Publications by authors named "Theodore DeWeese"

155 Publications

External Validation of the Bone Metastases Ensemble Trees for Survival (BMETS) Machine Learning Model to Predict Survival in Patients With Symptomatic Bone Metastases.

JCO Clin Cancer Inform 2021 Mar;5:304-314

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

Purpose: The Bone Metastases Ensemble Trees for Survival (BMETS) model uses a machine learning algorithm to estimate survival time following consultation for palliative radiation therapy for symptomatic bone metastases (SBM). BMETS was developed at a tertiary-care, academic medical center, but its validity and stability when applied to external data sets are unknown.

Patients And Methods: Patients treated with palliative radiation therapy for SBM from May 2013 to May 2016 at two hospital-based community radiation oncology clinics were included, and medical records were retrospectively reviewed to collect model covariates and survival time. The Kaplan-Meier method was used to estimate overall survival from consultation to death or last follow-up. Model discrimination was estimated using time-dependent area under the curve (tAUC), which was calculated using survival predictions from BMETS based on the initial training data set.

Results: A total of 216 sites of SBM were treated in 182 patients. Most common histologies were breast (27%), lung (23%), and prostate (23%). Compared with the BMETS training set, the external validation population was older (mean age, 67 62 years; < .001), had more primary breast (27% 19%; = .03) and prostate cancer (20% 12%; = .01), and survived longer (median, 10.7 6.4 months). When the BMETS model was applied to the external data set, tAUC values at 3, 6, and 12 months were 0.82, 0.77, and 0.77, respectively. When refit with data from the combined training and external validation sets, tAUC remained 0.79.

Conclusion: BMETS maintained high discriminative ability when applied to an external validation set and when refit with new data, supporting its generalizability, stability, and the feasibility of dynamic modeling.
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http://dx.doi.org/10.1200/CCI.20.00128DOI Listing
March 2021

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer.

Clin Cancer Res 2021 Mar 15;27(6):1623-1630. Epub 2021 Jan 15.

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.

Purpose: To investigate whether radium-223 increases peripheral immune responses to sipuleucel-T in men with bone-predominant, minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).

Patients And Methods: A total of 32 patients were randomized 1:1 in this open-label, phase II multicenter trial. Patients in the control arm received three sipuleucel-T treatments, 2 weeks apart. Those in the combination arm received six doses of radium-223 monthly, with sipuleucel-T intercalated between the second and fourth doses of radium-223. The primary endpoint was a comparison of peripheral antigen PA2024-specific T-cell responses (measured by proliferation index). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and PSA responses.

Results: We enrolled 32 patients, followed for a median of 1.6 years. Six weeks after the first sipuleucel-T dose, participants in the control arm had a 3.2-fold greater change in PA2024-specific T-cell responses compared with those who received combination treatment ( = 0.036). Patients in the combination arm were more likely to have a >50% PSA decline [5 (31%) vs. 0 patients; = 0.04], and also demonstrated longer PFS [39 vs. 12 weeks; HR, 0.32; 95% confidence interval (CI), 0.14-0.76] and OS (not reached vs. 2.6 years; HR, 0.32; 95% CI, 0.08-1.23).

Conclusions: Our data raise the possibility of greater clinical activity with the combination of sipuleucel-T and radium-223 in men with asymptomatic bone mCRPC, despite the paradoxically lower immune responses observed. Additional study to confirm these findings in a larger trial is warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4476DOI Listing
March 2021

Magnetic nanoparticle hyperthermia for treating locally advanced unresectable and borderline resectable pancreatic cancers: the role of tumor size and eddy-current heating.

Int J Hyperthermia 2020 Dec;37(3):108-119

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Purpose: Tumor volume largely determines the success of local control of borderline resectable and locally advanced pancreatic cancer with current therapy. We hypothesized that a tumor-mass normalized dose of magnetic nanoparticle hyperthermia (MNPH) with alternating magnetic fields (AMFs) reduces the effect of tumor volume for treatment.

Methods: 18 female athymic nude mice bearing subcutaneous MiaPaCa02 human xenograft tumors were treated with MNPH following intratumor injections of 5.5 mg Fe/g tumor of an aqueous suspension of magnetic iron-oxide nanoparticles. Mice were randomly divided into control ( = 5) and treated groups having small (0.15 ± 0.03 cm,  = 4) or large (0.30 ± 0.06 cm,  = 5) tumors. We assessed the clinical feasibility of this approach and of pulsed AMF to minimize eddy current heating using a finite-element method to solve a bioheat equation for a human-scale multilayer model.

Results: Compared to the control group, both small and large MiaPaCa02 subcutaneous tumors showed statistically significant growth inhibition. Conversely, there was no significant difference in tumor growth between large and small tumors. Both computational and xenograft models demonstrated higher maximum tumor temperatures for large tumors compared to small tumors. Computational modeling demonstrates that pulsed AMF can minimize nonspecific eddy current heating.

Conclusions: MNPH provides an advantage to treat large tumors because the MION dose can be adjusted to increase power. Pulsed AMF, with adjusted treatment time, can enhance MNPH in challenging cases such as low MION dose in the target tissue and/or large patients by minimizing nonspecific eddy current heating without sacrificing thermal dose to the target. Nanoparticle heterogeneity in tumors remains a challenge for continued research.
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http://dx.doi.org/10.1080/02656736.2020.1798514DOI Listing
December 2020

Drug-Radiotherapy Combinations in 2020-A Landmark Year?

JAMA Oncol 2021 Mar;7(3):349-350

Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Bethesda, Maryland.

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http://dx.doi.org/10.1001/jamaoncol.2020.6139DOI Listing
March 2021

Impact of radiation dose on recurrence in high-risk prostate cancer patients.

Prostate 2020 11 17;80(15):1322-1327. Epub 2020 Aug 17.

Division for Radiology and Nuclear Medicine, Department of Research and Development, Oslo University Hospital, Oslo, Norway.

Background: Dose escalated radiation therapy (RT) combined with long-term androgen deprivation therapy (ADT) is a standard of care option for men with high-risk and locally advanced prostate cancer (PCa). However, the optimal dose of escalated RT and ADT is not known. Here we assessed the impact of radiation dose and length of ADT on biochemical recurrence in a multi-institutional cohort stratified by the Cambridge prognostic group (CPG). We hypothesized that radiation dose and length of ADT would impact outcome in similar risk groups of our patients.

Methods: Two-hundred and forty-four patients were included, 132 from Oslo University Hospital, Department of Oncology and 112 from Johns Hopkins Hospital, Department of Radiation Oncology. Biochemical recurrence was defined as prostate-specific antigen (PSA) nadir +2 ng/mL. Time to recurrence was estimated using Kaplan-Meier analysis and when stratified by CPG the log-rank test was used. Cox regression analysis was performed to identify factors associated with risk of recurrence. Site of recurrence was investigated.

Results: The median follow-up time was 7.4 years. The vast majority (71%) of patients were classified as high-risk (CPG 4) or very high-risk features (CPG 5). Significantly more PSA recurrences occurred in CPG 5 (41%) compared with CPG 4 (25%) (P = .04) and five-year cumulative recurrence-free survival was lower for CPG 4 and 5 (89% and 68%) compared with CPG 1, 2, and 3 (100%, 100%, and 93%). The recurrence-free survival for CPG 5 was significantly higher for prostate irradiation of 80 Gy as compared with 74 Gy (P = .011). For CPG 4 and 5 no local recurrences were detected in patients receiving 80 Gy. On stepwise Cox regression analysis neither age nor length of ADT were independent prognostic factors for recurrence free survival.

Conclusion: Prostate dose escalation from 74 to 80 Gy decreases risk of recurrence in high-risk PCa. Further studies are needed to identify the optimal combination of ADT and RT.
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http://dx.doi.org/10.1002/pros.24059DOI Listing
November 2020

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate.

JAMA Oncol 2020 12;6(12):1912-1920

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

Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus.

Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer.

Design, Setting, And Participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019.

Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy.

Main Outcomes And Measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts.

Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782).

Conclusions And Relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.
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http://dx.doi.org/10.1001/jamaoncol.2020.4922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582232PMC
December 2020

Confronting Racism in Radiation Oncology: Now Is the Time and Today Is the Day.

Adv Radiat Oncol 2020 Sep-Oct;5(5):793-794. Epub 2020 Jul 7.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.adro.2020.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557187PMC
July 2020

Is This Au Revoir or a Permanent Farewell to In-Person Meetings?

Int J Radiat Oncol Biol Phys 2020 10;108(2):470-471

American Society for Radiation Oncology, Arlington, Virginia.

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http://dx.doi.org/10.1016/j.ijrobp.2020.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462875PMC
October 2020

Initial Impact and Operational Responses to the COVID-19 Pandemic by American Radiation Oncology Practices.

Int J Radiat Oncol Biol Phys 2020 Oct;108(2):356-361

Department of Radiation Oncology, The University of Tennessee Health Science Center, Memphis, Tennessee; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: In February 2020, the COVID-19 pandemic reached the United States. The impact of the pandemic on the US radiation oncology field remains unknown. The American Society for Radiation Oncology surveyed US radiation oncology practice leaders to gauge initial impact and immediate operational responses to the pandemic.

Methods And Materials: From April 16 to April 30, 2020, the American Society for Radiation Oncology surveyed US radiation oncology practice leaders by email to gauge initial impact and immediate operational responses to the COVID-19 pandemic.

Results: Two hundred twenty-two (43%) of 517 leaders responded from community and academic practices (62% and 34%, respectively), hospital-based and free-standing centers (69% and 29%), and metro and rural locations (88% and 12%). Practices reported treating an average of 1086 patients per year in 2019 (range, 0-7900) with an average daily treatment volume of 70 patients (range, 5-400). All practices reported uninterrupted operation. On average, practices were treating 68% of their typical volume (range, 10%-95%), with 92% implementing planned treatment postponement for lower risk patients. An estimated revenue decrease of 20% or more was experienced by 71% of practices. Confirmed COVID-19 patient cases were treated by 39% of practices. Seventy percent experienced staff shortages. Almost all (98%) practices implemented formal operational procedures to protect patients and staff, although personal protective equipment/infection control supply shortages were reported by 78% of practices. Seventy-four percent used telemedicine for virtual follow-up surveillance, and 15% leveraged telemedicine for on-treatment assessment.

Conclusions: The clinical and financial impacts of the COVID-19 pandemic on US radiation oncology were deep and broad. Despite reported shortages in personal protective equipment, declines in revenue, and reduced patient volumes, practices adapted quickly by refining standard processes of care, implementing recommended safety measures, and employing telemedicine to facilitate treatment continuity. Patients with higher risk disease experienced uninterrupted access to care. We plan to continue regular surveying across the lifespan of the pandemic to document the geographic and temporal impact of COVID-19 on the field and its patients.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462779PMC
October 2020

Patterns of Recurrence and Modes of Progression After Metastasis-Directed Therapy in Oligometastatic Castration-Sensitive Prostate Cancer.

Int J Radiat Oncol Biol Phys 2021 Feb 14;109(2):387-395. Epub 2020 Aug 14.

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

Purpose: Metastasis-directed therapy (MDT) is increasingly used in castration-sensitive oligometastatic prostate cancer because it prolongs progression-free survival (PFS) and androgen deprivation free survival. Here we describe patterns of recurrence and identify modes of progression after MDT using SABR.

Methods And Materials: Two hundred fifty-eight patients with castration-sensitive oligometastatic prostate cancer (≤5 lesions at staging) were retrospectively identified from a multi-institutional database. Descriptive patterns of recurrence and modes of progression were reported. Other outcomes including median time to prostate-specific antigen (PSA) recurrence, time to next intervention, distant metastasis-free survival, overall survival, and biochemical PFS (bPFS) were reported. Survival analysis was performed using the Kaplan-Meier method, and multivariable analysis was performed.

Results: Median follow-up was 25.2 months, and 50.4% of patients received concurrent androgen deprivation. Median time to PSA recurrence was 15.7 months, time to next intervention was 28.6 months, distant metastasis-free survival was 19.1 months, and bPFS was 16.1 months. Two-year overall survival was 96.8%. On multivariable analysis, factors associated with bPFS included age (hazard ratio [HR], 1.03; P = .04), N1 disease at diagnosis (HR, 2.00; P = .02), M1 disease at diagnosis (HR, 0.44; P = .01), initial PSA at diagnosis (HR, 1.002; P = <.001), use of androgen deprivation therapy (HR, 0.41; P < .001), pre-SABR PSA (HR, 1.02; P = .01), and use of enhanced imaging for staging (HR, 2.81; P = .001). Patterns of progression favored an osseous component at recurrence; in patients initially treated to a bone lesion alone, the vast majority (86.5%) experienced a recurrence that included an osseous site. Patients treated initially to a nodal site alone tended to recur in a node only (64.5%); however, there was also a significant minority with an osseous component of recurrence at progression (32.3%). Modes of progressors were class I (patients with long term control [no recurrence ≥18 months after therapy]) occurring in 40.9%, class II (oligoprogressors [≤3 lesions at recurrence]) occurring in 36% (including 7.9% of patients with PSA recurrence but no metastatic disease), and class III (polyprogressors [>3 lesions]) occurring in 23.1% of patients.

Conclusions: After MDT, the majority of patients have long-term control or oligoprogression (class I or II). Recurrence tended to occur in osseous sites. These findings, if validated, have implications for future integration of MDT and clinical trial design.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856169PMC
February 2021

Metastasis-directed Therapy Prolongs Efficacy of Systemic Therapy and Improves Clinical Outcomes in Oligoprogressive Castration-resistant Prostate Cancer.

Eur Urol Oncol 2020 Jun 11. Epub 2020 Jun 11.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Available therapies for castrate-resistant prostate cancer (CRPC) confer minimal survival advantage; thus, there is interest in metastasis-directed therapy (MDT) for oligometastatic or oligoprogressive disease to improve outcomes. Here, we describe outcomes of oligoprogressive CRPC treated with stereotactic ablative radiotherapy (SABR).

Objective: To report outcomes of oligoprogressive CRPC treated with MDT using SABR.

Design, Setting, And Participants: Patients with oligoprogressive CRPC were retrospectively evaluated, and outcomes following MDT were reported. Outcomes were additionally compared with oligoprogressive CRPC treated with change in systemic therapy alone.

Intervention: SABR to oligoprogressive lesions.

Outcome Measurements And Statistical Analysis: Outcomes of interest were time to prostate-specific antigen (PSA) failure, time to next intervention (TTNI), distant metastasis-free survival (DMFS), and overall survival. Survival analysis was performed using the Kaplan-Meier method, and univariable analysis and multivariable analysis (MVA) were performed.

Results And Limitations: A total of 68 patients were included. After MDT, median time to PSA recurrence, TTNI, and DMFS were 9.7, 15.6, and 10.8 months, respectively. A total of 112 lesions were treated, and the cumulative incidences of local failure at 12 and 24 months were 2.1% and 13.8%, respectively. Factors associated with the risk of local recurrence on univariable analysis were age (hazard ratio [HR] 1.07, p =  0.03) and Gleason grade group (HR 2.20, p =  0.07). Compared with change in systemic therapy alone (n = 52), MDT (n = 31) was associated with improved median time to PSA failure (9.7 vs 4.2 months, p =  0.066)), TTNI (14.9 vs 8.8 months, p =  0.025), and DMFS (12.7 vs 8.9 months, p = 0.045), and remained associated with improved outcomes on MVA.

Conclusions: In a retrospective cohort of oligoprogressive CRPC patients, MDT was associated with favorable outcomes and improved cancer control as compared with change in systemic treatment alone. Future prospective trials are needed to confirm these findings.

Patient Summary: In this report, we retrospectively analyzed outcomes of patients with oligoprogressive castrate-resistant prostate cancer treated with radiation therapy to progressing lesions. Our results suggest that treatment of these lesions with radiation therapy can result in sustained periods of disease-free survival and might add benefit in addition to systemic therapy at the time of progression. These results need to be verified in a prospective trial to identify the optimal integration of radiation therapy into metastatic castrate-resistant prostate cancer.
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http://dx.doi.org/10.1016/j.euo.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788526PMC
June 2020

A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS).

BMC Cancer 2020 Jun 1;20(1):492. Epub 2020 Jun 1.

Department of Radiation Oncology & Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB2 Rm 406, Baltimore, MD, 21231, USA.

Background: Metastasis directed therapy (MDT) for patients with oligometastatic disease is associated with improvements in progression free survival (PFS) and overall survival (OS) compared to systemic therapy alone. Additionally, within a prostate-cancer-specific cohort, MDT is able to forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be safe and effective in HSOPCa, a large percentage of men will eventually have disease recurrence. Patterns of failure in HSOPCa demonstrate patients tend to have recurrence in the bone following MDT, raising the question of sub-clinically-apparent osseous disease. Radium-223 dichloride is a radiopharmaceutical with structural similarity to calcium, allowing it to be taken up by bone where it emits alpha particles, and therefore might have utility in the treatment of micrometastatic osseous disease. Therefore, the primary goal of the phase II RAVENS trial is to evaluate the efficacy of MDT + radium-223 dichloride in prolonging progression free survival in men with HSOPCa.

Methods: Patients with HSOPCa and 3 or less metastases with at least 1 bone metastasis will be randomized 1:1 to stereotactic ablative radiation (SABR, also known as stereotactic body radiation therapy (SBRT)) alone vs SABR + radium-223 dichloride with a minimization algorithm to balance assignment by institution, primary intervention, prior hormonal therapy, and PSA doubling time. SABR is delivered in one to five fractions and patients in the SABR + radium-223 dichloride arm will receive six infusions of radium-223 dichloride at four-week intervals. The primary end point is progression free survival. The secondary clinical endpoints include toxicity and quality of life assessments, local control at 12 months, locoregional progression, time to distant progression, time to new metastasis, and duration of response.

Discussion: The RAVENS trial will be the first described phase II, non-blinded, randomized study to compare SABR +/- radium-223 dichloride in patients with HSOPCa and 3 or less metastases with at least one bone metastasis. The primary hypothesis is that SABR + radium-223 dichloride will increase median progression-free survival from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm.

Trial Registrations: Clinicaltrials.gov. Identifier: NCT04037358. Date of Registration: July 30, 2019. Date of First Participant Enrolled: August 9, 2019. Date of Last Approved Amendment: October 16, 2019. Protocol Version: Version 5.
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http://dx.doi.org/10.1186/s12885-020-07000-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268477PMC
June 2020

Developing an Improved Statistical Approach for Survival Estimation in Bone Metastases Management: The Bone Metastases Ensemble Trees for Survival (BMETS) Model.

Int J Radiat Oncol Biol Phys 2020 11 22;108(3):554-563. Epub 2020 May 22.

Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Purpose: To determine whether a machine learning approach optimizes survival estimation for patients with symptomatic bone metastases (SBM), we developed the Bone Metastases Ensemble Trees for Survival (BMETS) to predict survival using 27 prognostic covariates. To establish its relative clinical utility, we compared BMETS with 2 simpler Cox regression models used in this setting.

Methods And Materials: For 492 bone sites in 397 patients evaluated for palliative radiation therapy (RT) for SBM from January 2007 to January 2013, data for 27 clinical variables were collected. These covariates and the primary outcome of time from consultation to death were used to build BMETS using random survival forests. We then performed Cox regressions as per 2 validated models: Chow's 3-item (C-3) and Westhoff's 2-item (W-2) tools. Model performance was assessed using cross-validation procedures and measured by time-dependent area under the curve (tAUC) for all 3 models. For temporal validation, a separate data set comprised of 104 bone sites treated in 85 patients in 2018 was used to estimate tAUC from BMETS.

Results: Median survival was 6.4 months. Variable importance was greatest for performance status, blood cell counts, recent systemic therapy type, and receipt of concurrent nonbone palliative RT. tAUC at 3, 6, and 12 months was 0.83, 0.81, and 0.81, respectively, suggesting excellent discrimination of BMETS across postconsultation time points. BMETS outperformed simpler models at each time, with respective tAUC at each time of 0.78, 0.76, and 0.74 for the C-3 model and 0.80, 0.78, and 0.77 for the W-2 model. For the temporal validation set, respective tAUC was similarly high at 0.86, 0.82, and 0.78.

Conclusions: For patients with SBM, BMETS improved survival predictions versus simpler traditional models. Model performance was maintained when applied to a temporal validation set. To facilitate clinical use, we developed a web platform for data entry and display of BMETS-predicted survival probabilities.
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http://dx.doi.org/10.1016/j.ijrobp.2020.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954525PMC
November 2020

Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial.

JAMA Oncol 2020 05;6(5):650-659

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT).

Objective: To determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer.

Design, Setting, And Participants: The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated with a university hospital from May 2016 to March 2018 with a data cutoff date of May 20, 2019, for analysis. Of 80 men screened, 54 men with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6 months of enrollment or 3 or more years total were randomized.

Interventions: Patients were randomized in a 2:1 ratio to receive SABR or observation.

Main Outcomes And Measures: The primary outcome was progression at 6 months by prostate-specific antigen level increase, progression detected by conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Predefined secondary outcomes were toxic effects of SABR, local control at 6 months with SABR, progression-free survival, Brief Pain Inventory (Short Form)-measured quality of life, and concordance between conventional imaging and prostate-specific membrane antigen (PSMA)-targeted positron emission tomography in the identification of metastatic disease.

Results: In the 54 men randomized, the median (range) age was 68 (61-70) years for patients allocated to SABR and 68 (64-76) years for those allocated to observation. Progression at 6 months occurred in 7 of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation (P = .005). Treatment with SABR improved median progression-free survival (not reached vs 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P = .002). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at 6 months (16% vs 63%; P = .006). No toxic effects of grade 3 or greater were observed. T-cell receptor sequencing identified significant increased clonotypic expansion following SABR and correlation between baseline clonality and progression with SABR only (0.082085 vs 0.026051; P = .03).

Conclusions And Relevance: Treatment with SABR for oligometastatic prostate cancer improved outcomes and was enhanced by total consolidation of disease identified by PSMA-targeted positron emission tomography. SABR induced a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates.

Trial Registration: ClinicalTrials.gov Identifier: NCT02680587.
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http://dx.doi.org/10.1001/jamaoncol.2020.0147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225913PMC
May 2020

Who Benefits From a Prostate Rectal Spacer? Secondary Analysis of a Phase III Trial.

Pract Radiat Oncol 2020 May - Jun;10(3):186-194. Epub 2020 Jan 21.

The Department of Radiation Oncology, Beaumont Hospital, Dearborn, Michigan. Electronic address:

Purpose: Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit.

Methods And Materials: Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical benefit and plan quality. Mean bowel QOL was assessed at 15 and 36 months posttreatment and the likelihood of 1× (5 points) or 2× (10 points) minimally important difference changes were assessed.

Results: Rectal V70 was correlated with physician scored toxicity (P = .033) and was used as a surrogate for plan quality. There was no correlation between prostate volume and rectal V70 (r = 0.077). Rectal V70 pre- and post-hydrogel was 13% and 3% for the smallest prostates (<40 mL) and 12% and 2% for the largest (>80 mL). The relative reduction in rectal V70 of 78% did not vary by prespacer V70, but the absolute reduction was greater for a higher V70. All spacer plans met the 5 QUANTEC rectal dose constraints, although 92% of control plans met all constraints. At 3 years, those not meeting all QUANTEC goals had a 15.0-point (standard deviation 15.1) decline, control patients meeting QUANTEC goals had a 4.0-point (9.5) decline, and spacer had >0.5 (7.6; P < .01). Previous surgery was not correlated with QOL (P = .8). Across prognostic groups, including age, body mass index, previous surgery, target volume, or quality of radiation plans, there was no statistically significant heterogeneity in the relative benefit of spacer in decreasing the risk of 1× or 2× the minimally important difference declines.

Conclusions: There was little heterogeneity in the likelihood of spacer reducing the risk of declines in bowel QOL across clinical and dosimetric variables. Even for the >95% of plans meeting QUANTEC rectal criteria, hydrogel spacer provided potentially meaningful benefits.
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http://dx.doi.org/10.1016/j.prro.2019.12.011DOI Listing
December 2020

Design and construction of a Maxwell-type induction coil for magnetic nanoparticle hyperthermia.

Int J Hyperthermia 2020 ;37(1):1-14

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

We describe a modified Helmholtz induction coil, or Maxwell coil, that generates alternating magnetic fields (AMF) having field uniformity (≤10%) within  = 3000 cm volume of interest for magnetic hyperthermia research. Two-dimensional finite element analysis (2D-FEA) was used for electromagnetic design of the induction coil set and to develop specifications for the required matching network. The matching network and induction coil set were fabricated using best available practices and connected to a 120 kW industrial induction heating power supply. System performance was evaluated by magnetic field mapping with a magnetic field probe, and tests were performed using gel phantoms. Tests verified that the system generated a target peak AMF amplitude along the coil axis of ∼35 kA/m (peak) at a frequency of 150 ± 10 kHz while maintaining field uniformity to >90% of peak for a volume of ∼3000 cm. The induction coil apparatus comprising three independent loops, i.e., Maxwell-type improves upon the performance of simple solenoid and Helmholtz coils by providing homogeneous flux density fields within a large volume while minimizing demands on power and stray fields. Experiments with gel phantoms and analytical calculations show that future translational research efforts should be devoted to developing strategies to reduce the impact of nonspecific tissue heating from eddy currents; and, that an inductor producing a homogeneous field has significant clinical potential for deep-tissue magnetic fluid hyperthermia.
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http://dx.doi.org/10.1080/02656736.2019.1704448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956739PMC
October 2020

Improvements in Physician Clinical Workflow Measures After Implementation of a Dashboard Program.

Pract Radiat Oncol 2020 May - Jun;10(3):151-157. Epub 2019 Dec 5.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland. Electronic address:

Purpose: To determine whether a combination of data-driven, personalized feedback and implementation of a graduated, sequential intervention model improved key measures of physician workflow and quality in radiation treatment planning.

Methods And Materials: All radiation oncologists across 3 facilities at a single academic institution were prospectively evaluated on 5 predefined metrics of timeliness and accuracy in the treatment-planning process using a web-based institutional data repository and an institutional incident learning system. The study period encompassed 10 quarters from 2014 to 2016, with 2013 serving as a retrospective baseline. Physicians received quarterly individualized reports of their compliance metrics (a practice labeled the Physician Dashboard), and administrative interventions were initiated if >20% noncompliance with any metric was exceeded within a quarter. Consecutive quarters of noncompliance resulted in escalating interventions, including progress meetings with department leadership, and culminated in financial penalties. Rates of noncompliance were compared before and after implementation of this model.

Results: Three thousand six hundred sixty pre-Dashboard and 9497 post-Dashboard simulations were analyzed. After Dashboard implementation, significant reductions were observed in the rates of simulation orders requiring signature by a covering physician (14.1% vs 7.4%, P < .001), and the submission of plan contours ≥1 day (43.1% vs 23.1%, P < .001) or ≥2 days (30.8% vs 18.3%, P = .002) after the due date. There was some decrease in rates of inaccurate or incomplete plan submissions (6.2% vs 3.9%, P = .08). Seven of the 12 physicians received at least 1 intervention, with only 2 receiving all levels of intervention.

Conclusions: Regular assessment and targeted feedback using the Physician Dashboard significantly improved radiation oncologist compliance with clinically meaningful treatment planning responsibilities at a high-volume academic center.
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http://dx.doi.org/10.1016/j.prro.2019.11.014DOI Listing
December 2020

Frequency of Complicated Symptomatic Bone Metastasis Over a Breadth of Operational Definitions.

Int J Radiat Oncol Biol Phys 2020 03 2;106(4):800-810. Epub 2019 Dec 2.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Purpose: Numerous randomized trials have demonstrated noninferiority of single- versus multiple-fraction palliative radiation therapy (RT) in the management of uncomplicated bone metastases; yet there is neither a clear definition of what constitutes a complicated lesion, nor substantial data regarding the prevalence of such complicating features in clinical practice. Thus, we identify a range of evidence-based operational definitions of complicated symptomatic bone metastases and characterize the frequency of such complicating features at a high-volume, tertiary care center.

Methods And Materials: A retrospective review of patients seen in consultation for symptomatic bone metastases between March 1, 2007, and July 31, 2013, at Johns Hopkins Hospital identified patient and disease characteristics. Descriptive statistics characterized the frequency of the following complicating features: prior RT, prior surgery, neuraxis compromise, pathologic fracture, and soft tissue component at the symptomatic site. A range of definitions for complicated bone metastases was evaluated based on combinations of these features. Uni- and multivariable logistic regressions evaluated the odds of complicated bone metastases as a function of site of primary cancer and of the symptomatic target lesion.

Results: A total of 686 symptomatic bone metastases in 401 patients were evaluated. Percent of target sites complicated by prior RT was 4.4%, prior surgery was 8.9%, pathologic fracture was 20.6%, neuraxis compromise was 52.0% among spine and medial pelvis sites, and soft tissue component was 38.6%. More than 96 possible definitions of complicated bone metastases were identified. The presence of such complicated lesions ranged from 2.3% to 67.3%, depending on the operational definition used. Odds of a complicated lesion were significantly higher for spine sites and select nonbreast histologies.

Conclusions: In this retrospective study, we found complicated symptomatic bone metastases may be present in up to two-thirds of patients. Literature review also demonstrates no clear standard definition of complicated bone metastases, potentially explaining underutilization of single-fraction palliative RT in this setting.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954524PMC
March 2020

Metastasis-Directed Therapy in Prostate Cancer. Why, When, and How?

Oncology (Williston Park) 2019 Oct 28;33(10). Epub 2019 Oct 28.

Metastatic prostate cancer remains a life-limiting disease; while we have seen significant advances in systemic approaches which form the backbone of management, no curative paradigm yet exists. Metastasis-directed therapy (MDT) with stereotactic ablative radiotherapy (SABR) has emerged as a promising complementary technique for the management of low-volume metastatic prostate cancer. Herein we will review the rationale, potential benefits, and practical considerations associated with this approach.
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October 2019

Examinations in Radiation Oncology: Listening, Learning, and Looking Forward Together.

Int J Radiat Oncol Biol Phys 2020 01 21;106(1):29-31. Epub 2019 Oct 21.

John Hopkins School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.ijrobp.2019.10.012DOI Listing
January 2020

Analysis of Spatial Dose-Volume Relationships and Decline in Sexual Function Following Permanent Brachytherapy for Prostate Cancer.

Urology 2020 Jan 24;135:111-116. Epub 2019 Aug 24.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, MD. Electronic address:

Objective: To explore relationships between dose to periprostatic anatomic structures and erectile dysfunction (ED) outcomes in an institutional cohort treated with prostate brachytherapy.

Methods: The Sexual Health Inventory for Men (SHIM) instrument was administered for stage cT1-T2 prostate cancer patients treated with Pd-103 brachytherapy over a 10-year interval. Dose volume histograms for regional organs at risk and periprostatic regions were calculated with and without expansions to account for contouring uncertainty. Regression tree analysis clustered patients into ED risk groups.

Results: We identified 115 men treated with definitive prostate brachytherapy who had 2 years of complete follow-up. On univariate analysis, the subapical region (SAR) caudal to prostate was the only defined region with dose volume histograms parameters significant for potency outcomes. Regression tree analysis separated patients into low ED risk (mean 2-year SHIM 20.03), medium ED risk (15.02), and high ED risk (5.54) groups. Among patients with good baseline function (SHIM ≥ 17), a dose ≥72.75 Gy to 20% of the SAR with 1 cm expansion was most predictive for 2-year potency outcome. On multivariate analysis, regression tree risk group remained significant for predicting potency outcomes even after adjustment for baseline SHIM and age.

Conclusion: Dose to the SAR immediately caudal to prostate was predictive for potency outcomes in patients with good baseline function. Minimization of dose to this region may improve potency outcomes following prostate brachytherapy.
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http://dx.doi.org/10.1016/j.urology.2019.08.014DOI Listing
January 2020

Radiation Therapy in the Definitive Management of Oligometastatic Prostate Cancer: The Johns Hopkins Experience.

Int J Radiat Oncol Biol Phys 2019 12 13;105(5):948-956. Epub 2019 Aug 13.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:

Purpose: The use of radiation therapy (RT) in consolidating oligometastatic prostate cancer (OPCa) is a rapidly evolving treatment paradigm. We review our institutional experience using metastasis-directed therapy in the definitive management of men with OPCa.

Methods And Materials: Patients with OPCa treated with definitive RT were included. The Kaplan-Meier method and multivariable Cox regression analysis were performed to assess biochemical progression-free survival (bPFS) and time to next intervention. Cumulative incidence functions were used to calculate rates of local failure. Toxicity was assessed using Common Terminology Criteria for Adverse Events (version 4).

Results: This study analyzed 156 patients with OPCa and 354 metastatic lesions with median follow-up of 24.6 months. Of 150 patients with toxicity data, 53 (35%) experienced acute grade 1 toxicity, 8 (5%) had grade 2, and none had grade 3 toxicity. Only 13 patients (9%) had late toxicities. At 24 months, the cumulative incidence of local failure was 7.4%. Median bPFS for the entire cohort was 12.9 months and 52% at 1 year. On multivariable analysis, factors associated with prolonged bPFS were peri-RT androgen deprivation therapy (ADT), lower gross tumor volume, and hormone-sensitive (HS) OPCa. Median time to next intervention, including repeat RT, was 21.6 months. Median bPFS for men with HS prostate cancer was 17.2 months compared with 7.2 months in men with castrate-resistant OPCa (P < .0001), and cumulative incidence of local failure at 24 months was lower with HS OPCa (4.8% vs 12.1%; P = .034). We analyzed 28 men with HS OPCa treated with a course of peri-RT ADT (median, 4.3 months) with recovery of testosterone. At a median follow-up of 33.5 months, 20 patients had not developed bPFS, median bPFS had not been reached, and 24-month bPFS was 77%.

Conclusions: Metastasis-directed therapy can be effective across a wide range of OPCa subtypes, but with differential efficacy. Further study is warranted to investigate the use of RT across the wide range of patients with OPCa.
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http://dx.doi.org/10.1016/j.ijrobp.2019.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050213PMC
December 2019

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA).

BMC Cancer 2019 Jun 13;19(1):572. Epub 2019 Jun 13.

Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 1550 Orleans Street, CRB2 Rm 406, Baltimore, MD, 21231, USA.

Background: In men with a rising PSA following radical prostatectomy, salvage radiation therapy (SRT) offers a second chance for cure. Hormonal therapy can be combined with SRT in order to increase prostate tumor control, albeit with associated higher rates of treatment side effects. This trial studies the effectiveness of SRT combined with hormonal therapy using a more potent anti-androgen with a favorable side effect profile. Enzalutamide, a next generation selective androgen receptor antagonist, is approved by the Food and Drug Administration for the treatment of metastatic castrate-resistant prostate cancer (CRPC) where it has been shown to improve overall survival in combination with androgen deprivation therapy. The primary objective of this study is to evaluate the efficacy of combination SRT and enzalutamide for freedom-from-PSA-progression. Secondary objectives include time to local recurrence within the radiation field, metastasis-free survival and safety as determined by frequency and severity of adverse events.

Methods/design: This is a randomized, double-blind, phase II, prospective, multicenter study in adult males with biochemically recurrent prostate cancer following radical prostatectomy. Following registration, enzalutamide 160 mg or placebo by mouth (PO) once daily will be administered for 6 months. Following two months of study drug, external beam radiotherapy to 66.6-70.2 Gray (Gy) will be administered to the prostate bed over 7-8 weeks while continuing daily placebo/enzalutamide. This is followed by two additional months of placebo/enzalutamide.

Discussion: The SALV-ENZA trial is the first phase II placebo-controlled double-blinded randomized study to test SRT in combination with a next generation androgen receptor antagonist in men with high-risk recurrent prostate cancer after radical prostatectomy. The primary hypothesis of this study is that clinical outcomes will be improved by the addition of enzalutamide compared to standard-of-care SRT alone and pave the path for phase III evaluation of this combination.

Trial Registrations: ClinicaltTrials.gov Identifier: NCT02203695 Date of Registration: 06/16/2014. Date of First Participant Enrollment: 04/16/2015.
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http://dx.doi.org/10.1186/s12885-019-5805-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567492PMC
June 2019

Adoption of an incident learning system in a regionally expanding academic radiation oncology department.

Rep Pract Oncol Radiother 2019 Jul-Aug;24(4):338-343. Epub 2019 Jun 1.

Johns Hopkins University, Department of Radiation Oncology and Molecular Radiation Sciences, 40 North Broadway, Baltimore, MD 21231, USA.

Aim And Background: We describe a successful implementation of a departmental incident learning system (ILS) across a regionally expanding academic radiation oncology department, dovetailing with a structured integration of the safety and quality program across clinical sites.

Materials And Methods M: Over 6 years between 2011 and 2017, a long-standing departmental ILS was deployed to 4 clinical locations beyond the primary clinical location where it had been established. We queried all events reported to the ILS during this period and analyzed trends in reporting by clinical site. The chi-square test was used to determine whether differences over time in the rate of reporting were statistically significant. We describe a synchronous development of a common safety and quality program over the same period.

Results: There was an overall increase in the number of event reports from each location over the time period from 2011 to 2017. The percentage increase in reported events from the first year of implementation to 2017 was 457% in site 1, 166.7% in site 2, 194.3% in site 3, 1025% in site 4, and 633.3% in site 5, with an overall increase of 677.7%. A statistically significant increase in the rate of reporting was seen from the first year of implementation to 2017 ( < 0.001 for all sites).

Conclusions: We observed significant increases in event reporting over a 6-year period across 5 regional sites within a large academic radiation oncology department, during which time we expanded and enhanced our safety and quality program, including regional integration. Implementing an ILS and structuring a safety and quality program together result in the successful integration of the ILS into existing departmental infrastructure.
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http://dx.doi.org/10.1016/j.rpor.2019.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545410PMC
June 2019

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

Eur Urol 2020 01 13;77(1):3-10. Epub 2019 Apr 13.

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

Background: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases.

Objective: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).

Design, Setting, And Participants: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT).

Outcome Measurements And Statistical Analysis: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment.

Results And Limitations: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS).

Conclusions: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted.

Patient Summary: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.
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http://dx.doi.org/10.1016/j.eururo.2019.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521828PMC
January 2020

Immunomodulatory Effects of Stereotactic Body Radiation Therapy: Preclinical Insights and Clinical Opportunities.

Int J Radiat Oncol Biol Phys 2019 Mar 2. Epub 2019 Mar 2.

Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.ijrobp.2019.02.046DOI Listing
March 2019

Patterns of Incident Reporting Across Clinical Sites in a Regionally Expanding Academic Radiation Oncology Department.

J Am Coll Radiol 2019 Jul 7;16(7):915-921. Epub 2019 Feb 7.

Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland. Electronic address:

Purpose: We evaluated patterns of event reporting across five clinical locations within an academic radiation oncology department, with the goal of better understanding variability across sites.

Methods And Materials: We analyzed 1,351 events reported to a departmental incident learning system over 1 calendar year across the five locations with respect to volume of events, event type, process map location of origin and detection, and event reporter.

Results: We found marked variability in reporting patterns, including reporting rate, event type, event severity, event location of origin and detection within the departmental process map, and discipline of event reporters. These differences relate both to variability in process and workflow (reflected by frequency of specific workflow events at each site) and in reporting culture (reflected by volume or rate of event reporting, and discipline of event reporter).

Conclusions: These data highlight the variability in reporting culture even within a single department, and therefore the need to tailor and individualize safety and quality programs to the unique clinical site, with the long-term goal of achieving a common culture of safety while supporting unique processes at individual locations. This work also raises concern about extrapolating single-institution incident learning system results without understanding the unique workflow and culture of clinical sites.
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http://dx.doi.org/10.1016/j.jacr.2018.12.010DOI Listing
July 2019

Association of a Simulated Institutional Gender Equity Initiative With Gender-Based Disparities in Medical School Faculty Salaries and Promotions.

JAMA Netw Open 2018 12 7;1(8):e186054. Epub 2018 Dec 7.

Department of Radiation and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Despite progress in narrowing gender-based salary gaps, notable disparities persist in the scientific community. The significance of pay difference may be underestimated, with little data evaluating its effect on lifetime wealth after accounting for factors like time to promotion and savings.

Objectives: To characterize gender disparities in salary and assess the outcomes associated with a gender equity initiative (GEI).

Design, Setting, And Participants: Quality improvement study with simulations of salary and additional accumulated wealth (AAW) using retrospectively reviewed Johns Hopkins University School of Medicine annual salary and promotion data. All academic faculty were included in the faculty salary analysis from 2005 (n = 1481) and 2016 (n = 1885).

Main Outcomes And Measures: Salary and longitudinal promotion data from 2005 to 2016 were used to estimate gender-based differences in salary and time to promotion. The effect of these differences on total salary and AAW, including retirement and salary-based investments, was simulated for a representative male and female faculty member over a 30-year career in 3 scenarios: (1) pre-GEI, (2) post-GEI, and (3) in real time for GEI, beginning with and progressing through these initiatives.

Results: Analyses of salaries of 1481 faculty (432 women) in 2005 and 1885 faculty (742 women) in 2016 revealed that a decade after GEI implementation, the overall mean (SE) salary gap by gender decreased from -2.6% (1.2%) (95% CI, -5.6% to -0.3%) to -1.9% (1.1%) (95% CI, -4.1% to 0.3%). Simulation of pre-GEI disparities correlated with male faculty collecting an average lifetime AAW of $501 416 more than the equivalent woman, with disparities persisting past retirement. The AAW gap decreased to $210 829 in the real-time GEI simulation and to $66 104 using post-GEI conditions, reflecting success of GEI efforts.

Conclusions And Relevance: Even small gender-based salary gaps are associated with substantial differences in lifetime wealth, but an institutional commitment to achieving equitable promotion and compensation for women can appreciably reduce these disparities. The findings of this study support broad implementation of similar initiatives without delay, as results may take more than a decade to emerge. A modifiable version of the simulation is provided so that external users may assess the potential disparities present within their own institutions.
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http://dx.doi.org/10.1001/jamanetworkopen.2018.6054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324345PMC
December 2018

Needs and Challenges for Radiation Oncology in the Era of Precision Medicine.

Int J Radiat Oncol Biol Phys 2019 03 15;103(4):809-817. Epub 2018 Dec 15.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland.

Modern medicine, including the care of the cancer patient, has significantly advanced, with the evidence-based medicine paradigm serving to guide clinical care decisions. Yet we now also recognize the tremendous heterogeneity not only of disease states but of the patient and his or her environment as it influences treatment outcomes and toxicities. These reasons and many others have led to a reevaluation of the generalizability of randomized trials and growing interest in accounting for this heterogeneity under the rubric of precision medicine as it relates to personalizing clinical care predictions, decisions, and therapy for the disease state. For the cancer patient treated with radiation therapy, characterizing the spatial treatment heterogeneity has been a fundamental tenet of routine clinical care facilitated by established database and imaging platforms. Leveraging these platforms to further characterize and collate all clinically relevant sources of heterogeneity that affect the longitudinal health outcomes of the irradiated cancer patient provides an opportunity to generate a critical informatics infrastructure on which precision radiation therapy may be realized. In doing so, data science-driven insight discoveries, personalized clinical decisions, and the potential to accelerate translational efforts may be realized ideally within a network of institutions with locally developed yet coordinated informatics infrastructures. The path toward realizing these goals has many needs and challenges, which we summarize, with many still to be realized and understood. Early efforts by our group have identified the feasibility of this approach using routine clinical data sets and offer promise that this transformation can be successfully realized in radiation oncology.
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http://dx.doi.org/10.1016/j.ijrobp.2018.11.017DOI Listing
March 2019

Local failure is a dominant mode of recurrence in locally advanced and clinical node positive prostate cancer patients treated with combined pelvic IMRT and androgen deprivation therapy.

Urol Oncol 2019 04 13;37(4):289.e19-289.e26. Epub 2018 Nov 13.

Department of Radiation Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. Electronic address:

Background: The recurrence patterns of high-risk, N1 prostate cancer after radiation therapy (RT) including the pelvic lymph nodes have not been fully investigated.

Material And Methods: We have a prospective clinical study since 2004 that has followed 138 men with locally advanced prostate cancer (T1-T4N0-N1M0) treated with definitive RT encompassing the prostate and pelvic lymph nodes and long-term androgen deprivation therapy (ADT). Forty nine of the 52 patients that developed recurrence were imaged at biochemical failure to detect the site of recurrence.

Results: Imaging identified the site of recurrence in 46 patients. Twenty five patients had prostatic recurrence only, none had local lymph node recurrence only, 11 had distant metastases only, 7 had prostatic recurrence and distant metastases, 2 had prostatic recurrence, local nodal recurrence and distant metastases, and 1 had local nodal recurrence with distant metastases. The mean time to recurrence was 62 months for prostate only, 40 months for distant only and 50 months for prostate and distant recurrence. There was a 69% recurrence rate for patients with magnetic resonance imaging -detected N1 disease. There was significantly longer survival for patients with prostate recurrence only compared to patients with distant recurrence (P < 0.018). Five-year prostate cancer-specific survival were 85% for prostate only, 44% for distant only and 48% for prostate and distant recurrence (prostate only vs. distant only; P = 0.008, prostate only vs. prostate and distant; P = 0.018, distant vs. prostate and distant; P = 0.836).

Conclusions: The predominant recurrence pattern for high-risk, N1 prostate cancer was prostatic recurrence and distant spread after pelvic RT and androgen deprivation therapy. Our data argue for further local dose escalation and pelvic nodal radiation to prevent recurrence in these sites. Lymph node metastasis at initial staging with an magnetic resonance imaging was a strong predictor of recurrence and poor survival and may identify patients in need of more aggressive treatment.
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http://dx.doi.org/10.1016/j.urolonc.2018.09.016DOI Listing
April 2019