bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A systematic review and meta-analysis of randomized trials.
Authors: Ciliberto Domenico , Botta Cirino , Correale Pierpaolo , Mazzanti Roberto , Mantovani Giovanni , Tassone Pierfrancesco , Tagliaferri Pierosandro 
Published: March 2020

e14577 Background: Pancreatic cancer is the 4th leading cause of cancer-related death worldwide. Single-agent chemotherapy with gemcitabine represents a cornerstone for advanced disease treatment. To date, almost all trials, designed to evaluate the benefit of the addition of a second agent to gemcitabine, failed to demonstrate an improvement in overall survival (OS). We performed a systematic review and a meta-analysis of randomized clinical trials to assess the efficacy and safety of gemcitabine-based combination regimens versus gemcitabine alone in the management of pancreatic cancer. Methods: Clinical trials were selected by searching Medline database and abstracts from major cancer meetings. We considered the Jan 1997 - Jan 2012 time frame. Primary end-point was OS, secondary end-points were response rate (RR), disease control rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR and risk ratios of grade 3-4 toxicity rates, were extracted as presented in retrieved studies and used for statistical analysis. Meta-analytic estimates were derived using random-effects model. Results: Thirty-three trials for a total of 10371 patients were selected and included in the final analysis. The analysis showed for combination chemotherapy a benefit in terms of OS (HR: 0.92; 95%CI: 0.88-0.96; p < 0.001). OR of both RR and DCR demonstrated a significant advantage for combination therapy (OR for RR: 0.63, 95%CI: 0.50-0.80, p=0.006; OR for DCR: 0.78; 95%CI: 0.64-0.94; p=0.002). Toxicities were more frequent in the combination treatment group and a significant value in term of risk ratio was reached for diarrhea (0.53, 95%CI: 0.36-0.79), nausea (0.74, 95%CI: 0.56-0.96), neutropenia (0.74, 95%CI: 0.62-0.89) and thrombocytopenia (0.59, 95%CI: 0.44-0.79). Conclusions: Combinationchemotherapy compared to gemcitabine alone significantly improves OS. However, this advantage seems to be marginal and at the cost of increased toxicity, suggesting the use of gemcitabine-based combination regimens only in selected patients. New approaches based on preclinical findings, in the era of targeted therapy, are eagerly awaited on this specific topic.
Risk factors for venous thromboembolism (VTE) in outpatients with pancreatic cancer.
Authors: Ruch Joshua Michael , Anderson Michelle A , Sood Suman Lata 
Published: March 2020

e14578 Background: The incidence of VTE is increased in pancreatic cancer. Predictive models for cancer-associated VTE have been developed, but none specific for the pancreas. Our primary objective was to identify risk factors for VTE in outpatients with pancreatic cancer. Secondary objective was to develop a predictive model. Methods: Patients seen at the University of Michigan Comprehensive Cancer Center (UMCC) and previously consented and enrolled in a prospective cohort study were eligible. Inclusion criteria included a diagnosis of pancreatic adenocarcinoma, evaluation at UMCC, and follow up in the Electronic Medical Record (EMR) at least every 6 months. Demographics, clinical data, and VTE events (defined as deep vein thrombosis [DVT], portal vein thrombosis [PVT], or pulmonary embolism [PE]) were obtained from the EMR. A retrospective cohort study was performed including univariate and multivariate regression analysis. Results: Between 2005 and 2011, 92 patients were eligible for analysis. Median follow-up was 263.5 (18-2433) days. Twenty (21.7%) patients had a VTE; 10 (50%) DVT, 2 (10%) PE, 4 (20%) PVT, and 4 (20%) multiple VTEs. Mean (SD) age was 63.4 (8.9) with and 65.6 (11.8) without VTE. 55% of patients with and 47% without VTE were women. Higher body mass index (BMI) (median 28.8 [21.2-44.7] vs. 25.5 [16.4-43.3], p=0.02) and lower platelet count (median 241 [145-323] vs. 288 [75-645], p=0.04) were associated with VTE in univariate analysis. In multivariate regression analysis, lower platelet count (β -0.01, SE 0.004) and lower hemoglobin (β -0.44, SE 0.20) were predictive of VTE after adjusting for BMI, tumor location, and treatment with surgery, chemotherapy or radiation (area under the ROC curve 0.78). Conclusions: Pancreatic cancer outpatients with higher BMI, lower platelet count, and lower hemoglobin were more likely to develop VTE. Other clinical variables did not add additional predictive information. Given the small magnitude of difference, basic clinical criteria alone may be inadequate to identify patients at highest risk for developing VTE who may benefit from thromboprophylaxis. Additional studies are warranted to further define risk factors for VTE in this population, including novel biomarkers.
The efficacy and toxicity of 3-weekly TS-1 containing chemotherapy in patients with unresectable advanced gastric cancer.
Authors: Kim Tae Yong , Lee Byeong IL , Kim Gyu IM , Kim Ju Young , Ahn Jin Seok , Rhee Jiyoung , Rha Sun Young , Ryu Min-Hee , Lee Hyun Woo , Lee Keun Wook , Zang Dae Young , Kang Byung Woog , Kang Jin Hyoung , Kang Hye Jin , Song Eun-Kee , Cho Jae Yong , Kim Tae-You , Kim Yeul Hong 
Published: March 2020

e14580 Background: TS-1 has shown good efficacy against unresectable advanced gastric cancer (AGC). Conventionally TS-1 containing chemotherapy (CTx) is performed on 5-weekly or 6-weekly basis. We lack robust evidence for the efficacy and safety of 3-weekly TS-1 containing CTx. In Korea, 3-weekly TS-1 containing CTx can be used as off-label under permission of Health Insurance Review and Assessment service (HIRA). We and HIRA conducted this study to confirm the efficacy and tolerability of 3-weekly TS-1 containing CTx in unresectable AGC. Methods: We retrospectively analyzed patients with unresectable AGC who received 3-weekly TS-1 containing CTx between June 2007 and January 2011. In 3-weekly TS-1 monotherapy, TS-1 40-60mg depending on patient’s body surface area was administered orally twice a day for 14 days followed by a 1-week rest every 3 weeks. In 3-weekly TS-1/cisplatin combination CTx, TS-1 40mg/m2 was given orally twice a day for 14 days followed by 1-week rest and cisplatin 60 mg/m2 on day 1 was given by intravenous infusion every 3 weeks. Results: A total of 1372 patients (TS-1 monotherapy: 265 (19.3%), TS-1/cisplatin : 1107 (80.7%)) were enrolled from 31 institutions. Response rate of 3-weekly TS-1 monotherapy was 18.1%. Progression-free survival (PFS) and overall survival (OS) were 5.2 months (95% C.I., 4.5-5.9) and 14.3 months (95% C.I., 10.6-17.9), respectively. Response rate of 3-weekly TS-1/cisplatin was 29.4%. PFS and OS of 3-weekly TS-1/cisplatin were 6.8 months (95% C.I., 6.3-7.4) and 16.1 months (95% C.I., 14.4-17.9) respectively. Common toxicities of TS-1 monotherapy included nausea/vomiting (N/V) (13.6%), anemia (13.2%) and neutropenia (10.2%). However, the incidences of more grade 3/4 toxicities were less than 3.0%. All grades of neutropenia, N/V and anemia occurred in 35.4%, 21.1% and 13.3% of patients receiving 3-weekly TS-1/cisplatin. However, grade 3/4 toxicities including neutropenia, N/V and anemia occurred in only 17.8%, 3.0% and 2.9%. Conclusions: Three-weekly TS-1 monotherapy or TS-1/cisplatin CTx showed good efficacy and well tolerability. Our study suggests that 3-weekly scheduled regimens may be a good treatment option for unresectable AGC patients.
Second interim analysis of Global Investigation of Therapeutic Decisions in Unresectable HCC and of its Treatment with Sorafenib (GIDEON): U.S. versus global perspective on patient and disease characteristics, treatment history, and sorafenib use.
Authors: Goldenberg Alec , El-Khoueiry Anthony B. , Martin Robert C. G. , Venook Alan Paul , Mantry Parvez , Gholam Pierre Michel , McGuire Brendan , Sanyal Arun , Geschwind Jean-Francois , Marrero Jorge A. 
Published: March 2020

e14581 Background: GIDEON is a global, prospective, noninterventional study of patients (pts) treated with sorafenib (SOR) for unresectable hepatocellular carcinoma (uHCC). Regions evaluated included US, Europe, Japan, Asia Pacific, and Latin America. Using data from the second interim analysis, we compare safety and efficacy of sorafenib in US pts with the entire (global) study population. Methods: Eligible pts had uHCC and were treated with SOR. Demographics, disease etiology, treatment history, and SOR dosing were compared in a descriptive, preplanned subgroup analysis. Results: The safety population comprised 1571 pts. In the 313 US pts, hepatitis B was less common (18% vs 37% global), but hepatitis C was more frequent (53% vs 32% global) (Table). Rate of alcoholic liver disease was higher in US pts (41% vs 29% global). At start of SOR, fewer US pts had BCLC stage C-D disease (49% vs 60% global), but more US pts were Child-Pugh (CP) B or C status (38% vs 25% global) (Table). Rates of prior surgery and locoregional treatment (LRT) were similar in US (11% and 49%, respectively) and global pts (19% and 55%, respectively). US pts received fewer TACE procedures (≥3 treatments: 13.8% vs 38.9% global); most (59%) TACE-treated pts in the US received 1 treatment. In US vs global pts, median time from prior surgery to start of SOR was 10 months (range 1-61) vs 14 months (range 1-181) and median time from last TACE to start of SOR was 3.2 months vs 3.1 months. Conclusions: Disease characteristics and treatment patterns differ in the US and global GIDEON populations. Although its limitations as an observational study must be considered, GIDEON is a valuable repository of data reflecting real-world practices in a variety of regions and pt types. [Table: see text]
Quantitative analysis of intrahepatic hepatitis B (HBV) DNA and cccDNA and their impact on survival posthepatectomy in HBV-associated hepatocellular carcinoma (HCC) patients.
Authors: Wang Qin , Luan Wei , Fiel M. Isabel , Blank Sima , Kim Ki Won , Hiotis Spiros P. 
Published: March 2020

e14583 Background: Little is known about the prognostic significance of total intrahepatic HBV DNA (ihHBV DNA) and cccDNA, a stable episome that accumulates in the nuclei and serves as the template for viral replication. This study aims to quantitate ihHBV DNA and cccDNA in the non-neoplastic liver and to assess their impact on prognosis in HBV-HCC patients. Methods: 111 patients, many on HBV antivirals, who underwent liver resection for HBV-HCC from 1991 to 2008 were assessed by real time PCR for ihHBV DNA, cccDNA, and albumin. Liver fibrosis and necroinflammation was assessed using the modified Ishak method. Independent variables associated with survival were analyzed using multivariate Cox regression model, with a median follow up for survivors of 52 months. Results: Serum HBV DNA was detectable in only 42% of patients, but 106 patients (95%) had detectable ihHBV DNA (median: 0.018copy/hepatocyte); and 89 patients (80%) had detectable cccDNA (0.00058 copy/hepatocyte). Median cccDNA/ihHBV DNA ratio was 0.019. ihHBV DNA correlated with histologic activity index (p = 0.04) and serum ALT (p = 0.004). Patients in the lowest quartile of cccDNA/ihHBV DNA ratio (<0.0032) trended towards poor overall 5-year survival by univariate analysis (p = 0.09), with higher mortality at 2 years (89% vs. 45%, p = 0.03). In multivariate analysis, AFP > 20, Ishak fibrosis stage 6 (established cirrhosis), cccDNA/ihHBV DNA < 0.0032, and large tumor diameter were independently associated with poor overall survival (Table). Conclusions: ihHBV DNA levels were associated with severity of liver necroinflammation and injury. ihHBV DNA and cccDNA levels were not associated with survival; rather, low proportion of total HBV DNA in the form of cccDNA was independently associated with poor overall survival. Thus, viral behavior at the time of liver resection influences clinical outcome for HBV-HCC patients. [Table: see text]
Association of low total lymphocyte count with overall and disease-free survival in patients with resected pancreatic adenocarcinoma receiving the GM-CSF secreting pancreatic tumor vaccine in combination with adjuvant chemoradiation.
Authors: Schueneman Aaron , Sugar Elizabeth , Uram Jennifer , Bigelow Elaine , Herman Joseph M. , Edil Barish H , Jaffee Elizabeth M. , Zheng Lei , Laheru Dan 
Published: March 2020

e14585 Background: Pancreatectomy, though necessary for potential cure of pancreatic ductal carcinoma (PDA), can be associated with immune dysregulation. Low total lymphocyte count (TLC) has been found to be a poor prognostic indicator in several different tumor types. The goal of this study was to determine whether low TLC could affect response to therapy and survival in resected pancreatic cancer patients who received a GMCSF-secreting cell-based tumor vaccine (GVAX) in addition to standard adjuvant therapy. Methods: Retrospective analysis of 60 patients enrolled in a phase II trial evaluating the safety, efficacy and immune activation of GVAX tumor vaccine administered in an adjuvant setting in resected PDA. Blood counts were analyzed from 8 weeks after surgery and then monthly after the completion of adjuvant chemoradiation. Results: The TLC just prior to the first vaccine was 1977 (range: 700-3890) and 10 patients had TLC < 1500. After adjusting for the prognostic factors identified in the original study (lymph node + and margin status), OS was significantly lower for those patients with TLC < 1500 (median 18.4 mos., 95% CI: 8.63 to infinity) as compared to those with TLC > 1500 (median 28.4 mos., 95% CI: 23.9 to 32.6, hazard ratio [HR] = 2.43, 95% CI: 1.09 to 5.41, p = 0.03). TLC < 1500 prior to first vaccine was also associated with shorter disease free survival (HR: 3.18 p < 0.01). Adjuvant chemoradiation consistently decreased TLC with a mean reduction of 1224 (range 450 to 2740). After adjuvant therapy, TLC < 500 was associated with reduced OS (HR: 4.86, 95% CI: 1.70 to 13.87, p < 0.01). Conclusions: Low TLC after surgery and after adjuvant chemoradiation is associated with poor survival in patients who receive pancreatic GVAX. This result suggests that immune suppressive conditions associated with current standard pancreatectomy and chemoradiation significantly compromise the efficacy of immunotherapy. Less invasive laparoscopic surgical approaches that result in less immune dysregulation and chemotherapy regimens that have lower immunosuppression should be considered.
Phase I trial of docetaxel (D), cisplatinum (C), and continuous capecitabine (CAP) (TCX) in advanced esophagogastric cancer (AEC).
Authors: Gollins Simon , Lloyd Arwel , Morris Jackie , Smith Nick , Haylock Brian , Smith David , Garcia-Alonso Angel 
Published: March 2020

e14587 Background: This phase I study assessed the combination of D, C, and continuous CAP in AEC to develop a regimen of acceptable toxicity to take forward to phase II study. Methods: Patients with AEC were treated in cohorts of 3, at one of 3 dose levels (DL). DL0: D at 60 mg/m2 IV on day 1, C at 60 mg/m2 IV on day 1, CAP at 1,000 mg/m2 per day in two divided doses days 1-21, every 3 weeks. DL1: CAP increased to 1,250 mg/m2 per day. DL2: D increased to 75 mg/m2 IV day 1 and CAP to 1,250 mg/m2 per day. Prophylactic colony stimulating factors were not used. Patients received a maximum of 6 cycles. Blood counts and biochemistry were assessed twice weekly and daily for grade 3/4 abnormality. Results: Between 1.11.07 and 24.6.09 15 patients were enrolled: male/female:14/1, WHO PS:0/1:10/5, median age 63 yr (range 46-69), primary site oesophagus/GOJ/stomach:7/3/5, adeno/squamous:14/1, T2/3/4:2/9/4, N0/1/2:1/13/1, M0/1:1/14. 6 patients were treated at DL0, 6 at DL1 and 3 at DL2. All patients received 6 cycles apart from 2 at DL 1 who received 3 because of disease progression. Dose intensity: DL0: D 95%, C 100%, CAP 85%; DL1: D 91%, C 98.2%, CAP 79%; DL2: D 86%, C 100%, CAP 79%. There were no deaths on chemotherapy or within 30d of the last dose. The main dose limiting toxicity was febrile or infective neutropenia developing in 1/6 DL0, 2/6 DL1 and 3/3 DL2 (see table of most common treatment-related adverse events below: serious toxicity is gr 3 unless specified gr 4). The maximum length of gr 4 neutropenia was 5d. Best response (RECIST): 1 CR, 11PR, 2 SD and 1PD. 11 patients received second-line chemotherapy. Median and 1 yr overall survival: 17.5m and 60%. Median and 1 yr progression-free survival: 7m and 27%. Conclusions: TCX DLO is recommended for further study in a phase II trial. Encouraging response and survival were seen. [Table: see text]
Outcome of adjuvant therapy for biliary tract cancers.
Authors: Horgan Anne , Walter Thomas , McNamara Mairead , McKeever Elizabeth , Min Trisha , Wallace Elaine Margaret , Hedley David W , Krzyzanowska Monika K. , Moore Malcolm J. , Cleary Sean P , Gallinger Steven , Greig Paul David , Serra Stefano , Dawson Laura A. , Knox Jennifer J. 
Published: March 2020

e14592 Background: There are high rates of recurrence following definitive surgery in patients (pts) with biliary tract cancers (BTCs). Our aim was to review patterns of use and effectiveness of adjuvant therapy (AT) (chemotherapy (CT) +/- radiotherapy (RT)) in pts who underwent definitive surgery for BTC at a tertiary referral centre (Princess Margaret Hospital, Toronto). Methods: The clinical/pathological characteristics, treatment details and survival data of all pts with a diagnosis of BTC who had definitive surgery from Jan 1987 to Sept 2011 were reviewed. Results: The cohort includes 297 pts of which 42% were male, with a median age of 63 yrs, performance status 0-1 in 88%. 56 (19%) had well differentiated, 144 (48%) moderately and 60 (2%) poorly differentiated tumors, 37 (12%) data not available (NA). 125 (42%) and 41 (14%) had R0/R1 resection respectively, 131 (44%) NA. 122 (41%) were node positive, 72 (24%) NA. AT was given in 78 (27%) pts, 49 receiving adjuvant CT and 29 concurrent CT/RT; 34% receiving AT in distal bile duct, 14% in gallbladder, 12% in intrahepatic and 27% in klatskin. 179 (60%) pts recurred; 56/78 (72%) in the AT group (grp) and 123/179 (68%) in non-AT grp, 40 (13%) NA. In the AT and non-AT grps, local recurrence was seen in 7/56 (13%) and 26/123 (21%), distant in 32/56 (57%) and 73/123 (59%), and both in 176/56 (30%) and 24/123 (20%) respectively. In multivariate analysis, node positivity, HR 0.54, 95% CI 0.37 – 0.77, (p=0.001) was the only prognostic factor of DFS after definitive surgery. In node positive population (n=48 with AT, 50 without AT), median DFS was greater in AT grp; 13.8mo vs. 10.4mo (p=0.068). DFS and overall survival (OS) for entire cohort is detailed in Table. Conclusions: Given the limits of this retrospective cohort analysis and potential bias to treat higher risk pts, it does appear that pts receiving adjuvant therapy with node positive disease derived DFS advantage following definitive surgery, though not significant, and is probably an effective option for node positive, curative resected, BTC. However, larger prospective trials are paramount. [Table: see text]
The prognostic value of β-catenin and LEF-1 expression in patients with gastric carcinoma.
Authors: Kaya Serap , Gumus Mahmut , Gurbuz Yesim , Temiz Suleyman , Cabuk Devrim , Acikgoz Ozgur , Uygun Kazim 
Published: March 2020

e14618 Background: Wnt signal transduction pathway plays an important role in carcinogenesis. Wnt signal transduction pathway is a key component of the β-catenin-TCF / LEF family of transcription factors interact with and activate the transcription of Wnt target genes. The aim of this study is to evaluate the prognostic value of β-katenin and LEF-1 expression in patients with operable gastric cancer and the relationship between demographic and histopathological variables. Methods: In this study, 82 gastric cancer patients treated with adjuvant treatment after operation and followed in Oncology Department between 2006-2010 were included. β-katenin and LEF-1 expression were examined by immunuhistochemical analysis in paraffin embedded tumor tissues of the patients. Results: In this study, median age was 56 (26-81) years and median follow up was 19 (4-61) months. Performance status (ECOG PS) were 0-1 in all patients. Men/women ratio was 53/29 (64.6/35.4%). Median disease free survival (DFS) time was 17 months (SE:3 95% CI: 11-23) in 19 months of follow up. 3 years DFS rate was 39.7%. In all patients group, median overall survival (OS) time was 28 months (SE:4 95% CI: 20-36) and 3 years OS rate was 41,2%. There was no statistical correlation between β-catenin and LEF-1 expression and age, gender, performance status, tumor localization, T and N stage, lymphovascular, perinoral invasion, grade and operation type (>0.05). In addition, there was also no correlation between β-catenin and LEF-1 expression. According to univariate analysis, we did not find significant effect on age, gender, T stage, lymphovascular, perinoral invasion, grade and operation type on overall survival (p>0.05). Good performans status (ECOG 0), tumor infiltration without diffuse type like linitis plastica, and lower N stage had positive effect on survival (p=0.04, 0.033 and 0.005, respectively). In multivariate cox regression analysis, only N stage was found as an independent prognostic factor (p<0.05). Conclusions: In this study group, we found that the only N stage as an independent prognostic factor. Demographic features of the patients, histopathological characteristics other than N stage, β-catenin and LEF-1 prognostic effects have not been shown.
Overall survival with everolimus, sunitinib, and placebo for advanced pancreatic neuroendocrine tumors: A matching-adjusted indirect comparison of randomized trials.
Authors: Signorovitch James E. , Swallow Elyse , Kantor Evan , Wang Xufang , Hass Tomas , Klimovsky Judith , Metrakos Peter 
Published: March 2020

e14621 Background: No randomized trial has compared everolimus (EVE) and sunitinib (SUN) for treatment of advanced pancreatic neuroendocrine tumors (pNET). This study indirectly compared overall survival (OS) with EVE vs. placebo (PBO), and OS and progression-free survival (PFS) with EVE vs. SUN. Methods: Individual patient data were used from the RADIANT-3 trial of EVE 10 mg/day vs. PBO (cutoff: April 2010); published summary data were used from the A6181111 trial of SUN 37.5 mg/day vs. PBO (cutoff: June 2010). To adjust for cross-trial differences, RADIANT-3 patients were subjected to A6181111 exclusion criteria and weighted to match A6181111 baseline demographics, performance status, time since diagnosis, disease sites, distant metastases and prior therapy. After matching, OS was compared between balanced trial populations for EVE vs. the PBO arm from A6181111 (which had access to SUN after progression or early stopping) and vs. the SUN arm. PFS was also compared. Analyses did not adjust for early stopping of A6181111, which may bias towards longer PFS and OS with SUN vs. PBO. Results: 394 patients from RADIANT-3 (after excluding 15 with worse performance status than allowed in A6181111 and 1 missing baseline data) and all 171 patients in A6181111 were included. RADIANT-3 patients differed from A6181111 patients in baseline performance status, prior use of somatostatin analogues, and prior use of systemic chemotherapy before matching. After matching, all baseline characteristics were well-balanced between trials. EVE was associated with significantly prolonged OS vs. PBO in A6181111 (hazard ratio [HR] for death = 0.61, 95% CI = 0.38-0.98, p=0.04), corresponding to a 1-year number needed to treat of 8.3 patients to prevent 1 death. OS and PFS were longer, but not statistically different, with EVE vs. SUN (HR for death = 0.81, 95%CI=0.49-1.31, HR for progression = 0.84, 95% CI=0.46-1.53). Conclusions: After adjusting for cross-trial differences, treatment of advanced pNET with everolimus was associated with significantly prolonged OS compared to placebo. OS and PFS were longer, but not statistically different, with everolimus compared to sunitinib.