bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world overall survival of patients diagnosed with recurrent versus de novo metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: O'Reilly Eileen Mary , Yu Kenneth H. , Lamarre Neil , Surinach Andy , Cockrum Paul 
Published: June 2021

e16250 Background: PDAC is a lethal malignancy which accounted for the third most cancer related deaths in 2020. Patients (pts) who are initially diagnosed with stage I-III PDAC have a 5-year relative survival of 13.3 – 39.4%; those with metastatic disease at diagnosis have a 5-year relative survival of 2.9%. Limited data are published comparing the outcomes of pts with stage I-III who develop metastases (recurrent) compared to pts with de novo mPDAC (de novo). This analysis seeks to compare demographic, clinical characteristics, and survival outcomes of pts with recurrent versus de novo mPDAC in a community oncology setting. Methods: Using the Flatiron Health database, a retrospective observational study was conducted abstracting deidentified data from ≥280 US cancer clinics. Pts with mPDAC diagnosed from 01/2016 to 08/2020 with a known stage at initial diagnosis were included. Pts were stratified based on initial stage at diagnosis. Median overall survival (OS) from time of metastasis was derived using Kaplan-Meier analysis. Unadjusted and multivariable Cox proportional hazards models were used to compare survival between recurrent and de novo cohorts. Results: N = 6,543 pts analyzed; 70.1% (n = 4,586) had de novo mPDAC and 29.9% (n = 1,957) had recurrent mPDAC. Median age at time of metastasis was similar for both cohorts: 69 years (IQR: 62 – 76). The most common site of primary tumor location was head for both cohorts (recurrent mPDAC: 69.8%; de novo mPDAC: 40.3%). Approximately 45% of pts with recurrent mPDAC underwent a Whipple procedure (pre diagnosis of metastasis). A similar proportion of pts in both cohorts received treatment in the metastatic setting (recurrent mPDAC: 74.3%; de novo mPDAC: 77.3%). Pts with recurrent mPDAC had a longer median OS compared to the de novo cohort: 8.0 months (95% CI: 7.5 – 8.6) versus 6.1 (95% CI: 5.7 – 6.4) [unadjusted hazard ratio (HR): 0.79 (95% CI: 0.74 – 0.84); adjusted HR: 0.73 (0.68 – 0.78), p < 0.0001]. Conclusions: The results of this real-world study indicate that pts with recurrent mPDAC are more likely to have a head primary and to experience longer OS from time of metastasis than those with de novo mPDAC. These data suggest stratification for clinical trial enrollment for recurrent vs de novo is necessitated.
Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for patients with advanced pancreatic cancer.
Authors: Zhu Huayun , Sun Xiaofeng , Pan Xuan , Wu Pingping , Chen Jia 
Published: June 2021

e16257 Background: This study aimed to evaluate the efficacy and safety of Sindilimab combined with nab-paclitaxel plus gemcitabine as first-line treatment for advanced pancreatic cancer. Methods: This was a single-arm, simple-center, exploratory trial, which included advanced pancreatic cancer pts. Patients received Sindilimab combined with nab-paclitaxel plus gemcitabine. Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take Sindilimab as single agent until disease progression or intolerable toxicity. Response was assessed every 8 weeks. Results: 16 eligible patients were enrolled and 14 pts were evaluable for efficacy analysis. Baseline characteristics are shown in Table 2. Conclusions: This study has showed high anti-tumor efficacy and tolerant toxicity in first-line regimen for advanced pancreatic cancer. Furthermore, it is needed to be proved in update results and large scale studies. Efficacy As shown in Table 3, among 14 evaluable pts, unconfirmed ORR was 57.1% and DCR was 92.8%. 8 pts got partial response (PR), 5 pts stable disease (SD) and 1 pts progressive disease(PD) at best. PFS: The primary endpoint 6-month PFS rate was 2%(95% CI 50.4%-72.4%). Which indicated that the primary endpoint of the study was reached. And mPFS was 7.3 months(95% CI 5.9-8.1). OS: Median OS was not reached and 6m-OS rate was 85.7% (95%CI 5%-91.3%). Safety. All 16 pts were included in the safety analysis (Table 4). The overall AE incidence rate was 93.75% .≥Grade 3 irAE included GGT increased (37.5%) and peripheral neuropathy (6.25%). No TRAE led to death.[Table: see text][Table: see text][Table: see text][Table: see text]
G2M checkpoint signaling among six-cell proliferation-related pathway as a biomarker for prediction and prognosis in pancreatic cancer.
Authors: Oshi Masanori , Le Lan , Tokumaru Yoshihisa , Yan Li , Matsuyama Ryusei , Endo Itaru , Takabe Kazuaki 
Published: June 2021

e16264 Background: Given the poor survival and severe side effects of treatments for pancreatic cancer, prognostic and predictive biomarkers to guide management are in urgent need. We hypothesized that the cell proliferation-related pathway is associated with drug response and survival in pancreatic cancer. Methods: Six hallmark cell proliferation-related gene sets (G2M checkpoint, E2F targets, MYC targets V1 and V2, mitotic spindle, p53 pathway) defined by MSigDB in gene set variant analysis (GSVA) was evaluated in 3 independent cohorts, TCGA-PDAC ( n = 176), GSE57495 ( n = 63), and GSE62452 ( n = 69). Results: Although G2M and E2F correlated strongly with each other (Spearman’s r = 0.976), Mitotic and p53 pathway scores correlated highly with the other cell function gene sets. All pathways were significantly associated with high expression of MKI67 and with proliferation score (all p > 0.001), but none with pathologically complete resection (R0). Mitotic spindle pathway alone associated with high cytolytic activity ( p = 0.020). All pathways were significantly associated with high expression of KRAS and TP53 genes and with high rate of KRAS gene alteration except for MYC v1. G2M, E2F, and p53 pathways were significantly associated with high rate of TP53 gene alteration ( p = 0.026, 0.011, and 0.07, respectively). Interestingly, different pathway correlated with AUC of different agents, such as gemcitabine (mitotic: r=0.706 [ p = 0.01]), paclitaxel (MYC v2: r = -0.636 [ p < 0.05]), apatinib (mitotic: r = -0.556 [ p = 0.03]), palbociclib (E2F: r =0.675 [ p < 0.01]), and sorafenib (G2M: r = -0.593 [ p = 0.03]), for pancreatic cancer. Among all six pathways, only G2M was significantly associated with worse patient survival consistently in all 3 cohorts. Conclusions: Each proliferation-related pathway was predictive of the unique agent, and the G2M score predicts survival of pancreatic cancer.
Efficacy of olaparib therapy in metastatic pancreatic ductal adenocarcinoma (PDAC) with homologous recombination deficiency (HRD).
Authors: Tan Elaine , Hicks James Kevin , Blue Kirsten , Kim Richard D. , Carballido Estrella M. , Kim Dae Won 
Published: June 2021

e16266 Background: Pancreatic cancer is one of the deadliest malignancies, with a 5 year OS of around 3%. Up to 3% of unselected patients (pts) with (PDAC) have the BRCA 1/2 mutation, while up to 15% possess HRD (ARID1A, ATM, BAP1, BARD1, BRIP1, CHEK1/2, FANCA, PALB2, RAD50, RAD51). PARP inhibitors, like olaparib, demonstrate clinical benefit in metastatic PDAC with BRCA mutations (mBRCA) and may have a role in those with HRD. The objective of this study is to determine the role of PARP inhibition in PDAC with HRD. Methods: This was a retrospective chart review of metastatic PDAC pts with germline (g) or somatic (s) mBRCA or HRD who received olaparib. An analysis of PFS and OS was performed for PDAC pts with mBRCA vs. HRD. Results: Forty-six pts with metastatic pancreatic cancer were identified to have mBRCA (n = 13) or HRD (n = 23) and received olaparib in our database. Median age was 73 years for mBRCA and 66 years for HRD. Five pts received olaparib as maintenance therapy after disease control with platinum: 2 mBRCA and 3 HRD pts. Six pts with mBRCA and 7 pts with HRD were platinum naïve prior to olaparib. Zero pts with mBRCA and 3 pts with HRD received olaparib after disease progression on platinum. The median (med)PFS for mBRCA vs. HRD was 6.1 months vs. 2.8 months (HR 0.5, 95% CI: 0.2-1.1, p = 0.07). The medOS for mBRCA vs. HRD was 7.7 vs. 5.3 months (HR 0.7, 95% CI: 0.2-1.9, p = 0.4). Of those with mBRCA who received olaparib, prior cisplatin exposure (n = 8) vs. cisplatin naïve (n = 5) led to medPFS of 6.1 vs. 7.8 months (HR 1.8, 95% CI 0.5-6.7, p = 0.3) and medOS of 6.8 months vs. 9.5 months (HR 1.5, 95% 0.3-6.4, p = 0.6). Six pts with HRD including gCHEK2 c.407T > C, gCHEK2 c.1461+1 G > A, gPALB2 gain (exon 11), sFANCI p.N1252S, sATM p.V2716A, sARID1A Q944fs*14 were noted to have disease control of at least 3 months on olaparib. Only one of these pts received olaparib as maintenance therapy after platinum. The medPFS was 6.1 months and medOS was not reached. One pt with HRD (sFANCI N1252S) had progressive disease on platinum prior to olaparib, but had stable disease > 5 months with olaparib. Conclusions: Our study suggests olaparib may have anticancer activity in PDAC with certain HRD. In addition, olaparib may have a role outside maintenance therapy in PDAC with mBRCA. Prospective studies are needed to confirm these findings.
Early detection of pancreatic cancers by novel nanobiosensor-based protease biomarkers using hierarchical decision structure.
Authors: Kasi Anup , Sun Weijing , Ehsan Sumia , Covarrubias Jose , Eschliman Kayla , Neri Raul , Agarwal Deepesh , Zambrano Obdulia Covarrubias , Bossmann Stefan H , Natarajan Bala 
Published: June 2021

e16273 Background: There is a critical need to develop fast, reliable, and cost-effective methods for the detection of pancreatic cancer (PC) at the earliest stage to maximize the impact of treatment. To-date, early detection of PC is close to impossible due to the location of the pancreas and the absence of characteristic symptoms in early cancer stages. Methods: Our team of clinicians and scientists has established a fast and reliable nanobiosensor technology that comprises iron/iron oxide nanoparticles attached to a protease or arginase activatable FRET pair (tetrakis (4- carboxyphenyl) porphyrin (TCPP) /cyanine 5.5). Arginase and seven proteases (MMP1, 3, and 9, cathepsin B, and E, urokinase plasminogen activator, and neutrophil elastase) were identified using the Gene Expression Omnibus (GEO) web tool based on their different expression pattern in pancreatic cancer patients, pancreatitis and healthy control subjects. Protease/arginase activities were measured in serum after 1h of incubation. Based on this data, a novel engineering approach to improved early stage detection of pancreatic cancer is reported here. This study was funded by American Cancer Society Institutional Research Grant (IRG‐16‐194‐07), awarded to the University of Kansas Medical Center. Results: In our study, 159 patients were enrolled at KU Cancer Center from 2000-2019, 47 with metastatic PC, 36 with localized PC, 26 pancreatitis and 50 healthy controls using KUCC Biospecimen Repository. The problem of early stage detection of pancreatic cancer can be modeled as a multi-class classification problem. Conventional classification approaches provide at most 77% accuracy for the dataset under consideration. A new hierarchical decision structure with specific feature engineering at each step is introduced here to improve the performance of the classifier. The fundamental premise of this information fusion-based framework involves tailoring the statistically most significant features with appropriate weights to execute an efficient binary classification task at each hierarchical step. An overall accuracy of 95% was achieved for the detection of patients with early pancreatic cancer (see table). Conclusions: Because of the dire survival statistics of pancreatic cancer, detection at the earliest possible time by means of a liquid biopsy will offer the greatest benefit. Novel nanobiosensor based protease biomarkers achieved high accuracy in early detection of pancreatic cancers by applying hierarchical decision structure. Our results need validation in a larger cohort. Predicted true class considering the following combination of classification methods: Step1 – kNN*, step2 – kNN*, step3 – RFC* (Accuracy = 94.97%).[Table: see text]
Accuracy of an urine-based liquid biopsy genetic test in detecting renal pelvic cancer.
Authors: Xu Yansheng , Shi Min , Liang Yiming , Li Hongzhao , Ma Xin , Zhang Xu , Che Dongxue , Guo Weihua 
Published: June 2021

e16500 Background: Renal pelvis cancer is accounting for about two-thirds of upper tract urinary carcinoma. Lesions in renal pelvis often lead to a differential diagnosis that requires ureteroscopic biopsy. Besides causing discomfort and pain, ureteroscopy prior to surgery increases risk of tumor implantation and recurrence. Although urine cytology and FISH were applied, more effective non-invasive diagnostic method is imperative for diagnosis of renal pelvic cancer. Methods: A total of 141 patients with one or more lesions in renal pelvis detected by ultrasound were enrolled. 50-ml first-void urine sample was collection before ureteroscopic biopsy and was analysis by Genetron uro-18 genes panel, by which mutations in 17 genes and methylation status of ONECUT2 were analysis using high-throughput sequencing. If mutations and/or ONECUT2 methylation were detected in urine sediment DNA, the patients were considered as high risk of renal pelvis cancer. The results of the urine-based liquid biopsy genetic test were compared with pathology report and urine FISH results of urinary cells. Results: According to pathological analysis with ureteroscopic biopsy, 42 out of 141 patients (29.7%) were diagnosis with renal pelvic cancer: 13 low-grade, 24 high-grade, 5 equivocal. For 33 renal pelvic cancer patients with FISH testing result of urinary cells, only 54.5% (18/33) samples were positive. By Genetron uro-18 genes test, 95 patients (67.4%) were classified as high risk and 46 (32.6%) patients were low risk. The overall specificity was 88.0% (88/95) and overall sensitivity was 92.9% (39/42), which is significant higher than FISH test of urinary cells. Conclusions: With high specificity and sensitivity, Genetron uro-18 genes test could be incorporated in renal pelvic cancer diagnosis, especially for patients with a ultrasound detectable lesions. Ureteroscopy prior to surgery could be reduced, which may lead to decrease risk of tumor implantation and recurrence.
The process of urinary bladder cancer recurrence in 33 patients with 113 tumors, analyzed by changes in IHC features of 80 pairs of subsequent tumors.
Authors: Kurbel Sven , Dmitrovic Branko , Matić Mate , Vrbanec Damir 
Published: June 2021

e16507 Background: The aim was to define IHC changes between the two subsequent urinary bladder cancers (UBC). Methods: IHC data on EGFR, HER2, HER3, Ki-67, MLH1, MSH2, MSH6 and PMS2 in 113 UHC from 24 male and 9 female patients (1 to six recurrences) were used. Except for the Ki-67 value, other markers were stratified: “0” for no positive cells; “1” < = 10% positive cells; “2” 1%-30% positive cells; and “3” 31%-100% positive cells. Data of consecutive tumors were paired in 80 processes of recurrence (PoR). Changes between the latter and the former tumor were calculated: in +/- % for Ki-67 values, and as integer sums of absolute changes in expression for HER markers and for Lynch markers. EM clustering was applied for recognition of relevant IHC changes. Results: Three aspects were tested: the speed of recurrence, was it the first, or later recurrence and whether PoRs depended on the total number of tumors in that patient. Early and late PoRs clustered along the Lynch score, while the intermediate clustered along the delta Ki-67 value. The first PoRs clustered along the HER score and all subsequent PoRs depended on the Lynch score. Conclusions: Even in this limited group of patients Lynch and HER markers showed complex differences between early and late recurrent tumors. The speed of the recurrence and changes of IHC features depended mainly on the rate of change in Lynch markers, suggesting that they should be tested as predictors of UBC recurrence.[Table: see text]
Parameters of local cellular immunity in patients with bladder cancer.
Authors: Belyakova Lyubov I. , Sagakyants Aleksandr B. , Shevchenko Alexey N. , Filatova Elena V. , Bondarenko Elena S. , Shulgina Oksana G. , Khvan Viktor K. , Shvyrev Dmitry A. , Khomutenko Irina A. 
Published: June 2021

e16508 Background: Bladder cancer (BC), which accounts for 4.5% of the total cancer incidence, is the cause of frequent severe disability and a significant deterioration in the quality of life of patients. BC development is determined by a number of factors, involving the immune system; however, its role is poorly understood. The purpose of the study was to determine characteristics of parameters of the cellular immunity in patients with non-muscle invasive BC. Methods: The study included 14 patients with newly diagnosed stage I BC. Patients were divided into two groups: with low-grade tumors (LG), n = 7, mean age 57 years; with high-grade tumors (HG), n = 6, mean age 60 years. All patients underwent transurethral resection of the bladder, and tumor tissues (TT, size up to 1.5 cm) and perifocal tissues (PT, at least 0.5 cm from the tumor) were obtained. The specimens were disintegrated to obtain the cell suspension. The relative numbers of the main populations of leukocytes and T- and B-lymphocytes, as well as some subpopulations of T-lymphocytes, were determined using the BD FACSCanto II flow cytometer and a panel of antibodies according to the manufacturer's instructions (Becton Dickinson, USA). Results: Reduction of lymphoid tissue infiltration by 78% was observed in TT in HG patients, compared to the LG group; levels of CD8+ lymphocytes, CD3+CD4-CD8- and CD3+CD4+CD8+ cells, NK- and B-lymphocytes were lower by 27%, 33%, 51%, 45% and 62%, respectively. Levels of Treg in HG TT were 32% lower than in LG. The numbers of activated CD4+, CD8+ cells were unchanged, but TT infiltration by naive lymphocytes of both populations was increased by 28% and 31%, respectively. In HG PT, a decrease in the total number of lymphocytes by 27% was observed, together with higher levels of CD3+CD4+CD8+ cells and NK- and B-lymphocytes by 200%, 213% and 31%, respectively. Conclusions: BC patients with various tumor grades demonstrate different distributions of lymphocyte populations in tumor and perifocal tissues; the functional activity of these cells can both contribute to the disease development and determine the risk of recurrence.
Cancer stem cells as markers of bladder cancer recurrence.
Authors: Belyakova Lyubov I. , Sagakyants Aleksandr B. , Shevchenko Alexey N. , Filatova Elena V. , Khvan Viktor K. , Khomutenko Irina A. , Shvyrev Dmitry A. , Ulianova Elena P. , Bondarenko Elena S. , Novikova Inna A. 
Published: June 2021

e16511 Background: Bladder cancer (BC) is an urgent problem of oncology in the world, and without appropriate and timely treatment it can lead to severe disability and a significant deterioration in the quality of life of patients. BC accounts for 4.5% of the total cancer incidence. Cancer stem cells (CSCs) are actively involved in the development of recurrent malignant tumors, and also play an important role in the development of chemotherapy and radioresistance of tumor cells. CSCs in BC are poorly studied. Our purpose was to determine the CSC numbers in patients with non-muscle invasive BC. Methods: The study included 7 patients with newly diagnosed stage I BC, G2, intermediate prognosis according to the EORTC scoring system. All patients underwent transurethral resection of the bladder, and tumor tissues (TT, size up to 1.5 cm) and perifocal tissues (PT, at least 1.0 cm from the tumor) were obtained. The specimens were disintegrated to obtain the cell suspension, and the CSC percentages were determined using the FACS Canto II flow cytometer with monoclonal antibodies to CD45-APC-Cy7, CD24-FITC, and CD133–PE according to the manufacturer's instructions (BD, USA). Numbers of cells with CSC markers (CD24+, CD44+, CD133+, CD24+CD44+, CD44+CD133+) were calculated as the percentage from the total number of CD45--cells. The results of statistical processing were presented as the arithmetic mean and the standard error of the arithmetic mean. The significance of differences between the samples was assessed using the Mann-Whitney’s nonparametric test. Results: The numbers of CD45--cells were similar in TT and PT (61.3±5.8 and 71.8±12.6). The relative numbers of cells with CSC phenotypic markers, such as CD24, CD44, were 77% and 58% higher in TT than in PT: 18.3±3.5 vs. 4.3±2.1 and 15.5±5.3 vs. 6.5±0.8, respectively; p≤0.05. The number of CD133+ cells was 83% higher in PT compared to TT - 41.6±12.1 vs. 22.7±7.6. The numbers of CD44+CD24+ and CD44+CD133+ cells in TT were higher than in PT by 80% and 63%, respectively: 10.3±4.9 vs. 2.1±0.4, 9.0±4.5 vs. 3.3±0.9, p≤0.05. CD44-CD24+ CD133+ cells were not detected in PT. Conclusions: The results indicate the peculiarities of the distribution of CSCs in TT and PT, which can be used to predict the risk of the disease recurrence and/or progression, and also help to evaluate results of the treatment.
Opioid use in locally advanced or metastatic urothelial carcinoma patients and matched non-cancer controls.
Authors: Grewal Simrun Kaur , Hepp Zsolt , Liu Yutong , Fuldeore Rupali , Sesterhenn Steve , Chang Nancy N. , Galsky Matt D. 
Published: June 2021

e16517 Background: There are currently no published data on the patient experience with pain and pain medication use among the locally advanced or metastatic urothelial carcinoma (la/mUC) population. In this study, we quantified opioid use, as a proxy for pain, in patients with la/mUC and in matched non-cancer controls, using real-world data. Methods: We performed a retrospective claims analysis of adults diagnosed with UC who initiated ≥1 la/mUC therapy between 5/2016-6/2019 using the IBM MarketScan databases. Non-cancer controls were identified in 2 steps: 1) exact match on age/gender at index, 2) nearest neighbor propensity score matching (1:3 ratio) based on age, gender, region, insurance type, index year, enrollment time, and major comorbidities. Index was the date of first la/mUC therapy; index for controls was aligned to claims activity for matched patients with la/mUC. Baseline was the 6 months pre-index; follow-up was from index until disenrollment, death or study end (12/2019). Analyses examined the proportion of opioid users, number of opioid prescriptions, and daily morphine equivalent dose (MEQ). Results: A total of 1,293 patients with la/mUC and 3862 controls were included; mean (standard deviation [SD]) age at index was 64.1 (11.9) years for the la/mUC cohort and 64.8 (12.0) for controls, and most were male (60.2% and 61.3%, respectively). Mean (SD) follow-up was 15.1 (8.9) and 15.5 (8.6) months, respectively. A higher proportion of patients with la/mUC used opioids than controls during both baseline and follow-up (Table). Among opioid users, trends in opioid use were similar between the cohorts during baseline, with differences during follow-up (Table). At baseline, 63.6% (n=822) of patients with la/mUC had ≥1 opioid prescription which decreased during first-line (1L) treatment to 38.8% (n=502) and subsequently increased to 47.0% (n=159 of 338) during second-line (2L) treatment. The mean (SD) number of opioid prescriptions also increased during later therapy lines (1L: 0.92 [0.99], 2L: 1.37 [1.24]) along with increases in mean (SD) daily MEQ (1L: 69.8 [274], 2L: 133 [586]). Conclusions: This study underscores the impact of pain among patients with la/mUC, which is common at diagnosis, higher than matched controls, and worsens as the patient progresses. Improved disease control with more effective therapies may reduce pain in this population. [Table: see text]