bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of plasma tumor DNA (ptDNA) with increased risk of venous thromboembolism (VTE) in metastatic castration resistant prostate cancer patients (mCRPC).
Authors: Conteduca Vincenza , Scarpi Emanuela , Wetterskog Daniel , Ferroni Fabio , Rossi Alice , Romanel Alessandro , Gurioli Giorgia , Bleve Sara , Gianni Caterina , Brighi Nicole , Schepisi Giuseppe , Lolli Cristian , Cortesi Pietro , Barone Domenico , Demichelis Francesca , Paganelli Giovanni , Beltran Himisha , Attard Gerhardt , De Giorgi Ugo 
Published: June 2021

5048 Background: Cancer is a risk factor for VTE. In mCRPC, ptDNA is an independent predictor of outcome ( Romanel, Sci Transl Med 2015; Conteduca, Br J Cancer 2020). We firstly aimed to investigate the association between ptDNA and VTE in mCRPC men treated with androgen receptor signaling inhibitors (ARSI) Methods: This prospective biomarker study included mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation. Targeted next-generation sequencing was performed to determine ptDNA fraction from pre-treatment plasma samples. Assessment of VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR) Results: Median age of 180 enrolled patients was 74 years (range 42-90). Of these, 60 (33.3%) were chemotherapy-naive. At a median follow-up of 58 months (range 0.5-111.0), 21 patients experienced VTE (venous thrombosis and/or pulmonary embolism) with a cumulative incidence of VTE at 12 months of 17.1% (95% CI 10.3-23.9). Before starting ARSI, ptDNA fraction above median value of 0.175, presence of visceral metastasis (mets), prior chemotherapy and serum lactate dehydrogenase (LDH) were significantly associated with higher incidence of VTE compared with patients with no thrombosis (12-month estimate, 18.6 vs 3.5%, P=0.0003; 44.4 vs 14.8%, P=0.015; 24.7 vs 4.5%, P=0.006; and 30.0 vs 13.5%, P=0.050, respectively). In the multivariate analysis (Table) including baseline ptDNA level, visceral, liver and lung mets, number of lesions, LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% confidence interval [CI] 1.63-20.44, P=0.006). All these patients received anticoagulant therapy for VTE. No ARSI discontinuation and VTE-related death were reported, and no significant difference in progression-free/overall survival was observed in mCRPC patients with and without VTE. Conclusions: These results suggest that baseline ptDNA fraction in mCRPC patients treated with ARSI is associated with increased risk of VTE. These patients may be followed up more closely for the risk of VTE and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA concentration. Validation of these findings in larger multicenter trials is warranted.[Table: see text]
Long-term adverse events (AE) in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving prostate-specific membrane antigen (PSMA)-based targeted radionuclide therapy (TRT).
Authors: Sun Michael , Thomas Charlene , Ho Benedict , Niaz Muhammad Junaid , Molina Ana M. , Sternberg Cora N. , Nanus David M. , Bander Neil Harrison , Tagawa Scott T. 
Published: June 2021

5055 Background: PSMA-TRT is a promising investigational treatment for patients with mCRPC. Expected short-term toxicities associated with PSMA-TRT include dose-dependent myelosuppression and xerostomia. However, there is a lack of information regarding long-term effects of PSMA-TRT on marrow, renal, and liver function. Additionally, potential organ dose limits for radiation are derived from studies of external beam radiation, which may not be applicable to TRT. Methods: Men treated on prospective clinical trials of PSMA-TRT, from 2003 through 2020 with at least six months of follow-up were included. Variables included treatment, co-morbidities, baseline and most recent renal, liver, and marrow function, along with respective short-term ( < 6 months) and long-term toxicities. AEs were graded using CTCAE version 5 and attribution was assessed with most recent clinical follow up. Multivariable logistic regression was used to control for type of TRT, comorbidities, and subsequent therapies. Results: 71 (59.7%) patients who received 177Lu-J591, 30 (25.2%) 177Lu-PSMA-617, 11 (9.2%) 225Ac-J591, and 7 (5.9%) 90Y-J591 were included, with median follow up 18 months (range 6-133). Long-term (most recent) laboratory values and AEs are summarized in the table. A majority of AEs were attributed to alternate etiologies. 5 of 14 cases of grade (Gr) ≥2 creatinine increase, 3 of 36 cases of Gr ≥2 platelets, 2 of 14 cases of Gr ≥2 bilirubin, 1 of 15 cases of Gr ≥2 AST increase, and 1 of 5 cases of Gr ≥2 ALT increase were deemed possibly related to PSMA-TRT. Only two Gr ≥3 AEs were attributed to possibly being related to PSMA-TRT: one case of Gr 4 creatinine elevation and one case of Gr 3 ALT elevation. On multivariable analysis, alpha-TRT was associated with hepatic AEs (OR 4.38, p = 0.047), and there was a trend towards higher Charlson Comorbidity scores associating with hematologic AEs (OR 1.27, p = 0.095). Conclusions: This is the largest analysis to-date of long-term AEs in patients who have received PSMA-TRT. Long-term effects on renal, liver, and marrow function are infrequent.[Table: see text]
Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: A propensity score-based analysis.
Authors: Duarte Mateus Bringel Oliveira , Leal Frederico , Argenton Juliana Luz Passos , Carvalheira Jose Barreto Campello 
Published: June 2021

5067 Background: Previous studies suggested that androgen deprivation therapy (ADT) may reduce severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infectivity. However, it is unknown whether there is an association between ADT and a higher survival in prostate cancer patients with COVID-19. Methods: We performed a retrospective analysis of prostate cancer (PC) patients hospitalized to treat COVID-19 in Brazil’s public health system. We compared patients with the active use of ADT versus those with non-active ADT, past use. We constructed propensity score models of patients in active versus non-active use of ADT. All variables were used to derive propensity score estimation, and for the outcome analysis we performed a multivariate backward elimination process to select variables to add to the propensity score model. Results: We analyzed 109 PC patients with COVID-19 that presented past or current use of ADT. In total, 52.8% of our patients were less than 75 years old, 44.0% (48/109) were in active ADT, and most were using a GnRH analog (73%, 35/48). Also, 63.3% of our cohort died from COVID-19. ADT active use were protective factor in our logistic regression model (OR 0.28, 95% CI 0.12–0.66, P = 0.0036). We noticed a significant imbalance in the propensity score of patients in active and those in non-active ADT. Then, when we performed a propensity score-based inverse weight double robust estimation model, we observed that ADT remained statistically associated with improved overall survival (average treatment effect [ATE] -0.26, 95% CI -0.45 to -0.08, P = 0.0058). Conclusions: The active use of ADT was associated with a reduced risk of death in patients with COVID-19.
Retrospective cohort study of estrogen receptor low positive early breast cancer using real world data.
Authors: Bari Shahla , Khong Hung T. , Czerniecki Brian J. , Costa Ricardo L 
Published: June 2021

525 Background: Estrogen receptor (ER) positive breast cancer (BC) is a heterogeneous disease, with ongoing debate on the optimal cut off point for clinically relevant ER expression. Tumors harboring ≤10% ER expression are associated with poor outcomes. We used a real-world database to assess prognostic and predictive value of an alternative ER expression cut points. Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. During the study period, the de-identified data originated from approximately 280 US cancer clinics (̃800 sites of care). We evaluated the association between ER expression (assessed locally by immunohistochemistry according to ASCO/CAP guidelines) with tumor characteristics, and treatment patterns of patients with early-stage BC (stage I-III) using descriptive statistics. Recurrence free survival and overall survival was defined as time in months from date of surgery until the data of documented cancer recurrence or death respectively. We used Kaplan Myer survival curves to calculate recurrence free (RFS) and overall survival (OS) of patients with ER low, ER intermediate and ER high tumors. To define an alternative ER expression cut point, the data set was divided into 2/3 training and 1/3 test data. A cut point analysis was performed on the training data set to find the optimum cut point of ER+ staining based on correlation with recurrence free survival as the outcome. Results: Among 4,697 ER positive early-stage BC patients, 83 (1.8%) had ER low (ER expression :1-10%) and 36 (0.8%) had ER intermediate BC (11-20%). Median follow up time was 63 months (range 24-84). ER low tumors were associated with higher tumor grade, larger size, and higher axillary tumor burden compared to ER high positive tumors ( > 20% ER expression). African American patients had a higher prevalence of both triple negative and ER low positive BCs compared to ER high tumors- 21%, 22%, and 8% respectively. No significant differences in patient- or tumor-associated characteristics were observed between Low ER and intermediate-ER positive BC patients. Both ER low and intermediate positive tumor patients had survival outcomes similar to patients with TNBC and worse than ER high positive tumors (p < 0.001). No significant correlations between endocrine therapy and RFS or OS were observed among patients with either ER low or intermediate BCs (HR 1.47 and 2.57, p > 0.05; respectively). Sensitivity analysis showed that tumors with ≤ 20% ER expression were associated with worse RFS in both univariate and multivariate analyses (p < 0.05). Conclusions: These findings suggest that patients with ER expression rates ≤ 20% have poor outcomes and derive minimal benefit from endocrine therapies.
The impact of COVID-19 on breast cancer stage at diagnosis.
Authors: Lloyd Maxwell Roger , Stephens Sarah Jo , Hong Julian C. , James Ted A. , Mehta Tejas , Recht Abram , Spiegel Daphna 
Published: June 2021

528 Background: During the SARS-CoV-2 pandemic, routine screening mammography (SM) was stopped and diagnostic mammography (DM) was limited for several months across the United States in order to reduce patient exposure and redeploy medical personnel. We hypothesized that this delay would result in patients presenting with later-stage disease following the initial shutdown. Methods: Patients diagnosed with invasive breast cancers from 2016-2020 were identified using the Beth Israel Deaconess Medical Center Cancer Registry. Baseline patient characteristics, demographics, and clinical information were gathered and cross-referenced with our electronic medical record. Late-stage disease was defined as initial anatomic stage III-IV disease in the AJCC 8th edition staging system. The control cohort consisted of patients diagnosed from 2016-2019; patients diagnosed in 2020 were the test cohort. Chi-squared analysis was used to compare monthly distributions in stage at diagnosis between the control and test cohorts. Multivariate analysis was performed using a logistic regression model. Results: There were 1597 patients diagnosed with invasive breast cancer between 2016-2019 and 333 in 2020. Median age at diagnosis was 60 years; 99% were female, and 69.1% were white. Mammography was limited from 3/16/20-6/8/20, with 90% reduction in volume during this time. The number of screening studies performed in March, April, May, and June of 2020 were 987, 1, 4, and 721 compared to 2042, 2141, 2241, and 2142 in 2019. The volume of new diagnoses per month decreased substantially during the shutdown (see table). The proportion of patients diagnosed with late-stage disease was 6.6% in the control cohort compared to 12.6% in the 2020 test cohort (p < 0.001); 92.9% of late-stage diagnoses in 2020 occurred from June to December following the shutdown period. On multivariate analysis, year of diagnosis (2020 vs 2016-2019; OR = 4.25 95% CI 0.035-0.095, p < 0.001), lower income (<200% of the federal poverty level; OR = 2.73 95% CI 0.016-0.099, p = 0.006) and increased Charlson Comorbidity Index (OR = 12.01 95% CI 0.037-0.052, p < 0.001) were associated with later stage at diagnosis. Conclusions: Patients were more likely to be diagnosed with late-stage breast cancer following the global shutdown due to the SARS-CoV-2 pandemic. Patients with lower income and medical comorbidities were disproportionately affected. These data raise significant concerns regarding the impact of SARS-CoV-2 on cancer diagnoses and long-term outcomes, especially in vulnerable patient populations.[Table: see text]
Chemotherapy induced profound neutropenia (PN) in patients (pt) with breast cancer (BC) after chemotherapy and plinabulin (Plin) plus pegfilgrastim (Peg) combination versus (vs) peg alone: Final phase 3 results from protective-2 (BPI-2358-106).
Authors: Shi Yuankai , Blayney Douglas W. , Adamchuk Hryhorii , Zhang Qingyuan , Du Lihua , Huang Lan , Mohanlal Ramon 
Published: June 2021

546 Background: PN [absolute neutrophil count (ANC) of <0.1 cells x 10E9/L)] is the most severe form of chemotherapy (Chemo)-induced neutropenia (CIN), and is associated with severe adverse clinical outcome. According to literature, PN leads to 80% death in first week of infection1, 48% FN and 50% Infection2. Peg is standard of care for the prevention of CIN. Peg has a slow onset of action with absolute neutrophil count (ANC) recovery occurring in week 2 of the cycle (C), leaving patients (pts) vulnerable in the first week of the Cycle (C), which >75% of negative clinical consequences occur. Plin, which received breakthrough designation from FDA, is a novel, non-G-CSF small molecule agent for the prevention of CIN and has CIN protection in week 1 (Blayney JAMA Onc 2020), which is the rationale for adding Plin to Peg to achieve superior protection against CIN throughout the entire cycle vs Peg alone (Blayney, St Gallen 2019; ASCO 2019). Methods: Plin is given on Day (D)1 after the last Chemo, has a favorable safety profile, and also has anticancer activity. A phase 3 study evaluating Plin as an anticancer agent (DUBLIN-3; NCT02504489) in NSCLC pts, is fully enrolled, with anti-cancer OS results expected in 2021. In PROTECTIVE-2 (Study 106; NCT0329457), we compare the CIN preventive effects of Plin (on D1) added to Peg (on D2) vs Peg alone. Here we report on PN results. Study 106 is a global multicenter randomized (1:1) double-blind study to evaluate Plin 40 mg + Peg 6mg (Arm 1) versus Peg 6mg + Plac (Arm 2) in early-stage BC (node positive or node negative with a high risk of recurrence) pts (n=221) with ECOG status 0 or 1, receiving docetaxel (75 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (TAC). Primary objective was to compare the prevention of severe (Gr 4) neutropenia between Plin+Peg and Peg+Plac. As an exploratory objective in C1, we evaluated PN between the Plin/Peg and Peg/Plac. ANC (Covance Central Laboratory) was assessed in Cycle 1 (C1) on D 1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 13, and 15. Results: Shown in the table below. Conclusions: In conclusion, Peg still cannot protect patients with the most severe form of neutropenia, PN, at 46.4% in this study. Adding Plin to Peg offers superior protection for the prevention of profound neutropenia by reducing > 50% of PN, and its clinical sequelae in FN and hospitalization as compared to Peg alone. References: 1. Bodey et al. Ann Intern Med 64(2): 328 (1966); 2. Bodey et al. Cancer 41(4): 1610 (1978). Clinical trial information: NCT03531099. [Table: see text]
Validation of the RSClin risk calculator using the National Cancer Database (NCDB).
Authors: Howard Frederick , Pearson Alexander T. , Nanda Rita , Olopade Olufunmilayo I. , Huo Dezheng 
Published: June 2021

549 Background: Clinical practice guidelines recommend the use of genomic assays to aid decision making regarding the use of adjuvant chemotherapy (CT) for hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (EBC). Recently, the RSClin clinical tool, which integrates the 21-gene recurrence score (RS) and clinicopathologic features, was developed using data from the TAILORx trial. By integrating clinical and genomic risk, RSClin demonstrated greater precision in guiding adjuvant CT use in HR+/HER2- EBC than the 21-gene RS alone. As outcomes differed by race and ethnicity in TAILORx, further validation in real world datasets of diverse populations is needed. Methods: This study includes patients (pts) from the NCDB who were diagnosed with HR+/HER2- EBC from 2010-2017 and received adjuvant endocrine therapy (ET) with or without CT. RSClin provides a predicted absolute reduction in distant recurrence at 10 years with CT, while the NCDB database only provides overall survival (OS) metrics. While OS underestimates distant recurrence, we correlated RSClin predictions with survival differences between pts receiving ET versus those who received ET plus CT. Inverse probability of treatment weighting was used to correct for differences in age, comorbidity index, insurance, and race/ethnicity. OS benefit of CT was assessed in pts with low (< 2%), intermediate (2-5%), and high (>5%) absolute CT benefit (ACB) per RSClin using the log-rank test. Results: 150,268 pts with EBC were included. Average (avg) age was 59 yrs; 84% were white, 8% black, 4% Hispanic, and 4% Asian/Pacific Islander. Avg tumor size was 1.7 cm, avg RS 17, and 82% had lymph node (LN) negative disease. A significant OS benefit with CT was seen in the intermediate (HR 0.70) and high (HR 0.66) RSClin predicted ACB in the LN negative pts. When analyzed by racial / ethnic subgroup, all pts with a high RSClin ACB had improvement in survival with CT; in pts with an intermediate RSClin ACB, only white pts demonstrated significantly higher OS with CT (HR 0.72). Conclusions: Although developed to predict distant recurrence rates, the RSClin tool also correlates with OS in pts receiving ET with or without CT, which can aid in clinical decision making in pts with HR+/HER2- EBC. Predictive accuracy of RSClin differs by race/ethnicity. Accurate risk stratification in diverse populations is essential in ensuring equitable treatment and mitigating disparities in breast cancer outcomes in different racial/ethnic groups.
Maintenance vigil immunotherapy in newly diagnosed advanced ovarian cancer: Efficacy assessment of homologous recombination proficient (HRP) patients in the phase IIb VITAL trial.
Authors: Rocconi Rodney Paul , Ghamande Sharad A. , Barve Minal A. , Stevens Erin E. , Aaron Phylicia , Stanbery Laura , Bognar Ernest , Manning Luisa , Nemunaitis John J. , O'Malley David M. , Herzog Thomas J. , Monk Bradley J. , Coleman Robert L. ,   The Vigil Team
Published: June 2021

5502 Background: In the VITAL (NCT02346747) trial, maintenance therapy with Vigil, an autologous tumor cell vaccine transfected with a DNA plasmid encoding GMCSF and bi-shRNA-furin for TGFβ expression control, following frontline platinum-based chemotherapy led to a recurrence-free survival (RFS) benefit in patients with advanced high-grade ovarian cancer (HR=0.69, 90% CI 0.44–1.07, p=0.078) and significantly in BRCA-wt patients (HR=0.51, 90% CI 0.30-0.88, p=0.020) ( Rocconi et al. Lancet Oncol. 2020). Here we report post-hoc HR deficiency (HRD) subgroup analysis and identification of an additional molecular subgroup sensitive to Vigil therapy involving STRING analysis. Methods: This double-blind, placebo-controlled, Phase 2b study randomized 92 patients with newly diagnosed stage III/IV ovarian cancer with a complete clinical response (CR) to frontline surgery and chemotherapy. Patients received 1 x 10e7 cells/ml of Vigil or placebo intradermally once a month for up to 12 doses or disease progression. RFS was the primary endpoint assessed by blinded independent central review. HRD status was determined according to the Myriad Genetics myChoice CDx assay (HRD score < 42 for proficient). Using tumor annotated DNA polymorphism data, a protein-protein interaction network was constructed using the STRING database. Properties of this network including topological distance and the identification of hub genes were used to predict a target molecular population sensitive to Vigil. Results: In the per-protocol population (PP, n=91), 62 BRCA-wt patients were tested for HRD status. Forty-five patients were HR proficient (HRP) and 17 patients were HR deficient (HRD). No HRP patients in the Vigil group reported treatment related Grade 3 or higher adverse events. From the time of study randomization median RFS was improved with Vigil (n=25) in HRP patients compared to placebo (n=20) (Table 1). Similarly, overall survival (OS) benefit was observed in the Vigil group compared to placebo (Table 1). Improved RFS was demonstrated for a subset of patients with STRING predicted molecular profile. Conclusions: Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed clinical benefit in both BRCA-wt and HRP molecular profile patients. Results suggest a unique molecular network that enhances sensitivity to Vigil therapy. Clinical trial information: NCT02346747. [Table: see text]
The correlation between BRCA status and surgical cytoreduction in high-grade serous ovarian carcinoma.
Authors: Kim Rachel Soyoun , Malcolmson Janet , Li Xuan , Bernardini Marcus , Hogen Liat Frida , May Taymaa 
Published: June 2021

5543 Background: High grade serous ovarian cancers (HGSC) with BRCA mutation are biologically unique, with distinct molecular and clinical behaviour from sporadic cases. It is unclear if these biological differences translate to favorable outcomes at the time of primary cytoreductive surgery (PCS). The aim of this study is to compare the amount of residual disease following PCS in BRCA-mutated (BRCAm) and wildtype (BRCAwt) HGSC, and to assess whether BRCA status is an independent predictor of residual disease. Methods: We conducted a retrospective analysis of patients with HGSC with known germline and somatic BRCA mutation status, treated with PCS from 2000 to 2017. We compared the cytoreduction outcomes between the BRCAm and the BRCAwt cohorts and built a predictive model to assess whether BRCA status was associated with amount of residual disease at the time of PCS. Results: Of 355 women, 144 harbored germline or somatic BRCA mutations (41%) and 211 were BRCAwt (59%). BRCAm women tended to be younger (54 vs. 59; p < 0.001), but there were no differences between the two groups in stage, disease burden at presentation, surgical complexity score, length of surgery, or perioperative complications. The BRCAm group had a higher rate of complete cytoreduction to no residual disease (0mm) [75% vs. 54%], and a lower rate of optimal cytoreduction (1-9mm) [16% vs. 34%] or suboptimal cytoreduction (≥10mm) [9% vs. 12%] (p < 0.001). In our predictive model, after accounting for length of surgery, CA-125 level, stage, disease scores and surgical complexity scores, BRCAm status was predictive of complete cytoreduction to 0mm residual disease (OR 4.78; 95% CI 2.32-9.85; p < 0.001). Conclusions: BRCA status is predictive of complete cytoreduction at time of PCS in HGSC. Timely availability of BRCA testing is paramount as it may aid in the therapeutic decision making between PCS or neoadjuvant chemotherapy in women with newly diagnosed HGSC.