bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of EGFR, VEGF, and K-ras mutation as predictors for response of cetuximab in colorectal cancer patients
Authors: Hwang D. , Jung E. , Cho S. 
Published: August 2020

e15147 Background: Cetuximab has been effective in metastatic colorectal cancer (CRC) patients. EGFR is involved in CRC through its downstream signaling pathways, including RAS and MAKP pathway and angiogenesis. We evaluated the predictive value of EGFR and VEGF expressions and K-ras mutation status in colorectal cancer patients treated with cetuximab in combination with chemotherapy Methods: Our study included 29 CRC patients treated with cetuximab in combination with chemotherapy (20 patients with FOLFIRI and 5 patients with FOLFOX, and 4 patients with monotherapy). Paraffin blocked tumor tissues were analyzed for EGFR and VEGF expression using quantitative real time PCR and K-ras mutation status (codons 12 and 13) using direct sequencing. Results: 12 patients (43%) had a partial response (PR) and 6 patients (21%) with stable disease (SD) and 11 patients (38%) with progressive disease (PD). EGFR expression was not correlated with the response of cetuximab (p=0.60) The median EGFR expression level was 0.30 x 10-3 in PR and 0.25 x 10-3 in SD and 0.26 x 10-3 in PD. High VEGF expression was associated with the response of cetuximab (p=0.03). The mean VEGF expression level was 4.3 x 10-3 in PR and 1.64 x 10-3 in SD and 1.72 x 10-3 in PD. A K-ras mutation was present in 45 % (13/29) and did not significantly correlated with non-response of cetuximab (p=0.05). A K-ras mutation was detected 33% (4/12) in PR and 33% (2/6) in SD and 70 % (7/10) in PD. Conclusions: VEGF expression in tumor may be a potential predictor for the response of cetuximab. But EGFR expression and K-ras mutation status is not significantly correlated with clinical outcome of cetuximab. And a K-ras mutation is found in the response group. [Table: see text]
Preliminary results of a multicenter phase II study of imatinib and fluorourcail/leucovorin (FU/LV) in patients with unresectable or metastatic gallbladder or biliary tract cancer
Authors: Sprenger K. , Moehler M. , Kettner E. , El-Batran S. , Hegewisch-Becker S. , Steffens C. , Pustowka A. , Goekkurt E. , Ehninger G. , Stoehlmacher J. 
Published: August 2020

e15502 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Monotherapies with gemcitabine or FU/LV achieve occasional responses and a median overall survival of about 6 months. By blocking PDGFR a decreased intrastromal pressure may increase therapy effects of chemotherapy. The combination of imatinib and FU/LV has been shown to be safe and feasible in a previous Phase I trial. This multicenter phase II trial was designed to investigate the disease control rate (DCR) of FU/LV and imatinib. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), performance status < 2, adequate organ function and no clinically significant cardiovascular disease. Enrolment of 44 chemonaive patients (pts.) was planned. Pts. received LV 200 mg/m2 followed by FU 2000 mg/m2 as a 24-hour infusion on days 1 and 2 combined with 600mg imatinib on days -4 to 4 (8 days). Cycles were repeated every 2 weeks up to 12 cycles. Radiological assessments were performed every 4 cycles. Results: 41 pts (19 GBC; 22 BTC) were enrolled in this phase II study since May 2007. Median age was 62 years (range 33–77), male/female=24/17, ECOG 0/1/2=13/23/5. 35 pts. showed metastatic disease at baseline. Treatment was well tolerated. Treatment related grade 3/4 toxicities included (number of pts): diarrhea (2), edema (1), neutropenia (2), nausea (2), transient SGPT elevation (4). The DCR of 26 pts. available for response assessment at time of analysis 1 was 58% (15 pts) (1 CR, 1 PR,13 SD of at least 4 cycles). 11 pts. showed progressive disease (PD) per RECIST criteria. 3 pts. had disease stabilization after 12 cycles and continue on treatment. We present these preliminary data as they represent a large patient number in this entity and response data are promising. Conclusions: This preliminary analysis suggests that the combination of FU/LV and imatinib can be safely administrated in pts. with GBC/BTC. Early evidence of antitumor activity was seen with some pts. achieving long term stabilization of the disease. [Table: see text]
Weekly cetuximab (CET) plus oxaliplatin (OX), infusional 5-fluorouracil (5-FU) and radiation therapy (RT) as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC): A phase I study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: Lordick F. , Meyer zum Büschenfelde C. , Thuss-Patience P. , Röthling N. , Geinitz H. , Budach V. , Schumacher G. , Friess H. , Siewert J. R. , Peschel C. 
Published: August 2020

e15507 Background: CET, a chimeric monoclonal IgG1 antibody that targets the epidermal growth factor receptor (EGFR), has proven activity in a variety of SCC models in vitro and in vivo and has also been shown to enhance the activity of both chemo- and radiotherapy. Methods: Patients (pts) with locally advanced ESCC received CET for 2 weeks at an initial dose of 400mg/m2 (d - 15) i.v. followed by 250mg/m2(d -8) before they started a neoadjuvant dose escalation regimen. Pts received weekly CET 250mg/m2 plus RT 25 x 1.8 Gy (cumulative dose 45 Gy) d1–33. Cohort 1–3 received escalating doses of OX 45–50 mg/m2 d1,8,22,29 plus 5-FU 180–200–225 mg/m2/d; d1–5,8–12,15–19,22–26,29–33). Surgery was scheduled 4–6 weeks after RT. Toxicity was assessed according to NCI-CTC. Response was categorized according to the histopathologic score. Results: 15 pts were enrolled (2 female, 13 male; mean age 62 years, ECOG-PS 0 or 1). All pts had locally advanced SCC (uT2–4, cNx, cM0–1a) of the cervical (n=1), the upper (n=5) or the distal (n=7) esophagus. 6 pts were treated in cohort 1 and 3 pts in cohort 2 without any dose limiting toxicity (DLT). Of 6 pts treated in cohort 3, 1 pt developed grade 3 diarrhea and mucositis. All other observed toxicities were mild or moderate: anemia n=12, neutropenia n=2, thrombocytopenia n=3, nausea/vomiting n=8, mucositis n=6, diarrhea n=4, neuropathy n=4, hand-foot-syndrome n=8, skin rash n=14, no infection and no infusion-related reactions were observed. 12 pts underwent abdomino-thoracic esophagectomy with no postop. mortality; 3 pts were not resected. 8/12 resected pts had an R0 resection (67%) and 4 pts (33%) achieved a histopathological complete response (score 1a). Conclusions: 2 weeks of CET (400mg/m2 and 250mg/m2) followed by weekly CET (250mg/m2) plus OX 50mg/m2 d1,8,22,29, 5-FU 225 mg/m2/d d1–5,8–12,15–19,22–26,29–33 and RT 45 Gy (1.8Gy/f) was shown to be safe as neoadjuvant treatment for locally advanced ESCC. The anti-tumor activity of this regimen is promising and is being further investigated in an ongoing phase II study. [Table: see text]
Multicenter phase II study of gemcitabine (GEM) plus S-1 in patients (pts) with advanced biliary tract cancer (BTC)
Authors: Sasaki T. , Isayama H. , Nakai Y. , Ito Y. , Togawa O. , Yagioka H. , Kogure H. , Yasuda I. , Hasebe O. , Maetani I. 
Published: August 2020

e15516 Background: Pts with advanced BTC have a poor prognosis and no standard palliative chemotherapy has been defined. The purpose of this prospective multicenter phase II study was to evaluate the efficacy and safety of GEM plus S-1 combination therapy in pts with advanced BTC. Methods: Pts with advanced BTC, with at least one measurable lesion were eligible for this study. Other eligibility criteria included: no previous palliative chemotherapy, ECOG performance status ≤ 2, and adequate organ function. S-1 was given orally at a dose of 80mg/m2 daily from day 1 to day 14. GEM was given intravenously at a dose of 1,000mg/m2 over 30 min on day 1 and day 15, repeated every 4 weeks. Tumor response was the primary endpoint and was assessed according to RECIST every 8 weeks. Planned sample size was 35 according to Simon's two stage method. Results: 35pts were enrolled: median age 67; M/F (22/13); ECOG performance status 0/1/2 (16/18/1). The primary tumor site was; 14 pts in gallbladders, 14 pts in intrahepatic bile ducts, 6 pts in extrahepatic bile ducts, and 1 pt in Vater of papilla. Seven pts had previous surgical resection. Complete and partial responses were achieved in 2 and 9 pts, respectively. Eighteen pts had stable disease. Overall response rate was 31.4% and overall disease control rate was 82.9%. The median TTP was 6.1 months (95%CI, 4.0–8.1 months) and the overall survival was 11.7 months (95%CI, 7.3- months). The grade 3/4 toxicities were: neutropenia (31.4%), anemia (17.1%), thrombocytopenia (2.9%), anorexia (2.9%). No treatment-related deaths occurred during the study. Conclusions: GEM plus S- 1 combination therapy showed promising efficacy and good tolerability in pts with advanced BTC. No significant financial relationships to disclose.
Evaluation of response in the multimodality treatment of esophageal cancer by [18F]-fluorodeoxyglucose-positron emission tomography: A systematic review and meta-analysis
Authors: Vallbohmer D. , Holscher A. H. , Brabender J. , Metzger R. , Mönig S. , Schmidt M. , Dietlein M. , Bollschweiler E. 
Published: August 2020

e15520 Background: Neoadjuvant therapy followed by surgery is frequently applied to improve the prognosis of patients with esophageal cancer. However, only a major histopathological response will provide a survival benefit. On the other hand, evidence suggests that patients with response to chemoradiation have no additional benefit from surgery compared with definitive chemoradiation. Consequently, effective methods for early and late response assessment are required in order to perform these different individualised, response-guided treatment concepts. The value of [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) for this diagnostic purpose is still under debate. This systematic review and meta-analysis aims to evaluate the potential of FDG-PETfor the assessment of response in the multimodality treatment of patients with esophageal cancer. Methods: A systematic literature search of studies published between 1990 and September 2008 was performed. The meta-analysis estimated the pooled sensitivity and specificity of histopathological response assessment by FDG-PET using a random effect model. Results: Thirty relevant studies with 1151 patients (865 adenocarcinoma, 493 squamous cell cancer) were identified and included in the systematic review. Mainly neoadjuvant chemoradiation (22 studies) was performed. FDG-PET was conducted mostly before and after neoadjuvant therapy (21 studies) and second most (6 studies) the subsequent FDG-PET was scheduled 7–14 days after the initiation of preoperative therapy. Sixteen studies were included in the meta-analysis. For metabolic response assessment 7–14 days after the initiation of therapy, including 254 patients (with 5 studies from one center), the pooled sensitivity was 85.5% (95% CI: 75.5%-92.8%) and specificity 76.1% (95% CI: 69.3%-82.0%). For late response assessment, including 446 patients, the pooled sensitivity was 77.1% (95% CI: 72.8%- 81.0%) and specificity 59.0% (95% CI: 55.3%-62.7%). Conclusions: For early response assessment FDP-PET seems to be useful in the multimodality treatment of esophageal cancer. In contrast, this study suggests FDG-PET invaluable for late response assessment. No significant financial relationships to disclose.
Standardized treatment and follow-up protocol of hepatocellular carcinoma with transcatheter arterial chemoembolization: Survival, clinical, and tumor control outcome over 12 years at a U.S. center
Authors: Liapi E. , Hong K. , Georgiades C. S. , Wahlin T. , Reyes D. , Kamel I. R. , Geschwind J. H. 
Published: August 2020

e15522 Background: To report the outcome of the care of patients with hepatocellular carcinoma (HCC) treated with standardized transcatheter arterial chemomembolization (TACE), with a focus on tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST), progression of underlying cirrhosis [Child-Pugh (CP) score], time to progression (TTP) and survival from 1996 to 2008. Methods: TACE was performed on 365 patients in 1,035 sessions. According to a standardized protocol, all patients received imaging (MRI and/or CT) at baseline and at 4–6 weeks after each session and were clinically, biochemically and radiologically evaluated before each session. Liver disease status was evaluated before and at the end of the treatment period with the CP class system and tumor size measurements according to the RECIST. The Barcelona Clinic Liver Cancer (BCLC) classification was employed to stage patients. Three chemotherapeutic agents and lipiodol, followed by non-occlusive embolization were utilized during TACE. Complete vessel occlusion was avoided at all times. Overall survival and TTP were calculated according to the Kaplan-Meier method. The log-rank test was used to calculate differences between groups in the subgroup analysis. Results: All patients (78% male, mean age: 63.5 years) received an average of 3 TACE sessions (range: 1–10 and average interval between sessions: 75 days). Sixty six percent of patients had 3 or more tumors, with a mean tumor size at presentation of 6.9 cm. Partial response was achieved in 32 % of patients, while 65% remained stable over the course of 3 TACEs. CP class remained unchanged for 75% of patients over the above course of treatment. Median survival for the entire cohort was 20 months and TTP was 14 months. Interestingly, advanced BCLC patients achieved similar tumor response (PR:33%), TTP of 13.4 months and median survival of 13.7 months. Conclusions: Patients with HCC treated with the aforementioned standardized TACE and follow-up protocol showed durable survival, stable liver disease and effective tumor control. [Table: see text]
Macrophage migration inhibitory factor and long-term survival in gastric cancer
Authors: Mohri Y. , Kageyama S. , Mohri T. , Tanaka K. , Ohi M. , Yokoe T. , Kusunoki M. 
Published: August 2020

e15525 Background: Our study aimed to evaluate whether pretherapeutic serum macrophage migration inhibitory factor (MIF) is an independent factor predicting long-term survival in gastric cancer. Gastric cancer is the second leading cause of cancer-related deaths worldwide, but no satisfactory tumor marker exists. We recently found serum MIF expression was progressively increased in gastric cancer. Methods: One hundred five patients, 73 men and 32 women, mean (±SD) age 63±14 years, with histologically proven gastric adenocarcinoma were included in the study. Pretherapeutic serum was collected and MIF assayed using a commercially available enzyme-linked immunosorbent assay kit. Results: Ninety-three percent of patients received curative surgery. Mean follow up was 53.5±28.3 months, and five-year survival was 65.3 percent. The mean pretherapeutic level of MIF was 72.9ng/ml (range, 2.6 to 852.1). There were no significant correlations between serum MIF level and histopathological findings (Wilcoxon test). Mean pretherapeutic levels of carcinoembryonic antigen, C-reactive protein, and albumin were 27.5ng/ml (range, 0.1 to 778 ng/ml), 0.67mg/dl (range, 0.2 to 7.82mg/dl), and 3.6g/dl (range, 2.4 to 4.4g/dl), respectively. By multivariate analysis, serum MIF was found to be an independent factor predicting long-term survival (Odds ratio, 2.84; 95% C.I. 1.27–6.68). The five-year survival rate for patients with an MIF serum level greater than 23ng/ml was 55 percent, and that for patients with an MIF serum level less than 23ng/ml was 75 percent (p=0.03; log rank test). Conclusions: The serum level of MIF is a potentially valuable pretherapeutic prognostic factor in patients with gastric cancer. No significant financial relationships to disclose.
Induction chemotherapy followed by concurrent chemoradiotherapy with/without esophagectomy for locally advanced esophageal squamous cell carcinoma
Authors: Lin C. , Hsu C. , Cheng J. C. , Lee J. , Tsai Y. , Luo J. , Hsu F. , Wang H. , Lee Y. , Cheng A. 
Published: August 2020

e15526 Background: To assess the feasibility of preoperative induction chemotherapy in addition to concurrent chemoradiotherapy (CCRT) followed by esophagectomy if possible for locally advanced esophageal squamous cell carcinoma (ESCC) with a special emphasis on M1a or nodal M1b disease. Methods: Patients who had histologic proof of T3N1M0, M1a, or nodal M1b ESCC first received up to 3 courses of induction chemotherapy (paclitaxel 70 mg/m2 or docetaxel 40 mg/m2 IV 1-hr D 1, 8; cisplatin 35 mg/m2 IV 2-hr D 1, 8; 5-fluorouracil 2000 and leucovorin 300 mg/m2 IV 24-hr D 1, 8; repeated every 28 days). This was followed by CCRT (paclitaxel 35 mg/m2 1-hr D 1, 4 /wk, cisplatin 15 mg/m2 1-hr D 2, 5/wk, and radiotherapy 2 Gy D 1–5 /wk) (Lin CC et al. Ann Oncol 18:93–8,2007). When the accumulated radiation dose reached 40 Gy, the feasibility of esophagectomy was evaluated in all patients. In patients for whom esophagectomy was not feasible, CCRT was continued to a dose of 60 Gy. Results: Fifty-six patients (M:F = 51:5, median age 58, range 41–78) with locally advanced (T3N1M0:M1a:M1b[nodal] = 30:7:19) ESCC (upper:mid:lower = 15:25:16) were enrolled from June 22, 2006 to December 17, 2008. By December 31, 2008, 10 patients are still under protocol treatment. Eighteen (T3N1:M1a:M1b[nodal] = 14:3:1) (40%) and 20 of 46 patients underwent surgery and continued CCRT up to 60 Gy, respectively. Nine (T3N1:M1a:M1b[nodal] = 7:2:0) (20%) and 5 patients had pathologic complete response and microscopic residual disease, respectively. With a median follow-up of 8.4 months (range 0.5–30.8), 17 (T3N1:M1a:M1b[nodal] = 9:2:6) patients had relapse. Four and 13 patients had local recurrence and distant metastasis, respectively. The median progression-free survival was 20.3 months. The median overall survival had not reached yet with 1- and 2-year overall survival being 76 and 57%, respectively. There was no difference in progression- free or overall survival among patients with T3N1M0, M1a, or nodal M1b disease. Conclusions: Three-step strategy of preoperative taxane-based induction chemotherapy then CCRT followed by esosphagectomy if possible appears quite active in locally advanced ESCC patients with 46% having M1a or nodal M1b disease. No significant financial relationships to disclose.
HOGG1 polymorphism and gastric cancer/atrophic gastritis
Authors: Cheng J. , Sun L. 
Published: August 2020

e15535 Objective: 8-Hydroxydeoxyguanine (8-OHdG) formation is one of the most common types of oxidative DNA damage leading to gastric cancer development and human oxoguanine glycosylase 1(hOGG1) is responsible for repairing 8-OHdG lesions. Among several hOGG1 gene polymorphisms, the Ser→Cys polymorphism at position 326 is related to decreased repair function. We aimed to investigate the association between Ser326Cys hOGG1 polymorphism and gastric cancer/atrophic gastritis. Methods: 488 subjects (73 with gastric cancer, 160 with atrophic gastritis and 255 controls) were prospectively enrolled from 2005 to 2008 in Sir Run Run Shaw Hospital. Genomic DNA was obtained from peripheral blood and PCR-RFLP analysis was performed to distinguish the genotyping of hOGG1 Ser326Cys polymorphism. Statistical analysis was conducted by two-sample t-test or generalized regression models for continuous variables and the Pearson χ2 test for categorical variables. Logistic regression models were fitted to find the risk factors for gastric cancer and atrophic gastritis. For all analyses, significance was determined at the P < 0.05 level (two-tailed). Results: Patients with gastric cancer were significantly older than the control group (59.6±11.2yrs vs 43.6±10.3 yrs, P<0.0001) and atrophic gastritis group (59.6±11.2yrs vs 51.4±10.6 yrs, P<0.0001). Gastric cancer group had significantly higher rate of male than atrophic gastritis group (65.8% vs 48.7% in atrophic gastritis, p=0.02). Neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with gastric cancer, compared with the Ser/Ser genotype (OR: 0.96, 95% CI (0.51–1.84) and OR: 1.1, 95% CI: (0.48–2.1)). Ser/Cys and Cys/Cys were significantly associated with atrophic gastritis (OR: 1.76, 95% CI: 1.03–3.0) and OR: 2.38, 95%CI: 1.34–4.23)). After controlling for age, gender, smoking and alcohol, these significant associations still held with OR: 2.05, 95% CI: (1.14–3.68) for Ser/Cys and OR: 2.76, 95% CI: (1.47–5.18) for Cys/Cys. Conclusions: Our study supported that hOGG1 polymorphisms (genotype Ser/Cys and Cys/Cys) are associated with atrophic gastritis. These associations still exist after controlling for age, gender, smoking and alcohol. No significant association was detected between hOGG1 polymorphisms (genotype Cys/Cys or Ser/Cys) and gastric cancer. No significant financial relationships to disclose.
Correlation of Cks1 and p27kip1 with tumor biologic aggressiveness and survival in gastrointestinal stromal tumor
Authors: Horvath J. W. , Frankel W. , Bellizzi A. , Guenterberg K. , Iwenofu O. H. 
Published: August 2020

e15549 Background: The biologic behavior of gastrointestinal stromal tumors (GIST) based upon morphologic parameters is unpredictable. Cyclin dependent kinase-1 (Cks1) plays an important role in the ubiquitination and proteolysis of p27kip1, a negative regulator of protein kinase Cdk2/cyclin E and Cdk2/cyclin A. This study was to ascertain whether Cks1 overexpression and p27kip1 downregulation were predictive of biologic aggressiveness and overall survival in GIST. Methods: Tissue microarray was built from 61 patients with GIST. Pathology reports as well as clinical follow-up were retrieved. Sections were stained with antibodies to p27kip1 and Cks1. Staining was scored for quantity of tumor cells (%) and intensity (0, 1+ weak staining, 2+ strong staining), and a score was calculated from the product of intensity and %. Tumors were evaluated for correlation of p27kip1 and Cks1 expression level with overall survival time and tumor risk stratification. Tumor risk stratification was classified into very low risk, low risk, intermediate risk, and high risk, and is reflective of intrinsic biologic aggressiveness. Actuarial survival curves were estimated using Kaplan Meier method. Results: The tumors show a high frequency of Cks1 expression (92%; 1+, n=39; 2+, n=17). The % expression ranged from 0–90% (mean 37%). The p27kip1 positive rate is 85% (1+, n=20; 2+, n=32). The % expression ranged from 0–90% (mean 48%). Overall survival ranged from 0.1–10.7 years. By univariate analysis of overall survival using Cox regression model, increased p27kip1 expression (continuous variable) is significantly correlated with overall survival (p=0.04), but Cks1 expression does not (p=0.84). In a univariate analysis of p27kip1 and Cks1 (continuous variables) with risk stratification of the tumor using F-test, higher tumor grade has significantly higher Cks1 expression values (p=0.0045). Conclusions: Our study shows that with univariate analysis high expression of Cks1 expression is significantly associated with increased intrinsic biologic aggressiveness, while high expression of p27kip1 is associated with increased overall survival. The lack of correlation of Cks1 and p27kip1 suggests additional p27kip1 independent mechanisms might play a role in the oncogenesis of GIST. No significant financial relationships to disclose.