Publications by authors named "Adam P Dicker"

254 Publications

Longitudinal plasma proteomic profiling of patients with non-small cell lung cancer undergoing immune checkpoint blockade.

J Immunother Cancer 2022 Jun;10(6)

Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the cancer therapy landscape due to long-term benefits in patients with advanced metastatic disease. However, robust predictive biomarkers for response are still lacking and treatment resistance is not fully understood.

Methods: We profiled approximately 800 pre-treatment and on-treatment plasma proteins from 143 ICI-treated patients with non-small cell lung cancer (NSCLC) using ELISA-based arrays. Different clinical parameters were collected from the patients including specific mutations, smoking habits, and body mass index, among others. Machine learning algorithms were used to identify a predictive signature for response. Bioinformatics tools were used for the identification of patient subtypes and analysis of differentially expressed proteins and pathways in each response group.

Results: We identified a predictive signature for response to treatment comprizing two proteins (CXCL8 and CXCL10) and two clinical parameters (age and sex). Bioinformatic analysis of the proteomic profiles identified three distinct patient clusters that correlated with multiple parameters such as response, sex and TNM (tumors, nodes, and metastasis) staging. Patients who did not benefit from ICI therapy exhibited significantly higher plasma levels of several proteins on-treatment, and enrichment in neutrophil-related proteins.

Conclusions: Our study reveals potential biomarkers in blood plasma for predicting response to ICI therapy in patients with NSCLC and sheds light on mechanisms underlying therapy resistance.
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http://dx.doi.org/10.1136/jitc-2022-004582DOI Listing
June 2022

Variation in Molecularly Defined Prostate Tumor Subtypes by Self-identified Race.

Eur Urol Open Sci 2022 Jun 26;40:19-26. Epub 2022 Apr 26.

Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.

Background: Socioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men.

Objective: To compare differences in PC subtype frequency and genomic aggressiveness by self-identified race.

Design Setting And Participants: Five molecular subtype classifiers were applied for 426 Black and 762 White PC patients in the Decipher Genomics Resource Information Database (GRID).

Outcome Measurements And Statistical Analysis: Differences in subtype frequency and tumor genomic risk (Decipher score >0.6) by race were evaluated using χ tests and multivariable-adjusted logistic regression models.

Results And Limitations: Subtype frequencies differed by race for four classifiers. Subtypes characterized by the presence of mutations, overexpression, and neuroendocrine differentiation were more common among Black men. and fusion-positive subtypes were more frequent among White men, with no clear differences for subtypes reflecting luminal versus basal lineage. The hypothesized low-risk Kamoun S2 subtype was associated with a lower Decipher score among White men only ( = 0.01 for heterogeneity), while the aggressive You PCS1 subtype was associated with a higher Decipher score among White men only ( = 0.001 for heterogeneity). The Tomlins ERG subtype was associated with a higher Decipher score relative to all other subtypes among Black men, with no association among White men ( = 0.007 for heterogeneity).

Conclusions: The frequency of PC molecular subtypes differed by self-identified race. Additional studies are required to evaluate whether our observations suggest differences in the tumor genomic risk of progression by self-identified race.

Patient Summary: We studied five classifiers that identify subtypes of prostate tumors and found that subtypes differed in frequency between Black and White patients. Further research is warranted to evaluate how differences in tumor subtypes may contribute to disparities in prostate cancer mortality.
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http://dx.doi.org/10.1016/j.euros.2022.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142751PMC
June 2022

A Pilot Feasibility Study of Digital Health Coaching for Men With Prostate Cancer.

JCO Oncol Pract 2022 Apr 8:OP2100712. Epub 2022 Apr 8.

Department of Radiation Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Purpose: Prostate cancer is the most common cancer among men in the United States. The majority of prostate cancer treatment occurs in the ambulatory setting, and patients and their caregivers take on significant responsibility for monitoring and managing treatment and disease-related toxicity. Digital health coaching has shown promise as a tool to positively influence outcomes. We completed a single-arm pilot study to assess the feasibility of digital health coaching in men with prostate cancer.

Methods: Men with a history of prostate cancer requiring treatment in the past 2 years were eligible for inclusion. Participants engaged in a 12-week health coaching program, consisting of a combination of at least one telephone call and up to four digital nudges (defined as content delivered via text, e-mail, or app on the basis of the participant's preference) per week. Prostate cancer-specific content addressed one of the following topics each week: fatigue, pain management, healthy eating, exercise, managing incontinence, sexual health, managing stress and anxiety, financial toxicity, goal setting during treatment, managing side effects, communicating with the health care team, and medication adherence. Services were provided at no cost to the participant.

Results: A hundred patients were consented for the study, and 88 enrolled. The feasibility threshold of 60% was met with 63 of the 88 enrolled individuals completing the 3-month program (proportion = 71.6%; 90% CI, 62.6 to 79.4; = .016).

Conclusion: Digital health coaching for men with prostate cancer is feasible. These findings support further evaluation of digital health coaching for men with prostate cancer in larger randomized controlled trials.
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http://dx.doi.org/10.1200/OP.21.00712DOI Listing
April 2022

Coeliac plexus radiosurgery for pain management in patients with advanced cancer : study protocol for a phase II clinical trial.

BMJ Open 2022 03 24;12(3):e050169. Epub 2022 Mar 24.

Radiation Oncology, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Introduction: Pancreatic cancer is characterised by severe mid-back and epigastric pain caused by tumour invasion of the coeliac nerve plexus. This pain is often poorly managed with standard treatments. This clinical trial investigates a novel approach in which high-dose radiation (radiosurgery) is targeted to the retroperitoneal coeliac plexus nerve bundle. Preliminary results from a single institution pilot trial are promising: pain relief is substantial and side effects minimal. The goals of this study are to validate these findings in an international multisetting, and investigate the impact on quality of life and functional status among patients with terminal cancer.

Methods And Analysis: A single-arm prospective phase II clinical trial. Eligible patients are required to have severe coeliac pain of at least five on the 11-point BPI average pain scale and Eastern Cooperative Oncology Group performance status of two or better. Non-pancreatic cancers invading the coeliac plexus are also eligible. The intervention involves irradiating the coeliac plexus using a single fraction of 25 Gy. The primary endpoint is the complete or partial pain response at 3 weeks. Secondary endpoints include pain at 6 weeks, analgesic use, hope, qualitative of life, caregiver burden and functional outcomes, all measured using validated instruments. The protocol is expected to open at a number of cancer centres across the globe, and a quality assurance programme is included. The protocol requires that 90 evaluable patients" be accrued, based upon the assumption that a third of patients are non-evaluable (e.g. due to death prior to 3-weeks post-treatment assessment, or spontaneous improvement of pain pre-treatment), it is estimated that a total of 120 patients will need to be accrued. Supported by Gateway for Cancer Research and the Israel Cancer Association.

Ethics And Dissemination: Ethic approval for this study has been obtained at eight academic medical centres located across the Middle East, North America and Europe. Results will be disseminated through conference presentations and peer-reviewed publications.

Trial Registration Number: NCT03323489.
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http://dx.doi.org/10.1136/bmjopen-2021-050169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948399PMC
March 2022

Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy.

Urol Oncol 2022 01 17;40(1):5.e1-5.e13. Epub 2021 Sep 17.

Department of Radiation Oncology, University of Toronto; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Techna Institute, University Health Network, Toronto, Ontario, Canada. Electronic address:

Purpose/objective: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT.

Material/methods: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates.

Results: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P = 0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P = 0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index = 0.737 (95%CI 0.662-0.813)).

Conclusions: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.
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http://dx.doi.org/10.1016/j.urolonc.2021.08.013DOI Listing
January 2022

Meta-Analysis of Quality of Life in Cancer Patients Treated With Immune Checkpoint Inhibitors.

J Natl Cancer Inst 2022 Jun;114(6):808-818

Department of Health Outcomes and Behavior, Moffitt Cancer Center,  Tampa, FL, USA.

Background: Trials of immune checkpoint inhibitors (ICIs) have published patient-reported quality of life (QOL), but the size and heterogeneity of this literature can make patient education difficult. This meta-analysis aimed to describe change in QOL and symptomatology in patients receiving ICIs for cancer.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases were searched through November 2019 for articles or abstracts of prospective, original studies reporting longitudinal QOL in adult cancer patients treated with ICIs. The prespecified primary outcomes were change in global QOL among patients treated with ICIs and difference in change since baseline in global QOL between patients treated with ICI vs non-ICI active treatment. Secondary outcomes included physical functioning and symptomatology. All statistical tests were 2-sided.

Results: Of 20 323 publications, 26 met inclusion criteria. Global QOL did not change over time in patients treated with ICIs (k = 26, n = 6974; P = .19). Larger improvements in global QOL was observed in patients receiving ICI vs non-ICI regimens (k = 16, ICI: n = 3588; non-ICI: n = 2948; P < .001). Physical functioning did not change in patients treated with ICIs (k = 14, n = 3169; P = .47); there were no differences in mean change between ICI vs non-ICI regimens (k = 11, n = 4630; P = .94). Regarding symptoms, appetite loss, insomnia, and pain severity decreased, but dyspnea severity increased in patients treated with ICIs (k = 14, n = 3243-3499; P < .001). Insomnia severity was higher in patients treated with ICIs than non-ICI regimens (k = 11, n = 4791; P < .001).

Conclusions: This study is among the first to quantitatively summarize QOL in patients treated with ICIs. Findings suggest ICI recipients report no change in global QOL and higher QOL than patients treated with non-ICI regimens.
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http://dx.doi.org/10.1093/jnci/djab171DOI Listing
June 2022

Machine Learning Using Multiparametric Magnetic Resonance Imaging Radiomic Feature Analysis to Predict Ki-67 in World Health Organization Grade I Meningiomas.

Neurosurgery 2021 10;89(5):928-936

Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Although World Health Organization (WHO) grade I meningiomas are considered "benign" tumors, an elevated Ki-67 is one crucial factor that has been shown to influence tumor behavior and clinical outcomes. The ability to preoperatively discern Ki-67 would confer the ability to guide surgical strategy.

Objective: In this study, we develop a machine learning (ML) algorithm using radiomic feature analysis to predict Ki-67 in WHO grade I meningiomas.

Methods: A retrospective analysis was performed for a cohort of 306 patients who underwent surgical resection of WHO grade I meningiomas. Preoperative magnetic resonance imaging was used to perform radiomic feature extraction followed by ML modeling using least absolute shrinkage and selection operator wrapped with support vector machine through nested cross-validation on a discovery cohort (n = 230), to stratify tumors based on Ki-67 <5% and ≥5%. The final model was independently tested on a replication cohort (n = 76).

Results: An area under the receiver operating curve (AUC) of 0.84 (95% CI: 0.78-0.90) with a sensitivity of 84.1% and specificity of 73.3% was achieved in the discovery cohort. When this model was applied to the replication cohort, a similar high performance was achieved, with an AUC of 0.83 (95% CI: 0.73-0.94), sensitivity and specificity of 82.6% and 85.5%, respectively. The model demonstrated similar efficacy when applied to skull base and nonskull base tumors.

Conclusion: Our proposed radiomic feature analysis can be used to stratify WHO grade I meningiomas based on Ki-67 with excellent accuracy and can be applied to skull base and nonskull base tumors with similar performance achieved.
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http://dx.doi.org/10.1093/neuros/nyab307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510851PMC
October 2021

Digital Literacy at an Urban Cancer Center: Implications for Technology Use and Vulnerable Patients.

JCO Clin Cancer Inform 2021 08;5:872-880

Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Purpose: eHealth literacy, or the ability to seek, find, understand, and appraise health information from electronic sources, has become increasingly relevant in the era of COVID-19, when so many aspects of patient care became dependent on technology. We aimed to understand eHealth literacy among a diverse sample of patients with cancer and discuss ways for health systems and cancer centers to ensure that all patients have access to high-quality care.

Methods: A cross-sectional survey of patients with cancer and caregivers was conducted at an NCI-designated cancer center to assess access to the Internet, smartphone ownership, use of mobile apps, willingness to engage remotely with the health care team, and use of the patient portal. Descriptive statistics and bivariate analyses were used to assess frequencies and significant differences between variables.

Results: Of 363 participants, 55% (n = 201) were female, 71% (n = 241) identified as non-Hispanic White, and 29% (n = 85) reported that their highest level of education was a high school diploma. Most (90%, n = 323) reported having access to the Internet and most (82%, n = 283) reported owning a smartphone. Younger patients or those with a college degree were significantly more likely to own a smartphone, access health information online, know how to download an app on their own, have an interest in communicating with their health care team remotely, or have an account on the electronic patient portal.

Conclusion: As cancer centers increasingly engage patients through electronic and mobile applications, patients with low or limited digital literacy may be excluded, exacerbating current cancer health disparities. Patient-, provider- and system-level technology barriers must be understood and mitigated.
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http://dx.doi.org/10.1200/CCI.21.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807016PMC
August 2021

A Pilot Trial Using Telemedicine in Radiation Oncology: The Future of Health Care Is Virtual.

Telemed Rep 2021 14;2(1):171-178. Epub 2021 Jun 14.

Department of Radiation Oncology, Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Social determinants of health directly affect cancer survival. Driven by advances in technology and recent demands due to COVID-19, telemedicine has the ability to improve patient access to care, lower health care costs, and increase workflow efficiency. The role of telemedicine in radiation oncology is not established. We conducted an IRB-approved pilot trial using a telehealth platform for the first post-radiation visit in patients with any cancer diagnosis. The primary endpoint was feasibility of using telehealth defined by completion of five telehealth visits per month in a single department. Secondary endpoints included the ability to assess patients appropriately, patient and physician satisfaction. Physicians were surveyed again during the pandemic to determine whether viewpoints changed. Between May 27, 2016 and August 1, 2018, 37 patients were enrolled in the Telehealth in Post-operative Radiation Therapy (TelePORT) trial, with 24 evaluable patients who completed their scheduled telehealth visit. On average, 1.4 patients were accrued per month. All patients were satisfied with their care, had enough time with their physician and 85.7% believed the telehealth communication was excellent. All physicians were able to accurately assess the patient's symptoms via telehealth, whereas 82.3% felt they could accurately assess treatment-related toxicity. Physicians assessing skin toxicity from breast radiation were those who did not feel they were able to assess toxicity. Both health care providers and patients have identified telemedicine as a suitable platform for radiation oncology visits. Although there are limitations, telemedicine has significant potential for increasing access of cancer care delivery in radiation oncology.
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http://dx.doi.org/10.1089/tmr.2021.0007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259074PMC
June 2021

Immune Checkpoint Inhibitor Therapy Toxicities.

JAMA 2021 07;326(1):87

Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1001/jama.2021.6030DOI Listing
July 2021

Next-Generation Implementation of Chimeric Antigen Receptor T-Cell Therapy Using Digital Health.

JCO Clin Cancer Inform 2021 06;5:668-678

Department of Radiation Oncology, Jefferson University, Philadelphia, PA.

Chimeric antigen receptor T-cell (CAR-T) therapy is a paradigm-shifting immunotherapy modality in oncology; however, unique toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome limit its ability to be implemented more widely in the outpatient setting or at smaller-volume centers. Three operational challenges with CAR-T therapy include the following: (1) the logistics of toxicity monitoring, ie, with frequent vital sign checks and neurologic assessments; (2) the specialized knowledge required for toxicity management, particularly with regard to CRS and immune effector cell-associated neurotoxicity syndrome; and (3) the need for high-quality symptomatic and supportive care during this intensive period. In this review, we explore potential niches for digital innovations that can improve the implementation of CAR-T therapy in each of these domains. These tools include patient-facing technologies and provider-facing platforms: for example, wearable devices and mobile health apps to screen for fevers and encephalopathy, electronic patient-reported outcome assessments-based workflows to assist with symptom management, machine learning algorithms to predict emerging CRS in real time, clinical decision support systems to assist with toxicity management, and digital coaching to help maintain wellness. Televisits, which have grown in prominence since the novel coronavirus pandemic, will continue to play a key role in the monitoring and management of CAR-T-related toxicities as well. Limitations of these strategies include the need to ensure care equity and stakeholder buy-in, both operationally and financially. Nevertheless, once developed and validated, the next-generation implementation of CAR-T therapy using these digital tools may improve both its safety and accessibility.
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http://dx.doi.org/10.1200/CCI.21.00023DOI Listing
June 2021

BRCA1 Protein Expression Predicts Survival in Glioblastoma Patients from an NRG Oncology RTOG Cohort.

Oncology 2021 6;99(9):580-588. Epub 2021 May 6.

Department of Radiation Oncology, Weill Cornell Medicine, New York, New York, USA.

Purpose: Glioblastoma, the most common malignant brain tumor, was associated with a median survival of <1 year in the pre-temozolomide (TMZ) era. Despite advances in molecular and genetic profiling studies identifying several predictive biomarkers, none has been translated into routine clinical use. Our aim was to investigate the prognostic significance of a panel of diverse cellular molecular markers of tumor formation and growth in an annotated glioblastoma tissue microarray (TMA).

Methods And Materials: A TMA composed of archived glioblastoma tumors from patients treated with surgery, radiation, and non-TMZ chemother-apy, was provided by RTOG. RAD51, BRCA-1, phosphatase and tensin homolog tumor suppressor gene (PTEN), and miRNA-210 expression levels were assessed using quantitative in situ hybridization and automated quantitative protein analysis. The objectives of this analysis were to determine the association of each biomarker with overall survival (OS), using the Cox proportional hazard model. Event-time distributions were estimated using the Kaplan-Meier method and compared by the log-rank test.

Results: A cohort of 66 patients was included in this study. Among the 4 biomarkers assessed, only BRCA1 expression had a statistically significant correlation with survival. From univariate analysis, patients with low BRCA1 protein expression showed a favorable outcome for OS (p = 0.04; hazard ratio = 0.56) in comparison with high expressors, with a median survival time of 18.9 versus 4.8 months.

Conclusions: BRCA1 protein expression was an important survival predictor in our cohort of glioblastoma patients. This result may imply that low BRCA1 in the tumor and the consequent low level of DNA repair cause vulnerability of the cancer cells to treatment.
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http://dx.doi.org/10.1159/000516168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491475PMC
September 2021

Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer: An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial.

JAMA Oncol 2021 04;7(4):544-552

Department of Radiation Oncology, Johns Hopkins University, Baltimore, Maryland.

Importance: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer.

Objective: To validate the GC in the context of a randomized phase 3 trial.

Design, Setting, And Participants: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network-approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019.

Intervention: Salvage radiotherapy (sRT) with or without 2 years of bicalutamide.

Main Outcomes And Measures: The preplanned primary end point of this study was the independent association of the GC with the development of DM.

Results: In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (-7.8% vs 4.6%).

Conclusions And Relevance: This ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT.

Trial Registration: ClinicalTrials.gov identifier: NCT00002874.
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http://dx.doi.org/10.1001/jamaoncol.2020.7671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879385PMC
April 2021

Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors.

Cancers (Basel) 2020 Dec 31;13(1). Epub 2020 Dec 31.

Jefferson Center for Digital Health, Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, but few studies have reported on patient-reported outcomes (PROs) outside the context of a clinical trial. The goal of the current study was to assess PROs in participants of a lung cancer registry who had been treated with an ICI. Patients participating in the GO Foundation's Lung Cancer Registry who reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited to participate in a survey about their experiences during treatment. Quality of life was evaluated using the Functional Assessment of Cancer Therapy-General (FACT-G). Common symptomatic adverse events were evaluated using an item bank generated for ICIs. Internationally, 226 patients (mean age 61, 75% female) participated. Patients reported worse quality of life at the time of assessment than U.S. population and cancer normative samples. The most common moderate to severe adverse events during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Due to toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization. This study is among the first to our knowledge to report on PROs of ICIs outside the context of a clinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials.
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http://dx.doi.org/10.3390/cancers13010103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795027PMC
December 2020

Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019.

J Clin Oncol 2020 08 9;38(24):2798-2811. Epub 2020 Jun 9.

Advocate Aurora Health, Milwaukee, WI.

Purpose: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.

Methods: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).

Results: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included and mismatch repair genes, with broader testing, such as , for clinical trial eligibility. was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for carriers, with consideration in , and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.

Conclusion: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
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http://dx.doi.org/10.1200/JCO.20.00046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430215PMC
August 2020

Innovations in research and clinical care using patient-generated health data.

CA Cancer J Clin 2020 05 20;70(3):182-199. Epub 2020 Apr 20.

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

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.
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http://dx.doi.org/10.3322/caac.21608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488179PMC
May 2020

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer.

Brachytherapy 2020 May - Jun;19(3):282-289. Epub 2020 Mar 23.

Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.

Purpose: High dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer.

Methods And Materials: Forty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition.

Results: With a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities.

Conclusion: Fifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease.
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http://dx.doi.org/10.1016/j.brachy.2020.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172676PMC
January 2021

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

Histopathology-validated machine learning radiographic biomarker for noninvasive discrimination between true progression and pseudo-progression in glioblastoma.

Cancer 2020 06 4;126(11):2625-2636. Epub 2020 Mar 4.

Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Imaging of glioblastoma patients after maximal safe resection and chemoradiation commonly demonstrates new enhancements that raise concerns about tumor progression. However, in 30% to 50% of patients, these enhancements primarily represent the effects of treatment, or pseudo-progression (PsP). We hypothesize that quantitative machine learning analysis of clinically acquired multiparametric magnetic resonance imaging (mpMRI) can identify subvisual imaging characteristics to provide robust, noninvasive imaging signatures that can distinguish true progression (TP) from PsP.

Methods: We evaluated independent discovery (n = 40) and replication (n = 23) cohorts of glioblastoma patients who underwent second resection due to progressive radiographic changes suspicious for recurrence. Deep learning and conventional feature extraction methods were used to extract quantitative characteristics from the mpMRI scans. Multivariate analysis of these features revealed radiophenotypic signatures distinguishing among TP, PsP, and mixed response that compared with similar categories blindly defined by board-certified neuropathologists. Additionally, interinstitutional validation was performed on 20 new patients.

Results: Patients who demonstrate TP on neuropathology are significantly different (P < .0001) from those with PsP, showing imaging features reflecting higher angiogenesis, higher cellularity, and lower water concentration. The accuracy of the proposed signature in leave-one-out cross-validation was 87% for predicting PsP (area under the curve [AUC], 0.92) and 84% for predicting TP (AUC, 0.83), whereas in the discovery/replication cohort, the accuracy was 87% for predicting PsP (AUC, 0.84) and 78% for TP (AUC, 0.80). The accuracy in the interinstitutional cohort was 75% (AUC, 0.80).

Conclusion: Quantitative mpMRI analysis via machine learning reveals distinctive noninvasive signatures of TP versus PsP after treatment of glioblastoma. Integration of the proposed method into clinical studies can be performed using the freely available Cancer Imaging Phenomics Toolkit.
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http://dx.doi.org/10.1002/cncr.32790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893811PMC
June 2020

Phase I Trial of Weekly Cabazitaxel with Concurrent Intensity Modulated Radiation and Androgen Deprivation Therapy for the Treatment of High-Risk Prostate Cancer.

Int J Radiat Oncol Biol Phys 2020 04 3;106(5):939-947. Epub 2020 Feb 3.

Department of Medical Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.

Purpose: Cabazitaxel has been demonstrated to improve the overall survival for men with metastatic castrate-resistant prostate cancer. The purpose of this study was to determine the maximum tolerated dose for concurrent cabazitaxel with androgen deprivation and intensity modulated radiation therapy in men with high-risk prostate cancer.

Methods And Materials: Twenty men were enrolled in this institutuional review board-approved phase I clinical trial using a 3 + 3 design. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition.

Results: With a median follow-up time of 56 months, the maximum tolerated dose of concurrent cabazitaxel was 6 mg/m. The 5-year biochemical disease-free survival was 73%, despite 75% of patients having very high risk prostate cancer per the National Comprehensive Cancer Network guidelines. Four patients were unable to complete chemotherapy owing to dose-limiting toxicities (eg, rectal bleeding, diarrhea, and elevated transaminase). There was no significant minimally important difference in Expanded Prostate Index Composite patient-reported outcomes for either the urinary or bowel domains; however, there was a significant decrease in the sexual domain.

Conclusions: This is the first clinical trial of prostate cancer to report on the combination of cabazitaxel and radiation therapy. The maximum tolerated dose of concurrent cabazitaxel with radiation and androgen deprivation therapy was determined to be 6 mg/m. Despite the aggressive nature of the disease, robust biochemical control was observed.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186272PMC
April 2020

Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators.

J Cancer Metastasis Treat 2020 13;6. Epub 2020 Mar 13.

Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Aim: To develop a comprehensive item library of patient-reported, immunotherapy-related adverse events (irAEs) that draws from and expands on the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System.

Methods: Literature review and iterative expert input. Based on a literature review of irAEs, we developed a framework of immunotherapy classes and their associated symptoms. Clinical experts then reviewed iterations of symptom summaries and item maps linked to the immunotherapy framework. Experts provided content review and feedback was shared across experts until consensus was reached. The iterative process facilitated creation of a Primary Symptom List associated with immune checkpoint modulators (ICMs), drawn from the larger set of symptoms. Existing FACIT items were mapped to the symptom list, and new items were written as needed to create the item library.

Results: The full item library of irAEs is comprised of 239 items, covering 142 unique symptoms across 75 inflammatory reactions/immune conditions. A subset of 66 items comprises a Primary Symptom List considered most common/relevant to ICM treatment. This includes gastrointestinal, skin, pulmonary, neurologic, musculoskeletal, and multiple miscellaneous and constitutional symptoms.

Conclusion: The FACIT Immunotherapy Item Library is a compilation of 239 self-report items that capture the wide range of AEs experienced by people receiving immune treatments. A subset of 66 items comprises a Primary Symptom List meant for ICM therapy. Use of items selected from this library is encouraged in clinical research and clinical practice evaluation.
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http://dx.doi.org/10.20517/2394-4722.2019.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594877PMC
March 2020

Prospective study to define the clinical utility and benefit of Decipher testing in men following prostatectomy.

Prostate Cancer Prostatic Dis 2020 06 12;23(2):295-302. Epub 2019 Nov 12.

Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

Background: Genomic classifiers (GC) have been shown to improve risk stratification post prostatectomy. However, their clinical benefit has not been prospectively demonstrated. We sought to determine the impact of GC testing on postoperative management in men with prostate cancer post prostatectomy.

Methods: Two prospective registries of prostate cancer patients treated between 2014 and 2019 were included. All men underwent Decipher tumor testing for adverse features post prostatectomy (Decipher Biosciences, San Diego, CA). The clinical utility cohort, which measured the change in treatment decision-making, captured pre- and postgenomic treatment recommendations from urologists across diverse practice settings (n = 3455). The clinical benefit cohort, which examined the difference in outcome, was from a single academic institution whose tumor board predefined "best practices" based on GC results (n = 135).

Results: In the clinical utility cohort, providers' recommendations pregenomic testing were primarily observation (69%). GC testing changed recommendations for 39% of patients, translating to a number needed to test of 3 to change one treatment decision. In the clinical benefit cohort, 61% of patients had genomic high-risk tumors; those who received the recommended adjuvant radiation therapy (ART) had 2-year PSA recurrence of 3 vs. 25% for those who did not (HR 0.1 [95% CI 0.0-0.6], p = 0.013). For the genomic low/intermediate-risk patients, 93% followed recommendations for observation, with similar 2-year PSA recurrence rates compared with those who received ART (p = 0.93).

Conclusions: The use of GC substantially altered treatment decision-making, with a number needed to test of only 3. Implementing best practices to routinely recommend ART for genomic-high patients led to larger than expected improvements in early biochemical endpoints, without jeopardizing outcomes for genomic-low/intermediate-risk patients.
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http://dx.doi.org/10.1038/s41391-019-0185-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237345PMC
June 2020

A Pilot Study of Radiation Therapy in Combination With Pembrolizumab in Patients With Metastatic Renal Cell Cancer.

Am J Clin Oncol 2020 02;43(2):82-86

Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Objectives: There is no study published regarding the benefit of radiation therapy (RT) in combination with immune checkpoint inhibitors (ICIs) for the treatment of metastatic renal cell cancer (mRCC). This report is part of an exploratory study aiming to determine the immunomodulatory activity of RT alone or in combination with pembrolizumab in solid tumors.

Materials And Methods: mRCC patients were treated with a combination of RT (8 Gy×1 or 4 Gy×5) followed by pembrolizumab with or without lead-in dose of pembrolizumab. Treatment response was measured based on the modified Response Evaluation Criteria in Solid Tumors criteria. Adverse events were monitored and graded. Pre-RT and post-RT tumor biopsies were obtained to evaluate programmed death-ligand 1 expression. Immune markers from peripheral blood before, during, and after treatment were analyzed using flow cytometry.

Results: Twelve mRCC patients who progressed on prior antiangiogenic therapy were enrolled. Half had 2 lines of prior therapy. Two patients (16.7%) had partial responses and were on study for 12.4 and 14.5 months. Three patients had stable disease for a period ranging from 4.2 to 10.4 months, whereas 7 patients had progressive disease. Median progression-free survival was 8.6 months and median overall survival was 32.3 months. Three patients had grade ≥3 events (hyperglycemia, thrombocytopenia, transaminitis). Biopsied tissue programmed death-ligand 1 expression and tumor-infiltrating lymphocytes were numerically higher in responders comparing to nonresponders (Modified Proportion Score 45% vs. 30.45%; tumor-infiltrating lymphocytes odds ratio 4.92).

Conclusion: Combining RT with pembrolizumab in pretreated mRCC is well-tolerated and appears to have comparable efficacy with single-agent nivolumab.
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http://dx.doi.org/10.1097/COC.0000000000000636DOI Listing
February 2020

Clinical Outcome Assessments Toolbox for Radiopharmaceuticals.

Front Oncol 2019 10;9:1028. Epub 2019 Oct 10.

Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, United States.

For nearly 40 years, the U.S. National Cancer Institute (NCI) has funded health-related quality-of-life (HRQOL) and symptom management in oncology clinical trials as a method for including a cancer patient's experience during and after treatment. The NCI's planned scope for HRQOL, symptom and patient-reported outcomes management research is explained as it pertains to radiopharmaceutical clinical development. An effort already underway to support protocol authoring via an NCI Cancer Therapy Evaluation Program (CTEP) Centralized Protocol Writing Service (CPWS) is described as this service aids incorporation of HRQOL, symptom and patient-reported outcomes management research into sponsored protocols.
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http://dx.doi.org/10.3389/fonc.2019.01028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795707PMC
October 2019

Transcriptomic Heterogeneity of Androgen Receptor Activity Defines a low AR-Active Subclass in Treatment Naïve Primary Prostate Cancer.

Clin Cancer Res 2019 11 12;25(22):6721-6730. Epub 2019 Sep 12.

Department of Urology, Feinberg School of Medicine, Northwestern University, Illinois.

Purpose: The heterogeneity of androgen receptor (AR)-activity (AR-A) is well-characterized in heavily treated metastatic castration-resistant prostate cancer (mCRPC). However, the diversity and clinical implications of AR-A in treatment-naïve primary prostate cancer is largely unknown. We sought to characterize AR-A in localized prostate cancer and understand its molecular and clinical implications.

Experimental Design: Genome-wide expression profiles from prostatectomy or biopsy samples from 19,470 patients were used, all with independent pathology review. This was comprised of prospective discovery ( = 5,239) and validation ( = 12,728) cohorts, six retrospective institutional cohorts with long-term clinical outcomes data ( = 1,170), and The Cancer Genome Atlas ( = 333).

Results: A low AR-active subclass was identified, which comprised 9%-11% of each cohort, and was characterized by increased immune signaling, neuroendocrine expression, and decreased DNA repair. These tumors were predominantly and basal subtype. Low AR-active tumors had significantly more rapid development of recurrence or metastatic disease across cohorts, which was maintained on multivariable analysis [HR, 2.61; 95% confidence interval (CI), 1.22-5.60; = 0.014]. Low AR-active tumors were predicted to be more sensitive to PARP inhibition, platinum chemotherapy, and radiotherapy, and less sensitive to docetaxel and androgen-deprivation therapy. This was validated clinically, in that low AR-active tumors were less sensitive to androgen-deprivation therapy (OR, 0.41; 95% CI, 0.21-0.80; = 0.008).

Conclusions: Leveraging large-scale transcriptomic data allowed the identification of an aggressive subtype of treatment-naïve primary prostate cancer that harbors molecular features more analogous to mCRPC. This suggests that a preexisting subgroup of patients may have tumors that are predisposed to fail multiple current standard-of-care therapies and warrant dedicated therapeutic investigation.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-1587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858964PMC
November 2019

Big Data From Small Devices: The Future of Smartphones in Oncology.

Semin Radiat Oncol 2019 10;29(4):338-347

Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.. Electronic address:

Technological advancements in the capabilities of modern smartphones offer tremendous potential to generate big data from small devices that could influence oncologists' decision-making. Here we describe the value of patient-generated health data (PGHD) that can be captured using mobile devices. We comment on the current use of smartphones in oncology clinical research and describe how smartphones will bring big data into the oncology clinic by enabling continuous patient monitoring, information sharing, and personalized clinical decision making in cancer care. Lastly, we describe practical considerations about how we can access and store PGHD in the future, describing how to harness the clinical value of PGHD and comment on the emerging applications for digital biomarkers captured by smartphones.
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http://dx.doi.org/10.1016/j.semradonc.2019.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130844PMC
October 2019

Tumor-Derived Extracellular Vesicles Require β1 Integrins to Promote Anchorage-Independent Growth.

iScience 2019 Apr 27;14:199-209. Epub 2019 Mar 27.

Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, USA; Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA 19107, USA; Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address:

The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation in the prostatic epithelium (β1), do not. We find that sEVs, from cancer cells or TRAMP blood, are functional and co-express β1 and sEV markers; in contrast, sEVs from β1/TRAMP or wild-type mice lack β1 and sEV markers. Our results demonstrate that β1 integrins in tumor-cell-derived sEVs are required for stimulation of anchorage-independent growth.
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http://dx.doi.org/10.1016/j.isci.2019.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461598PMC
April 2019

Telemedicine Training in Undergraduate Medical Education: Mixed-Methods Review.

JMIR Med Educ 2019 Apr 8;5(1):e12515. Epub 2019 Apr 8.

Department of Radiation Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States.

Background: Telemedicine has grown exponentially in the United States over the past few decades, and contemporary trends in the health care environment are serving to fuel this growth into the future. Therefore, medical schools are learning to incorporate telemedicine competencies into the undergraduate medical education of future physicians so that they can more effectively leverage telemedicine technologies for improving the quality of care, increasing patient access, and reducing health care expense. This review articulates the efforts of allopathic-degree-granting medical schools in the United States to characterize and systematize the learnings that have been generated thus far in the domain of telemedicine training in undergraduate medical education.

Objective: The aim of this review was to collect and outline the current experiences and learnings that have been generated as medical schools have sought to implement telemedicine capacity-building into undergraduate medical education.

Methods: We performed a mixed-methods review, starting with a literature review via Scopus, tracking with Excel, and an email outreach effort utilizing telemedicine curriculum data gathered by the Liaison Committee on Medical Education. This outreach included 70 institutions and yielded 7 interviews, 4 peer-reviewed research papers, 6 online documents, and 3 completed survey responses.

Results: There is an emerging, rich international body of learning being generated in the field of telemedicine training in undergraduate medical education. The integration of telemedicine-based lessons, ethics case-studies, clinical rotations, and even teleassessments are being found to offer great value for medical schools and their students. Most medical students find such training to be a valuable component of their preclinical and clinical education for a variety of reasons, which include fostering greater familiarity with telemedicine and increased comfort with applying telemedical approaches in their future careers.

Conclusions: These competencies are increasingly important in tackling the challenges facing health care in the 21st century, and further implementation of telemedicine curricula into undergraduate medical education is highly merited.
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http://dx.doi.org/10.2196/12515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475822PMC
April 2019
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