Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma.

Background: Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects.

RWD-derived response in multiple myeloma.

Real-world data (RWD) are important for understanding the treatment course and response patterns of patients with multiple myeloma. This exploratory pilot study establishes a way to reliably assess response from incomplete laboratory measurements captured in RWD. A rule-based algorithm, adapted from International Myeloma Working Group response criteria, was used to derive response using RWD.

Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome.

We present primary results from the phase 1b GO29754 study evaluating the safety and tolerability of atezolizumab, a programmed death-ligand 1 inhibitor, alone and in combination with azacitidine, a hypomethylating agent (HMA), in patients with relapsed/refractory (R/R) or HMA-naïve myelodysplastic syndrome (MDS). Patients with R/R MDS received atezolizumab for 12 months (cohort A) or atezolizumab plus azacitidine for 6 cycles followed by atezolizumab as maintenance for 8 cycles (cohort B). Patients with HMA-naïve MDS received atezolizumab plus azacitidine until loss of clinical benefit (cohort C).

Low Tristetraprolin Expression Is Associated with Lethal Prostate Cancer.

Background: Inflammation is linked to prostate cancer progression and is mediated by NF-κB. Tristetraprolin is a key node of NF-κB activation and we investigated its biological and prognostic role in lethal prostate cancer.

Methods: assays assessed the function of tristetraprolin and the association between low mRNA tristetraprolin levels and lethal prostate cancer (metastatic disease or death) was assessed across independent prostatectomy cohorts: (i) nested case-control studies from Health Professionals Follow-up Study and Physicians' Health Study, and (ii) prostatectomy samples from Cleveland Clinic, Mayo Clinic, Johns Hopkins and Memorial Sloan Kettering Cancer Center.

Development and Validation of a Prostate Cancer Genomic Signature that Predicts Early ADT Treatment Response Following Radical Prostatectomy.

Currently, no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy for high-risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT. A training set consisting of 284 radical prostatectomy patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT (a-ADT)-treated and no ADT-treated groups.

Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy.

Background: Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men.

Objective: To evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively.

Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses.

Gene Expression Correlates of Site-specific Metastasis Among Men With Lymph Node Positive Prostate Cancer Treated With Radical Prostatectomy: A Case Series.

Predictors of site-specific metastasis after radical prostatectomy (RP) are unknown despite prognostic differences between metastatic sites. We performed RNA expression analysis for 19 genes known to be correlated with aggressive prostate cancer in primary tumors of 63 men pN+ at RP (N = 35 developing metastases after RP vs N = 28 without metastases after RP). Of the men developing metastases, 22 (62.

Low PCA3 expression is a marker of poor differentiation in localized prostate tumors: exploratory analysis from 12,076 patients.

Background: Prostate cancer antigen 3 () is a prostate cancer diagnostic biomarker that has been clinically validated. The limitations of the diagnostic role of in initial biopsy and the prognostic role are not well established. Here, we elucidate the limitations of tissue to predict high grade tumors in initial biopsy.

Ability of a Genomic Classifier to Predict Metastasis and Prostate Cancer-specific Mortality after Radiation or Surgery based on Needle Biopsy Specimens.

Background: Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP).

Objective: To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT).

Design, Setting, And Participants: Two hundred and thirty-five patients treated with either RP (n=105) or RT±androgen deprivation therapy (n=130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers.

Analytic, Preanalytic, and Clinical Validation of p53 IHC for Detection of Missense Mutation in Prostate Cancer.

missense mutations may help to identify prostate cancer with lethal potential. Here, we preanalytically, analytically, and clinically validated a robust IHC assay to detect subclonal and focal missense mutations in prostate cancer. The p53 IHC assay was performed in a CLIA-accredited laboratory on the Ventana Benchmark immunostaining system.

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study.

Background: Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT.

Methods: A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled.

Validation of a Genomic Risk Classifier to Predict Prostate Cancer-specific Mortality in Men with Adverse Pathologic Features.

Background: Risk of prostate cancer-specific mortality (PCSM) is highly variable for men with adverse pathologic features at radical prostatectomy (RP); a majority will die of other causes. Accurately stratifying PCSM risk can improve therapy decisions.

Objective: Validate the 22 gene Decipher genomic classifier (GC) to predict PCSM in men with adverse pathologic features after RP.

Individual Patient-Level Meta-Analysis of the Performance of the Decipher Genomic Classifier in High-Risk Men After Prostatectomy to Predict Development of Metastatic Disease.

Purpose To perform the first meta-analysis of the performance of the genomic classifier test, Decipher, in men with prostate cancer postprostatectomy. Methods MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports between 2011 and 2016 of men treated by prostatectomy that assessed the benefit of the Decipher test. Multivariable Cox proportional hazards models fit to individual patient data were performed; meta-analyses were conducted by pooling the study-specific hazard ratios (HRs) using random-effects modeling.

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010.

Comprehensive Determination of Prostate Tumor ETS Gene Status in Clinical Samples Using the CLIA Decipher Assay.

ETS family gene fusions are common in prostate cancer and molecularly define a tumor subset. ERG is the most commonly rearranged, leading to its overexpression, followed by ETV1, ETV4, and ETV5, and these alterations are generally mutually exclusive. We validated the Decipher prostate cancer assay to detect ETS alterations in a Clinical Laboratory Improvement Amendments-accredited laboratory.

Pan-Cancer Analysis of Genomic Sequencing Among the Elderly.

Purpose: We hypothesized that elderly patients might have age-specific genetic abnormalities yet be underrepresented in currently available sequencing repositories, which could limit the effect of sequencing efforts for this population.

Methods And Materials: Leveraging The Cancer Genome Atlas (TCGA) data portal, 9 tumor types were analyzed. The frequency distribution of cancer by age was determined and compared with Surveillance, Epidemiology, and End Results data.

Transcriptome evaluation of the relation between body mass index and prostate cancer outcomes.

Background: Large epidemiological studies indicate that an increased body mass index (BMI) is associated with increased prostate cancer (PCa) mortality. Data indicate that there is no association between elevated metabolic pathway proteins and PCa mortality. There are no published studies evaluating the relation between BMI and metabolic pathways with respect to PCa outcomes with a genomics approach.

Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality.

Objectives: To determine the prognostic potential of a 24-gene signature, Sig24, for identifying patients with prostate cancer who are at risk of developing metastases or of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP).

Patients And Methods: Sig24 scores were calculated from previously collected gene expression microarray data from the Cleveland Clinic and Mayo Clinic (I and II). The performance of Sig24 was determined using time-dependent c-index analysis, Cox proportional hazards regression and Kaplan-Meier survival analysis.

SPINK1 Defines a Molecular Subtype of Prostate Cancer in Men with More Rapid Progression in an at Risk, Natural History Radical Prostatectomy Cohort.

Purpose: Prostate cancer is clinically and molecularly heterogeneous. We determined the prognosis of men with ERG-ETS fusions and SPINK1 over expression.

Materials And Methods: Men were identified with intermediate or high risk localized prostate cancer treated with radical prostatectomy and no therapy before metastasis.

Molecular Analysis of Low Grade Prostate Cancer Using a Genomic Classifier of Metastatic Potential.

Purpose: We determined how frequently histological Gleason 3 + 3 = 6 tumors have the molecular characteristics of disease with metastatic potential.

Materials And Methods: We analyzed prostatectomy tissue from 337 patients with Gleason 3 + 3 disease. All tissue was re-reviewed in blinded fashion by genitourinary pathologists using 2005 ISUP (International Society of Urological Pathology) Gleason grading criteria.

Evaluation of a genomic classifier in radical prostatectomy patients with lymph node metastasis.

Objective: To evaluate the performance of the Decipher test in predicting lymph node invasion (LNI) on radical prostatectomy (RP) specimens.

Methods: We identified 1,987 consecutive patients with RP who received the Decipher test between February and August 2015 (contemporary cohort). In the contemporary cohort, only the Decipher score from RP specimens was available for analysis.

Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk.

Objectives: To evaluate the ability of the Decipher genomic classifier in predicting metastasis from analysis of prostate needle biopsy diagnostic tumor tissue specimens.

Materials And Methods: Fifty-seven patients with available biopsy specimens were identified from a cohort of 169 men treated with radical prostatectomy in a previously reported Decipher validation study at Cleveland Clinic. A Cox multivariable proportional hazards model and survival C-index were used to evaluate the performance of Decipher.

Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy.

Background: Despite salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) after radical prostatectomy (RP), some patients still progress to metastases. Identifying these men would allow them to undergo systemic therapy including testing novel therapies to reduce metastases risk.

Objective: To test whether the genomic classifier (GC) predicts development of metastatic disease.

Clinical Validation of the 2005 ISUP Gleason Grading System in a Cohort of Intermediate and High Risk Men Undergoing Radical Prostatectomy.

In 2005, the International Society of Urological Pathology (ISUP) introduced several modifications to the original Gleason system that were intended to enhance the prognostic power of Gleason score (GS). The objective of this study was to clinically validate the 2005 ISUP Gleason grading system for its ability to detect metastasis. We queried our institutional RP database for men with NCCN clinically localized intermediate to high-risk disease undergoing radical prostatectomy (RP) between 1992 and 2010 with no additional treatment until the time of metastatic progression.