CI, 1.05-1.13; P < .001), but not for SBRT (2.2% vs 1.8%, respectively; OR, 1.26; 95% CI, 0.79-2.00; P = .34). Noncompletion was associated with worse survival in a propensity-adjusted multivariable analysis (hazard ratio, 1.25; 95% CI, 1.22-1.29; P < .001).

Conclusions: SBRT was associated with lower rates of RT noncompletion among men with localized prostate cancer. African American race was associated with greater rates of treatment noncompletion, although the disparity may be decreased among men receiving SBRT.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.064DOI Listing
April 2021

Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy (ADT) Improves Metastasis-Free Survival Compared to Neoadjuvant ADT: An Individual Patient Meta-Analysis.

J Clin Oncol 2021 Jan 4;39(2):136-144. Epub 2020 Dec 4.

Medical College of Wisconsin, Milwaukee, WI.

Purpose: There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa.

Methods: MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS).

Results: The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% 3%, = .33) or genitourinary toxicity (5% 5%, = .76) between groups.

Conclusion: The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.
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http://dx.doi.org/10.1200/JCO.20.02438DOI Listing
January 2021

Pelvic nodal radiotherapy in Gleason grade group 5 prostate cancer.

Transl Androl Urol 2020 Oct;9(5):2326-2328

Deparmtnet of Radiation Oncology, University of California, Suite B265, Los Angeles, CA 90095, USA.

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http://dx.doi.org/10.21037/tau-20-917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658165PMC
October 2020

Local failure in high grade prostate cancer: the importance of local and systemic therapy.

Transl Androl Urol 2020 Oct;9(5):2315-2317

Cedars Sinai Medical Center, Los Angeles, CA 90095, USA.

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http://dx.doi.org/10.21037/tau-20-910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658116PMC
October 2020

Stereotactic body radiation therapy use for high risk prostate cancer in the United States.

Prostate Cancer Prostatic Dis 2020 Nov 13. Epub 2020 Nov 13.

Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.

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http://dx.doi.org/10.1038/s41391-020-00300-5DOI Listing
November 2020

Prostate Cancer Radiation Therapy Recommendations in Response to COVID-19.

Adv Radiat Oncol 2020 Nov 29;5(Suppl 1):26-32. Epub 2020 Oct 29.

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.

Purpose: During a global pandemic, the benefit of routine visits and treatment of patients with cancer must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers radiation oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiation therapy management decisions.

Methods And Materials: Radiation oncologists from the United States and the United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage patients with prostate cancer during the COVID-19 pandemic. A RADS framework was created: remote visits, and avoidance, deferment, and shortening of radiation therapy was applied to determine appropriate approaches.

Results: Recommendations were provided by the National Comprehensive Cancer Network risk group regarding clinical node-positive, postprostatectomy, oligometastatic, and low-volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits of between 1 and 6 months were deemed safe based on stage of disease. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node-positive, recurrence postsurgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4 to 6 months as necessary. Ultrahypofractionation is preferred for localized, oligometastatic, and low-volume M1, and moderate hypofractionation is preferred for postprostatectomy and clinical node positive disease. Salvage is preferred to adjuvant radiation.

Conclusions: Resources can be reduced for all identified stages of prostate cancer. The RADS (remote visits, and avoidance, deferment, and shortening of radiation therapy) framework can be applied to other disease sites to help with decision making in a global pandemic.
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http://dx.doi.org/10.1016/j.adro.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598436PMC
November 2020

Executive Summary of the American Radium Society Appropriate Use Criteria for Radiation Treatment of Node-Negative Muscle Invasive Bladder Cancer.

Int J Radiat Oncol Biol Phys 2021 Mar 27;109(4):953-963. Epub 2020 Oct 27.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT.

Methods And Materials: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework.

Results: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent.

Conclusions: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.031DOI Listing
March 2021

Analysis of Geometric Performance and Dosimetric Impact of Using Automatic Contour Segmentation for Radiotherapy Planning.

Front Oncol 2020 23;10:1762. Epub 2020 Sep 23.

Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

To analyze geometric discrepancy and dosimetric impact in using contours generated by auto-segmentation (AS) against manually segmented (MS) clinical contours. A 48-subject prostate atlas was created and another 15 patients were used for testing. Contours were generated using a commercial atlas-based segmentation tool and compared to their clinical MS counterparts. The geometric correlation was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). Dosimetric relevance was evaluated for a subset of patients by assessing the DVH differences derived by optimizing plan dose using the AS and MS contours, respectively, and evaluating with respect to each. A paired -test was employed for statistical comparison. The discrepancy in plan quality with respect to clinical dosimetric endpoints was evaluated. The analysis was repeated for head/neck (HN) with a 31-subject atlas and 15 test cases. Dice agreement between AS and MS differed significantly across structures: from (L:0.92/R: 0.91) for the femoral heads to seminal vesical of 0.38 in the prostate cohort, and from 0.98 for the brain, to 0.36 for the chiasm of the HN group. Despite the geometric disagreement, the paired -tests showed the lack of statistical evidence for systematic differences in dosimetric plan quality yielded by the AS and MS approach for the prostate cohort. In HN cases, statistically significant differences in dosimetric endpoints were observed in structures with small volumes or elongated shapes such as cord ( = 0.01) and esophagus ( = 0.04). The largest absolute dose difference of 11 Gy was seen in the mean pharynx dose. Varying AS performance among structures suggests a differential approach of using AS on a subset of structures and focus MS on the rest. The discrepancy between geometric and dosimetric-end-point driven evaluation also indicates the clinical utility of AS contours in optimization and evaluating plan quality despite of suboptimal geometrical accuracy.
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http://dx.doi.org/10.3389/fonc.2020.01762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546883PMC
September 2020

Prostate-specific Membrane Antigen Positron Emission Tomography-guided Radiotherapy.

Eur Urol Focus 2021 Mar 10;7(2):250-253. Epub 2020 Oct 10.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.

Radiotherapy has curative potential for patients with newly diagnosed localized prostate cancer and biochemical recurrence after radical prostatectomy, and can offer durable treatment responses for patients with oligometastatic disease. The success of radiotherapy in these settings relies on an accurate understanding of the extent of disease that is present and the precise anatomic localization of sites of disease. In this mini review, we provide an overview of recent data evaluating the role of positron emission tomography for assessing prostate-specific membrane antigen distribution in guiding radiotherapy in these settings. PATIENT SUMMARY: This mini review examines current evidence for the use of prostate-specific membrane antigen positron emission tomography/computed tomography to guide radiotherapy for patients with newly diagnosed localized prostate cancer, those with recurrences after radical prostatectomy, and those with oligometastatic disease.
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http://dx.doi.org/10.1016/j.euf.2020.09.020DOI Listing
March 2021

Dose-response with stereotactic body radiotherapy for prostate cancer: A multi-institutional analysis of prostate-specific antigen kinetics and biochemical control.

Radiother Oncol 2021 Jan 7;154:207-213. Epub 2020 Oct 7.

Department of Radiation Oncology, University of California, Los Angeles, USA; Department of Urology, University of California, Los Angeles, USA. Electronic address:

Background And Purpose: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens.

Materials And Methods: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS).

Results: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21).

Conclusion: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.
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http://dx.doi.org/10.1016/j.radonc.2020.09.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956167PMC
January 2021

A generative adversarial network-based (GAN-based) architecture for automatic fiducial marker detection in prostate MRI-only radiotherapy simulation images.

Med Phys 2020 Dec 19;47(12):6405-6413. Epub 2020 Oct 19.

Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

Purpose: Clinical sites utilizing magnetic resonance imaging (MRI)-only simulation for prostate radiotherapy planning typically use fiducial markers for pretreatment patient positioning and alignment. Fiducial markers appear as small signal voids in MRI images and are often difficult to discern. Existing clinical methods for fiducial marker localization require multiple MRI sequences and/or manual interaction and specialized expertise. In this study, we develop a robust method for automatic fiducial marker detection in prostate MRI simulation images and quantify the pretreatment alignment accuracy using automatically detected fiducial markers in MRI.

Methods And Materials: In this study, a deep learning-based algorithm was used to convert MRI images into labeled fiducial marker volumes. Seventy-seven prostate cancer patients who received marker implantation prior to MRI and CT simulation imaging were selected for this study. Multiple-Echo T -VIBE MRI images were acquired, and images were stratified (at the patient level) based on the presence of intraprostatic calcifications. Ground truth (GT) contours were defined by an expert on MRI using CT images. Training was done using the pix2pix generative adversarial network (GAN) image-to-image translation package and model testing was done using fivefold cross validation. For performance comparison, an experienced medical dosimetrist and a medical physicist each manually contoured fiducial markers in MRI images. The percent of correct detections and F classification scores are reported for markers detected using the automatic detection algorithm and human observers. The patient positioning errors were quantified by calculating the target registration errors (TREs) from fiducial marker driven rigid registration between MRI and CBCT images. Target registration errors were quantified for fiducial marker contours defined on MRI by the automatic detection algorithm and the two expert human observers.

Results: Ninety-six percent of implanted fiducial markers were correctly identified using the automatic detection algorithm. Two expert raters correctly identified 97% and 96% of fiducial markers, respectively. The F classification score was 0.68, 0.75, and 0.72 for the automatic detection algorithm and two human raters, respectively. The main source of false discoveries was intraprostatic calcifications. The mean TRE differences between alignments from automatic detection algorithm and human detected markers and GT were <1 mm.

Conclusions: We have developed a deep learning-based approach to automatically detect fiducial markers in MRI-only simulation images in a clinically representative patient cohort. The automatic detection algorithm-predicted markers can allow for patient setup with similar accuracy to independent human observers.
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http://dx.doi.org/10.1002/mp.14498DOI Listing
December 2020

Editorial: Optimizing Local Therapy for High-Risk Prostate Cancer: Evidence and Emerging Options.

Front Oncol 2020 27;10:1616. Epub 2020 Aug 27.

Department of Radiation Oncology, School of Medicine, University of Virginia, Charlottesville, VA, United States.

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http://dx.doi.org/10.3389/fonc.2020.01616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481351PMC
August 2020

Time-Driven Activity-Based Costing Analysis of Telemedicine Services in Radiation Oncology.

Int J Radiat Oncol Biol Phys 2020 10;108(2):430-434

Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California.

Purpose: Health systems have increased telemedicine use during the SARS-CoV-2 outbreak to limit in-person contact. We used time-driven activity-based costing to evaluate the change in resource use associated with transitioning to telemedicine in a radiation oncology department.

Methods And Materials: Using a patient undergoing 28-fraction treatment as an example, process maps for traditional in-person and telemedicine-based workflows consisting of discrete steps were created. Physicians/physicists/dosimetrists and nurses were assumed to work remotely 3 days and 1 day per week, respectively. Mapping was informed by interviews and surveys of personnel, with cost estimates obtained from the department's financial officer.

Results: Transitioning to telemedicine reduced provider costs by $586 compared with traditional workflow: $47 at consultation, $280 during treatment planning, $237 during on-treatment visits, and $22 during the follow-up visit. Overall, cost savings were $347 for space/equipment and $239 for personnel. From an employee perspective, the total amount saved each year by not commuting was $36,718 for physicians (7243 minutes), $19,380 for physicists (7243 minutes), $17,286 for dosimetrists (7210 minutes), and $5599 for nurses (2249 minutes). Patients saved $170 per treatment course.

Conclusions: A modified workflow incorporating telemedicine visits and work-from-home capability conferred savings to a department as well as significant time and costs to health care workers and patients alike.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462887PMC
October 2020

False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial.

Eur J Nucl Med Mol Imaging 2021 Feb 17;48(2):501-508. Epub 2020 Aug 17.

Departments of Radiology and Biomedical Imaging and Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.

Purpose: Readers need to be informed about potential pitfalls of [Ga]Ga-PSMA-11 PET interpretation.

Methods: Here we report [Ga]Ga-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer.

Results: Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (n = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n = 2), pelvic nodes (N, n = 2), or extra pelvic lesions (M, n = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (n = 5), pelvic nodes (n = 1), and extra pelvic lesions (n = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake.

Conclusion: [Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [Ga]Ga-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants.

Trial Registration Number: ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.
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http://dx.doi.org/10.1007/s00259-020-04945-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835157PMC
February 2021

Practical Safety Considerations for Integration of Magnetic Resonance Imaging in Radiation Therapy.

Pract Radiat Oncol 2020 Nov - Dec;10(6):443-453. Epub 2020 Aug 8.

Department of Radiation Oncology, University of California, Los Angeles, California. Electronic address:

Interest in integrating magnetic resonance imaging (MRI) in radiation therapy (RT) practice has increased dramatically in recent years owing to its unique advantages such as excellent soft tissue contrast and capability of measuring biological properties. Continuous real-time imaging for intrafractional motion tracking without ionizing radiation serves as a particularly attractive feature for applications in RT. Despite its many advantages, the integration of MRI in RT workflows is not straightforward, with many unmet needs. MR safety remains one of the key challenges and concerns in the clinical implementation of MR simulators and MR-guided radiation therapy systems in radiation oncology. Most RT staff are not accustomed to working in an environment with a strong magnetic field. There are specific requirements in RT that are different from diagnostic applications. A large variety of implants and devices used in routine RT practice do not have clear MR safety labels. RT-specific imaging pulse sequences focusing on fast acquisition, high spatial integrity, and continuous, real-time acquisition require additional MR safety testing and evaluation. This article provides an overview of MR safety tailored toward RT staff, followed by discussions on specific requirements and challenges associated with MR safety in the RT environment. Strategies and techniques for developing an MR safety program specific to RT are presented and discussed.
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http://dx.doi.org/10.1016/j.prro.2020.07.008DOI Listing
August 2020