bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term outcome in patients with advanced malignant peritoneal mesothelioma (AbM) treated with a pemetrexed/platin combination.
Authors: Karthaus Meinolf , Taghizadeh Kambiz 
Published: February 2017

295 Background: Advanced mesothelioma is associated with a short overall-survival (OS 9-12 mo). Peritoneal mesothelioma is a rare and aggressive cancer of the peritoneum. Data on long-term outcome of AbM are rare. Pemetrexed (Pem)+cisplatinum (DDP) has been reported effectively for AbM previously with the optimal ctx duration remaining still undetermined. We evaluated the efficacy and safety of Pem + Platinum for the treatment of AbM prospectively. A part of our data has been published previously (ASCO GI 2006). This is a 10-year OS update. Methods: We analyzed the long-term OS of a cohort of AbM that started treatment between 02/2002 and 03/2006. All AbM pts received Pem (500 mg/m2) +DDP (75 mg/m2) or carboplatin (AUC 5) prospectively on d1 (repeated on d22 for 6 cycles or disease progression). Folinic acid 400 μg po/d and vit B12 1000 μg i.m. qw 9 wks was administered to prevent AE. Study endpoints were best response (CR/PR), time to progression (TTP), OS and safety. Results: A total of 95 mesothelioma pts were observed from 12/2002 until 05/2006 in a single institution. Four patients (1 AbM, 1 MPM, 2 MPM+AbM) were excluded due to renal impairment (n = 1) or death prior to chemotherapy (n = 3). Staging procedures revealed AbM in 22 patients, while this was pleural mesothelioma in 64 patients. Five additional patients had malignant mesothelioma on both sites of the diaphragm. Initial ctx was with DDP in all pts with AbM, except one who died prior to therapy initiation. Pem was administered a median of 6 cycles (range 1 –33+). Major toxicity (WHO > III/IV) was nausea and neutropenia (2/11). Benefit for AbM was observed in 77%, with objective RR in 36% while a response or stabilization was observed in 4 out 5 pts with AbM + MPM (80%). Mean time to progression was 11.5 months (range 0 to 35+) in AbM vs 15.4 pts with AbM +MPM. Mean survival was 32.6 months (range 1 to 147+ months) in AbM and 48.4 months in pts with AbM + MPM (18-146+ months). Conclusions: The natural course of AbM is different from pleural mesothelioma. Pts with an AbM had a much longer TTP and overall survival when compared to pleural mesothelioma. Pemetrexed with platinum is well tolerated and has substantial activity for malignant peritoneal mesothelioma.
Concordance of HER2 status between local and central review in gastric and gastroesophageal junction cancers: A French observational study of 394 specimens (HERable study).
Authors: Monges-Ranchin Genevieve , Terris Benoit , Chenard Marie-Pierre , Bibeau Frederic , Penault-Llorca Frederique Madeleine , Bougrini Mouna , Conde Da Silva Fraga Emmanuele , Doucet Laurent 
Published: February 2017

30 Background: As some gastric (GC) and gastroesophageal junction adenocarcinoma (GEJC) overexpress HER2, HER2 testing should be part of routine assessment to decide target treatment initiation. Thus, the study objective was to assess the concordance of HER2 status between local and central laboratories. Methods: From July 2012 to February 2014, this observational study tested tumor samples from patients (pts) with GC or GEJC, regardless of disease stage. HER2 positive (+) status was defined as immunohistochemistry (IHC)3+ or IHC2+/In Situ Hybridization (ISH)+. The concordance was analyzed between HER2 status assessed by local laboratories (any technique) and centralized laboratory (IHC 4B5 and silver (S) ISH for all specimens). Results: 394 specimens from 367 pts were analyzed by 19 local laboratories. Pts' characteristics were: mean age 66±13 years, male 69%, GC 60%, intestinal type 55%. The specimens were surgical resections (52%), biopsies (41%), adenopathy (4%) and distant metastasis (3%). HER2+ status was found in 18% of locally tested specimens (69/394: 52 IHC3+; 17 IHC2+/ISH+) and in 19% of centralized specimens (73/394: 56 IHC3+; 17 IHC2+/SISH+). Among HER2+ specimens, 53% (39/73) were GC and 73% (53/73) were of intestinal histological type. Regarding amplification, 20% of centralized SISH tests (79/393) were amplified. The concordance between HER2 status (n = 393) assessed by local and centralized laboratories was acceptable according to Landis and Koch classification with a kappa coefficient of 0.69 (95%CI [0.60-0.78]). The discordance between HER2 status assessed by local and centralized laboratories was 9%. The rate of false negative was 27% and false positive 5%. Conclusions: The HERable study is the first large French study to evaluate concordance between HER2 status assessed by local and centralized laboratories. The cumulative rate of false negative and false positive in GC and GEJC is 9% (95% CI [6%; 12%]). Quality control should be setup to improve the quality of this test. [Table: see text]
Emibetuzumab plus ramucirumab: Simultaneous targeting of MET and VEGFR-2 in patients with advanced hepatocellular cancer in a phase 1b/2 study.
Authors: Harding James J. , Bendell Johanna C. , Fuchs Charles S. , Wang Xuejing , Wacheck Volker , Zhu Andrew X. 
Published: February 2017

300 Background: The mesenchymal-epithelial transition factor (MET) pathway is upregulated by anti-vascular endothelial growth factor (VEGF) therapies in vivo. Emibetuzumab (E) is a bivalent monoclonal anti-MET antibody that inhibits ligand-dependent and ligand-independent MET signaling. Here we report safety and initial anti-tumor activity for the combination of E plus ramucirumab (R), a human VEGFR-2 antibody in patients (pts) with advanced hepatocellular cancer (HCC) as part of a Phase 1b/2 study (NCT02082210). Methods: Pts with Child Pugh A advanced or metastatic HCC and no further standard therapy available received E (750 mg flat dose) and R (8mg/kg) intravenously every 2 weeks (Q2W) on a 28 day cycle. The primary objective was to evaluate safety and tolerability of the E+R dose and schedule in this patient population. As a co-primary objective, preliminary antitumor activity by RECIST v1.1 was studied. Exploratory objectives included evaluation of biomarkers for MET/HGF and VEGF pathways from fresh pre-treatment tumor biopsies. Results: As of July 2015, 15 pts were treated with E + R in the HCC expansion cohort. Most of the pts had ECOG PS of < 2, and prior sorafenib therapy. Ten pts (67%) experienced ≥ 1 drug-related adverse events (AEs). Commonly related AEs included fatigue (33%), peripheral edema (33%), hypertension (27%), and hypophosphatemia (27%). Most of these events were mild or moderate in severity and the only ≥ grade 3 related events reported included 1 case each of grade 3 fatigue, hypertension, neutropenia, leukopenia, and lymphopenia. In the 9 pts evaluable for response, there were 2 partial responses (PR; 1 unconfirmed, pt still ongoing) and 5 additional pts had stable disease for a disease control rate of 47% (7/15). Six pts were not evaluable and 5 pts remained on treatment at the time of data cut-off. Five pts received 4 or more cycles of therapy, including 1 pt ongoing in cycle 10. Both patients with PR were positive for MET expression. Updated results will be presented at the meeting. Conclusions: The combination of 750 mg E plus 8mg/kg R at Q2W demonstrated an acceptable safety profile and early evidence of antitumor activity in pts with advanced HCC. Clinical trial information: NCT02082210.
Association of reduction of tumor metabolism with prognosis of advanced gastric cancer patients treated with palliative chemotherapy: Prospective cohort study.
Authors: Park Seongyeol , Ha Seunggyun , Kwon Hyun Woo , Kim Woo Hyoung , Kim Tae-Yong , Oh Do-Youn , Cheon Gi Jeong , Bang Yung-Jue 
Published: February 2017

31 Background: Although tumor metabolism can be measured by 18F-FDG PET, the meaning of metabolic response by chemotherapy in gastric cancer patients has not been well studied. The purpose of this study is to identify prognostic value of tumor metabolic response in gastric cancer. Methods: Advanced gastric cancer patients were enrolled in this prospective cohort study before initiation of palliative chemotherapy. At the baseline and at the first tumor response evaluation, 18F-FDG PET was taken to measure tumor metabolism. We measured maximum standardized uptake value (SUVmax), and total lesion glycolysis (TLG) calculated as multiplying mean SUV by metabolic tumor volume (MTV) using threshold SUVs of 2.5 (TLG2.5) in each patients. Correlation of clinicopathological factors and survival were analyzed. Results: A total of 87 patients were enrolled. Baseline high SUVmax and TLG2.5 were associated with HER2 positivity, histologic differentiation and tumor size. High SUVmax and TLG2.5 were also associated with worse overall survival (OS) (HR 2.14, P = 0.025; HR 2.23, P = 0.037, respectively). Comparing RECIST evaluation, 30% of the reduction of sum of target lesions was correlated with 50% reduction of SUVmax, and 50% reduction of TLG2.5. The larger reduction of SUVmax (HR 0.43, P = 0.006 for Progression-free survival (PFS); HR 0.38, P = 0.007 for OS), and TLG2.5 (HR 0.27, P < 0.001 for PFS; HR 0.27, P = 0.001 for OS) was associated with better OS. In multivariate analysis, SUVmax and TLG2.5 were independent prognostic factors along with age, histologic type, gastrectomy history and HER2 status. Conclusions: Tumor metabolic response measured by SUVmax or TLG2.5 was associated with prognosis of advanced gastric cancer patients treated with chemotherapy.
Chemotherapy versus best supportive care in patients with advanced biliary tract carcinoma: A propensity score-matched analysis.
Authors: Ji Jun Ho , Kim Rock Bum , Kim Young Saing , Lee Soon Il , Han Kyu Hyung , Oh Sung Yong , Choi Seong Hee , Seo A Young , Kang Jung Hun 
Published: February 2017

316 Background: Although chemotherapy is endorsed by various guidelines for advanced biliary tract cancer (BTC), the evidence of chemotherapy over best supportive care (BSC) is limited. However, prospective randomized trial with BSC control arm is unrealizable. The aim of this study is to investigate the survival benefit of chemotherapy over BSC in patients with advanced BTC. Methods: Advanced BTC patients with good performance status (ECOG 0-2) were eligible for the study. Data were retrospectively collected in the four tertiary cancer centers and analyzed through propensity score-matching (PSM) to minimize bias. Of 810 enrolled patients cohort, 206 patients received BSC only without any palliative chemotherapy, versus 604 patients were treated with chemotherapy. PSM analysis was performed using the following variables: Age, ECOG, Carcinoembryonic antigen (CEA) and White blood cell (WBC). The sample size of each group was 171 patients after PSM. Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and prognostic factors were investigated by cox proportional regression. Results: In pre-PSM analysis, the OS for chemotherapy group and BSC group, respectively, were as follows: total population, 15.2 vs 7.0 months (p < 0.001); metastatic disease, 12.7 vs 6.2 months (p < 0.001); locally advanced disease, 28.0 vs 13.4 months (p = 0.01); ECOG 0-1, 17.0 vs 8.8months (p < 0.001); CA 19-9 < 100, 13.9 vs 5.9 months (p = 0.001) and CA 19-9 ≥ 100, 11.8 vs 6.0 months (p < 0.001). In post-PSM 171 pair analysis, the respective OS for chemotherapy group and BSC group were depending on the prognostic factors as follows : total population, 12.7 vs 7.0 months (p < 0.001); metastatic disease, 10.9 vs 8.1 months(p= 0.001); locally advanced disease, 20.8 vs 15.9 months (p = 0.416); ECOG 0-1, 14.5 vs 11.5 months(p < 0.001); CA 19-9 < 100, 12.8 vs 12.7 months (p = 0.472) and CA 19-9 ≥ 100, 11.8 vs 8.2 months (p < 0.001). Conclusions: Chemotherapy improved OS in advanced BTC with good performance status compared BSC. However, the survival benefit was not demonstrated in BTC patients with locally advanced disease or with lower serum CA19-9 tumor marker.
Feasibility and impact on resectability of FOLFIRINOX in locally-advanced and borderline pancreatic cancer.
Authors: Portales Fabienne , Gagniard Benedicte , Thezenas Simon , Samalin Emmanuelle , Assenat Eric , Alline Mathias , Colombo Pierre-Emmanuel , Rouanet Philippe , Carrere Sebastien , Quenet François , Riou Olivier , Llacer Carmen , Mazard Thibault , Ychou Marc 
Published: February 2017

318 Background: Pancreatic cancer (PC) has a poor prognostic. Only patients who undergo a complete R0 surgery have longer survival rates. Treatment of locally-advanced (LA) and borderline (BL) PC is controversial. Folfirinox is considered as a standard first-line treatment in metastatic patients. The aim of our study was to evaluate the impact of Folfirinox in LA and BL PC. Methods: We performed a retrospective analysis of prospectively-collected data from LA and BL PC patients treated with original Folfirinox in our institution between January 2010 and February 2015. Results: 35 patients were enrolled, 20(57.1%) pancreatic head adenocarcinoma, 19(54.3%) LA and 16(45.7%) BL PC, 54.3% male, median age 60 years old [44-74]. OMS was 0, 1, 2 for 21(61.8%), 11(32.4%), 2(5.9%) patients. Median CA19.9 level was 5N [1-33]. All patients had Folfirinox in first-line followed by radiochemotherapy (RTCT) in 23(65.7%) patients, with Gemzar and Xeloda in 21 and 2 patients. Median number of chemotherapy cycles was 4 [1-13]. The grade 3-4 toxicity rate was 17.1% (n = 6), mainly digestive (67%), hematologic (16.7%), none neurologic. There was no toxic death. 17(46%) patients underwent surgery, 7 LA and 10 BL, with a R0 resection in 13 patients, mainly 8 PT3 (57.1%), no PT0, and 14N+. The morbidity rate was 40%, including 3 fistulae and 2 hemorrhages. Median overall survival was 24 months (95%CI:14-44), 53 (95%CI:26-.) and 12 months (95%CI: 9-19) in surgery versus no-surgery patients (p< 0.001). Progression-free survival was 13.9 months (95%CI:11.2-17.1), 16.2 (95%CI:13.7-25.3) and 9.5 (95%CI:7.4-15.9) months in surgery versus no-surgery patients. 13 patients were still alive at the time of analysis, with a median follow-up of 44 months (95%CI:7-53). 30 patients had disease progression, locally, distant or both in 7(24.1%), 20(69.0%) and 3(13.1%) patients. Weight loss, OMS status, abdominal pain and CA199 level at diagnosis were not correlated with better survival. Conclusions: Folfirinox, followed or not by RTCT, as inductive treatment for LA and BL PC is feasible with acceptable toxicity, and allowed resectability in 37.1% patients, and thus a longer survival. Further studies are needed to confirm these encouraging results.
Rates and patterns of recurrence following complete resection of Hilar cholangiocarcinoma: Results from the U.S. Extrahepatic Biliary Consortium.
Authors: Mogal Harveshp , O'Connor Sean , Fino Nora , Ethun Cecilia Grace , Pawlik Timothy M. , Poultsides George A. , Tran Thuy , Idrees Kamran , Isom Chelsea A , Fields Ryan C. , Jin Linda , Weber Sharon M. , Salem Ahmed I. , Martin Robert C. G. , Scoggins Charles Raben , Schmidt Carl Richard , Beal Eliza W , Hatzaras Ioannis , Maithel Shishir Kumar , Shen Perry 
Published: February 2017

324 Background: Data for incidence and patterns of recurrence after surgical resection of Hilar cholangiocarcinoma have been derived largely from single institution series. We sought to assess factors associated with recurrence, recurrence patterns and their impact on outcomes. Methods: Patients with Hilar cholangiocarcinoma that underwent R0/R1 resection without 30-day mortality from surgery were analyzed from a 10-institution database. Results: 193 patients with recurrence data available were identified. Of these 95 (49%) recurred with median time to recurrence of 15.2 months and overall survival (OS) of 24.3 months. Univariate analysis identified age (HR 1.02, CI 1.004-1.036; p = 0.01), pre-op CA 19-9 (HR 1.02, CI 1.004-1.035; p = 0.02), positive lymph nodes (HR 1.72, CI 1.187-2.478; p = 0.004) and perineural invasion (HR 1.78, CI 1.125-2.802, p = 0.01) as factors predicting worse disease free survival. On multivariate analysis, only age (HR 1.032, CI 1.01-1.06, p = 0.007) and pre-op CA 19-9 (HR 1.02, CI 1.01-1.04, p = 0.013) remained significant. 67 patients (70.5%) had distant recurrence (DR) with or without locoregional recurrence (LR) while 28 patients (29.5%) had LR only. Of patients that had DR, 42 (63.6%) had liver, 23 (34.9%) had peritoneal, 8 (12.1%) had lung and 5 (7.6%) had other sites including distant nodal metastases. Median time to recurrence (13.6 vs 17.7 months, p = 0.07), time from recurrence to death (5.9 vs 4.5 months, p = 0.72) and OS (24.4 vs 25.3 months, p = 0.3), was not significantly different between patients who had LR or DR with or without LR. Among patients that recurred, tumor size, lymph node status, resection status (R0/R1), extent of resection and adjuvant therapy were not significantly associated with the type of recurrence. Conclusions: Hilar cholangiocarcinoma is an aggressive cancer with high rates of predominantly distant recurrence associated with poor survival. Further investigation is warranted to determine the role and potential type of adjuvant therapy in order to improve outcomes after surgical resection.
Economic burden of advanced gastric cancer (AGC) in Taiwan.
Authors: Hong Jihyung , Tsai Yiling , Novick Diego , Hsiao Frank , Cheng Rebecca , Chen Jen-Shi 
Published: February 2017

33 Background: Gastric cancer is one of the leading causes of cancer deaths in both sexes worldwide, especially in East Asia. This study aimed to estimate the economic burden of advanced gastric cancer (AGC) in Taiwan. Methods: The costs of AGC in 2013 were estimated using resource use data from a chart review study (n = 122 with AGC) and national statistics. Annual per-patient costs were estimated from 82 patients who had complete resource use data. The costs were composed of direct medical costs (inpatient, outpatients, and chemotherapy-related costs), direct non-medical costs (healthcare travel and caregiver costs), morbidity costs, and mortality costs. Relevant unit costs were retrieved mainly from literature and national statistics, and applied to the resource use data. Broad definitions of morbidity and mortality costs were employed to value the productivity loss in patients with unpaid employment, economically inactive and unemployed as well as the life years after the age of retirement. Narrow definitions were also used in sensitivity analyses, using age- and/or sex-specific employment rates. Forgone future earnings/productivity loss were discounted at 3%. Annual per-patient costs were projected to estimate the total costs of AGC at the national level with an estimated number of patients with AGC (N = 2,611) in 2013 in Taiwan. Results: The mean age of the 82 patients was 59.3 (SD: 11.9) years, and 67.1% were male. Per-patient costs were US$26,431 for direct medical costs, US$4,669 for direct non-medical costs, US$5,758 for morbidity costs, and US$145,990 for mortality costs (per death). These per-patient costs were projected to incur total AGC costs of US$423 million in 2013 in Taiwan. Mortality costs accounted for 77.3% of the total costs, followed by direct medical costs (16.3%), morbidity costs (3.6%), and direct non-medical costs (2.9%). Conclusions: The total costs of AGC in Taiwan were estimated to be about US$423million in 2013. Such high costs, despite relatively low AGC incidence/prevalence rates in Taiwan, were mainly due to high mortality rates and high mortality costs (per death). Reducing mortality rates and providing effective treatments may help to reduce its burden on patients, caregivers and society as a whole.
A phase I trial of cabozantinib (XL184) and gemcitabine in advanced pancreatic cancer.
Authors: Zhen David Bing , Griffith Kent A. , Ruch Joshua Michael , Morgan Meredith , Kim Edward Jae-hoon , Sahai Vaibhav , Simeone Diane M. , Zalupski Mark 
Published: February 2017

334 Background: Hepatocyte growth factor (HGF) and its receptor (c-Met) are activated in pancreatic ductal adenocarcinoma (PDAC). Preclinical data showed a combination of cabozantinib (cabo) and gemcitabine (gem) improved tumor control through inhibition of c-Met. We sought to determine the maximum tolerated dose (MTD) of cabo and gem in patients with advanced PDAC. Methods: Patients with unresectable or metastatic PDAC with ≤1 prior treatment and adequate organ function/performance status were eligible. Cabo was given orally once daily for 7 days and continued with gem infused IV over 30 min on days 1, 8, and 15 of a 28 day schedule. Doses were assigned in accordance with a Time to Event Continual Reassessment Method (TITE-CRM) per table below. Primary endpoint was MTD, defined as the highest dose level at which ≤25% of patients incurred a dose-limiting toxicity (DLT) in the first 35 days of therapy. Secondary endpoints included response rate, progression-free survival (PFS), and overall survival (OS). Results: Twelve patients were treated from July 2012 – May 2015. Median number of cycles given was 3 (range: 1-6). MTD was not determined. The probability of DLT was >25% for all dose levels attempted. Four of 10 evaluable patients experienced DLT (shown in table below), including grade 3 ALT/AST elevations (n=3) and thrombocytopenia (n=2). Five of 6 patients who continued therapy beyond cycle 2 incurred at least one grade 3 adverse event. Three patients had a partial response, but each discontinued therapy due to toxicity. Median PFS and OS were 4.7 (95% CI: 1.4 – 9.7) and 10.1 months (95% CI: 3.6 – 20.6), respectively, in treated patients. Conclusions: While the combination of cabo and gem demonstrated activity in PDAC, this regimen is impractical due to DLT at low doses and continuing toxicities despite dose reductions and schedule changes. Clinical trial information: NCT01663272. [Table: see text]