bluuebunny/crossref_metadata_2025_split huggingface dataset:
F-box and WD repeat domain-containing 7 (FBXW7) mRNA and outcome in biliary tract cancer.
Authors: Arroyo Gerardo F. , Kaen Diego , Salvatierra Alejandro , Rojo Sandra Viviana , Kowalyszyn Ruben Dario , Ortiz Marcos , Carballido Marcela , Kaen Luis Alberto , Zarba Juan Jose , Roca Enrique Luis , Costa Carlota , Molina-Vila Miguel Angel , Bertran-Alamillo Jordi , Mayo Clara , Gimenez Capitan Ana , Sanchez Jose Javier , Benlloch Susana , Lemoine Antoinette , Taron Miquel , Rosell Rafael 
Published: March 2020

e14521 Background: Thestandard treatment for biliary tract cancer is gemcitabine plus platinum, but median progression-free survival (PFS) is only 5-8 months (m) (Valle et al, NEJM 2010). Gene expression or somatic mutations may influence the clinical phenotype, which will affect decisions on individualized treatment. Methods: We retrospectively analyzed tissue blocks from 54 advanced or metastatic cholangiocarcinoma, gallbladder or ampulllary cancer patients (p) treated with single-agent gemcitabine or gemcitabine plus carboplatin or cisplatin. Using RT-PCR, we analyzed the mRNA expression levels of oncogenes, tumor suppressors and DNA repair genes (BRCA1, RRM1, AEG-1, RAP80, SPINK1 and FBXW7) and correlated results with PFS, overall survival (OS) and response. In addition, FBXW7 hotspot mutations were assessed. Results: p characteristics: 72% females; median age, 60 (40-87). Only FBXW7 expression correlated with PFS and OS. When FBXW7 levels were dichotomized at the median value, PFS was 4.2 m for p with low levels vs 12.6 m for p with high levels (p=0.02). When FBXW7 expression was divided by terciles, PFS was 4.9 m for p in the lowest tercile, 7.6 for p in the intermediate tercile, and 26.9 m for p in the highest tercile (p=0.08). OS was 6.2 m for p in the lowest tercile, 8 m for p in the intermediate tercile, and not reached for p in the highest tercile. No other significant correlation was observed between expression levels of the other genes examined and PFS or OS. Only AEG-1 expression correlated with response (p=0.05). No FBXW7 hotspot mutations were detected. Conclusions: Although we did not find the FBXW7 hotspot mutations previously described in biliary tract cancer, FBXW7 mRNA expression significantly influenced PFS and OS. A separate cohort of p is being analyzed to validate the prognostic role of FBXW7.
Prognostic analysis of the patients with operable gastric cancer and the importance of tolerability of therapy: Study of Anatolian Society of Medical Oncology.
Authors: Kucukoner Mehmet , Arpaci Erkan , Isikdogan Abdurrahman , Bilici Mehmet , Uncu Dogan , Cetin Bulent , Dane Faysal , Cayir Kerim , Inanc Mevlude , Ekinci Ahmet Siyar , Inal Ali , Yetisyigit Tarkan , Ozdemir Nuriye , Kaplan Muhammed Ali , Aksoy Sercan , Alkis Necati , Tekin Salim Basol , Eroglu Celalettin , Turhal Serdar , Buyukberber Suleyman 
Published: March 2020

e14526 Background: The aims of this study were to evaluate the tolerability and toxicity with adjuvant chemoradiotherapy (CRT) and prognostic analysis of patients with operable gastric cancer. Methods: The retrospective analysis included 723 patients with operable gastric cancer, stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. Patients’ age, sex, tumor localization, Lauren classification, grade, stage, type of dissection, toxicity and tolerability status were analyzed. Results: 73.9% of the patients were with stage III- IVM0. 61.0% of the patients were in the intestinal type, 51.1% of the patients were with the distal type of gastric cancer and 61.4% of the patients had undergone D2 dissection. 545 (75.4%) of patients completed the entire of adjuvant CRT. The median follow-up period was 20.8 months. Overall Survival (OS) rates were 80% and 52% while relapse free survival (RFS) rates were 75% and 48%, at 1, 3 years, respectively. In univariate analysis of groups, according to the group under the age of 65 and above (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), toxicity (p=0.062 / p=0.077), tolerability of therapy (p=0.002 / p=0.001) were significantly different in both RFS and OS. In multivariate analysis, three independent prognostic factors were identified on RFS / OS; stage (ods ratio (OR)=3.0, 95% confidence interval (CI):1.8-5.0, / OR=3.2, CI=1.8-5.4), for Lauren classification (OR=1.5, CI=0.9-2.2 / OR=1.5, CI= 1.1-2.2), for tolerability of therapy (OR=2.0, CI=1.0-3.8 / OR=1.9, CI=1.0-3.6). Conclusions: We found a new independent prognostic factor whether or not tolerate adjuvant CRT because of toxicity, except for the known prognostic factors like tumor stage and Lauren classification. We suggest that the treatment of the patients with intolerable to adjuvant CRT, is to change with less toxic adjuvant therapies.
A phase I/II study (TaxXel) on the treatment with docetaxel in combination with capecitabin in patients with metastatic esophageal cancer or cancer in the cardia region.
Authors: Friesland Signe , Wickart-Johansson Gun , Kadar Lianna , Bratthall Charlotte , Letocha Henry , Franzen Lars , Jacobsen Anne-Birgitte , Weber Hauge Petra , Wagenius Gunnar , Hatlevoll Ingunn , Glenjen Nils 
Published: March 2020

e14531 Background: This is an open label, non-randomized, multicenter phase I-II study with Docetaxel (Doc) given in combination with capecitabine (Cap) in patients (pts) with metastatic oesophageal cancer (mEC) or cancer in the cardia region (mCCR). Methods: In phase I, pts were treated with Cap day 1-14, 22-36 and Doc day 1, 8, 15, 22, 29. Cap was dose escalated from 1300 mg up to 1650mg/m2 per day according to modified Fibonacci design. The dose of Doc was fixed to 30mg/m2 in both Phase I-II. In Phase II 1650mg/m2 Cap was given. The primary objective in phase I was to define a dose of Cap recommended for the Phase II and to determine the feasibility and safety of this treatment. The primary objective in the phase II was to determine the response rate (RR), safety profile, quality of life and survival.The median age was 64.8 years, PS was 0 in 23 pts, I in 57 and II in 13 pts. The histology was as follows: 58 adenoca, 33 squamous cell ca and 2 poorly diff ca. Forty-three pts had previously been treated with chemotherapy, 41 with radiotherapy, 50 were chemotherapy-naive and 31 had underwent surgery. Results: From March 2006 to Oct 2010, 93 eligible pts with measurable disease were enrolled in the study. Fourteen were treated in phase I and 79 in phase II. Four pts (1 in ph I and 3 in ph II) did not receive any study treatment. Twenty-seven pts of 93 (29%) were not evaluable according to study protocol which included CT after 6 w of treatment due to rapid tumour progression and deterioration of general condition. RR was 29%, 2 CR and 25 PR, 15 pts (16%) had SD and 24 pts (26%) had PD. Median OS was 7.3 months (5.76-8.9) and median PFS was 4.2 months (2.3-4.7 months).Treatment related grad 3 or 4 toxicity was as follows: 60% of pts experienced any grade 3 or 4 toxicity, 30% related to infections, 24% had nausea, diarrhea, vomiting, mucositis, <10% had cardiac related symptoms, <1% had an allergic reaction to Doc. Conclusions: Cap together with Doc appears tolerable and has a RR of 29% in selected group of patients with mET and mCCR. Majority of treatment courses were given on out-patient bases. However, there is un urgent need to define an optimal therapy regime and further studies are warranted.
Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).
Authors: Gunturu Krishna Soujanya , Thumar Jaykumar Ranchodbhai , Hochster Howard S. , Stein Stacey , Yao Xiaopan , Cong Xiangyu , Lacy Jill 
Published: March 2020

e14534 Background: FOLFIRINOX significantly increases survival in metastatic PC compared to gemcitabine (Conroy. New Engl J Med 2011;364). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in advanced PC pts. Methods: We performed a retrospective review of dose, toxicity, and efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 07/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and RR were compared to Conroy’s data using one sample proportion test. Overall survival (OS) and progress free survival (PFS) were estimated by Kaplan-Meier method. Results: 35 pts with ECOG PS 0/1 were treated. Pt characteristics: LAPC 16; MPC 19; median age 61 yrs (range 48-77); male 13; prior chemotherapy 5. Median (med) number of cycles was 10 (range 1-26). FOLFIRINOX was dose attenuated with the first cycle in 29 pts: IRI reduced in 27 and omitted in 1, OX reduced in 10, bFU reduced in 9 and omitted in 7, LV decreased in 11, FU infusion reduced in 3. Med doses of OX, IRI, bFU, and infusion FU were 90%, 68%, 68%, and 100%, respectively, compared to 78%, 81%, 82%, and 82%, respectively, in Conroy’s FOFIRINOX arm (control). We are following pts for PFS and OS. RRs were 50% and 47% in pts with LAPC and MPC. RR in MPC didnot differ significantly from the control (p=0.19). We observed significantly less grade 3/4 fatigue (p=0.008) and neutropenia (p<0.0001) compared to the control group. Conclusions: Our findings suggest that dose attenuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent RR compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.
BDNF expression and systemic dissemination via anoikis resistance in gastric cancer.
Authors: Okugawa Yoshinaga , Inoue Yasuhiro , Tanaka Koji , Kawamura Mikio , Saigusa Susumu , Hiro Junichiro , Toiyama Yuji , Ohi Masaki , Mohri Yasuhiko , Uchida Keiichi , Yanagi Hidenori , Kusunoki Masato 
Published: March 2020

e14541 Background: Anoikis (apoptosis resulting from loss of cell-matrix interaction) has been suggested to act as a physiological barrier to metastasis, and resistance to anoikis is necessary for cancer cell survival during systemic dissemination and metastasis. Brain-derived neurotrophic factor (BDNF) is one of the member of neurotropin family known to activate the high affinity tyrosine kinase (Trk)B receptor as a specific suppressor of anoikis. TrkB activation by BDNF has been shown to facilitate the progression of several cancers, however no reports have shown the clinical and biological effects of BDNF/TrkB axis in gastric cancer. Methods: BDNF expression in gastric cancer tissue and clinicopathological data from 153 consective patients were analyzed by real-time PCR and immunohistochemistry. The extent of target gene expression was calculated from the standard curve, with quantitative normalization of the cDNA in each sample performed using GAPDH gene as an internal control. Recombinant human BDNF and Trk antagonist K252a were used for in vitro assays to evaluate the biological role of the BDNF/TrkB axis in gastric cancer cell lines. Results: The mean BDNF level in gastric cancer tissue was 284.5 (0-2834). One hundred eighteen (77.1%) of 153 patients showed detectable BDNF levels, whereas the remainder had no detectable. BDNF positive expression was significantly associated with histological diffuse type (p=0.019), lymph node metastasis (p<0.001), peritoneal dissemination (p=0.028) and poor prognosis (p=0.022). In addition, BDNF expression is an independent risk factor for lymph node metastasis and peritoneal dissemination. Immunohistochemical analysis indicated intense BDNF expression in the cytoplasm of cancer cells, and intense TrkB expression in the nuclei of cancer cells, respectively. In vitro, administration of recombinant human BDNF promoted proliferation, anoikis resistance, and partial migration. In addition, these effects were generally inhibited by Trk antagonist K252a. Conclusions: BDNF appears to play an important role in gastric cancer progression, and blocking BDNF/TrkB axis might be clinically useful in developing therapies for patients with gastric cancer.
Outcomes after treatment of resectable, node-negative esophageal cancer: A risk-adjusted analysis of the Surveillance, Epidemiology, and End Results registry.
Authors: Martin Jeremiah Thomas , Worni Mathias , Zwischenberger Joseph Bertram , Pietrobon Ricardo , D'Amico Thomas A. , Berry Mark Francis 
Published: March 2020

e14562 Background: Esophageal cancer has poor prognosis even in early stages. We examined survival for patients with resectable tumors in the absence of nodal disease in order to assess the benefits of surgery and radiation. Methods: Patients with T1-T3N0M0 squamous cell or adenocarcinoma of the mid or distal esophagus were identified using the SEER database from 1998-2008. The Kaplan-Meier approach and risk-adjusted Cox proportional-hazard models were used to assess 5-year overall survival. Survival risk among treatment modality subgroups (surgery only (SO), radiotherapy only (RO), combined surgery and radiotherapy (CT), and local tumor resection (LR)) was evaluated for the overall patient cohort and stratified among T-stage. SEER does not record chemotherapy use, which therefore wasn’t analyzed. Results: Overall 5-year survival for 4,251 patients identified (mean age 67.7±11.4 years, 966 (22.7%) female) was 37.6% (95% CI: 35.8-39.4). Survival correlated with T-stage: T1N0 48.0% (45.4-50.6); T2N0 29.8% (26.1-33.5); and T3N0 25.8% (22.9-28.7), p<0.001. For T1N0 patients, risk-adjusted survival was better with SO compared to CT (HR: 0.84, CI: 0.74-0.96, p=0.01) while LR and SO were not significantly different (p=0.24) (Table). Treatment with SO or CT had better survival compared to RO for T2N0 and T3N0 patients. The addition of radiation to surgery (CT vs. SO) improved survival for T3N0 patients (HR 0.79, CI 0.65-0.97, p=0.03) but not T2N0 patients (HR: 1.05, CI: 0.81-1.37, p=0.71). Conclusions: Surgical resection without radiation therapy is adequate for T1N0 esophageal cancer, but combined radiation and surgery has the best outcomes for T3N0 patients. Prognoses of T2N0 cancers are more similar to T3N0 cancers than T1N0 cancers, but no survival benefit to adding radiation to surgery for T2N0 patients was seen in this study. [Table: see text]
Sorafenib as bridging therapy in patients with intermediate hepatocellular carcinoma.
Authors: Vitale Alessandro , Lombardi Giuseppe , Ramirez Morales Rafael , Lonardi Sara , Zanus Giacomo , Zagonel Vittorina , Cillo Umberto 
Published: March 2020

e14563 Background: Patients with intermediate stage hepatocellular carcinoma (HCC) obtaining an unsatisfactory response after loco regional (LR) therapies are at high risk of drop-out from a new chance of LR treatment or progression to advanced-terminal stages of disease. We prospectively used Sorafenib in this particular category of patients as a bridge therapy. The aim was to decrease the risk of tumour progression and to make them again eligible for loco regional therapies. Methods: Primary endpoint: disease control (DC) with Sorafenib, defined as complete/partial response or stable disease as by the modified RECIST criteria, maintained for ≥ 28 days from the first indications of response. Secondary endpoints: proportion of patients progression free at 2 months; median overall and progression free survivals. Patients obtaining DC with Sorafenib were again considered eligible for LR therapy. Inclusion criteria: a) intermediate stage; b) Child Pugh class A; c) performance status 0; d) unsatisfactory response to LR therapies (resection, ablation, chemoembolization), defined as incomplete response after at least 2 LR therapies. Study period: 01/04/2008–31/10/2011. End of follow-up: 31/01/2012. Results: Forty one patients were enrolled according to the study design. Thirty seven patients (90%) were progression free at the 2 months evaluation. A persistent DC was obtained in 29 patients (71%). According to the study hypothesis these patients were considered again eligible for loco regional therapies: 19 patients (65%) had ablation ± chemoembolization; 6 had liver transplantation (22%); 3 had liver resection (13%); 1 had radioembolization. Median duration of therapy with Sorafenib was 5 months (1–22). Sixteen patients (55%) had Sorafenib therapy both before and after LR therapy. Fourteen patients (48%) had more than one LR procedure. Median survival was 21 months (range, 1–39) in the whole group, while it was 25 months (range, 2–39) in the DC subgroup (median time to progression = 21 months, range 2–39). Conclusions: Sorafenib achieves high DC rates in BCLC B HCC patients with unsatisfactory response to LR therapies making them again eligible for LR therapies.
Multicenter randomized phase II study of weekly docetaxel alone versus weekly docetaxel plus oxaliplatin as a second-line chemotherapy in patients with advanced gastric cancer: Preliminary response and safety results.
Authors: Kim Jin Young , Do Young Rok , Park Keon Uk , Ryoo Hun-Mo , Bae Sung Hwa , Chae Yee Soo , Kim Min Kyoung , Lee Kyung Hee , Lee Sun Ah , Kim Jong Gwang , Song Hong-Suk ,   Daegu-Gyeongbuk Oncology Group
Published: March 2020

e14570 Background: Gastric cancer is a frequent malignancy with worldwide estimated incidence of 990,000 cases, representing 7.8% of all cancers in 2008. There are limited data suggesting a benefit for doublet second-line chemotherapy in advanced gastric cancer. Methods: The eligibility criteria were patients 1) with prior exposure to cisplatin based chemotherapy and advanced or recurrent stomach cancer 2) with pathologically proven gastric adenocarcinoma, 3) with an ECOG performance status 0 to 2, 4) with measurable lesions. Each treatment cycle was consisted of docetaxel 36 mg/m2 in docetaxel mono therapy group and docetaxel 36 mg/m2, oxaliplatin 80 mg/m2 in docetaxel/oxaliplatin doublet therapy group on days 1, 8. The primary end point of this study was response rate, and secondary end points included toxicity, progression free and overall survival. Results: Fifty two patients were enrolled; median age was 63 years; male (n=42) and female (n=10); docetaxel mono therapy (n=27) and docetaxel/oxalliplatin doublet therapy (n=25). The median number of cycles administered was 2.5 (range,1-9). Fourty eight patients were assessable for efficacy. Four partial responses, 7 stable diseases in mono therapy group (RR; 4/27, 14.8%) and 1 complete remission, 4 partial responses, 13 stable diseases in double therapy group (RR; 5/25, 20.0%) were confirmed (p=0.198). Median progression free survival was 1.97 months in the mono therapy group and 4.93 months in doublet therapy group (p=0.007). Median overall survival was 11.57 months in the mono therapy group and 8.13 months in doublet therapy group (p=0.650). Grade 3 or 4 adverse events were reported in 11 of 52 patients; G3 pain were in 2 patients and G3 pneumonia was in 1 patient in mono group, G3/4 neutropenia were 5 patients in the combination group, G3 nausea, vomiting, general weakness was 1 patient each group in combination group. Conclusions: Weekly docetaxel/oxaliplatin doublet therapy showed superior progression free survival to monotherapy group as second line therapy in cisplatin pretreated advanced gastric cancer patients.
Gastric tube cancer after esophagectomy for esophageal cancer: A single-center experience with meta-analysis of 145 cases.
Authors: Lee Geun Dong , Kim Yong-Hee , Park Seung-Il , Kim Dong Kwan , Kim Hyeong Ryul 
Published: March 2020

e14573 Background: Gastric tube cancer (GTC) defined as carcinoma arising in the gastric conduit after esophagectomy, is often crucial in long-term survivors of esophageal cancer. The aim of this study was to determine the optimal approach to manage GTC. Methods: We reviewed data of 863 patients who underwent esophagectomy and reconstruction with the gastric conduit for esophageal cancer at Asan Medical Center from 1993 to 2011 and identified 28 cases of GTC. We also searched through the PubMed database and included additional 117 cases of GTC from 13 studies to conduct meta-analysis. Results: In our cases, the incidence rate of GTC was 3.2%. The median interval between esophagectomy and GTC detection was 3.1 (0.6-15.2) years. Twelve (42.9%) patients were asymptomatic and diagnosed by periodic endoscopy. The Most common histologic type of GTC was adenocarcinoma (57.1%) and fifteen (53.6%) were located on the lower third of gastric tube. Chemotherapy, total gastrectomy or palliative treatment was performed in 10, 5, 2 patients, respectively. Eleven (39.3%) patients refused the further treatment for GTC. Mean survival duration of 28 patients after the diagnosis of GTC was 29.1 months. In meta-analysis, The cumulative occurrence of 5, 8 years was 59.5%, 87.8%, respectively. Two-year survival rate of the patients who underwent endoscopic resection, surgical resection or palliative treatment was 100%, 61.6%, 5.2%, respectively. The patients who underwent endoscopic resection had a better prognosis than those who underwent surgical resection or those who received palliative treatment (p=0.047, p=0.000, respectively). Conclusions: After esophagectomy for esophageal cancer, patients had a constant risk of GTC occurrence up to 8 years approximately. The patients who diagnosed as advanced-state GTC had a poor prognosis. However, endoscopic resection as a minimally invasive treatment for early-GTC represented a feasible prognosis compared with those of operative resection or palliative treatment. Therefore, a long-term follow-up including detailed endoscopy is essential for the better outcomes in patients who underwent esophagectomy for esophageal cancer.