Publications by authors named "Neil Desai"

83 Publications

Metastasis-directed radiation therapy after radical cystectomy for bladder cancer.

Urol Oncol 2021 Jun 29. Epub 2021 Jun 29.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address:

Purpose: Metastasis-directed radiation therapy (MDRT) may improve oncologic and quality of life outcomes in patients with metastatic cancer, but data on its use in metastatic bladder cancer is severely limited. We sought to review our institutional experience with MDRT in patients with metastatic bladder cancer following radical cystectomy.

Materials And Methods: We reviewed records of patients who underwent radical cystectomy and subsequent MDRT at our institution between 2009 and 2020. Baseline demographic and clinical/pathologic factors were collected, as were details of treatment including systemic therapy and MDRT. Cases were categorized by treatment intent as consolidative (intended to prolong survival) and palliative (intended only to relieve symptoms). Response to treatment, survival, and toxicity outcomes were reviewed.

Results: A total of 52 patients underwent MDRT following radical cystectomy. MDRT was categorized as consolidative in 40% of cases and palliative in 60%. Toxicity (CTCAE Grade ≥ 2) was reported in 15% of patients, none of which exceeded Grade 3. Most patients undergoing consolidative MDRT were treated with SBRT techniques (76%) and a majority (67%) received concurrent treatment with an immuno-oncology agent. Among patients treated with consolidative intent, 2-year progression-free and overall survival were 19% and 60%, respectively.

Conclusion: MDRT is safe and well-tolerated by a majority of patients. A majority of patients treated with consolidative intent survived ≥ 2 years from treatment.
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http://dx.doi.org/10.1016/j.urolonc.2021.05.005DOI Listing
June 2021

Hydrogel Spacer Rectal Wall Infiltration Associated With Severe Rectal Injury and Related Complications After Dose Intensified Prostate Cancer Stereotactic Ablative Radiation Therapy.

Adv Radiat Oncol 2021 Jul-Aug;6(4):100713. Epub 2021 May 9.

Department of Radiation Oncology, University of Texas Southwestern, Dallas, Texas.

The risk of rectal toxicity during and after prostate cancer radiation therapy is common to all treatment regimens. Hydrogel rectal spacers are increasingly being used to mitigate this risk and to facilitate dose-escalation, but also may infiltrate the rectal wall, with unclear clinical implication. We present a case of significant infiltration associated with severe late rectal injury (grade 4) and further grade 3 to 4 sequelae (recto-urethral fistula and associated osteomyelitis requiring exenteration) after high-dose stereotactic body radiation therapy for localized prostate cancer. The injury's temporal pattern associated with the expected timing of gel dissolution and displacement of infiltrated rectal layers potentially toward high dose regions together suggest a contributing role of the infiltration to the injury. In light of the rapid increase of hydrogel rectal spacer utilization, we review the case's evolution, concerning imaging findings, and associated literature and make suggestions regarding treatment planning and endoscopic assessment in the setting of infiltration or expected injury.
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http://dx.doi.org/10.1016/j.adro.2021.100713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239444PMC
May 2021

A deep learning-based framework for segmenting invisible clinical target volumes with estimated uncertainties for post-operative prostate cancer radiotherapy.

Med Image Anal 2021 Aug 17;72:102101. Epub 2021 May 17.

Medical Artificial Intelligence and Automation Laboratory and Department of Radiation Oncology,University of Texas Southwestern Medical Center, Dallas, Texas, United States. Electronic address:

In post-operative radiotherapy for prostate cancer, precisely contouring the clinical target volume (CTV) to be irradiated is challenging, because the cancerous prostate gland has been surgically removed, so the CTV encompasses the microscopic spread of tumor cells, which cannot be visualized in clinical images like computed tomography or magnetic resonance imaging. In current clinical practice, physicians' segment CTVs manually based on their relationship with nearby organs and other clinical information, but this allows large inter-physician variability. Automating post-operative prostate CTV segmentation with traditional image segmentation methods has yielded suboptimal results. We propose using deep learning to accurately segment post-operative prostate CTVs. The model proposed is trained using labels that were clinically approved and used for patient treatment. To segment the CTV, we segment nearby organs first, then use their relationship with the CTV to assist CTV segmentation. To ease the encoding of distance-based features, which are important for learning both the CTV contours' overlap with the surrounding OARs and the distance from their borders, we add distance prediction as an auxiliary task to the CTV network. To make the DL model practical for clinical use, we use Monte Carlo dropout (MCDO) to estimate model uncertainty. Using MCDO, we estimate and visualize the 95% upper and lower confidence bounds for each prediction which informs the physicians of areas that might require correction. The model proposed achieves an average Dice similarity coefficient (DSC) of 0.87 on a holdout test dataset, much better than established methods, such as atlas-based methods (DSC<0.7). The predicted contours agree with physician contours better than medical resident contours do. A reader study showed that the clinical acceptability of the automatically segmented CTV contours is equal to that of approved clinical contours manually drawn by physicians. Our deep learning model can accurately segment CTVs with the help of surrounding organ masks. Because the DL framework can outperform residents, it can be implemented practically in a clinical workflow to generate initial CTV contours or to guide residents in generating these contours for physicians to review and revise. Providing physicians with the 95% confidence bounds could streamline the review process for an efficient clinical workflow as this would enable physicians to concentrate their inspecting and editing efforts on the large uncertain areas.
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http://dx.doi.org/10.1016/j.media.2021.102101DOI Listing
August 2021

Effect of Repetitive Simulation Training on Emergency Medical Services Team Performance in Simulated Pediatric Medical Emergencies.

AEM Educ Train 2021 Jul 5;5(3):e10537. Epub 2020 Nov 5.

Department of Pediatrics Section of Pediatric Emergency Medicine University of Colorado School of Medicine Aurora CO USA.

Objective: Emergency medical services (EMS) professionals infrequently transport children leading to difficulty in recognition and management of pediatric critical illness. Simulation provides an opportunity to train EMS professionals on pediatric emergencies. The objective of this study was to examine the effect of serial simulation training over 6 months on EMS psychomotor and cognitive performance during team-based care.

Methods: This was a longitudinal prospective study of a simulation curriculum enrolling EMS professionals over a 6-month period during which they performed three high-fidelity simulations at 3-month intervals. The simulation scenarios included a 15-month-old seizure (T), 1-month-old with hypoglycemia (T), and 4-year-old clonidine ingestion (T). All scenarios were standardized and required recognition and management of respiratory failure and decompensated shock. Scenarios were videotaped and two investigators scored EMS team interventions during simulations using a standardized scoring tool. Inter-rater reliability was assessed on 30% of videos using kappa analysis. Volumes of administered intravenous fluid (IVF) and medications were measured to assess for errors in administration. The primary outcome was the change in scenario score from T to T.

Results: A total of 135 team-based simulations were conducted over the study period (48, 40, and 47 at T, T, and T, respectively). Inter-rater reliability between reviewers was very good (κ = 0.7). Median simulation score improved from T to T (24 vs 31, p < 0.001, maximum score possible = 42). The proportion of completed tasks increased across multiple categories including improved recognition of respiratory decompensation (19% vs. 56%), management of the pediatric airway (44% vs. 88%), and timeliness of vascular access (10% vs. 38%). Correct IVF administration varied by scenario (25% vs. 52% vs. 30%, p = 0.02).

Conclusion: Serial simulation improved EMS team-based care in both recognition and management of pediatric emergencies. A standardized pediatric simulation curriculum can be used to train EMS professionals on pediatric emergencies and improve performance.
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http://dx.doi.org/10.1002/aet2.10537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166302PMC
July 2021

Effect of the COVID-19 Pandemic on Patient Volumes, Acuity, and Outcomes in Pediatric Emergency Departments: A Nationwide Study.

Pediatr Emerg Care 2021 Jun 1. Epub 2021 Jun 1.

From the Divisions of Pediatric Emergency Medicine and Clinical Pharmacology and Toxicology Biostatistical Design and Analysis team, The Hospital for Sick Children, University of Toronto, Toronto Department of Pediatrics and Emergency Medicine, University of Ottawa and Children's Hospital of Eastern Ontario, Ottawa, Ontario Division of Pediatric Emergency Medicine, Montreal Children's Hospital, McGill University, Montreal, Quebec Department of Pediatrics, Division of Emergency Medicine, McMaster Children's Hospital, Hamilton, Ontario Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta Division of Pediatric Emergency Medicine, British Columbia Children's Hospital, Vancouver, British Columbia Department of Pediatrics and Emergency Medicine, University of Manitoba, Winnipeg, Manitoba Department of Emergency Medicine, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia Division of Pediatric Emergency Medicine, Department of Pediatrics, Schulich School of Medicine, Western University, London, Ontario Division Pediatric Emergency Medicine, Jim Pattison Children's Hospital, University of Saskatchewan, Saskatoon, Saskatchewan Division of Pediatric Emergency Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario Sections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Objectives: The aim of this study was to quantify the effect of the COVID-19 pandemic on pediatric emergency department (ED) utilization and outcomes.

Methods: This study is an interrupted-time-series observational study of children presenting to 11 Canadian tertiary-care pediatric EDs. Data were grouped into weeks in 3 study periods: prepandemic (January 1, 2018-January 27, 2020), peripandemic (January 28, 2020-March 10, 2020), and early pandemic (March 11, 2020-April 30, 2020). These periods were compared with the same time intervals in the 2 preceding calendar years. Primary outcomes were number of ED visits per week. The secondary outcomes were triage acuity, hospitalization, intensive care unit (ICU) admission, mortality, length of hospital stay, ED revisits, and visits for trauma and mental health concerns.

Results: There were 577,807 ED visits (median age, 4.5 years; 52.9% male). Relative to the prepandemic period, there was a reduction [-58%; 95% confidence interval (CI), -63% to -51%] in the number of ED visits during the early-pandemic period, with concomitant higher acuity. There was a concurrent increase in the proportion of ward [odds ratio (OR), 1.39; 95% CI, 1.32-1.45] and intensive care unit (OR, 1.20; 95% CI, 1.01-1.42) admissions, and trauma-related ED visits among children less than 10 years (OR, 1.51; 95% CI, 1.45-1.56). Mental health-related visits in children declined in the early-pandemic period (in <10 years, -60%; 95% CI, -67% to -51%; in children ≥10 years: -56%; 95% CI, -63% to -47%) relative to the pre-COVID-19 period. There were no differences in mortality or length of stay; however, ED revisits within 72 hours were reduced during the early-pandemic period (percent change: -55%; 95% CI, -61% to -49%; P < 0.001).

Conclusions: After the declaration of the COVID-19 pandemic, dramatic reductions in pediatric ED visits occurred across Canada. Children seeking ED care were sicker, and there was an increase in trauma-related visits among children more than 10 years of age, whereas mental health visits declined during the early-pandemic period. When faced with a future pandemic, public health officials must consider the impact of the illness and the measures implemented on children's health and acute care needs.
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http://dx.doi.org/10.1097/PEC.0000000000002484DOI Listing
June 2021

The scope of hospital medicine practice at night: a national survey of night shift hospitalists.

Hosp Pract (1995) 2021 Jun 8:1-6. Epub 2021 Jun 8.

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

: Although in-person hospitalist presence, increasingly staffed by dedicated nocturnists, has become the norm overnight in the hospital, the scope of nocturnist practice and typical workload has not been defined. This study examines the clinical responsibilities and patient safety perceptions of hospitalists who work night shifts in the United States.: In the fall of 2019, a cross-sectional, web-based survey was administered to physician and nurse practitioner/physician assistant (NP/PA) hospitalists who work night shifts. The questionnaire assessed night staffing structure, typical responsibilities, patient volume, perceptions of safety overnight, as well as demographic information. The survey was posted on the Society of Hospital Medicine (SHM) Hospital Medicine Exchange (HMX) Online Discussion Forum. Additionally, the survey was distributed by 'snowball method' by respondents to other night hospitalists. Responses were collected anonymously.: Of the 167 respondents, 157 reported working night shifts. There was at least one respondent from 32 different states. In addition to performing admissions to medicine services and covering inpatients, night hospitalists cover ICU patients, participate in RRT/Code teams and procedure teams, perform consults, participate in medical education, and take outpatient calls. Across institutions, there was a large distribution in numbers of patients covered in a night shift; however, patient volume fell into typical ranges: 5-10 admissions for physicians, 0-6 admissions for NP/PAs, and 25-75 patient cross-coverage census. When physicians perform more than five admissions per night, hospitalists were less likely to agree that they could provide safe care (88% vs. 63%, = 0.0006).: This is the first national study to examine the clinical responsibilities of hospitalists working overnight. Overnight responsibilities are heterogeneous across institutions. As hospitals are increasingly employing nocturnists, more research is needed to guide night staffing and optimize patient safety.
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http://dx.doi.org/10.1080/21548331.2021.1932507DOI Listing
June 2021

Combined immune checkpoint blockade and radiotherapy induces durable remission in relapsed natural killer/T-cell lymphoma: a case report and review of the literature.

J Med Case Rep 2021 Apr 30;15(1):221. Epub 2021 Apr 30.

Division of Hematologic Malignancies and Stem Cell Transplantation, Harold. C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Background: Extranodal natural killer/T-cell lymphoma is a rare, aggressive non-Hodgkin lymphoma that is treated upfront mostly with L-asparaginase containing regimens. Relapsed extranodal natural killer/T-cell lymphoma is associated with a poor prognosis, and there is no established standard of care.

Case Presentation: We report the case of a 72 year-old white male with a distant extranasal relapse of extranodal natural killer/T-cell lymphoma that has been managed successfully with a combination of radiation and immune checkpoint blockade with pembrolizumab. Pseudoprogression with new skin and bone lesions on positron emission tomography imaging was encountered during this Caucasian patient's immunotherapy and was successfully managed with supportive care and continuation of immune checkpoint blockade.

Conclusions: The patient has been in complete clinical, radiologic, and molecular remission for close to 3 years and has not had any immune-related adverse effects. Pseudoprogression is a clinical challenge that can be encountered while patients are treated with immunotherapy, and astute clinical acumen is needed for accurate management. We believe this is the longest duration of response to immune checkpoint blockade in relapsed extranodal natural killer/T-cell lymphoma reported to date in literature. There is a strong biologic rationale in combining radiation with immunotherapy. The optimal timing, dose, and duration of radiation combined with immunotherapy in extranodal natural killer/T-cell lymphoma need to be prospectively evaluated.
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http://dx.doi.org/10.1186/s13256-021-02798-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086114PMC
April 2021

A Multi-Institutional Phase 2 Trial of High-Dose SAbR for Prostate Cancer Using Rectal Spacer.

Int J Radiat Oncol Biol Phys 2021 Mar 19. Epub 2021 Mar 19.

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.

Purpose: High-dose SABR for prostate cancer offers the radiobiologic potency of the most intensified radiation therapy regimens but was associated with >90% rates of ulceration of the anterior rectal wall on endoscopic assessment; this infrequently progressed to severe rectal toxicity in prior prospective series. A multi-institutional phase 2 prospective trial was conducted to assess whether placement of a perirectal hydrogel spacer would reduce acute periprostatic rectal ulcer events after high-dose (>40 Gy) SABR.

Methods And Materials: Eligible patients included men with stage ≤T2c localized grade group 1 to 3 prostate cancer, a prostate-specific antigen (PSA) level ≤15 ng/mL, American Urological Association Symptom Index = AUA-SI scores ≤18, and a gland volume ≤80 cm. Patients underwent perirectal hydrogel spacer placement, followed by SABR of 45 Gy in 5 fractions every other day to the prostate only. Androgen deprivation was not allowed except for cytoreduction. The rectal wall was directly assessed by serial anoscopy during follow-up to determine whether the spacer would reduce acute periprostatic rectal ulcer events from >90% to <70% within 9 months of treatment.

Results: Forty-four men were enrolled and 43 were eligible for protocol analysis. The median follow-up for surviving patients was 48 months. Acute periprostatic ulcers were observed in 6 of 42 patients (14.3%; 95% confidence interval, 6.0%-27%; P < .001) at a median of 2.9 months posttreatment (range, 1.7-5.6 months). All ulcers (grade 1, 5 ulcers; grade 2, 1 ulcer) resolved on repeat anoscopy within 8 months of incidence. There were no grade ≥3 late gastrointestinal toxicities; the incidence of late grade-2 gastrointestinal toxicities was 14.3%, with a prevalence at 3 years of 0%. No toxicities greater than grade 3 occurred in any domain. Four-year freedom from biochemical failure was 93.8% (95% CI, 85.2%-100.0%).

Conclusions: Temporary hydrogel spacer placement before high-dose SABR treatment for localized prostate cancer and use of strict dose constraints are associated with a significant reduction in the incidence of rectal ulcer events compared with prior phase 1/2 trial results.
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http://dx.doi.org/10.1016/j.ijrobp.2021.03.025DOI Listing
March 2021

NCCN Guidelines Insights: Prostate Cancer, Version 1.2021.

J Natl Compr Canc Netw 2021 02 2;19(2):134-143. Epub 2021 Feb 2.

Huntsman Cancer Institute at the University of Utah; and.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel's discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.
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http://dx.doi.org/10.6004/jnccn.2021.0008DOI Listing
February 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

Predicting Adverse Outcomes for Shiga Toxin-Producing Escherichia coli Infections in Emergency Departments.

J Pediatr 2021 May 5;232:200-206.e4. Epub 2021 Jan 5.

Department of Pediatrics, Joseph M. Sanzari Women and Children's Hospital, Hackensack University Medical Center, Hackensack, NJ.

Objective: To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting.

Study Design: We reviewed medical records of children <18 years old infected with STEC and treated in 1 of 38 participating emergency departments in North America between 2011 and 2015. The HUS severity score (hemoglobin [g/dL] plus 2-times serum creatinine [mg/dL]) was calculated using first available laboratory results. Children with scores >13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure, and death) using discrimination and net benefit (ie, threshold probability), with subgroup analyses by age and day-of-illness.

Results: A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (area under the curve 0.71, 95% CI 0.63-0.79) and better among children <5 years old (area under the curve 0.77, 95% CI 0.68-0.87). For children <5 years, greatest net benefit was achieved for a threshold probability >26%.

Conclusions: The HUS severity score was able to discriminate between high- and low-risk children <5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.
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http://dx.doi.org/10.1016/j.jpeds.2020.12.077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084908PMC
May 2021

Dynamic differences between DNA damage repair responses in primary tumors and cell lines.

Transl Oncol 2021 Jan 20;14(1):100898. Epub 2020 Oct 20.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

The study of DNA damage repair response (DDR) in prostate cancer is restricted by the limited number of prostate cancer cell lines and lack of surrogates for heterogeneity in clinical samples. Here, we sought to leverage our experience with patient derived explants (PDEs) cultured ex vivo to study dynamics of DDR in primary tumors following application of clinically relevant doses of ionizing radiation (IR) to tumor cells in their native 3-dimensional microenvironment. We compared DDR dynamics between prostate cancer cell lines, PDEs and xenograft derived explants (XDEs) following treatment with IR (2Gy) either alone or in combination with pharmacological modulators of DDR. We have shown that following treatment with 2Gy, DDR can be consistently detected in PDEs from multiple solid tumors, including prostate, kidney, testes, lung and breast, as evidenced by γ-H2AX, 53BP1, phospho-ATM and phospho-DNA-PKcs foci. By examining kinetics of resolution of IR-induced foci, we have shown that DDR in prostate PDEs (complete resolution in 8 h) is much faster than in prostate cancer cell lines (<50% resolution in 8 h). The transcriptional profile of DDR genes following 2Gy IR appears to be distinct between PDEs and cell lines. Pre-treatment with drugs targeting DDR pathways differentially alter the kinetics of DDR in the PDEs and cell lines, as evidenced by altered kinetics of foci resolution. This study highlights the utility of PDEs as a robust model system for short-term evaluation of DDR in primary solid tumors in clinically relevant microenvironment.
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http://dx.doi.org/10.1016/j.tranon.2020.100898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576517PMC
January 2021

Evolving Brachytherapy Boost in Prostate Cancer in the Era of Hypofractionation.

Int J Radiat Oncol Biol Phys 2020 11;108(4):914-916

Department of Radiation Oncology, University of Texas Southwestern, Dallas, Texas.

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http://dx.doi.org/10.1016/j.ijrobp.2020.08.028DOI Listing
November 2020

Emergency Department Prescribing Patterns for Pharyngitis in Children.

Clin Pediatr (Phila) 2020 10 5;59(11):995-1003. Epub 2020 Jun 5.

Children's Hospital Colorado, Aurora, CO, USA.

Pharyngitis is commonly diagnosed in the emergency department (ED) and accounts for substantial antibiotic burden in pediatrics. This study describes ED patterns of group A streptococcal (GAS) pharyngitis diagnosis and antibiotic prescribing patterns. This was a secondary data analysis of the National Hospital Ambulatory Medical Care Survey. Diagnosis and antibiotic treatment for GAS and non-GAS (viral) pharyngitis were reported in all ages and specifically examined in children <3 years of age from 2010 to 2015. GAS pharyngitis was diagnosed in 29% of visits for children with pharyngitis; however, 60% of patients with any pharyngitis received antibiotics. Twenty percent of children <3 years were diagnosed with GAS pharyngitis, yet over half were given antibiotics. Broad-spectrum antibiotics were commonly prescribed. Antibiotic treatment of pharyngitis, including broad-spectrum antibiotics, remains high when compared with the known prevalence of GAS pharyngitis. Diagnosis and treatment of GAS pharyngitis in patients <3 years persists despite recommendations against testing.
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http://dx.doi.org/10.1177/0009922820927042DOI Listing
October 2020

ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy.

Am J Clin Oncol 2020 08;43(8):545-552

Department of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.

Aim/objectives/background: To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation.

Methods: The ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy was revised according to the process described on the ACR website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document.

Results: Given the complexities of SBRT, a separate document was created to develop a technical standard for the medical physics of SBRT (ACR-AAPM Technical Standard for Medical Physics Performance Monitoring of Stereotactic Body Radiation Therapy). Workflow, qualifications and responsibilities of personnel, specifications, documentation, quality control/safety/improvement, simulation/treatment, and follow-up were addressed in this practice parameter.

Conclusions: This practice parameter assists practitioners in providing safe and appropriate SBRT treatment and care for patients when clinically indicated. As technologies and techniques continue to evolve, this document will be reviewed, revised and renewed accordingly to a 5 year or sooner timeline specified by the ACR.
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http://dx.doi.org/10.1097/COC.0000000000000706DOI Listing
August 2020

Antibiotic Prescribing for Viral Respiratory Infections in the Pediatric Emergency Department and Urgent Care.

Pediatr Infect Dis J 2020 05;39(5):406-410

Section of Pediatric Emergency Medicine, University of Colorado.

Background: Viral acute respiratory tract infections (vARTI) are a frequent source of inappropriate antibiotic prescribing. We describe the prevalence of antibiotic prescribing for vARTI in the pediatric emergency department (ED) and urgent care (UC) within a health system, and identify factors associated with overall and broad-spectrum antibiotic prescribing.

Methods: Retrospective chart review within a single pediatric referral health system. Visits of patients, 3 months- 17 years old, with a discharge diagnosis of a vARTI from 2010 to 2015. Data collected included specific vARTI diagnosis, site type (ED or UC), provider type [pediatric emergency medicine subspecialist or physicians, nurse practitioners, physician assistants (non-PEM)] and discharge antibiotics. Odds ratios and 95% confidence intervals (CI) were calculated where appropriate.

Results: There were 132,458 eligible visits, mean age 4.1 ± 4.3 years. Fifty-three percent were treated in an ED. Advanced practice providers, a term encompassing nurse practitioners and physician assistants, were the most common provider type (47.7%); 16.5% of patients were treated by a pediatric emergency medicine subspecialist. Antibiotics were prescribed for 3.8% (95% CI: 3.72-3.92) of children with vARTI; 25.4% (95% CI: 24.2-26.6) of these were broad-spectrum, most commonly first-generation cephalosporins (11%; 95% CI 10.2-11.9). Patients treated in an ED or by a non-PEM and those receiving chest radiograph (CXR) received antibiotics most frequently. Prescribing rates varied by specific vARTI diagnosis.

Conclusions: Patients discharged from the pediatric ED or UC with vARTI receive inappropriate antibiotics at a lower rate than reported in other community settings; however, they frequently receive broad-spectrum agents.
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http://dx.doi.org/10.1097/INF.0000000000002586DOI Listing
May 2020

The challenge of matching assays to biology in DNA damage response biomarkers for response to radiotherapy in bladder cancer.

Transl Androl Urol 2019 Dec;8(Suppl 5):S514-S516

Department of Urology, University of Texas Southwestern, Dallas, TX, USA.

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http://dx.doi.org/10.21037/tau.2019.07.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989838PMC
December 2019

Prostate brachytherapy procedural training: incorporation of related procedures in resident training and competency assessment.

J Contemp Brachytherapy 2019 Dec 16;11(6):601-606. Epub 2019 Dec 16.

Department of Radiation Oncology, Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, TX USA.

Purpose: Inadequate procedural training is of increasing concern in resident training, especially in prostate brachytherapy (PB). Transperineal rectal spacer placement (TRSP) requires many of the same proficiencies as PB. This work describes the assessment of teaching techniques focusing on developing critical competencies for PB using related clinical procedures (TRSP).

Material And Methods: For PB and TRSP, key competencies were identified: 9 for PB and 7 for TRSP; 4 are shared between PB and TRSP. "Comfort level" with these procedures was assessed prior to and following participation in TRSP.

Results: 8 of 12 trainees at our institution participated in TRSP procedures. 2 of these trainees had prior experience with PB or related procedures and were excluded. Trainees self-reported "comfort levels" between 0 and 3 for four competency domains. Initial median comfort (MC) level for competency domains relevant to PB included: patient positioning (median 1, range 0-2), transrectal ultrasound imaging (median 1, range 0-1), fiducial placement (median 1, range 0-1), and hydrodissection (median 0, range 0-1). Median number of TRSP procedures performed by assessed trainees during the analysis period was 4 (range 1-6). Following TRSP procedure training, MC level increased: 2 points for patient positioning (median 3, range 1-3; < 0.01), 1.5 points for transrectal ultrasound imaging (median 2.5, range 1.3, < 0.001); 1 point for fiducial placement (median score 2, range 1-3; < 0.001); and 1.5 points for hydrodissection (median score 2, range 1-3; < 0.001).

Conclusions: Increasing trainee involvement in related procedures to develop core competencies may help facilitate increased comfort with common skills critical to the independent performance of PB.
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http://dx.doi.org/10.5114/jcb.2019.90984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964344PMC
December 2019

Pediatric Exposures Reported to the Toxicology Investigators Consortium, 2010-2015.

Pediatr Emerg Care 2019 Aug 23. Epub 2019 Aug 23.

Section of Pediatric Emergency Medicine, University of Colorado.

Background And Objective: Poisoning is the leading cause of injury death in pediatric patients. Hospital and provider readiness, including pharmacy stocking, depends on reliable surveillance data describing local patterns of age-specific clinically significant exposures and the therapeutic modalities employed in their treatment. We aimed to characterize trends in clinically significant toxic exposures and their management.

Methods: We performed a retrospective review of patients 18 years or younger in the American College of Medical Toxicology's Toxicology Investigators Consortium (ToxIC) Registry, a self-reporting database completed by bedside consulting medical toxicologists. We reviewed cases from January 1, 2010, through December 31, 2015. In 2015, ToxIC included 101 health care facilities. Data collected included demographics, geographic region, encounter and exposure details, survival, and therapeutic modalities employed, including antidotes, antivenoms, gastric decontamination, enhanced elimination, hyperbaric oxygen therapy, and extracorporeal membrane oxygenation.

Results: From 2010 to 2015, 11,616 consults were recorded in ToxIC. Pediatric consultations increased from 934 (23.7%) in 2010 to 2425 (29.9%) in 2015 (P < 0.001). Exposures were most commonly reported in females (57.8%) and adolescents (59.4%). Intentional ingestions (55.5%) comprised the majority of cases. The most frequent agents of exposure were analgesics (21.0%). There were 38 deaths reported (0.9%). The antidote used most commonly was N-acetylcysteine (11.0%). Geographic variation was demonstrated in prevalence of envenomations and heavy metal exposures, their respective treatments, and overall use of decontamination.

Conclusions: Toxicology consultations for pediatric exposures increased from 2010 to 2015. Understanding which pediatric exposures require toxicologist management, the therapies most frequently employed, and geographical patterns is paramount to facility-level planning, pharmacy stocking, and provider education.
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http://dx.doi.org/10.1097/PEC.0000000000001893DOI Listing
August 2019

Salvage Radiotherapy for Nodal Oligorecurrent Prostate Cancer: A Step Towards Predictive Criteria for Metastasis-Directed Therapy in Prostate Cancer?

Eur Urol 2019 12 14;76(6):740-742. Epub 2019 Aug 14.

Departments of Urology and Radiology, University of Texas Southwestern, Dallas, TX, USA.

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http://dx.doi.org/10.1016/j.eururo.2019.07.050DOI Listing
December 2019

Stereotactic Ablative Radiation Therapy (SAbR) Used to Defer Systemic Therapy in Oligometastatic Renal Cell Cancer.

Int J Radiat Oncol Biol Phys 2019 10 1;105(2):367-375. Epub 2019 Aug 1.

Department of Radiation Oncology; Kidney Cancer Program, Simmons Comprehensive Cancer Center. Electronic address:

Purpose: Stereotactic ablative radiotherapy (SAbR) is a promising alternative for selected patients with renal cell carcinoma (RCC) with oligometastasis. The objective of this study was to evaluate the potential of SAbR for longitudinal control in patients with persistently oligometastatic RCC. We report the impact of SAbR on tumor control rates as well as its tolerability in systemic therapy-naïve patients with oligometastatic disease (without brain metastases) and assess the effect of SAbR on subsequent first line systemic therapy by comparison to historical controls.

Methods And Materials: We reviewed patients with metastatic RCC treated with front-line SAbR with a curative intent from 2007 to 2017 at UT Southwestern Kidney Cancer Program. We analyzed local control rates (LCR), toxicity, freedom from systemic therapy (FST), type and duration of first-line systemic therapy, and overall survival (OS). Cox regression and Kaplan-Meier analyses were used.

Results: We identified 47 patients with oligometastatic RCC treated with SAbR to 88 metastases; 11 patients had more than 1 SAbR course. The local control rate was 91.5% at 2 years with no reported grade ≥3 toxicity. With a median follow-up of 30 months (interquartile range, 13.7-40.9), median FST from first SAbR was 15.2 months (95% confidence interval [CI], 8.8-40.1). The most common systemic therapies initiated after SAbR were pazopanib (60.7%) and sunitinib (14.3%). The duration of first line systemic therapy appeared unaffected by SAbR. Improved FST was observed in patients with metachronous disease (hazard ratio, 2.67; P = .02), solitary metastasis (HR, 2.26; P = .05), and non-bone metastasis (HR, 2.21; P = .04). One-year and 2-year OS after SAbR were 93.1% (95% CI, 80.1-97.7) and 84.8% (95% CI, 69.1-92.9), respectively. Median OS was not reached.

Conclusions: SAbR is an effective and safe treatment for selected patients with oligometastatic RCC, can provide longitudinal disease control without systemic therapy for over a year, and does not appear to adversely affect the effectiveness of first-line systemic therapy once initiated. Prospective validation of these findings is being sought through a phase 2 trial.
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http://dx.doi.org/10.1016/j.ijrobp.2019.07.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647381PMC
October 2019

Magnetic Resonance Imaging-guided In-bore and Magnetic Resonance Imaging-transrectal Ultrasound Fusion Targeted Prostate Biopsies: An Adjusted Comparison of Clinically Significant Prostate Cancer Detection Rate.

Eur Urol Oncol 2019 07 20;2(4):397-404. Epub 2018 Sep 20.

University of Texas Southwestern Medical Center, Dallas, TX, USA.

Background: With the increasing adoption of targeted prostate biopsies, it becomes important to understand the strengths and shortcomings of the techniques available for targeting suspicious lesions.

Objective: To compare clinically significant prostate cancer (csPCa) detection rate with magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion versus in-bore biopsy in men with abnormal multiparametric MRI (mpMRI).

Design, Setting, And Participants: This single-center, retrospective analysis of prospectively generated data included all men with abnormal mpMRI and fusion or in-bore biopsy between May 2017 and April 2018. Grade group (GG) 2-5 cancers were considered csPCa.

Outcome Measurements And Statistical Analysis: Detection of csPCa was adjusted according to patient- and lesion-related characteristics using propensity score weighting. Secondary endpoints included the detection of clinically insignificant tumors and the rate of GG upgrade from biopsy to prostatectomy specimen. Analyses were performed at patient and lesion levels.

Results And Limitations: A total of 103 and 300 men were included in the in-bore and fusion cohorts, respectively. On a per-patient basis, in-bore biopsies detected a higher proportion of csPCa (61%, 63/103) than fusion plus systematic biopsies (47%, 141/300; adjusted odds ratio [OR]: 2.1, 95% confidence interval [CI]: 1.6-2.8, p<0.0001). In-bore biopsies also detected fewer (11%, 11/103) clinically insignificant cancers than fusion biopsies (18%, 53/300; OR: 0.5, 95% CI: 0.3-0.8, p=0.001). Of those who had radical prostatectomy, GG upgrade after surgery was seen in 17% (4/24) of the men in the in-bore cohort and in 27% (22/82) of the men in the fusion cohort (p=0.55).

Conclusions: MRI-guided in-bore biopsies detected more clinically significant and fewer insignificant prostate cancers than MRI-TRUS fusion targeted biopsies. Further cost-utility and patient outcome analyses are needed.

Patient Summary: In-bore biopsies (where the patient is on the magnetic resonance imaging [MRI] scanner itself) detected more aggressive cancers and fewer indolent cancers than fusion (where software blends MRI and ultrasound images) biopsies. These findings may help patients and physicians choose the best biopsy approach.
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http://dx.doi.org/10.1016/j.euo.2018.08.022DOI Listing
July 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

Addition of Iodinated Contrast to Rectal Hydrogel Spacer to Facilitate MRI-Independent Target Delineation and Treatment Planning for Prostate Cancer.

Pract Radiat Oncol 2019 Nov 4;9(6):e528-e533. Epub 2019 Jun 4.

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

Purpose: Hydrogel spacers reduce rectal dose toxicity during prostate cancer radiation therapy. Current products require magnetic resonance imaging (MRI) for visualization during treatment planning, but MRI incompatibility and cost have prompted alternatives using computed tomography (CT). This case series evaluates the addition of iodinated contrast to hydrogel as such an alternative.

Methods And Materials: Three patients underwent rectal hydrogel spacer placement with iodinated contrast modification. CT was performed within 1 hour of injection and again 1 week later. MRI was obtained at the time of the second CT. Hydrogel delineation was compared between CT and MRI and between paired CT scans.

Results: Spacer enhancement was visible on CT immediately after hydrogel placement (mean Hounsfield units, 122; range, 52-193) but not at the second CT 1 week later (mean Hounsfield units, 8; range, -8 to 29). Delineated spacer volume did not significantly differ between immediate postprocedure CT and MRI ≥1 week later in 2 patients (patient 1: 16.6 vs 15.5 cm; patient 2: 12.6 vs 14.7 cm; paired t-test, P = .81).

Conclusions: CT visualization of rectal hydrogel admixed with contrast is feasible and allows delineation of interface with rectum/prostate.
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http://dx.doi.org/10.1016/j.prro.2019.05.013DOI Listing
November 2019

Predicting Hemolytic Uremic Syndrome and Renal Replacement Therapy in Shiga Toxin-producing Escherichia coli-infected Children.

Clin Infect Dis 2020 04;70(8):1643-1651

University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia.

Background: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care.

Methods: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children aged <18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible.

Results: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age (0.77 [.69-.85] per year), leukocyte count ≥13.0 × 103/μL (2.54 [1.42-4.54]), higher hematocrit (1.83 [1.21-2.77] per 5% increase) and serum creatinine (10.82 [1.49-78.69] per 1 mg/dL increase), platelet count <250 × 103/μL (1.92 [1.02-3.60]), lower serum sodium (1.12 [1.02-1.23 per 1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50 [1.14-5.46]). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (OR, 0.70 [95% CI, .54-.90]). RRT predictors (all shown as OR [95% CI]) included female sex (2.27 [1.14-4.50]), younger age (0.83 [.74-.92] per year), lower serum sodium (1.15 [1.04-1.27] per mmol/L decrease), higher leukocyte count ≥13.0 × 103/μL (2.35 [1.17-4.72]) and creatinine (7.75 [1.20-50.16] per 1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71 [1.18-6.21]).

Conclusions: The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.
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http://dx.doi.org/10.1093/cid/ciz432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931832PMC
April 2020

Stereotactic Ablative Radiotherapy (SAbR) in the Setting of Metastatic Nonseminomatous Germ Cell Tumor of Testis.

Clin Genitourin Cancer 2019 08 26;17(4):e768-e771. Epub 2019 Apr 26.

Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2019.04.005DOI Listing
August 2019

Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality: Competition Between Age and Time to Biochemical Failure.

Eur Urol Oncol 2018 09 28;1(4):276-282. Epub 2018 Sep 28.

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

Background: Disease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous.

Objective: To describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT.

Design, Setting, And Participants: A retrospective multi-institutional study included 547 consecutive men with lymph node-negative PC receiving SRT from 1985 to 2013. The median follow-up after SRT was 8.4 yr. Intervention All men received SRT with three-dimensional or intensity-modulated RT.

Outcome Measurements And Statistical Analysis: BCR was defined as a rise in prostate-specific antigen (PSA) ≥0.2ng/ml above the PSA nadir followed by a sequentially equal or higher value. Additional outcomes included distant metastasis (DM), PC-specific mortality (PCSM), and overall mortality (OM). Cox proportional hazards models, a landmark analysis, and comparison of c-indices were used. Cumulative incidence curves were estimated from a Fine and Gray regression model.

Results And Limitations: The estimated 10-yr cumulative incidence of BCR was 60%. Of the 274 men experiencing BCR, 149 (54%) had BCR within 18 mo of SRT. BCR ≤18 mo after SRT was associated with a higher risk of DM (hazard ratio [HR] 7.44, 95% confidence interval [CI] 4.91-11.3; p<0.001), PCSM (HR 12.3, 95% CI 5.95-25.2; p<0.001), and OM (HR 2.85, 95% CI 1.94-4.17; p<0.001). We provide a model to estimate the cumulative incidence of DM and PCSM using age and time to BCR. The retrospective nature of our analysis limits our findings.

Conclusions: A strikingly large proportion of men experience early BCR following SRT and are at higher risk of DM and PCSM. Novel predictive biomarkers are needed to identify men harboring micrometastatic disease to avoid potentially futile local therapies or allow for intensification of systemic therapies.

Patient Summary: Many men will develop biochemical recurrence of prostate cancer after salvage radiotherapy. Men with biochemical recurrence within 18 mo of salvage radiotherapy constitute a cohort at higher risk of distant metastasis and prostate cancer-specific mortality.
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http://dx.doi.org/10.1016/j.euo.2018.04.014DOI Listing
September 2018

Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies.

Int J Radiat Oncol Biol Phys 2019 07 6;104(4):778-789. Epub 2019 Apr 6.

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

Purpose: Utilization of stereotactic body radiation therapy (SBRT) for treatment of localized prostate cancer is increasing. Guidelines and payers variably support the use of prostate SBRT. We therefore sought to systematically analyze biochemical recurrence-free survival (bRFS), physician-reported toxicity, and patient-reported outcomes after prostate SBRT.

Methods And Materials: A systematic search leveraging Medline via PubMed and EMBASE for original articles published between January 1990 and January 2018 was performed. This was supplemented by abstracts with sufficient extractable data from January 2013 to March 2018. All prospective series assessing curative-intent prostate SBRT for localized prostate cancer reporting bRFS, physician-reported toxicity, and patient-reported quality of life with a minimum of 1-year follow-up were included. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were performed with random-effect modeling. Extent of heterogeneity between studies was determined by the I and Cochran's Q tests. Meta-regression was performed using Hartung-Knapp methods.

Results: Thirty-eight unique prospective series were identified comprising 6116 patients. Median follow-up was 39 months across all patients (range, 12-115 months). Ninety-two percent, 78%, and 38% of studies included low, intermediate, and high-risk patients. Overall, 5- and 7-year bRFS rates were 95.3% (95% confidence interval [CI], 91.3%-97.5%) and 93.7% (95% CI, 91.4%-95.5%), respectively. Estimated late grade ≥3 genitourinary and gastrointestinal toxicity rates were 2.0% (95% CI, 1.4%-2.8%) and 1.1% (95% CI, 0.6%-2.0%), respectively. By 2 years post-SBRT, Expanded Prostate Cancer Index Composite urinary and bowel domain scores returned to baseline. Increasing dose of SBRT was associated with improved biochemical control (P = .018) but worse late grade ≥3 GU toxicity (P = .014).

Conclusions: Prostate SBRT has substantial prospective evidence supporting its use, with favorable tumor control, patient-reported quality of life, and levels of toxicity demonstrated. SBRT has sufficient evidence to be supported as a standard treatment option for localized prostate cancer while ongoing trials assess its potential superiority.
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http://dx.doi.org/10.1016/j.ijrobp.2019.03.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770993PMC
July 2019

Alemtuzumab is an effective third-line treatment versus single-agent gemcitabine or pralatrexate for refractory Sézary syndrome: a systematic review.

Eur J Dermatol 2018 Dec;28(6):764-774

Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA.

The efficacy of alemtuzumab for the treatment of refractory Sézary syndrome (SS) versus other third-line agents such as pralatrexate and gemcitabine is poorly characterized. To elucidate the effectiveness of alemtuzumab versus other third-line options for the treatment of refractory SS, we conducted a meta-analysis of existing data. A systematic review was performed in March 2017 based on a search using Ovid-MEDLINE and OVID-EMBASE for articles evaluating single-agent alemtuzumab, gemcitabine, or pralatrexate for the treatment of SS and mycosis fungoides (MF). Twenty-two publications were identified that fulfilled all search criteria (total n = 323 patients), with six publications of lower quality being excluded from our analysis in order to decrease the risk of bias (final: n = 308 patients; 93 with SS and 147 with MF). Across all studies, alemtuzumab was significantly more effective in patients with SS (overall response rate [ORR]: 81%; complete response rate [CRR]: 38%) than patients with MF (ORR: 29%; CRR: 8%). However, gemcitabine was more effective than alemtuzumab or pralatrexate in treating MF. Alemtuzumab-treated patients had more frequent side effects, which were influenced by route of administration and dose. There was a lower incidence of lymphopenia and other serious adverse events in patients treated with subcutaneous (38%) compared to intravenous regimens (68%), and lower-dose (5%) compared to high-dose alemtuzumab regimens (54%). No significant differences were found in the effectiveness of different routes of administration or dosing regimens. Our review supports the use of low-dose subcutaneous alemtuzumab as a third-line treatment for SS.
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http://dx.doi.org/10.1684/ejd.2018.3444DOI Listing
December 2018

Comparison of outcomes in early-stage uterine clear cell carcinoma and serous carcinoma.

Brachytherapy 2019 Jan - Feb;18(1):38-43. Epub 2018 Oct 10.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Purpose: The treatment paradigm for uterine clear cell carcinoma is often linked to serous carcinoma. This study compares oncologic outcomes between women with uterine clear cell and serous carcinoma.

Methods And Materials: We reviewed 114 women with stage I-II uterine clear cell carcinoma (n = 17, 15%) or serous carcinoma (n = 97, 85%) who underwent hysterectomy and salpingo-oophorectomy at our institution from April 1992 to December 2011; 86 (76%) had stage IA, 14 (12%) had stage IB, and 14 (12%) had stage II disease. Median followup was 57 months.

Results: Patients with uterine clear cell and serous carcinoma did not differ significantly by age ≥60 years, stage, or rate of lymphovascular invasion. There was no difference in the number of patients with clear cell or serous histology who received adjuvant radiotherapy (71% vs. 84%, respectively; p = 0.31); however, significantly fewer patients with clear cell histology received adjuvant chemotherapy (35% vs. 67%, respectively; p = 0.02). At 5 years, there were no significant differences in disease-free survival (94% vs. 84%, respectively; p = 0.27), disease-specific survival (100% vs. 92%, respectively; p = 0.20), or overall survival (100% vs. 89%, respectively; p = 0.34). The differences in chemotherapy utilization did not impact pattern of relapse, specifically peritoneal spread (7% vs. 6%, respectively; p = 0.92) or other distant sites (0% vs. 9%, respectively; p = 0.17).

Conclusions: Oncologic outcomes and recurrence patterns of women with stage I-II uterine clear cell carcinoma compared favorably with those of women with serous carcinoma, despite significantly less adjuvant chemotherapy use. Potential reduction in adjuvant therapy in women with clear cell carcinoma should be studied prospectively.
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http://dx.doi.org/10.1016/j.brachy.2018.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615564PMC
April 2019