bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival and prognostic tests in a real-world phase II experience with a safe, moderate-dose, sequential chemotherapy (CT) algorithm (ALGO) for metastatic pancreatic adenocarcinoma (PANC).
Authors: De Jager Robert L. , Bruckner Howard , Bassali Fred , Hirschfeld Azriel , Gurell Daniel , Nghiem Van , Distenfeld Shoshana , Weinberger Noah , Book AJ 
Published: May 2020

e16763 Background: Gemcitabine (G), 5-fluorouracil (F), leucovorin (L), irinotecan (I), and oxaliplatin (O), (GFLIO) is safe, employs moderate 1/2-1/3 dosages, offers expanded eligibility (0-2 ECOG PS; no age limit)). Each step reverse resistance (RR) to CT; drug synergism 4-6 simultaneous pairs) improve responses (Rs) and survival (S) (Bruckner ASCO 05, 08, 11, AntiCancer Res 2016; 36 (1), 2018; 38 (1) (ACR), and the immune system (Correale P: J. Immunother 2014; 37). M Caraglia: Front Oncol. 2019). Methods: Eligibility: intent to treat active metastatic PANC, no prior CT: any age: PS 0-2 and expected > 6 weeks S. IRB required safety < 1/10 severe events. ALGO in mg/m2: G 500, F 12-1500 over 24 hrs, L 180, I 80, day2 O (GFLIO) q2 wks, and on progression added in sequence, day 2, docetaxel 20-25 and good counts only mitomycin C 3-6 then bevacizumab 10mg/kg with prior monitoring and modifications (ACR). Median 12, 18, 24 mos Overall Survival (OS), Kaplan Meier estimates with 95% CI were evaluated with age, sex and normal nl and abnl baseline bloods: neutrophils N ANC; Lymphs Ly ALC; platelets; albumin (ALB); Alkaline phosphatase (Alk Ph) abn N alb 3.5 N/L; 2.1 L/monocyte ratios and the A.L.A.N (AS) composite prognostic score (M. Salati E.J.Ca. 2019; 117: 84-90). Results: OS @ 6, 12, 18 & 24 mos, for 53 pts, was 75; 57; 36; 26 % (+/- 8-10%). Median M S was 14.5 mo (CI 9-17mos); S @ all ages ≥ 60, 65 or 70, was not inferior. Women's M S 17 mo. was > men's 10.5: 95/65; 75/46; 48/29; 42/29%. AS for abnl tests was: 0 (18pts): 93: 81: 48; 34% & MS 17 mo vs 1-2 (23)90: 58;42;32% & MS 15.5mo vs 3-4 (12)MS 3 mo. Pts with best 17-14.5 mo MS had nl AS 0 > Alb > AS 1-2 > APh > ANC. Pts with worst 3-6 mo MS had abnl: AS 3-4 < Alb < ANC. No pt had severe infection, neuropathy or gastroenteritis. Pts -/+ 75-100gm ascorbic acid, 25, did not have inferior S in ALAN subsets (H.Bruckner AACR 17). Conclusions: The sequential moderate dose CT ALGO improves eligbility and provides pts with metastatic PANC of any age a well tolerated CT regimen with a high therapeutic index and strong, 12, 18, 24 mo, survival. Prognostic tests can identify subgroups ≥ 75% with favorable vs. unfavorable criteria and improve personalized choices and measures to remedy individual risk factors. Clinical trial information: NCT01905150 .
GRP78 expression and clinical outcomes in pancreatic cancer: A single institution review.
Authors: Johnson Brian Ernest , Hemrajani Anshu , Ding Xianzhong , Wesolowski Michael , Hill Reginald , Zhang Echo , Dhanarajan Asha R. 
Published: May 2020

e16767 Background: Pancreatic Ductal Adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers. Poor prognosis can be attributed in part to late detection and chemoresistance. Perioperative chemotherapy with or without radiation is the standard treatment for resectable PDAC, however recurrence rates remain high. GRP78 (HSPA5/BiP) is an endoplasmic reticulum (ER) chaperone protein involved in regulation of the ER stress response that leads to pro-survival pathway activation and chemoresistance in tumor cells. Prior studies of suppression of GRP78 expression in PDAC cell lines led to increased pancreatic cell apoptosis in response to gemcitabine. In vivo studies of human PDAC xenografts showed that tumors with higher GRP78 expression were associated with increased chemoresistance. Methods: We conducted a single institution retrospective review of 53 patients who underwent resection of PDAC from 1/1/2009-7/1/2016. Archived tumor tissue expression of GRP78 was assessed by immunohistochemistry (IHC) and scored as 0-3+. GRP78 IHC scores of 0-1+ were categorized as low and scores of 2-3+ as high. Corresponding clinical data were collected. Adjusted effects of GRP78 expression on the hazard of treatment failure or death were estimated using Cox proportional hazards models. Type III Wald Chi-square p-values are reported for the overall effect in each model. Results: GRP78 expression level demonstrated a significant effect on disease free survival (DFS) in unadjusted analyses (HR 2.00, p = 0.05), as well as after adjusting for performance status (p = 0.03), initial overall stage (p = 0.05), pathological tumor stage (p = 0.02), pathological node stage (p < 0.01), resection margins (p = 0.05), and neoadjuvant therapy (p = 0.05) in separate models. In unadjusted analysis, high GRP78 expression showed a trend towards worsened overall survival (OS), but did not reach statistical significance (HR 1.8, p = 0.11). The effect on OS was significant when adjusting for pathological tumor stage (p = 0.04) and pathological node stage (p = 0.01). (575). Conclusions: Consistent with prior animal studies, our retrospective review revealed that high GRP78 expression was associated with worsened DFS in patients with resectable PDAC. When adjusting for pathological staging, high GRP78 expression had a similar impact on OS. These findings warrant further evaluation of the role of GRP78 in prognosis, response to therapy and as a potential treatment target.
Phase I, first-in-human study of AbGn-107, a novel antibody-drug conjugate (ADC), in patients with gastric, colorectal, pancreatic or biliary cancers.
Authors: Ko Andrew H. , Coveler Andrew L. , Schlechter Benjamin L. , Bekaii-Saab Tanios S. , Wolpin Brian M. , Clark Jeffrey William , Bockorny Bruno , Bai Li-Yuan , Cheng Yi-Lin , Cheng Ting-Ying , Langecker Peter J. , Lin Shih-Yao 
Published: May 2020

e16771 Background: AbGn-107 is an ADC directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in 24-61% of gastric (G), colorectal (CRC), pancreatic (PDA), and biliary (BIL) cancers. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a Phase Ia trial in patients with the aforementioned GI malignancies. Methods: Standard 3+3 dose escalation was used. Key eligibility included locally advanced or metastatic G, CRC, PDA, or BIL cancer, previously treated, ECOG PS 0-1; positive AG-7 expression was not required. Two dosing intervals were tested: AbGn-107 administered i.v. Q4 weeks (at doses ranging from 0.1-1.2 mg/kg) and Q2 weeks (at doses from 0.8-1.0 mg/kg). Dose limiting toxicities (DLT) were based on grade 3/4 hematologic and non-heme AEs occurring during the initial 4-week rx window. Patients were treated until disease progression or unacceptable toxicity, with tumor assessments Q8 weeks. 1o objectives: safety and MTD; 2o objectives: PK, immunogenicity, and efficacy defined by ORR (RECIST 1.1). Results: 35 patients were enrolled across 6 dose levels (median age 61.5 yo (range 40 – 81); G (0)/CRC (12)/PDA (20)/BIL (3); median # lines of prior rx = 3 (range 1-7). Safety: 5 patients experienced Grade 3 or 4 neutropenia, all at higher dose levels, inc. 1 episode of febrile neutropenia. Other frequent drug-related AEs, mostly grade 1/2, inc. fatigue (29%), nausea (20%), and diarrhea (14%). DLTs included grade 4 CK elevation (n = 1) at 0.8 mg/kg Q4W and grade 3 arthralgias (n = 1) at 1.2 mg/kg Q4W. Based on safety profile and PK data, 1.0 mg/kg Q2W was selected as the dose schedule for cohort expansion phase. Efficacy: Median duration of treatment = 56 days (range, 8 – 225 days). Six pts have demonstrated a minor response by RECIST (range, -1.3 to -21.1%); 4 pts (all PDA) have had durable dz control > 180 days. Conclusions: Overall, AbGn-107 appears well-tolerated with encouraging prelim signs of efficacy in unselected pts with heavily pre-treated advanced GI cancers. Updated safety and efficacy data will be provided at the time of the meeting for the cohort expansion phase of this study (currently open across multiple sites in U.S. and Taiwan), in which subjects with G, CRC, PDA, and BIL cancers are pre-screened for high levels of AG-7 tumor expression. Clinical trial information: NCT02908451 .
Expectations of overall survival for patients with metastatic pancreatic cancer (mPC).
Authors: Willey Joanne P. , Buettner Arden , Britton Susan Lynne , Lankford Maria L. , Scharf Mitchell , Singh Bhavana Pendurthi , Rocha Lima Caio Max Sao Pedro 
Published: May 2020

e16788 Background: Pancreatic cancer is the 4th leading cause of cancer-related death in the U.S. Metastatic pancreatic cancer has typically had a poor prognosis. However, the use of combination chemotherapy with novel agents have improved outcomes. First line therapy with either FOLFIRINOX (2011) or gemcitabine (gem)/nab-paclitaxel (2013) improved response rates (RR), progression-free survival (PFS) and OS versus (vs) gem alone. In 2015, second-line therapy with nanoliposomal irinotecan and fluorouracil (5FU) also improved RR, PFS, and OS vs 5FU. Since 2017, several newer agents have been approved for targeted patient populations – pembrolizumab for MSI-H/dMMR tumors, larotrectinib and entrectinib for NTRK gene fusion positive pts, and olaparib for germline BRCA-mutated pts. As more treatment (Tx) options become available, pts are more likely to receive Tx in later lines. A population-based study found that of mPC pts who completed 1st-line (1L) chemotherapy prior to December 31, 2014, 49% went on to receive 2nd-line (2L) Tx and 17% received 3rd-line (3L) Tx6. Methods: Prescribing patterns of 569 U.S.-based oncologists were studied using a validated, proprietary, case-based market research tool (Challenging Cases). Data were acquired using blinded, audience-response iPad technology at 8 live events during 2018-2019. Results: Estimate of mPC patients treated with 2L and 3L Tx in 2019 Estimates for mPC pts treated with 2L therapy rose from 2018 to 2019, with 46% treating > 60% of mPC patients with 2L in 2018 compared to 54% in 2019. Oncologists estimated median survivals to be 7.4 months (mos) from the regimens they prescribe in 1L, 4.3 mos in 2L, and 2.3 mos in 3L. Conclusions: With the addition of new and more effective treatments for mPC, more patients are treated in the 2L and 3L settings. However, oncologists may underestimate the survival expectation with novel agents or regimens, particularly in later lines of therapy. [Table: see text]
Cost-effectiveness of neoadjuvant FOLFIRINOX versus gemcitabine plus nab-paclitaxel in locally advanced/borderline resectable pancreatic cancer patients.
Authors: Ingram Myles , Lauren Brianna N , Pumpalova Yoanna S , Manji Gulam Abbas , Bates Susan Elaine , Hur Chin 
Published: May 2020

e16793 Background: The 2019 NCCN guidelines recommend neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine plus nab-paclitaxel (G-nP) for locally advanced and borderline resectable pancreatic ductal adenocarcinoma (BR/LA PDAC). Neoadjuvant FOLFIRINOX and G-nP have yet to be directly compared in a prospective, randomized trial with BR/LA PDAC patients. The purpose of our study was to incorporate treatment outcomes, toxicity profiles, costs, and quality-of-life measures to further inform clinical decision-making. Methods: We developed a decision-analytic mathematical model to compare the total cost and health outcomes of neoadjuvant FOLFIRINOX against G-nP over twelve years. Adjuvant gemcitabine (GEM) was used as a comparator. The inputs for the model were estimated using clinical trial data and published literature. We used single-institution retrospective studies to estimate our survival data in the absence of a prospective trial. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall (OS) and progression-free survival (PFS), total cost of care (USD), QALYs, patient resection rate, and monthly treatment-related adverse events (TRAE) costs (USD). Results: FOLFIRINOX was the cost-effective strategy, totaling incremental QALYs of 0.21 at a cost of $52,845.96 per QALY when compared to G-nP. G-nP was also on the efficiency frontier with an ICER of $46,430.73 compared to GEM. More patients received resection with FOLFIRINOX (82.15% vs. 72.40%), but had higher TRAE costs than G-nP ($12,051.26 vs. $4,666.97). A one-way sensitivity analysis found that the FOLFIRINOX ICER exceeds the WTP threshold when TRAE costs are higher and resection rates are lower. Conclusions: Our modeling analysis finds FOLFIRNOX is the cost-effective treatment compared to G-nP for BR/LA PDAC despite having a higher cost of total care due to TRAE costs. Trial data with sufficient follow-up are needed to confirm our findings. [Table: see text]
Phase I trial of nab-paclitaxel administered concurrently with radiotherapy in patients with locally advanced inoperable pancreatic adenocarcinoma (ART in LAP).
Authors: Roy Amitesh Chandra , Abbas Muhammad Nazim , Price Timothy Jay , Singhal Nimit , Vatandoust Sina , Leung John , Kichenadasse Ganessan , Koczwara Bogda , Sukumaran Shawgi , Kumar Rajiv , Woodman Richard John , Richards Alison , Scott-Hoy Alex , Karapetis Christos Stelios 
Published: May 2020

e16796 Background: Locally advanced pancreatic adenocarcinoma (LAPC) carries a poor prognosis with median overall survival of 12-18m. The optimal treatment is controversial. Nab-paclitaxel is active in advanced pancreatic cancer and has exhibited radio-sensitising anti-tumour efficacy. Methods: We conducted an investigator-initiated open-label, phase-I dose escalation trial of nab-paclitaxel with standard external beam radiotherapy (EBRT). All patients had biopsy-proven, untreated, localised, inoperable pancreatic adenocarcinoma; Patients received nab-paclitaxel on a weekly schedule for 6 weeks, concurrently with EBRT. A 3+3 cohort design was employed, with doses of nab-paclitaxel increasing from 25 mg/m2 (cohort 1), to 50 mg/m2 (cohort 2), 75 mg/m2 (cohort 3) and 100 mg/m2 (cohort 4). This principal objective of the trial was to establish the maximum tolerated dose (MTD) of nab-paclitaxel given concurrently with radiotherapy. Secondary objectives included safety and efficacy evaluation, including response rate, median PFS, median and 1- year OS. Results: Fourteen patients were recruited to the study, with a median age of 69 (range 40-86). 69% had a head or neck of pancreas tumour. Majority of patients had grade 1 or 2 toxicities with nausea (92%), fatigue (69%), diarrhoea (54%) and vomiting (54%) being the most common. Three patients were recruited in each of the first three cohorts, without any dose limiting toxicities (DLT). In cohort 4, DLT of febrile neutropenia and enterocolitis was observed in patient 1. The cohort was expanded with a subsequent DLT of febrile neutropenia and enterocolitis observed in patient 5. Both DLT events lead to death (grade 5). The MTD and recommended phase II study dose has been established as 75mg/ m2. The disease control (PR and SD) rate was 67%, median PFS 4.7 months (95% CI 2.5-27.5), 1 year OS 43% and median OS 11.4 months (95%CI 6.37-25.2). Conclusions: The combination of weekly nab-paclitaxel and fractionated radiation was generally well-tolerated at doses of nab-paclitaxel below 100 mg/m2. There were two treatment related DLTs leading to death in the nab-paclitaxel 100 mg/m2 cohort. The MTD and recommended phase II study dose for nab-paclitaxel combined with radiation therapy in the treatment of LAPC is 75mg/m2. Clinical trial information: ACTRN12613001013752 .
Genome-wide association study on genetic variations associated with treatment failure after intravesical bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer.
Authors: Shiota Masaki , Fujimoto Naohiro , Yamamoto Yoshiaki , Takeuchi Ario , Tatsugami Katsunori , Uchiumi Takeshi , Matsuyama Hideyasu , Eto Masatoshi 
Published: May 2020

e17000 Background: Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. Methods: This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in the distinct cohort. Results: The genome-wide association study indicated 19 candidate SNPs associated with BCG failure. Consistent results were obtained in six of these SNPs in the validation cohort. Following the combinational use of validated SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. Conclusions: This study showed that several SNPs were associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The combinational use of these SNPs may have value in clinical applications, although this should be confirmed in future studies.
Treatment of metastatic recurrence of urothelial carcinoma after previous cisplatin-based chemotherapy: A retrospective comparison of different chemotherapy regimens.
Authors: Do Olivia A , Ferris Lorin , Holt Sarah K , Ramos Jorge , Harshman Lauren C , Plimack Elizabeth R. , Crabb Simon J. , Pal Sumanta K. , De Giorgi Ugo , Ladoire Sylvain , Baniel Jack , Necchi Andrea , Vaishampayan Ulka N. , Golshayan Ali Reza , Bamias Aristotelis , Bellmunt Joaquim , Srinivas Sandy , Dorff Tanya B. , Galsky Matt D. , Yu Evan Y. 
Published: May 2020

e17005 Background: The optimal choice of first-line chemotherapy for urothelial carcinoma (UC) patients who recur after previous cisplatin-based chemotherapy for locally-advanced disease is unclear. Our objective is to compare the efficacy of platinum (PBC) versus non-platinum (NPBC) based first-line chemotherapy regimens for such patients after metastatic recurrence. Methods: Data was collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database consisting of patients with muscle-invasive or advanced UC from 28 centers between 2005 and 2012. Patient inclusion criteria included: 1) UC with no initial metastases (cT2-4, cN0-N3, and cM0), 3) receipt of cisplatin in the locally advanced setting, and 4) receipt of chemotherapy in the first-line metastatic setting. Overall survival (OS) was the primary endpoint. Secondary endpoints included progression-free survival (PFS) and response to chemotherapy. Kaplan-Meier and Cox regression models estimated OS, PFS, and response, adjusting for age, gender, Eastern Cooperative Oncology Group (ECOG-PS), Charlson comorbidity index (CCI), surgery, T and N stage, albumin, creatinine clearance, number of initial cisplatin cycles, and time from last chemotherapy. Results: 152 patients with metastatic UC (88 PBC and 64 NPBC) were analyzed. Twelve (7.9%) patients received local definitive radiation and 7 of these 12 also underwent cystectomy. The most common NPBC regimens included taxanes, gemcitabine, or pemetrexed. The median OS was 8.70 (95% CI: 7.53 to 11.16) and 10.27 months (95% CI: 7.37 to 13.10) for PBC and NPBC (HR: 1.04, 95% CI: .67 – 1.61, p = 0.86), respectively. Multivariable analysis showed an independent prognostic effect on OS for number of previous chemotherapy cycles (3-4 vs. 1-2) (HR: 0.44, 95% CI 0.20 – 0.96, P = 0.03) and whether surgery was performed (HR: 0.44, 95% CI 0.26 – 0.75, P = 0.003). Time from last chemotherapy was not prognostic for OS (HR: 0.99, 95% CI: 0.99 – 1.00, p = 0.19). There were no significant differences for both investigator-designated PFS (HR: 0.84, 95% CI: 0.57 – 1.24, p = .39) and response to chemotherapy between PBC and NPBC (p = 0.57). Conclusions: There is no significant outcome difference between PBC vs. NPBC in patients with metastatic-recurrent urothelial carcinoma who previously received cisplatin-based chemotherapy for locally advanced disease. Those who previously underwent radical surgery or who received 3-4 cycles of cisplatin had better OS with PBC.
Perioperative blood transfusion and postoperative outcomes in patients undergoing radical cystectomy for bladder cancer.
Authors: Diamantopoulos Leonidas Nikolaos , Sekar Rishi Robert , Khaki Ali Raza , Miller Natalie , Gadzinski Adam John , Psutka Sarah P. , Gore John L. , Schade George R. , Lin Daniel W. , Tretiakova Maria S. , Vakar-Lopez Funda , True Lawrence D. , Hsieh Andrew Caleb , Cheng Heather H. , Yu Evan Y. , Schweizer Michael Thomas , Yezefski Todd , Montgomery Robert B. , Grivas Petros , Wright Jonathan L. 
Published: May 2020

e17012 Background: Perioperative blood transfusion (PBT) has been associated with worse outcomes in surgical oncology across tumor types. We report our institutional experience of postoperative outcomes related to PBT utilization, in patients (pts) with bladder cancer (BC) treated with radical cystectomy (RC). We hypothesized that PBT is associated with worse clinical outcomes. Methods: Pts with BC treated with RC were retrospectively identified. Clinicopathologic and peri/post-operative data were extracted. PBT was defined as red blood cell transfusion during RC or postoperative hospitalization. Overall survival (OS, diagnosis to death) and recurrence free survival (RFS, RC to recurrence/death) were estimated with the KM method. T-test, χ2 and log-rank test were used for group comparison analysis. Univariate/multivariate logistic (LR) and Cox regression (CR) were used to identify variables associated with dependent dichotomous outcomes and OS/RFS, respectively. Results: 784 consecutive pts (78% men; median age 67) were identified. At least one post-operative complication (POC) occurred in 407 (52%) pts; most common were pyelonephritis and sepsis (11% each). PBT was administered to 238 pts (30%). Those with PBT had a higher proportion of POCs (35% vs 28%, p = .02). Median follow-up, OS and RFS were 66 (95% CI: 60 - 72), 94 (95% CI: 79 - 109) and 66 months (95% CI: 50 – 82), respectively. Pts who received PBT had shorter OS (51 vs 130 months, p < .001) and RFS (27 vs 86 months, p < .001). In multivariate LR and CR, PBT was independently associated with higher odds of POCs (OR 1.5, 95% CI: 1.03 – 2.2, p = .03), length of hospital stay (LOS) > 10 days (OR 2.0, 95% CI 1.1 – 3.5, p = .02), shorter OS (HR 1.6, 95% CI 1.2-2.0, p = .001), and RFS (HR 1.5, 95% CI 1.2 - 1.9, p = .001), after adjustment for other relevant clinicopathologic variables (age, gender, performance status, neoadjuvant chemotherapy, baseline hemoglobin, open/robotic approach, pT/N stage, surgical margins, lymphovascular invasion at RC, variant histologies). Conclusions: Pts who received PBT had higher odds of POC, longer LOS and poor outcomes after RC. This is hypothesis-generating due to inherent study limitations. Further studies are needed to validate this finding, explain underlying mechanisms and explore putative interventions to improve outcomes.