bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of baseline neutrophil-to-eosinophil ratio (NER) and neutrophil-to-lymphocyte ratio (NLR) with response to combination immunotherapy (IO) with ipilimumab plus nivolumab (ipi/nivo) in patients with metastatic renal cell carcinoma (mRCC).
Authors: Tucker Matthew D. , Brown Landon Carter , Kao Chester , Hirshman Nathan , Kinsey Emily Noelle , Chen Yu-Wei , Ancell Kristin Kathleen , Beckermann Katy , Davis Nancy B. , McAlister Renee , Schaffer Kerry , Armstrong Andrew J. , Harrison Michael Roger , George Daniel J. , Rathmell Wendy Kimryn , Rini Brian I. , Zhang Tian 
Published: June 2021

4563 Background: Previous reports have shown that the baseline neutrophil-to-lymphocyte ratio (NLR) is associated with prognosis in patients with mRCC. However, NLR has not been shown to reliably predict for response to IO. Retrospective analyses in metastatic melanoma and mRCC have shown an association of eosinophilia with improved outcomes to single agent immunotherapy. We sought to evaluate and compare the baseline NLR and NER with response to ipi/nivo in patients with mRCC. Methods: A retrospective review of patients with mRCC treated at the Vanderbilt-Ingram Cancer Center or Duke Cancer Institute with ipi/nivo was performed. Patients with clear cell histology and a baseline complete blood count with differential were included. Patients previously treated with IO were excluded. Patients were separated into groups (above and below the median) based on baseline median NER and baseline median NLR. Analyses of progression free survival (PFS) and overall survival (OS) were conducted using the log rank test. The odds ratio (OR) for objective response rate (ORR) was analyzed using Fisher’s exact test. Results: 111 patients met inclusion criteria. The median age was 60, 77% of patients were male, 68% had prior nephrectomy, 74% were naïve to systemic therapy, and 84% were IMDC intermediate/poor risk. The median NER was 25.0 and median NLR was 3.4. Patients with < median baseline NER had significant improvement in PFS, OS, and ORR (see table). Patients with < median baseline NLR had significant improvement in OS but not in PFS or ORR. Conclusions: Baseline NER was associated with improved outcomes with ipi/nivo. While both NER and NLR were associated with improved OS, only NER was additionally associated with both improved PFS and ORR. With multiple first-line treatment options for mRCC, baseline NER may serve as an early non-invasive predictor for response to ipi/nivo.[Table: see text]
Association of increased intensity of prostate-specific antigen screening in younger African American men with improved prostate cancer outcomes.
Authors: Qiao Edmund , Kotha Nikhil V. , Nalawade Vinit , Qian Alexander , Voora Rohith S. , Nelson Tyler J. , Stewart Tyler F. , Parsons John Kellogg , Rose Brent S. 
Published: June 2021

5004 Background: African-American (AA) men are substantially more likely to present with lethal prostate cancer (PCa) at younger ages than non-Hispanic White men. Despite this disparity, AA men are poorly represented in the prostate-specific antigen (PSA) screening studies on which evidence-based PCa screening guidelines are based. This limits proper PSA screening guidance for AA men, especially for those younger than 55. We examined associations of PSA screening intensity with disease severity at diagnosis and prostate cancer-specific mortality (PCSM) in AA men < 55 years of age. Methods: The earliest recommended age to begin discussion of PSA screening is 40 years. We identified AA men aged 40-55 years, diagnosed with PCa from 2004 to 2017 within the Veterans Health Administration. PSA screening was identified using procedural codes. Screening intensity was defined as percentage of years screened within the pre-diagnostic observation period. This included up to 5 years prior to diagnosis. Multivariable logistic regression assessed the influence of PSA screening intensity on metastatic disease at diagnosis. Lead-time correction using published screening-dependent lead times was performed. PCSM was evaluated using Fine-Gray regression and non-cancer death as a competing event. Additional analysis was performed stratifying PSA screening into ‘High’ and ‘Low’ groups centered on the mean. Results: The cohort included 4,654 AA men at a mean age of 51.8 years with mean PSA screening rate of 53.2%. The pre-diagnostic observation period ranged from 1 to 5 years (median = 5 years). Median follow-up was 7 years. At diagnosis, there was a higher prevalence of Gleason sum ≥ 8 (Grade Group ≥ 4) and metastatic disease in the ‘Low’ group compared with the ‘High’ group ([Gleason sum ≥ 8 (Grade Group ≥ 4)]: 18.6% vs. 14.4%, p < 0.01; Metastatic disease at diagnosis: 3.7% vs. 1.4%, p < 0.01). Increased PSA screening intensity was associated with significantly reduced odds of metastatic disease at diagnosis (odds ratio: 0.61, 95% confidence interval (CI) = [0.47-0.81], p < 0.01) and decreased risk of PCSM (sub-distribution hazard ratio: 0.75, 95% CI = [0.59-0.95], p = 0.02). Conclusions: In this large national cohort of AA men aged 40 to 55 years, PSA screening increased intensity was associated with decreased risk of lethal disease and metastases at time of diagnosis and decreased PCSM. These data support the hypothesis that PSA screening and early prostate cancer detection may improve outcomes in younger AA men.
Survival of veterans treated with enzalutamide and abiraterone in advanced prostate cancer.
Authors: Schoen Martin W. , Carson Kenneth Robert , Luo Suhong , Eisen Seth , Reimers Melissa Andrea , Drake Bettina F. , Bennett Charles L. , Knoche Eric Marshall , Yan Yan , Sanfilippo Kristen Marie 
Published: June 2021

5032 Background: Abiraterone (AA) and enzalutamide (ENZ) are two second generation antiandrogens used to treat advanced prostate cancer, but no large head-to-head trials have been performed. These oral therapies are commonly used in older patients with medical comorbidities who are not candidates for chemotherapy or clinical trials and have different mechanisms of action, adverse events, and drug interactions. To understand survival of patients with prostate cancer, we studied United States veterans treated prior to approval of AA and ENZ for metastatic hormone sensitive prostate cancer when both drugs had approval for metastatic castration resistant prostate cancer. Methods: We identified patients treated with AA or ENZ between 9/10/2014 and 6/3/2017 in the Veterans Health Administration and followed them to April 2020. Age, Elixhauser comorbidity score, treatment with androgen deprivation therapy (ADT) and docetaxel were collected. Cox proportional hazards modeling was used to assess the association between first oral treatment (AA or ENZ) and overall survival, while adjusting for covariates. Results: Of 5895 patients, 2562 (43.5%) were initially treated with ENZ, 3333 (56.5%) with AA, and 3040 (51.6%) received only one of the two drugs during the study period. Patients initially treated with ENZ compared to AA were older (mean 75.9 vs. 75.0 years, p = 0.001), had higher mean comorbidity score (6.2 vs. 5.9, p < 0.001), and were less likely to receive both ENZ and AA (45.2% vs. 51.0%, p < 0.001) or docetaxel (24.1% vs. 28.4%, p < 0.001). Patients who received only AA or ENZ and never received docetaxel were older (mean 78.3 vs. 73.2 years, p < 0.001) with higher mean comorbidity scores (6.4 vs. 5.7, p < 0.001). In the entire cohort, initial treatment with ENZ was associated with longer median survival (24.1 vs. 22.2 months, p = 0.003). After adjusting for age and comorbidities, ENZ was associated with a decreased risk of death compared to AA (HR 0.87, 95% CI 0.82-0.92). In 3317 patients who received two or more therapies (ENZ, AA, docetaxel) there was no difference in median survival between initial treatment with ENZ or AA (28.0 vs. 27.9 months). In 2578 patients (43.7%) who never received docetaxel and either ENZ or AA only, median survival was longer in patients treated with ENZ (18.9 vs. 13.6 months, p < 0.001) and was associated with decreased mortality when adjusting for age and comorbidities (HR 0.73, 95% CI 0.67-0.80). Conclusions: In the overall cohort, initial treatment with ENZ was associated with increased survival compared to AA. Patients who received only ENZ or AA and never received docetaxel had the largest benefit from ENZ, a difference of 5.3 months median survival. Efforts should be made to improve therapy selection for patients with prostate cancer, especially older patients with comorbidities.
The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.
Authors: Cooperberg Matthew R. , Brendel Paul , Lee Daniel J. , Doraiswami Rahul , Rajasekar Hariesh , Makarov Danil V. , Meeks William , Fang Raymond , Roe Matthew T , Shelton Jeremy B. 
Published: June 2021

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]
PSMA-PET/CT Registry for Recurrent Prostate Cancer (PREP): Initial findings from a single center.
Authors: Kapoor Anil , Zukotynski Katherine , Tajzler Camilla , Hoogenes Jen , Matsumoto Edward , Uy Michael , Bauman Glenn , Metser Ur , Finelli Antonio , Ding Maylynn , Shayegan Bobby 
Published: June 2021

5064 Background: Several lesion-targeted therapies exist for locally recurrent or limited stage metastatic prostate cancer (PCa) post-radiotherapy (RT) and radical prostatectomy (RP). However, detection of disease sites is limited using conventional imaging (CI) including computed tomography (CT) and bone scan. Prostate specific membrane antigen (PSMA) targeting PET radiopharmaceuticals like [18F]DCFPyL may help detect disease not seen on CI. Our objective was to assess the ability of PSMA targeted PET/CT to detect sites of disease recurrence and impact on patient management. Methods: This multi-center prospective registry study included six Ontario centers. Eligible patients in 1 of 7 clinical cohorts (Table) were identified and approved by Cancer Care Ontario (CCO) to have restaging with PSMA targeted PET/CT. Referring physicians were asked to complete a form indicating whether a change in management strategy would occur based on the PET/CT results. At 6 months post-PET/CT, actual patient management will be confirmed via provincial registries. These interim results are from a single center. Results: 253 patients were enrolled and had a PSMA targeted PET/CT. At baseline, median age was 71 years (range 50-102 years) and median PSA was 2.7 ng/mL (range 0.04-134.0 ng/mL). The majority of patients (n=59; 23.3%) were in cohort 2 (biochemical failure post-RP). In patients with negative CI, PSMA targeted PET/CT detected disease sites in 68.5% (170/248), resulting in a change in management for 67.8% (137/202) overall and 72.1% and 64.3% post-RT and post-RP, respectively. Conclusions: PSMA targeted PET/CT detected occult lesions on CI in the majority of patients enrolled, leading to a high rate of change in management. Our institutional results are in keeping with preliminary results reported for the provincial cohort. Clinical trial information: NCT03718260. [Table: see text]
Single-lesion PSMA protein expression and response to Lu-177 PSMA therapy in patients with castration-resistant prostate cancer.
Authors: Stangl-Kremser Judith , Rasul Sazan , Tosoian Jeffrey J. , Salami Simpa , Zaslavsky Alexander , Udager Aaron M. , Mazal Peter , Kain Renate , Comperat Eva , Pozo Salido Carmen , Steinbach Christina , Hassler-Di Fratta Melanie , Kramer Gero , Shariat Shahrokh , Palapattu Ganesh S. 
Published: June 2021

5065 Background: The recent introduction of Lu-177 PSMA for the treatment of castration-resistant prostate cancer (CRPC) has been met with much excitement. Initial reports of clinical response are promising, despite known inter- and intra-patient molecular heterogeneity. In this study, we examined the utility of PSMA protein expression in metastatic tumor tissues as a predictor of lesion-specific response to Lu-177 PSMA therapy in men with CRPC. Methods: Between 2015-2020, 19 patients with metastases at multiple sites underwent metastatic lesion biopsy, Ga-68 PSMA PET imaging, and subsequent treatment with three cycles of Lu-177 PSMA. A monoclonal anti-PSMA antibody (EPITOMICS (USA), 1:50) was used to semi-quantitatively assess PSMA protein expression in the biopsy specimen. The histoscore (range 0-300) was derived from intensity and extent of the immunohistochemistry staining and was determined by experienced genitourinary pathologists. Imaging evaluation was performed according to the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria. We assessed the association of the PSMA protein expression in metastatic tumor tissues and the lesion-specific response to Lu-177 PSMA therapy. Results: In 12 patients with biopsy specimens available for staining, PSMA expression correlated with enhancement (SUVmax) of the biopsy site on Ga-68 PSMA PET imaging (rs = 0.63). Of the nine patients with repeat imaging after Lu-177 PSMA therapy, five (55.6%) had a lesion-specific response at the site of biopsy. PSMA expression on immunohistochemistry was unable to accurately predict lesion-specific response in univariable analysis (p = 0.81, 95% CI 94.6-76.6). Among the five men with a lesion-specific response, three (60%) experienced overall progression based on PERCIST. There was no association between lesion-specific response and overall progression (p = 0.64). Conclusions: In patients with multiple metastases, PSMA protein expression from a single site biopsy was not predictive of site-specific Lu-177 PSMA response based on PERCIST. Additional studies are necessary to further interrogate the clinical consequence of PSMA expression heterogeneity in metastatic sites as well as the mechanisms underpinning resistance to Lu-177 PSMA in patients with CRPC.
De-escalation of five years adjuvant endocrine therapy duration in patients with ER-low positive (immunohistochemical 1% to 10%) early-stage breast cancer: A propensity-matched analysis from the prospectively maintained database.
Authors: Yu Keda , Cai Yuwen , Shao Zhiming 
Published: June 2021

538 Background: There are limited data on endocrine therapy benefits for patients with estrogen receptor (ER)-low positive breast cancer (staining 1% to 10% of tumor nuclei by immunohistology). We aimed to compare the effect of short-term 2-3 years versus standard 5 years of adjuvant endocrine therapy on survival outcomes in patients with ER-low positive early breast cancer. Methods: We used data from the prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center for this propensity-matched analysis. Women with ER-low positive, operable, and unilateral early-stage invasive ductal breast cancer were enrolled in this study. Patients with advanced disease, having received neoadjuvant chemotherapy or ovarian function suppression, or with unknown duration or longer than 5 years of adjuvant endocrine therapy were excluded. Enrolled patients were divided into three groups: received no endocrine therapy; received 2-3 years of endocrine therapy; and received approximately 5 years of endocrine therapy. The primary endpoint was disease-free survival (DFS). Multivariate Cox regression analysis and propensity score matching were performed to minimize bias. Hazard ratios (HR) with 95% CIs were calculated. Results: From 2012 to 2017, 634 patients with ER-low positive breast cancer in the database met the inclusion criteria. At a median follow-up of 60 months (interquartile range, 46-74), the 5-year DFS of the whole cohort was 84.9%, with 77.6% for patients who received no endocrine therapy (N = 89), 83.7% for patients who received 2-3 years endocrine treatment (N = 185), and 87.5% for patients who received 5 years endocrine therapy (N = 360). When compared with those receiving no endocrine therapy, patients receiving 5 years treatment was associated with a significantly improved DFS (HR, 0.55; 95% CI 0.32-0.95; P = 0.03); however, there was no significant difference in DFS between patients receiving 2-3 years and 5 years endocrine therapy (HR, 0.79; 95% CI, 0.48-1.28; P = 0.33). In the multivariate Cox regression analysis of the propensity score-matched samples of 360 patients, the DFS was not significantly better for patients who received 5 years of endocrine therapy than 2-3 years treatment (HR, 0.74; 95% CI 0.41-1.34; P = 0.32). An exploratory analysis of re-biopsy of the recurrence lesions indicated more than half of relapsed disease displayed ER-negative, and less than 5% lesions were proved to be ER ≥10% positive. Conclusions: Our data did not support the necessity of 5 years duration of endocrine therapy for patients with ER-low positive breast cancer. Short-term 2-3 years duration might be an alternative option. Further translational research on identifying endocrine-sensitive cases within ER-low positive patients is needed.
Differentiated activity profile for the PD-1 inhibitor balstilimab.
Authors: Joyce Cailin , Chand Dhan , Duckless Benjamin , Hidalgo Manuel , Grossman Joseph Elan , Kaleta Remigiusz , O'Malley David M. 
Published: June 2021

5529 Background: The development and clinical application of immune checkpoint inhibitors has transformed the therapeutic landscape for cancer treatment in recent years. Balstilimab (AGEN2034) is a fully human, monoclonal IgG4 antibody that binds with high affinity to programmed death 1 (PD-1), thus preventing the interaction between this receptor and its ligands programmed death ligand 1 and 2 (PD-L1, PD-L2). Emerging evidence suggests that balstilimab exhibits a differentiated activity profile compared to currently approved anti-PD-1 agents, including pembrolizumab and nivolumab. Methods: Balstilimab as monotherapy was evaluated in a large phase 2 study in patients (pts) with recurrent/metastatic cervical cancer who had relapsed after a platinum-based treatment regimen for advanced disease. Pts were dosed at 3 mg/kg once every 2 weeks for up to 24 months and antitumor activity was assessed using RECIST v1.1. The tumor cell killing activity of balstilimab was evaluated preclinically in a human co-culture system of (1) primary T cells engineered to recognize NY-ESO-1 and (2) NY-ESO-1+ cancer cell lines, including PD-L1 and/or PD-L2-deficient engineered lines. The co-culture system was maintained for ̃ two weeks to drive partial T cell exhaustion; a state where cytotoxicity is compromised but recoverable with PD-1 blockade. Cytotoxicity of these partially exhausted T cells was quantified against PD-L1/L2 double positive, single positive, or double negative cancer cells in the presence or absence of PD-(L)1 antibodies. Results: In the second-line treatment setting for pts with advanced cervical cancer, balstilimab showed a numerically higher objective response rate (ORR) in subjects with PD-L1+, squamous cell carcinoma (SCC) tumors (21%, 95% CI, 12.7-32.6%) than those reported for pembrolizumab. Unlike pembrolizumab, balstilimab showed activity in PD-L1(-) pts, and irrespective of tumor histology (ORR 7.9%, 95% CI, 2.7-20.8%). Despite lower overall PD-L1 positivity compared to SCC (41.7 v 72.9%), an ORR of 12.5% (95% CI, 5.9-24.7%) was observed in the subset of pts with a poorer prognosis, those with cervical adenocarcinoma. Concordant with clinical observations, balstilimab demonstrated superior rescue of antigen-specific T cell cytotoxicity in vitro relative to pembrolizumab, nivolumab, or atezolizumab. Balstilimab also induced cytotoxicity against PD-L1 and/or PD-L2 deficient target cancer cells. Conclusions: Taken together, these data suggest functional differentiation of balstilimab from other PD-1 inhibitors with potentially important implications for extending the therapeutic reach of anti-PD-1 therapy. Investigation of the underlying mechanistic basis for these findings is ongoing. Clinical trial information: NCT03104699.