Publications by authors named "Kosj Yamoah"

71 Publications

Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.

Commun Biol 2021 Jun 3;4(1):670. Epub 2021 Jun 3.

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA.

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.
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http://dx.doi.org/10.1038/s42003-021-02140-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175556PMC
June 2021

Management of locally advanced prostate cancer: appraisal of current paradigms and future directions.

Endocr Relat Cancer 2021 Jun 1. Epub 2021 Jun 1.

K Yamoah, Radiation Oncology, Moffitt Cancer Center, Tampa, United States.

The current standard for the management of locally advanced and early-stage metastatic prostate cancer relies on a backbone of androgen deprivation therapy (ADT) combined with radiotherapy (RT), a regimen that at a glance appears relatively straightforward. The emergence of newer diagnostic, genomic and imaging modalities have allowed for better disease risk-stratification and opened avenues for the development of more patient-centered treatment strategies. This review aims to highlight the central role of RT as part of a multi-modal approach, and discuss established and emerging data for the management of locally advanced disease, biochemical recurrence, and oligometastatic disease, as well as the use of immunotherapies and radio-isotopes. This review will also briefly discuss ongoing clinical trials that provide new insights into the paradigm shift in the management of locally advanced prostate cancer.
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http://dx.doi.org/10.1530/ERC-21-0073DOI Listing
June 2021

Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study.

NPJ Precis Oncol 2021 May 3;5(1):35. Epub 2021 May 3.

Department of Urology, Case Western Reserve University, Cleveland, OH, USA.

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p < 0.001, univariable hazard ratio [HR] = 2.83, 95% confidence interval [CI]: 2.03-3.93, concordance index [c-index] = 0.68, median years-to-BCR: 1.7). Histotyping was also prognostic in clinically stratified subsets, such as patients with Gleason grade group 3 (HR = 4.09) and negative surgical margins (HR = 3.26). Histotyping was prognostic independent of grade group, margin status, pathological stage, and preoperative prostate-specific antigen (PSA) (multivariable p < 0.001, HR = 2.09, 95% CI: 1.40-3.10, n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.
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http://dx.doi.org/10.1038/s41698-021-00174-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093226PMC
May 2021

Computationally Derived Cribriform Area Index from Prostate Cancer Hematoxylin and Eosin Images Is Associated with Biochemical Recurrence Following Radical Prostatectomy and Is Most Prognostic in Gleason Grade Group 2.

Eur Urol Focus 2021 Apr 30. Epub 2021 Apr 30.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH, USA. Electronic address:

Background: The presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement.

Objective: To investigate quantitative machine-based assessment of the extent and prognostic utility of ICC, especially within individual Gleason grade groups.

Design, Setting, And Participants: A machine learning approach was developed for ICC segmentation using 70 RP patients and validated in a cohort of 749 patients from four sites whose median year of surgery was 2007 and with median follow-up of 28 mo. ICC was segmented on one representative hematoxylin and eosin RP slide per patient and the fraction of tumor area composed of ICC, the cribriform area index (CAI), was measured.

Outcome Measurements And Statistical Analysis: The association between CAI and BCR was measured in terms of the concordance index (c index) and hazard ratio (HR).

Results And Limitations: CAI was correlated with BCR (c index 0.62) in the validation set of 411 patients with ICC morphology, especially those with Gleason grade group 2 cancer (n = 192; c index 0.66), and was less prognostic when patients without ICC were included (c index 0.54). A doubling of CAI in the group with ICC morphology was prognostic after controlling for Gleason grade, surgical margin positivity, preoperative prostate-specific antigen level, pathological T stage, and age (HR 1.19, 95% confidence interval 1.03-1.38; p = 0.018).

Conclusions: Automated image analysis and machine learning could provide an objective, quantitative, reproducible, and high-throughput method of quantifying ICC area. The performance of CAI for grade group 2 cancer suggests that for patients with little Gleason 4 pattern, the ICC fraction has a strong prognostic role.

Patient Summary: Machine-based measurement of a specific cell pattern (cribriform; sieve-like, with lots of spaces) in images of prostate specimens could improve risk stratification for patients with prostate cancer. In the future, this could help in expanding the criteria for active surveillance.
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http://dx.doi.org/10.1016/j.euf.2021.04.016DOI Listing
April 2021

KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.

Sci Rep 2021 Apr 29;11(1):9264. Epub 2021 Apr 29.

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90015, USA.

Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10) and 3145 (P < 1 × 10) SNP-SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene-gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP-SNP interactions were supported by gene expression and protein-protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
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http://dx.doi.org/10.1038/s41598-021-85169-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084951PMC
April 2021

Association of Health-Care System with Prostate Cancer-Specific Mortality in African American and Non-Hispanic White Men.

J Natl Cancer Inst 2021 Apr 21. Epub 2021 Apr 21.

Department of Radiation Medicine and Applied Sciences, University of California San Diego School of Medicine, La Jolla, California.

Background: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological and systemic factors. We evaluated drivers of these disparities in the Surveillance, Epidemiology and End Results (SEER) national registry and an equal-access system, the Veterans Health Administration (VHA).

Methods: We identified African American and White patients diagnosed with prostate cancer between 2004-2015 in SEER (N = 311,691) and the VHA (N = 90,749). We analyzed the association between race and metastatic disease at presentation using multivariable logistic regression adjusting for sociodemographic factors, and PCSM using sequential competing-risks regression adjusting for disease and sociodemographic factors.

Results: The median follow-up was 5.3 years in SEER and 4.7 years in the VHA. African American men were more likely than White men to present with metastatic disease in SEER (adjusted odds ratio = 1.23, 95% confidence interval [CI] = 1.17-1.30), but not in the VHA (adjusted odds ratio = 1.07, 95% CI = 0.98-1.17). African American versus White race was associated with an increased risk of PCSM in SEER (subdistribution hazard ratio [SHR] = 1.32, 95% CI = 1.10-1.60), but not in the VHA (SHR = 1.00, 95% CI: 0.93-1.08). Adjusting for disease extent, PSA, and Gleason score eliminated the association between race and PCSM in SEER (aSHR 1.04, 95% CI 0.93-1.16).

Conclusions: Racial disparities in PCSM were present in a nationally representative registry, but not in an equal-access healthcare system, due to differences in advanced disease at presentation. Strategies to increase healthcare access may bridge the racial disparity in outcomes. Longer follow-up is needed to fully assess mortality outcomes.Disparities between African American and non-Hispanic White (White) patients in cancer-specific mortality have been described across numerous cancer types and healthcare systems[1-5]. The survival gap between African American and White patients with prostate cancer has been well-characterized, with two-fold higher prostate cancer-specific mortality (PCSM) rates among African American patients depending on the setting[1, 6-10]. This disparity has been attributed to differences in prostate cancer biology in African American men, in addition to systemic factors in mediating this disparity, such as differential access to healthcare, Prostate-Specific Antigen (PSA) screening, and distrust in the healthcare system[1, 11-16].The Veterans Health Administration (VHA) is a relatively equal-access healthcare system that treats a large, ethnically diverse population of veterans. The Surveillance, Epidemiology and End Results (SEER) program is a national cancer registry program that collects data from the general United States (US) population. The goals of the present investigation were to 1) Compare PCSM between African American and White men within SEER and the VHA and 2) Identify modifiable system-level contributors to these disparities. We hypothesized that PCSM would be comparable among African American and White men in an equal-access setting, the VHA, but not in a national registry, SEER, and that this disparity in SEER would be in part driven by more advanced disease at presentation.
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http://dx.doi.org/10.1093/jnci/djab062DOI Listing
April 2021

Effectiveness and Safety of Prostatic Artery Embolization for the Treatment of Lower Urinary Tract Symptoms from Benign Prostatic Hyperplasia in Men with Concurrent Localized Prostate Cancer.

J Vasc Interv Radiol 2021 Mar 29. Epub 2021 Mar 29.

Department of Interventional Radiology, Miller School of Medicine, University of Miami, Miami, Florida.

Purpose: To assess the effectiveness and safety of prostatic artery embolization (PAE) on lower urinary tract symptoms (LUTS) in the setting of localized prostate cancer (PCa).

Materials And Methods: This was a retrospective, single-center, institutional review board-approved study from December 2016 to June 2020 of 21 patients (median age, 72; range, 63-83 years) with moderate LUTS and localized PCa. Clinical effectiveness was evaluated at 6 and 12 weeks using International Prostate Symptom Score (IPSS) and quality of life (QoL) improvement. Seventeen patients were scheduled to receive definitive radiotherapy (RT) after PAE; 13 patients completed RT. Short-term imaging signs of oncologic progression were evaluated at 6 and 12 weeks defined by at least one of the following on magnetic resonance imaging: increased Prostate Imaging-Reporting and Data System score of index lesion(s) to at least 4, new extracapsular extension, seminal vesicle involvement, or pelvic lymphadenopathy. Nonparametric Wilcoxon signed-rank test was used for analysis.

Results: IPSS improved by a median of 12 (n = 19, P < .0001) and 14 (n = 14, P < .0001) at 6 and 12 weeks, respectively. QoL improved by a median of 2 (n = 19, P < .0001) and 3 (n = 3, P < .0001) at 6 and 12 weeks. Prostate volume decreased by a median of 24% (n = 19, P < .0001) and 36% (n = 12, P = .015) at 6 and 12 weeks. No patients demonstrated disease progression at 6 (n = 16) or 12 (n = 8) weeks by imaging. No patients experienced increased prostate-specific antigen after RT, grade ≥3 adverse events, or greater genitourinary toxicity.

Conclusions: PAE is effective and safe for the treatment of men with LUTS from benign prostatic hyperplasia in the setting of concomitant, localized, non-obstructive PCa.
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http://dx.doi.org/10.1016/j.jvir.2021.03.534DOI Listing
March 2021

A Proof-of-Concept Study on the Use of Prostate Artery Embolization Before Definitive Radiation Therapy in Prostate Cancer.

Adv Radiat Oncol 2021 May-Jun;6(3):100619. Epub 2020 Nov 21.

Interventional Radiology, Moffitt Cancer Center, Tampa, Florida.

Purpose: Prostatic artery embolization (PAE) is an effective therapy for alleviating lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia; however, is not well studied in patients with concurrent prostate cancer (PCa). We demonstrate a proof of concept for PAE before definitive radiation therapy (RT) in patients with PCa.

Methods And Materials: From December 2017 to July 2019, 9 patients with PCa underwent PAE for the indication of LUTS from benign prostatic hyperplasia with concurrent PCa. Five received radiation and all follow-ups at our institution and were therefore included in the analysis. Median follow-up was 18 months from the time of PAE. Side effects during radiation were quantified using the Common Terminology Criteria for Adverse Events scoring system. Pre- and post-PAE plans were compared in the 5 patients by performing an isovolumetric expansion of the post-PAE plan (treated plan) equivalent to the measured volume reduction after PAE. Patient 1 (PT-01) and PT-02 had prostate RT alone whereas PT-03, PT-04, and PT-05 had prostate with elective nodal coverage RT. Mean doses to organs at risk were compared between the 2 plans.

Results: The mean International Prostate Symptom Score reduction after PAE was 13.8 (5.0-30.0; = .02). The mean prostatic volume reduction after PAE was 23.1% (7.2%-47.7%). There were no Common Terminology Criteria for Adverse Events grade 3 (severe) or higher during radiation. Post-PAE plans in PT-01 and PT-02 had on average 23.2%, 39.8%, and 22.9% decrease in mean dose across the bladder, rectum, and penile bulb, respectively, compared with the pre-PAE plans. There were no appreciable differences in dosimetry in PT03, PT-04, and PT-05 who had nodal coverage. There was no biochemical failure in any of the patients.

Conclusions: We demonstrate a proof of concept that PAE is a clinically significant adjunctive therapy for alleviating LUTS and achieving significant volume reduction before RT, resulting in decreased radiation-related toxicity from RT for PCa.
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http://dx.doi.org/10.1016/j.adro.2020.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966837PMC
November 2020

Novel Transcriptomic Interactions Between Immune Content and Genomic Classifier Predict Lethal Outcomes in High-grade Prostate Cancer.

Eur Urol 2020 Dec 7. Epub 2020 Dec 7.

University of California, San Francisco, CA, USA.

Grade group 4 and 5 (GG-45) prostate cancer (PCa) patients are at the highest risk of lethal outcomes, yet lack genomic risk stratification for prognosis and treatment selection. Here, we assess whether transcriptomic interactions between tumor immune content score (ICS) and the Decipher genomic classifier can identify most lethal subsets of GG-45 PCa. We utilized whole transcriptome data from 8071 tumor tissue (6071 prostatectomy and 2000 treatment-naïve biopsy samples) to derive four immunogenomic subtypes using ICS and Decipher. When compared across all grade groups, GG-45 samples had the highest proportion of most aggressive subtype-ICS/Decipher. Subsequent analyses within the GG-45 patient samples (n = 1420) revealed that the ICS/Decipher subtype was associated with increased genomic radiosensitivity. Additionally, in a multivariable model (n = 335), ICS/Decipher subtype had a significantly higher risk of distant metastasis (hazard ratio [HR] = 5.41; 95% confidence interval [CI], 2.76-10.6; p ≤  0.0001) and PCa-specific mortality (HR = 10.6; 95% CI, 4.18-26.94; p ≤  0.0001) as compared with ICS/Decipher. The novel immunogenomic subtypes establish a very strong synergistic interaction between ICS and Decipher in identifying GG-45 patients who experience the most lethal outcomes. PATIENT SUMMARY: In this analysis, we identified a novel interaction between the total immune content of prostate tumors and genomic classifier to identify the most lethal subset of patients with grade groups 4 and 5. Our results will aid in the subtyping of aggressive prostate cancer patients who may benefit from combined immune-radiotherapy modalities.
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http://dx.doi.org/10.1016/j.eururo.2020.11.038DOI Listing
December 2020

TMPRSS2-ERG fusion impacts anterior tumor location in men with prostate cancer.

Prostate 2021 02 3;81(2):109-117. Epub 2020 Nov 3.

Dana Farber Cancer Institute and Harvard TH Chan School of Public Health, Boston, Massachusetts, USA.

Background: In prostate cancer (PCa), lack of androgen receptor (AR) regulated TMPRSS2-ETS-related gene (ERG) gene fusion (ERG ) status has been associated with African American race; however, the implications of ERG status for the location of dominant tumors within the prostate remains understudied.

Methods: An African American-enriched multiinstitutional cohort of 726 PCa patients consisting of both African American men (AAM; n = 254) and European American men (EAM; n = 472) was used in the analyses. Methods of categorical analysis were used. Messenger RNA (mRNA) expression differences between anterior and posterior tumor lesions were analyzed using Wilcoxon rank-sum tests with multiple comparison corrections.

Results: Anti-ERG immunohistochemistry staining showed that the association between ERG status and anterior tumors is independent of race and is consistently robust for both AAM (ERG 81.4% vs. ERG 18.6%; p = .005) and EAM (ERG 60.4% vs. ERG 39.6%; p < .001). In a multivariable model, anterior tumors were more likely to be IHC-ERG (odds ratio [OR]: 3.20; 95% confidence interval [CI]: 2.14-4.78; p < .001). IHC-ERG were also more likely to have high-grade tumors (OR: 1.73; 95% CI: 1.06-2.82; p = .02). In the exploratory genomic analysis, mRNA expression of location-dependent genes is highly influenced by ERG status and African American race. However, tumor location did not impact the expression of AR or the major canonical AR-target genes (KLK3, AMACR, and MYC).

Conclusions: ERG tumor status is the strongest predictor of anterior prostate tumors, regardless of race. Furthermore, AR expression and canonical AR signaling do not impact tumor location.
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http://dx.doi.org/10.1002/pros.24086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810127PMC
February 2021

Prostatic Artery Embolization Is Safe and Effective for Medically Recalcitrant Radiation-Induced Prostatitis.

Adv Radiat Oncol 2020 Sep-Oct;5(5):905-909. Epub 2020 Apr 14.

Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.

Purpose: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents 90% of all chronic prostatitis cases and may occur after radiation therapy (RT) for localized prostate cancer. Medical therapy is effective in approximately 50% of cases, with no therapy demonstrating consistent efficacy in refractory cases. Prostatic artery embolization (PAE) is effective in men with lower urinary tract symptoms and benign prostatic hyperplasia. We report clinical improvement after PAE in a case series of men with CP/CPPS after RT.

Methods And Materials: Nine men (median age 72 years; range, 61-83 years) with CP/CPPS after RT for prostate cancer underwent PAE. Baseline International Prostate Symptom Score was recorded in 5 patients (median 23; range, 4-26), Chronic Prostatitis Symptom Index score in 6 patients (median 22.5; range, 6-34), and quality of life (QoL) score in 8 patients (median 5; range, 2-6). Median baseline prostate volume was 49 cm (range, 22-123 cm). Patients were followed up at 6 and 12 weeks with QoL, International Prostate Symptom Score, and/or Chronic Prostatitis Symptom Index score and magnetic resonance imaging.

Results: Technical success (ie, bilateral embolization) was achieved in 78% (n = 7) of patients with the other 2 patients having undergone unilateral embolization with no major complications. Clinical success was seen in 89% (n = 8) of patients and QoL improved in 78% (n = 7) during the follow-up period.

Conclusion: CP/CPPS after RT for localized prostate cancer is a highly morbid condition, with medical therapy successful in only 50% of cases. PAE may be a successful therapy for medically recalcitrant CP/CPPS, and further studies are necessary to understand the best patient selection and scenario for PAE in the setting of CP/CPPS.
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http://dx.doi.org/10.1016/j.adro.2020.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557125PMC
April 2020

Comparative Genomics Reveals Distinct Immune-oncologic Pathways in African American Men with Prostate Cancer.

Clin Cancer Res 2021 Jan 9;27(1):320-329. Epub 2020 Oct 9.

Department of Cancer Epidemiology, H Lee Moffitt Cancer Center & Research Institutes, Tampa, Florida.

Purpose: The role of immune-oncologic mechanisms of racial disparities in prostate cancer remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American men (AAM) and European American men (EAM) prostate tumor microenvironment (TME).

Experimental Design: A total of 1,173 radiation-naïve radical prostatectomy samples with whole transcriptome data from the Decipher GRID registry were used. Transcriptomic expressions of 1,260 immune-specific genes were selected to assess immune-oncologic differences between AAM and EAM prostate tumors. Race-specific differential expression of genes was assessed using a rank test, and intergene correlational matrix and gene set enrichment was used for pathway analysis.

Results: AAM prostate tumors have significant enrichment of major immune-oncologic pathways, including proinflammatory cytokines, IFNα, IFNγ, TNFα signaling, ILs, and epithelial-mesenchymal transition. AAM TME has higher total immune content score (ICS) compared with 0 (37.8% vs. 21.9%, = 0.003). AAM tumors also have lower DNA damage repair and are genomically radiosensitive as compared with EAM. (IFN-inducible transmembrane protein 3) was one of the major proinflammatory genes overexpressed in AAM that predicted increased risk of biochemical recurrence selectively for AAM in both discovery [HR = 2.30; 95% confidence interval (CI), 1.21-4.34; = 0.01] and validation (HR = 2.42; 95% CI, 1.52-3.86; = 0.0001) but not in EAM.

Conclusions: Prostate tumors of AAM manifest a unique immune repertoire and have significant enrichment of proinflammatory immune pathways that are associated with poorer outcomes. Observed immune-oncologic differences can aid in a genomically adaptive approach to treating prostate cancer in AAM.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-2925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042600PMC
January 2021

Outcomes of Black men with prostate cancer treated with radiation therapy in the Veterans Health Administration.

Cancer 2021 Feb 9;127(3):403-411. Epub 2020 Oct 9.

Department of Radiation Medicine and Applied Sciences, University of California San Diego School of Medicine, La Jolla, California.

Background: Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors.

Methods: The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters.

Results: Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001).

Conclusions: The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.
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http://dx.doi.org/10.1002/cncr.33224DOI Listing
February 2021

Comparison of Definitive Cervical Cancer Management With Chemotherapy and Radiation Between Two Centers With Variable Resources and Opportunities for Improved Treatment.

JCO Glob Oncol 2020 10;6:1510-1518

Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.

Purpose: Cervical cancer remains a major health challenge in low- to middle-income countries. We present the experiences of two centers practicing in variable resource environments to determine predictors of improved radiochemotherapy treatment.

Methods And Materials: This comparative review describes cervical cancer presentation and treatment with concurrent chemoradiotherapy with high-dose-rate brachytherapy between 2014 and 2017 at the National Radiotherapy Oncology and Nuclear Medicine Center (NRONMC) in Korle-Bu Teaching Hospital, Accra, Ghana, and Moffitt Cancer Center (MCC), Tampa, FL.

Results: Median follow-up for this study was 16.9 months. NRONMC patients presented with predominantly stage III disease (42% 16%; = .002). MCC patients received para-aortic node irradiation (16%) and interstitial brachytherapy implants (19%). Median treatment duration was longer for NRONMC patients compared with MCC patients (59 52 days; < .0001), and treatment duration ≥ 55 days predicted worse survival on multivariable analysis (MVA; = .02). Stage ≥ III disease predicted poorer local control on MVA. There was a difference in local control among patients with stage III disease (58% 91%; = .03) but not in survival between MCC and NRONMC. No significant difference in local control was observed for stage IB, IIA, and IIB disease.

Conclusion: Although there were significant differences in disease presentation between the two centers, treatment outcomes were similar for patients with early-stage disease. Longer treatment duration and stage ≥ III disease predicted poor outcomes.
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http://dx.doi.org/10.1200/GO.20.00303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605379PMC
October 2020

Proof-of-principle Phase I results of combining nivolumab with brachytherapy and external beam radiation therapy for Grade Group 5 prostate cancer: safety, feasibility, and exploratory analysis.

Prostate Cancer Prostatic Dis 2021 03 10;24(1):140-149. Epub 2020 Jul 10.

Departments of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.

Background: To determine whether combining brachytherapy with immunotherapy is safe in prostate cancer (PCa) and provides synergistic effects, we performed a Phase I/II trial on the feasibility, safety, and benefit of concurrent delivery of anti-PD-1 (nivolumab) with high-dose-rate (HDR) brachytherapy and androgen deprivation therapy (ADT) in patients with Grade Group 5 (GG5) PCa.

Methods: Eligible patients were aged 18 years or older with diagnosis of GG5 PCa. Patients received ADT, nivolumab every two weeks for four cycles, with two cycles prior to first HDR, and two more cycles prior to second HDR, followed by external beam radiotherapy. The primary endpoint was to determine safety and feasibility. This Phase I/II trial is registered with ClinicalTrials.gov (NCT03543189).

Results: Between September 2018 and June 2019, six patients were enrolled for the Phase I safety lead-in with a minimum observation period of 3 months after nivolumab administration. Overall, nivolumab was well tolerated in combination with ADT and HDR treatment. One patient experienced a grade 3 dose-limiting toxicity (elevated Alanine aminotransferase and Aspartate aminotransferase) after the second cycle of nivolumab. Three patients (50%) demonstrated early response with no residual tumor detected in ≥4 of 6 cores on biopsy post-nivolumab (4 cycles) and 1-month post-HDR. Increase in CD8+ and FOXP3+/CD4+ T cells in tissues, and CD4+ effector T cells in peripheral blood were observed in early responders.

Conclusion: Combination of nivolumab with ADT and HDR is well tolerated and associated with evidence of increased immune infiltration and antitumor activity.
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http://dx.doi.org/10.1038/s41391-020-0254-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882397PMC
March 2021

A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry.

Eur Urol 2020 09 12;78(3):316-320. Epub 2020 May 12.

Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.
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http://dx.doi.org/10.1016/j.eururo.2020.04.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805560PMC
September 2020

Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier.

Prostate Cancer Prostatic Dis 2020 12 30;23(4):646-653. Epub 2020 Mar 30.

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

Background: Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date.

Methods: A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score.

Results: Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19-1.50, p < 0.001), while age, serum PSA, biopsy GG, and clinical T-stage were not (all p > 0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19-1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79-4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71.

Conclusions: Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.
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http://dx.doi.org/10.1038/s41391-020-0226-2DOI Listing
December 2020

Computationally Derived Image Signature of Stromal Morphology Is Prognostic of Prostate Cancer Recurrence Following Prostatectomy in African American Patients.

Clin Cancer Res 2020 04 5;26(8):1915-1923. Epub 2020 Mar 5.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.

Purpose: Between 30%-40% of patients with prostate cancer experience disease recurrence following radical prostatectomy. Existing clinical models for recurrence risk prediction do not account for population-based variation in the tumor phenotype, despite recent evidence suggesting the presence of a unique, more aggressive prostate cancer phenotype in African American (AA) patients. We investigated the capacity of digitally measured, population-specific phenotypes of the intratumoral stroma to create improved models for prediction of recurrence following radical prostatectomy.

Experimental Design: This study included 334 radical prostatectomy patients subdivided into training (V, = 127), validation 1 (V, = 62), and validation 2 (V, = 145). Hematoxylin and eosin-stained slides from resected prostates were digitized, and 242 quantitative descriptors of the intratumoral stroma were calculated using a computational algorithm. Machine learning and elastic net Cox regression models were constructed using V to predict biochemical recurrence-free survival based on these features. Performance of these models was assessed using V and V, both overall and in population-specific cohorts.

Results: An AA-specific, automated stromal signature, AAstro, was prognostic of recurrence risk in both independent validation datasets [V: AUC = 0.87, HR = 4.71 (95% confidence interval (CI), 1.65-13.4), = 0.003; V: AUC = 0.77, HR = 5.7 (95% CI, 1.48-21.90), = 0.01]. AAstro outperformed clinical standard Kattan and CAPRA-S nomograms, and the underlying stromal descriptors were strongly associated with IHC measurements of specific tumor biomarker expression levels.

Conclusions: Our results suggest that considering population-specific information and stromal morphology has the potential to substantially improve accuracy of prognosis and risk stratification in AA patients with prostate cancer.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165025PMC
April 2020

Validation of a genomic classifier for prediction of metastasis and prostate cancer-specific mortality in African-American men following radical prostatectomy in an equal access healthcare setting.

Prostate Cancer Prostatic Dis 2020 09 16;23(3):419-428. Epub 2019 Dec 16.

Department of Surgery, Division of Urology, Veteran Affairs Healthcare System, Durham, NC, USA.

Background: The Decipher 22-gene genomic classifier (GC) may help in post-radical prostatectomy (RP) decision making given its superior prognostic performance over clinicopathologic variables alone. However, most studies evaluating the GC have had a modest representation of African-American men (AAM). We evaluated the GC within a large Veteran Affairs cohort and compared its performance to CAPRA-S for predicting outcomes in AAM and non-AAM after RP.

Methods: GC scores were generated for 548 prostate cancer (PC) patients, who underwent RP at the Durham Veteran Affairs Medical Center between 1989 and 2016. This was a clinically high-risk cohort and was selected to have either pT3a, positive margins, seminal vesicle invasion, or received post-RP radiotherapy. Multivariable Cox models and survival C-indices were used to compare the performance of GC and CAPRA-S for predicting the risk of metastasis and PC-specific mortality (PCSM).

Results: Median follow-up was 9 years, during which 37 developed metastasis and 20 died from PC. Overall, 55% (n = 301) of patients were AAM. In multivariable analyses, GC (high vs. intermediate and intermediate vs. low) was a significant predictor of metastasis in all men (all p < 0.001). Consistent with prior studies, relative to CAPRA-S, GC had a higher C-index for 5-year metastasis (0.78 vs. 0.72) and 10-year PCSM (0.85 vs. 0.81). There was a suggestion GC was a stronger predictor in AAM than non-AAM. Specifically, the 5-year metastasis risk C-index was 0.86 in AAM vs. 0.69 in non-AAM and the 10-year PCSM risk C-index was 0.91 in AAM vs. 0.78 in non-AAM. However, the test for interaction of race and the performance of the GC in the Cox model was not significant for either metastasis or PCSM (both p ≥ 0.3).

Conclusions: GC was a very strong predictor of poor outcome and performed well in both AAM and non-AAM. Our data support the use of GC for risk stratification in AAM post-RP. While our data suggest that GC may actually work better in AAM, given the limited number of events, further validation is needed.
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http://dx.doi.org/10.1038/s41391-019-0197-3DOI Listing
September 2020

Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2019 12;17(12):1529-1554

28National Comprehensive Cancer Network.

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.
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http://dx.doi.org/10.6004/jnccn.2019.0058DOI Listing
December 2019

Commercial Gene Expression Tests for Prostate Cancer Prognosis Provide Paradoxical Estimates of Race-Specific Risk.

Cancer Epidemiol Biomarkers Prev 2020 01 22;29(1):246-253. Epub 2019 Nov 22.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: Commercial gene expression signatures of prostate cancer prognosis were developed and validated in cohorts of predominantly European American men (EAM). Limited research exists on the value of such signatures in African American men (AAM), who have poor prostate cancer outcomes. We explored differences in gene expression between EAM and AAM for three commercially available panels recommended by the National Comprehensive Cancer Network for prostate cancer prognosis.

Methods: A total of 232 EAM and 95 AAM patients provided radical prostatectomy specimens. Gene expression was quantified using NanoString for 60 genes spanning the Oncotype DX Prostate, Prolaris, and Decipher panels. A continuous expression-based risk score was approximated for each. Differential expression, intrapanel coexpression, and risk by race were assessed.

Results: Clinical and pathologic features were similar between AAM and EAM. Differential expression by race was observed for 48% of genes measured, although the magnitudes of expression differences were small. Coexpression patterns were more strongly preserved by race group for Oncotype DX and Decipher than Prolaris. Poorer prognosis was estimated in EAM versus AAM for Oncotype DX ( < 0.001), whereas negligible prognostic differences were predicted between AAM and EAM using Prolaris or Decipher ( > 0.05).

Conclusions: Because of observed racial differences across three commercial gene expression panels for prostate cancer prognosis, caution is warranted when applying these panels in clinical decision-making in AAM.

Impact: Differences in gene expression by race for three commercial panels for prostate cancer prognosis indicate that further study of their effectiveness in AAM with long-term follow-up is warranted.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942810PMC
January 2020

Biology vs Access to Care-Relative Contribution to Racial Disparities in Prostate Cancer.

JAMA Oncol 2019 12;5(12):1809-1810

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida.

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http://dx.doi.org/10.1001/jamaoncol.2019.4497DOI Listing
December 2019

Definitive Radiation Treatment Patterns and Outcomes for Low and Intermediate Risk Prostate Cancer Patients: A Cross-Continental Comparative Study.

Am J Clin Oncol 2019 12;42(12):937-944

Departments of Radiation Oncology.

Purpose: To evaluate early-stage prostate cancer (PCa) radiotherapy treatment patterns and outcomes among Ghanaian men (GM) compared with US men (USM).

Materials And Methods: This retrospective study consists of 987 National Comprehensive Cancer Network low risk, favorable intermediate risk, and unfavorable intermediate risk PCa patient subgroups; GM (173) and USM (814). Differences in baseline covariates and clinical characteristics between GM and USM were analyzed using χ and Mann-Whitney test while Cox Proportional Hazards model was used to assess freedom from biochemical failure differences between the study groups.

Results: Median follow-up for this study was 40 months. GM were diagnosed at a younger median age (64 vs. 68 y, P<0.001) with heavier unfavorable intermediate risk disease burden (32.4% vs. 19.2%) compared with USM. Significant differences were identified in median external beam radiotherapy dose (72.4 vs. 78 Gy, P<0.001); brachytherapy utilization (49.7% vs. 80.6%, P<0.001) and androgen deprivation therapy for intermediate risk disease (48.4% vs. 21.0%, P<0.001) between GM and USM, respectively. GM with low risk and favorable intermediate risk PCa were at increased risk of biochemical recurrence compared with USM with adjusted hazard ratio: 5.15 (1.27 to 20.7), P=0.02 and 4.64 (1.20 to 17.92), P=0.02, respectively.

Conclusions: Compared with USM, GM with low and favorable intermediate risk PCa may experience less durable disease control following standard treatment recommendations. Results suggest differences in radiation treatment and possible inherent differences between the 2 populations. This data will aid in developing research strategies to improve treatment outcomes in GM.
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http://dx.doi.org/10.1097/COC.0000000000000589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887629PMC
December 2019

African American Specific Gene Panel Predictive of Poor Prostate Cancer Outcome.

J Urol 2019 08 8;202(2):247-255. Epub 2019 Jul 8.

H. Lee Moffitt Cancer Center and Research Institute , Tampa , Florida.

Purpose: Most prostate cancer in African American men lacks the ETS (E26 transforming specific) family fusion event (ETS-). We aimed to establish clinically relevant biomarkers in African American men by studying ETS dependent gene expression patterns to identified race specific genes predictive of outcomes.

Materials And Methods: Two multicenter cohorts of a total of 1,427 men were used for the discovery and validation (635 and 792 men, respectively) of race specific predictive biomarkers. We used false discovery rate adjusted q values to identify race and ETS dependent genes which were differentially expressed in African American men who experienced biochemical recurrence within 5 years. Principal component modeling along with survival analysis was done to assess the accuracy of the gene panel in predicting recurrence.

Results: We identified 3,047 genes which were differentially expressed based on ETS status. Of these genes 362 were differentially expressed in a race specific manner (false discovery rate 0.025 or less). A total of 81 genes were race specific and over expressed in African American men who experienced biochemical recurrence. The final gene panel included APOD, BCL6, EMP1, MYADM, SRGN and TIMP3. These genes were associated with 5-year biochemical recurrence (HR 1.97, 95% CI 1.27-3.06, p = 0.002) and they improved the predictive accuracy of clinicopathological variables only in African American men (60-month time dependent AUC 0.72).

Conclusions: In an effort to elucidate biological features associated with prostate cancer aggressiveness in African American men we identified ETS dependent biomarkers predicting early onset biochemical recurrence only in African American men. Thus, these ETS dependent biomarkers representing ideal candidates for biomarkers of aggressive disease in this patient population.
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http://dx.doi.org/10.1097/JU.0000000000000193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882398PMC
August 2019

Interrelationship Between Health Insurance Status and Prostate Cancer Grade Can Have Critical Impact on Prostate Cancer Disease Control: A Retrospective Cohort Study.

Cancer Control 2019 Jan-Dec;26(1):1073274819837184

1 Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

The extent to which prostate cancer (PCa) pathology interacts with health insurance to predict PCa outcomes remains unclear. This study will assess the overall association of health insurance on PCa disease control and analyze its interrelationship PCa pathology. A total of 674 PCa patients, treated with prostatectomy from 1987 to 2015, were included in the study. Freedom from biochemical failure (FFbF) was used as a measure of PCa disease control. Methods of categorical and survival analysis were used to analyze the relationships between health insurance, PCa pathology, and FFbF. A total of 63.3% patients were privately insured, 27.1% were publicly insured, and 9.5% were uninsured. In a multivariable model, privately (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.42-0.97, P = .03) and publicly (HR = 0.65, 95% CI: 0.41-1.04, P = .07) insured patients showed improvement in FFbF compared to uninsured patients. The association of health insurance was significantly stronger for the patients with pathologically low grade PCa (pathologic Gleason Score 3+3 & preoperative prostate-specific antigen ≤10 ng/mL), likelihood ratio P = .009. Privately (HR = 0.22, 95% CI: 0.10-0.46) or publicly (HR = 0.26, 95% CI: 0.11-0.60) insured patients with low grade PCa demonstrated favorable association with FFbF. Patients with private and public insurance were more likely to experience favorable treatment. The association of health insurance on PCa disease control is significantly stronger among patients with pathologically low grade PCa. This study identifies health insurance status as pretreatment surrogate for PCa disease control.
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http://dx.doi.org/10.1177/1073274819837184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446254PMC
August 2019

Novel Genomic-Based Strategies to Personalize Lymph Node Radiation Therapy.

Semin Radiat Oncol 2019 04;29(2):111-125

Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL; Departments of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL. Electronic address:

Current standard radiotherapy doses have been derived from empiric methods rather than a scientific framework. Subclinical nodal dosing remains relatively uniform across most disease sites, despite heterogeneity in patient and tumor biology. It is now clear that there are subsets of patients who will benefit from genomically-informed radiotherapy planning, and there are increasing efforts toward prescribing radiation dose to match the radiosensitivity of the tumor. By using novel genomic biomarkers to personalize delivery of radiotherapy, there is an opportunity to improve loco-regional control and cure rates. We survey the current landscape of personalized radiation oncology across commonly treated disease sites.
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http://dx.doi.org/10.1016/j.semradonc.2018.11.003DOI Listing
April 2019

Predicting clinically significant prostate cancer using DCE-MRI habitat descriptors.

Oncotarget 2018 12 14;9(98):37125-37136. Epub 2018 Dec 14.

Department of Cancer Physiology, H.L. Moffitt Cancer Center, Tampa, FL, USA.

Prostate cancer diagnosis and treatment continues to be a major public health challenge. The heterogeneity of the disease is one of the major factors leading to imprecise diagnosis and suboptimal disease management. The improved resolution of functional multi-parametric magnetic resonance imaging (mpMRI) has shown promise to improve detection and characterization of the disease. Regions that subdivide the tumor based on Dynamic Contrast Enhancement (DCE) of mpMRI are referred to as in this study. The DCE defined perfusion curve patterns on the identified tumor habitat region are used to assess clinical significance. These perfusion curves were systematically quantified using seven features in association with the patient biopsy outcome and classifier models were built to find the best discriminating characteristics between clinically significant and insignificant prostate lesions defined by Gleason score (GS). Multivariable analysis was performed independently on one institution and validated on the other, using a multi-parametric feature model, based on DCE characteristics and ADC features. The models had an intra institution Area under the Receiver Operating Characteristic (AUC) of 0.82. Trained on Institution I and validated on the cohort from Institution II, the AUC was also 0.82 (sensitivity 0.68, specificity 0.95).
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http://dx.doi.org/10.18632/oncotarget.26437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324677PMC
December 2018

Optimizing Time to Treatment to Achieve Durable Biochemical Disease Control after Surgery in Prostate Cancer: A Multi-Institutional Cohort Study.

Cancer Epidemiol Biomarkers Prev 2019 03 9;28(3):570-577. Epub 2018 Nov 9.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: The impact of treatment delays on prostate cancer-specific outcomes remains ill-defined. This study investigates the effect of time to treatment on biochemical disease control after prostatectomy.

Methods: This retrospective study includes 1,807 patients who received a prostatectomy as a primary treatment at two large tertiary referral centers from 1987 to 2015. Multivariate cox model with restricted cubic spline was used to identify optimal time to receive treatment and estimate the risk of biochemical recurrence.

Results: Median follow-up time of the study was 46 (interquartile range, 18-86) months. Time to treatment was subcategorized based on multivariate cubic spline cox model. In multivariate spline model, adjusted for all the pertinent pretreatment variables, inflection point in the risk of biochemical recurrence was observed around 3 months, which further increased after 6 months. Based on spline model, time to treatment was then divided into 0 to 3 months (61.5%), >3 to 6 months (31.1%), and 6 months (7.4%). In the adjusted cox model, initial delays up to 6 months did not adversely affect the outcome; however, time to treatment >6 months had significantly higher risk of biochemical recurrence (HR, 1.84; 95% confidence interval, 1.30-2.60; < 0.01).

Conclusions: The initial delays up to 6 months in prostate cancer primary treatment may be sustainable without adversely affecting the outcome. However, significant delays beyond 6 months can unfavorably affect biochemical disease control.

Impact: Time to treatment can aid clinicians in the decision-making of prostate cancer treatment recommendation and educate patients against unintentional treatment delays.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100999PMC
March 2019