bluuebunny/crossref_metadata_2025 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.
Induction of hypertrophy of the left hepatic lobe by unilateral right hepatic arterial radioembolization (RE) using 90Y-labeled resin microspheres in patients with right-sided secondary malignant liver tumors.
Authors: Garlipp Benjamin , Seidensticker Max , Irmscher Romy , Damm Robert , Ricke Jens , Stuebs Patrick , Meyer Frank , Lippert Hans
Published: March 2020

e14630

Background: In patients with unilateral liver tumors who are candidates for extended liver resection but demonstrate insufficient future liver remnant (FLR) size, induction of FLR hypertrophy by contralateral portal vein embolization (PVE) is an established approach but concerns exist regarding tumor progression during the interval from PVE to liver surgery. We hypothesized that unilateral hepatic arterial radioembolization (RE) using 90Y-labelled resin microspheres achieves a similar degree of contralateral hypertrophy as PVE. Methods: 32 patients with right-sided secondary liver cancers (metastases from colorectal [n=20], breast [n=7], head and neck [n=2], and other [n=3] cancers) were treated with unilateral right hepatic arterial RE. Before and 44 (22-81) days following RE MRI-based volumetry of the total liver (TLV), the right (RLV, segments 4-8) and left (LLV, segments 2 and 3) hepatic lobes was performed. TLV, RLV, and LLV as well as the LLV/TLV ratio before and after RE were compared using the Mann-Whitney U-test. Results: Median values for TLV, RLV, LLV, and the LLV/TLV ratio are shown in table. Compared to baseline, RLV and TLV showed no significant change after right hepatic arterial RE (-3.7 [min/max, -37.7/+56.5] per cent [p=0.158] and +3.2 [-16.5/+47.4] per cent [p=0.282], respectively). In contrast, LLV as well as the LLV/TLV ratio were significantly increased after RE (+34.9 [-3.1/+146.2] per cent [p<0.001] and +29.4 [-24.3/+155.3] per cent [p<0.001], respectively). Conclusions: Right hepatic arterial RE achieved superior contralateral liver hypertrophy compared to hypertrophy reported after PVE and may be an alternative to PVE since it provides simultaneous treatment to the liver tumors during the interval from treatment to liver surgery, reducing the risk for tumor progression. These two methods should be directly compared within a prospective trial. [Table: see text]
Decrease in CA-19-9 after neoadjuvant chemoradiation therapy to predict survival in locally advanced pancreatic cancer.
Authors: Singh Jaswinder , Jafri Syed Faisal , Pabla Maninder , Freilich Bradley L , Cates Joe , Sheldon John M. , Shaeffer David , Connor Michael , Shah Raj , Rath Niharika , Cope Reed , Burt Michael , Mukherjee Srijita , Parikh Unnati , Feeback Jennifer Wanpen
Published: March 2020

e14632

Background: Carcinoma of the pancreas is among the most lethal of human cancers. Data on the overall survival rates of patients treated in the community hospital setting are limited; the purpose of this retrospective data collection study was to assess – Does CA-19-9 change during the neo adjuvant treatment of locally advanced pancreatic cancer patients predicts the overall survival (OS) at high volume community hospital setting. Methods: Eligibility included cytological or histological evidence of locally advanced unresectable and borderline resectable adenocarcinoma of the pancreas, not amenable for complete surgical resection. Their respectability was determined with EUS and CT scan / MRI and was discussed in the multi disciplinary conference. Patients diagnosed before July 2009 were essentially treated with continuous 5-FU 200 mg/m2 for 5 weeks with radiation of 1.8 Gy per daily fraction, for a total dose of 50.4 Gy over 5.5 weeks. Patients diagnosed after July 2009 received gemcitabine 400 mg/m2 intravenously (over 60 minutes) beginning on the first day of radiation therapy (before radiation), then weekly thereafter during radiation. Results: Data were abstracted on 64 patients (40 deceased; 24 alive) diagnosed between 6/2005 and 4/2011. The median age was 68 years (range: 41-87), and 52% were male. The majority of patients (97%) were diagnosed by endoscopic ultrasound (EUS) with biopsy. At diagnosis, 56 (88%) patients were locally advanced unresectable(without metastasis) or borderline unresectable; 49 of these had neoadjuvant treatment, and 13 were later resected. Median OS for all 64 patients was 45.4 weeks (95% CI: 29.6-61.3), with no significant differences in OS by sex of patient (p = 0.210) or smoking history (p = 0.625). Twenty-two patients (34%) had >75% decreases in CA19-9 from baseline; median OS was 89.4 weeks in this group compared to 41.3 weeks in patients with changes in CA19-9 <75% (p = 0.025). Conclusions: This trial demonstrates improved overall survival in patients for patients with locally advanced pancreatic cancer , who had significant decrease in CA -19-9 (>75% decreases in CA19-9 from baseline) in response to neo adjuvant chemotherapy and radiation.
Metabolomic discrimination of intestinal- and diffuse-type gastric cancer tissues using capillary electrophoresis time-of-flight mass spectrometry.
Authors: Terashima Masanori , Kusuhara Masatoshi , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Fujimori Tamaki , Yamamoto Hiroyuki , Kami Kenjiro , Ohashi Yoshiaki
Published: March 2020

e14635

Background: Clinicopathological characteristics of gastric cancer patients strongly depend on histological type. In contrast with gene and protein expressions, metabolic properties of intestinal- and diffuse-type gastric cancer have been largely unknown. Here, we conducted metabolome analysis of paired non-tumor and tumor gastric tissues by using capillary electrophoresis and liquid chromatography combined with time-of-flight mass spectrometry (CE- and LC-TOFMS, respectively) in order to metabolomically characterize non-tumors (NTs), intestinal-type tumors (ITs), and diffuse-type tumors (DTs). Methods: Tumor and surrounding non-tumor tissues were surgically excised pair-wise from 27 gastric cancer patients (18 ITs and 9 DTs) who underwent gastrectomy at our institution between February and May 2011. Following tissue homogenization and metabolite extraction, we measured 254 and 138 metabolites, respectively, by CE-TOFMS and LC-TOFMS. Results: Metabolomic profiles of tumor tissues, especially ITs, were well-distinguished from those of NTs: Lactate and most glycolytic intermediate levels in ITs were significantly higher than those in NTs, which reaffirms the Warburg effect of cancer, but the significance was lesser in DTs. Levels of all the measured amino acids were significantly higher in ITs and relatively higher in DTs than in NTs, showing high capacities of cancer cells for protein synthesis. Although levels of ATP, GTP, and energy charge in ITs and DTs were lower than those in NTs, purine contents were rather higher in the tumors than in NTs, which may support their high demand for DNA replication. Moreover, reduced glutathione in DTs were the lowest among others, implying their potential vulnerability against oxidative stress. Conclusions: Metabolomic profiles of NTs, ITs, and DTs were discriminated by CE- and LC-TOFMS analyses: Considerably high lactate, amino acid, and purine levels highlighted the metabolome of tumors, especially of ITs. Relatively low energy and redox statuses of DTs, however, could be targeted for developing more effective cancer therapeutics.
Correlation between serum tumor markers, tissue proliferative activity, and clinicopathologic factors in patients with locally advanced esophageal squamous cell carcinoma.
Authors: Sunpaweravong Somkiat , Sunpaweravong Patrapim , Puttawibul Puttisak , Boonyaphiphat Pleumjit , Nitiruangjaras Anupong
Published: March 2020

e14639

Background: Squamous cell carcinoma antigen (SCCA) and CYFRA 21-1 have been reported as useful tumor markers for esophageal squamous cell carcinoma (ESCC), but no information has yet been reported about the relationship between these serum tumor markers and tissue proliferative activity (Ki-67). The aim of this study was to compare SCCA, CYFRA 21-1 and Ki-67 with clinicopathological factors and survival in locally advanced ESCC patients. Methods: Pre-treatment SCCA and CYFRA 21-1 serum levels were measured by enzyme-linked immunoassays while the expression of tissue Ki-67 activity was calculated by immunohistochemical nuclear staining on paraffin-embedded tumor samples of locally advanced ESCC patients. The association between these biomarkers, clinicopathological factors, and overall survival were analyzed by Cox proportional hazards model. Results: 166 locally advanced ESCC patients from our institution (2002-6) were evaluated. Their median age was 62 years (39-90), M:F 144:22, location of tumor (upper:middle:lower 31:83:53) and histological grade (well:moderate:poor 50:73:43). 43% had received surgery, 22% chemoradiation and 35% best supportive care. Follow-up times ranged from 2 months to 38 months, and the median survival was 11.0 months. Elevated SCCA (>1.5 ng/mL) and CYFRA 21-1 (>3.5 ng/mL) before treatment were found in 79.1% and 50.4% of the patients, respectively, while 42.6% had both serum markers elevated. The SCCA and CYFRA 21-1 levels were not correlated (p=0.128) to each other, nor either to age, sex, T, N, M, location, grade or Ki-67. High Ki-67 expression levels were significantly correlated with T4 (p=0.010), M1 (p=0.010) and poor grade (p=0.015) but not to age, sex, N or location. Levels of SCCA, CYFRA 21-1 and Ki-67, alone or in any combination, were not correlated to survival of patients. Conclusions: This study suggests that the evaluation of SCCA and CYFRA 21-1 are of no particular correlation to clinicopathological factors and survival in locally advanced ESCC, but Ki-67 is correlated with T, M and grade.
Prognostic effects of 25-hydroxyvitamin d levels in gastric cancer.
Authors: Ren Chao , Xu Rui-hua
Published: March 2020

e14653

Background: Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown. Methods: 197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D. Results: The mean vitamin D levels of the 197 gastric patients was 49.85±23.68nmol/L, among whom 114(57.9%) were deficient in Vitamin D(<50nmol/L), 67(34%) were insufficient (50-75nmol/L) and 16(8.1%) were sufficient (>75nmol/L). Clinical stage (p=0.004) and lymph node metastasis classification (p=0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥50nmol/L) had a higher overall survival compared with the low vitamin D levels group (<50nmol/L)(p=0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (p=0.019). Conclusions: Vitamin D deficiency may be associated with poor prognosis in gastric cancer.
The tumor-log odds of positive lymph nodes-metastasis staging system, a new staging system for gastric cancer after D2 resection in China.
Authors: Xu Rui-hua , Qiu Miao-zhen
Published: March 2020

e14655

Background: In this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover we compared them with the 7th edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection. Methods: A total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7th edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the -2log likelihood and the hazard ratio. Results: The cut points of lymph node ratio (LNR) were set as 0, 0-0.3, 0.3-0.6, 0.6-1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as≤-0.5, -0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis shown that TLM staging system was better than the TRM or TNM system for the prognostic evaluation. Conclusions: The TLM systems was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection.
Risk factors for peritoneal carcinomatosis in gastric cancer patients, and outcomes following resection and hyperthermic intraperitoneal chemotherapy (HIPEC).
Authors: Kim Ki Won , Chow Oliver , Parikh Kunal , Blank Sima , Jibara Ghalib , Labow Daniel M. , Hiotis Spiros P.
Published: March 2020

e14656

Background: Gastric cancer (GC) contributes significantly to the burden of cancer death in the United States. Unfavorable prognosis in patients with gastric cancer and peritoneal carcinomatosis (GCPC) is well-documented. In this study, a model predictive of GCPC is proposed, and outcomes in patients with GCPC treated with surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are assessed. Methods: A single-institution analysis of 112 patients treated for GC between the years 2000 and 2011 was performed. Demographic and clinical-pathologic criteria were entered into univariate and multivariate analyses, to identify criteria independently predictive of GCPC. Overall survival in each cohort was determined via Kaplan-Meier analysis. Results: GCPC developed in 28/112 (25%) of GC patients. Several variables were associated with GCPC by univariate analysis (age, p = 0.018; tumor stage, p = 0.004; tumor location, p = 0.046), but only age (≤60) and tumor stage (T3/T4) were independently predictive of GCPC by multivariate analysis (HR = 3.949, p = 0.024; HR = 3.942, p = 0.049, respectively). Intermediate-term survival was not significantly impacted in nine GCPC patients treated with HIPEC (65% 1-year, 39% 3-year without HIPEC; vs. 73% 1-year, 39% 3-year with HIPEC, p = NS). Conclusions: A model to identify gastric cancer patients at highest risk for GCPC is proposed. Although intermediate term survival in a small number of GCPC patients (9) treated with HIPEC is not significantly improved, emerging experience with increased follow-up with HIPEC in larger cohorts is needed. Earlier application of HIPEC targeted at patients at highest risk may be feasible in utilizing a model predictive of GCPC.
Optimizing supportive measures for the safe administration of FOLFIRINOX as first-line treatment in advanced, inoperable pancreatic cancer (aPDAC) patients (pts) in routine clinical practice.
Authors: Vaccaro Vanja , Bria Emilio , Sperduti Isabella , Pino Maria Simona , Massari Francesco , Gelibter Alain , Auriemma Alessandra , Torsello Angela , Melisi Davide , Nuzzo Carmen , Frizziero Melissa , Vari Sabrina , Lucchini Eleonora , Garufi Carlo , Cottini Silvia , Zeuli Massimo , Ferraresi Virginia , Cognetti Francesco , Tortora Giampaolo , Milella Michele
Published: March 2020

e14661

Background: FOLFIRINOX is an important addition to our therapeutic armamentarium for the treatment of aPDAC; however, safety and tolerability issues (hematologic toxicity, increased risk of AE in pts carrying biliary stents) may limit its use in routine clinical practice. Methods: We reviewed the clinical charts of 36 aPDAC pts receiving first-line FOLFIRINOX at two different institutions and analyzed toxicity and outcomes according to the presence or absence of a biliary stent and whether they received (n=21) or not (n=15) primary prophylactic G-CSF (d 7-9-11). Results: 36 pts (M/F: 22/14; median age: 57 yrs, range: 37-70; stage III/IV: 10/26; ECOG PS 0/1: 33/3) and 241 cycles were analyzed. Toxicity was mild with G3/4 adverse events (AE) in <1% of cycles, except for G3/4 neutropenia (16.6% of pts, 3.7% of cycles); dose was reduced to 75% in 48/205 cycles (23%); 3 pts discontinued treatment after 1 cycle (G3 gastro-intestinal toxicity in 1 pt and early progressive disease, PD in 2 pts). Overall and G3/4 toxicities were not significantly different in 7 pts carrying a biliary stent. G3/4 neutropenia was observed in 5/155 (3.2%) and 4/86 (4.6%) cycles among pts receiving or not G-CSF prophylaxis (p=n.s.); anemia and thrombocytopenia (any grade) were more common among pts receiving G-CSF (p<0.001 and p=0.009, respectively). Palonosetron/aprepitant/dexamethasone achieved complete control of nausea/vomiting at cycle 1 in 72% (95% CI: 58-87%) and 86% (95% CI: 75-97%) of pts. Partial response (PR) occurred in 25% and stable disease (SD) in 43% of 28 evaluable pts (disease control rate, DCR: 68%, 95% CI: 51-85%). A >50% reduction in CA19.9 occurred in 61% of pts. Median PFS was 8 mos (95% CI: 6-9 mos). Conclusions: FOLFIRINOX is well tolerated and easily manageable on an outpatient basis in young (<70 yrs) and fit (PS 0-1) aPDAC pts and can be safely used in pts carrying biliary stents. Routine G-CSF prophylaxis is not currently recommended, but may be useful to carefully extend FOLFIRINOX use to older/less fit/comorbid pts with aPDAC.
Survival analysis of Hispanics with hepatocellular carcinoma at a large academic institution.
Authors: Lin Daniel , Kaubisch Andreas , Goel Sanjay , Lo Yungtai , Aparo Santiago
Published: March 2020

e14682

Background: Hepatocellular carcinoma (HCC) appears to have worse prognosis among Hispanics in the United States who have a higher mortality when compared toBlacks and Non-Hispanic Whites based on statistics from the Surveillance Epidemiology and End Results (SEER) database. There is paucity of data directly comparing Hispanics vs. Non-Hispanics. The aim of this study is to compare the overall survival (OS) of Hispanics and Non-Hispanics with HCC at a large academic institution. Methods: Men and women diagnosed and treated for HCC at Montefiore Medical Center (MMC) from 2000 to 2009 were identified using data from the MMC Cancer Registry. Patient’s characteristics obtained included age at diagnosis, gender, race, tumor stage, Model for End-stage Liver Disease (MELD) scores, Hepatitis B, C and HIV status, alcohol use, presence of cirrhosis, alpha-feto protein levels, performance status and treatment. A Cox proportional-hazard model was used to assess survival differences between Hispanics and Non-Hispanics adjusting for clinically relevant and statistically significant variables. Results: A total of 513 patients were identified from the Cancer Registry database. 76 patients were excluded (58 due to inability to confirm the diagnosis of HCC based on current radiologic criteria, 18 due to unavailable ethnicity data). The remaining 437 patients were used for modeling and final analysis. Of the final cohort of 437 patients, 49% (n=212) were Hispanic and 51% (n=225) were Non-Hispanic. Among Non-Hispanics, 55% were Black, 35% were White and 10% were “other” race. Median time of follow up for Hispanics was 13.5 months and for Non-Hispanics was 12.1 months. The median OS among Hispanics was 14.5 months and was not statistically different from the Non-Hispanic group (median OS of 13.1 months) with a p value of 0.49. In a multivariate analysis model the hazard ratio (HR) for survival among Hispanics was 0.81 (95% CI 0.61 to 1.07, p= 0.15) when compared to Non-Hispanics; after adjusting for gender, age at diagnosis, tumor stage, treatment, alpha-feto protein levels and MELD scores. Conclusions: Hispanics diagnosed and treated with HCC at Montefiore Medical Center do not seem to have worse survival when compared to Non-Hispanics.
A phase II trial of gemcitabine in combination with oxaliplatin and capecitabine in previously untreated metasetatic or recurrent pancreatic cancer.
Authors: Sym Sun Jin , Hong Junsik , Jung Minkyu , Koo Yang Seo , Park Yeon Ho , Kim Koen Kook , Park Jinny , Cho Eun Kyung , Lee Jae Hoon , Shin Dong Bok
Published: March 2020

e14685

Background: Treatment with single agent gemcitabine provides modest benefits in patients with metastatic pancreatic cancer.This study was performed to determine the efficacy of gemcitabine in combination with oxaliplatin and capecitabine in patient with recurrent or metastatic pancreatic adenocarcinoma. Methods: This was a prospective, single-arm, single center study in patients with chemotherapy-naive metastatic or recurrent pancreatic adenocarcinoma. The primary endpoint was objective response. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 18 patients. If at least two objective responses were obtained, then a further 25 patients would be enrolled into the study. If no more than two responses were obtained among these 18 patients, the study would be halted. The study patients received gemcitabine 800 mg/m2 on day1, plus oxaliplatin 100 mg/m2 on day 1 and capecitabine 800 mg/m2/day on days 1-7 every 14 days. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Results: Eighteen patients were enrolled. Median age was 63 years (range, 39-73 years). Among these 18 patients, only one patient (5.5%) achieved an objective response. Therefore, the accrual terminated. The median time to disease progression was 2.1 months, and the median overall survival duration was 4.9 months. One-year overall survival rates were 35.3%. The most frequently reported grade 3 or 4 adverse events were asthenia (16.6%), and nausea (5.5%). There were no unexpected toxicities. Conclusions: The addition of oxaliplatin and capecitabine to gemcitabine did not improve objective response in the first-line treatment of advanced pancreatic cancer patients.