bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant sunitinib following chemoradiotherapy (CRT) and surgery for esophageal cancer: A phase II trial
Authors: Horgan A. M. , Darling G. , Wong R. , Visbal A. , Guindi M. , Jonker D. , Liu G. , Hornby J. , Xu W. , Knox J. J. 
Published: August 2020

e15550 Background: Locally advanced esophageal cancer (LAEC) has a 5-year survival of < 30 %. Most patients (pts) fail after curative intent tri-modality treatment with distant metastatic disease. This phase II trial aims to determine if adjuvant targeted therapy, after neoadjuvant CRT plus surgery for resectable LAEC, may impact on systemic disease without significant toxicity. Methods: Pts with LAEC of the thoracic esophagus or gastroesophageal junction, ECOG PS 0,1 and surgical candidates treated with: preoperative Irinotecan (65mg/m2 initially, ammended to 50mg/m2) + Cisplatin (30mg/m2) on weeks 1,2,4,5,7,8 + concurrent conformal radiotherapy (50Gy/25 fractions) on weeks 4–8. Esophagectomy during weeks 15–18. Sunitinib 37.5mg daily (escalating to 50mg daily if tolerated) commenced 4–12 weeks post surgery, for 1 year. Primary endpoint is feasibility and efficacy of adjuvant sunitinib. Planned sample size 36pts. Results: 30pts enrolled from 11/06 to 12/08. Median age 64 yr (43–71), male: 22, adenocarcinoma: squamous 22:6; 10 pts stage IIA, 5 IIB and 13 III. 2 pts excluded with positive PET scan. 28 pts completed CRT - 18 pts (64%) received ≥80% of planned chemotherapy dose, 23 pts (82%) received full radiation dose. Grade 3/4 toxicity included: neutropenia (17/28), diarrhea (7/28), dehydration (4/28), febrile neutropenia (FN) (3/28) and nausea (2/28). 2 deaths on chemotherapy (1 bacterial meningitis, 1 FN) leading to irinotecan dose- reduction. Dysphagia improved in 14/23 pts during CRT. 18 pts have undergone esophagectomy. Complete pathological response in 4 (22%), downstaging in 3 (17%), stable disease in 11 (61%). 2 pts unresectable (metastases at laparotomy). 1 post-operative death due to pulmonary embolus. 9 pts have commenced sunitinib, 6 maintained at starting dose of 37.5mg; 2 dose reductions; 1 discontinued with poor wound healing. Grade 3 toxicity included: leukopenia (2/9), hand-foot reaction (1/9) and depression (1/9). Conclusions: In LAEC, induction Irinotecan/Cisplatin and radiotherapy followed by esophagectomy is associated with a significant but manageable toxicity profile. Early initiation of sunitinib is feasible and well-tolerated. Updated results to be presented. No significant financial relationships to disclose.
Perioperative morbidity and mortality after radical lymphadenectomy for operable esophageal cancer
Authors: Pramesh C. S. , Mistry R. C. 
Published: August 2020

e15554 Background: The role of radical lymphadenectomy in localized resectable esophageal cancer is controversial. Radical lymphadenectomy confers more accurate staging, and improves locoregional control rates. However, there is no convincing evidence yet for a definite improvement in overall survival. Higher morbidity and mortality rates with radical lymphadenectomy are often quoted as reasons to avoid these procedures during esophageal resection. Methods: We retrieved data from October 2003 to December 2008 from a prospective surgical database maintained at a single tertiary cancer centre. Demographic data, operative details and postoperative morbidity and mortality were analysed. Postoperative complications analysed included need for prolonged ventilation, pulmonary complications, recurrent laryngeal nerve (RLN) paresis, cardiac ischemia and arrhythmias, and anastomotic leaks. Results: Six hundred and forty five patients (453 men, 192 women, mean age 53.6 years, range 19–76 years) were operated by transthoracic total esophagectomy for esophageal cancer between October 2003 and December 2007. Three hundred and ninety eight patients underwent two-field lymphadenectomy and 247 underwent three field radical lymphadenectomy. There was a higher incidence of prolonged ventilation (13.4% vs 6.6%, p=0.003), RLN paresis (61.4% vs 32.5%, p=0.000), and pulmonary complications (38.5% vs 24.4%, p=0.000) with radical three field lymphadenectomy compared to two field lymphadenectomy. The incidence of cardiac events (1.6% vs 2.6%, p=0.230), cardiac arrhythmias (5.8% vs 7.1%, p=0.640), anastomotic leaks (6.7% vs 8.2%, p=0.258) and postoperative mortality (5% vs 5.3%, p=0.80) were similar in the two groups. Conclusions: Radical three field lymphadenectomy increases pulmonary complication rates but has no impact on cardiac complications, anastomotic leaks, or operative mortality. No significant financial relationships to disclose.
Correlation between FDG PET/CT and the expression of Ki-67, MMP-2, micro-vessel density (MVD), and pathological grading in squamous cell carcinoma of the esophagus
Authors: Liu L. , Huang Y. , Guo J. , Wang Z. H. , Song D. G. 
Published: August 2020

e15556 Background: Variable uptake of 18FDG has been noticed in positron emission tomography (PET) studies of patients with esophageal squamous cell carcinoma (ESCC). The aim of the present study was to determine if 18F-FDG PET/CT standardized uptake value (SUV) could quantitatively reflect tumor proliferation, invasion and angiogenesis, and to reveal the relationship between SUV and pathological grading of ESCC. Methods: Preoperative PET scans were performed in 47 patients with histologically proven ESCC. 18FDG uptake was semiquantitatively measured by SUV.Tumour sections were HE stained to determine the pathological grading,and were stained by immunohistochemistry for proliferation marker (Ki67), invasion marker (MMP-2), and angiogenic marker (CD34). The correlations between FDG SUVmax and Ki67 expression, MMP-2 expression, corresponding MVD were statistically analysed respectively. Results: Among all the 47 cases,there were 13 well- differentiated squamous cell tumors, 16 moderately differentiated tumors and 18 poorly differentiated tumors,45 of 47 tumors revealed FDG. accumulation in primary tumor foci confirmed by subsequently histopathologically. The mean FDG SUVmax value was 12.504 ± 6.805. Average Ki-67 index was (7.837±29.798) %, average MMP-2 index was (71.551%±27.126) % and average MVD was (18.429±9.603) accordingly. The SUV and Ki-67 index, MMP-2 index were positively correlated (r=0.581,0.594), and it was not correlated with MVD(P>0.05). The mean SUV of well-differentiated, moderately differentiated and poorly differentiated tumors were 9.787±1.477, 12.313±0.479, 15.053±2.147 respectively, and a significant difference could be determined between them by statistical analysis(P=0.000). Conclusions: A significant positive correlation is demonstrated between FDG PET/CT SUV and Ki-67 index, MMP-2 index of the primary ESCC. SUV could reflect proliferation and invasion potential of tumor. However, there is no significant correlation between SUV and MVD, thus it could not reflect tumor angiogenesis in ESCC. To some extent, SUV could reflect pathologic grading of ESCC. No significant financial relationships to disclose.
Mortality rate with irinotecan/cisplatin plus concomitant radiation therapy in patients with locally advanced esophageal squamous cell carcinoma
Authors: Geib G. , Machado M. W. , Pozzi B. , Lazaretti N. S. , Dutra C. , Pereira Lima M. N. , Ferreira P. R. , Azevedo S. J. , Schwartsmann G. 
Published: August 2020

e15560 Background: The cisplatin/irinotecan doublet plus concomitant radiation therapy has been tested in phase II studies as a non-infusional alternative for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC), showing good antitumoral activity and acceptable safety profile. Here, we describe our institutional experience with this combination, specially regarding its toxicity profile. Methods: A series of 26 patients with locally advanced, unresectable ESCC patients treated at our institution between September/2006-January/2008 is reported. Treatment consisted of cisplatin 30 mg/m2 and irinotecan 65 mg/m2 on weeks 1, 2, 4, 5, 8, 9, 11 and 12, and radiation therapy (50,4 Gy, 1,8 Gy/day) on weeks 8–12. Study endpoints were tumor response rate (RECIST), safety profile (CTCAE v3), overall and one year survival. Results: The mean age of patients was 61 years, with stage III disease in 88% of cases and performance status (ECOG) 0–1 in 90% of them. Twenty patients (77%) were available for response, with complete response, partial response/stable disease and progressive disease seen in 40%, 45% in 15% of cases, respectively. With a median follow up of 20 months, the overall survival was 9,2 months and the one-year survival 34,6%. All patients were evaluable for toxicity, with severe (grade 3–4) nausea/vomiting, diarrhea, neutropenia and thrombocytopenia documented in 45%, 33%, 18% and 13% of cases, respectively. Notably, treatment related deaths were observed in 5 cases (19%), mainly due to infectious complications, which led to the closured of this protocol due to excessive toxicity. Conclusions: In spite of its promising antitumor activity, this treatment regimen cannot be recommended for routine use due to its unacceptable treatment-related mortality. No significant financial relationships to disclose.
Pretreatment serum TIMP-1 levels and survival in advanced pancreatic cancer
Authors: Vargas R. , Shrivastava V. , Leitzel K. , Ali S. M. , Carney W. , Hamer P. , Brown-Shimer S. , Linnartz R. , Mietlowski B. , Lipton A. 
Published: August 2020

e15568 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have diverse multifunctional roles in tumorigenesis such as inhibition of the catalytic activity of MMPs, growth promotion, inhibition of apoptosis and regulation of angiogenesis. Elevated TIMP-1 has been associated with an unfavorable prognosis in many cancers including breast, colorectal, gastric, head and neck, lung, and lymphoma. VEGF is also intimately associated with angiogenesis. Methods: This study determined serum TIMP-1 and VEGF levels in a phase III clinical trial of 157 patients with advanced pancreatic cancer. ELISAs for TIMP-1 and VEGF (Oncogene Science / Siemens HealthCare Diagnostics, Cambridge, MA) were employed to measure pretreatment serum TIMP-1 levels in 157 pancreatic cancer patients enrolled in a randomized, double-blind, placebo-controlled phase III trial. Statistical analysis was performed with TIMP-1 and VEGF on a continuous and cutpoint basis. Serum biomarker levels were then correlated with patient survival using Kaplan -Meier life table analysis. Results: Serum TIMP-1 levels in 157 pancreatic patients had a median of 409.9 ng/mL, and ranged from 144 to 1078 ng/mL. Patients with higher serum TIMP-1 had significantly shorter survival on a continuous basis (p = 0.001), on quartile analysis (p = 0.004), and on a dichotomous cutpoint analysis of upper 25 % vs lower 75 % (median survival 101 days vs. 197 days)(p< 0.001). Serum VEGF level was not associated with survival on a continuous (p = 0.57) or cutpoint analysis (p= 0.93). Conclusions: Pancreatic cancer patients with higher serum TIMP-1 levels had significantly shorter overall survival. Serum TIMP-1 level should be evaluated as a predictive factor for response to novel treatment regimens. [Table: see text]
Effect of N-cadherin knock-down on invasiveness of esophageal squamous cell carcinoma
Authors: Ke L. , Wei H. , Na L. , Na L. , Xin W. , Qing-Xia F. 
Published: August 2020

e15571 Background: Cell adhesion molecules are of crucial importance in cancer invasion and metastasis. Epithelial to mesenchymal transition, characterized by reduced E-cadherin and increased N-cadherin expression, has been recognized as a feature of aggressive tumors, but the importance of this phenotype has not been settled in esophageal squamous cell carcinoma. Aim: To examine the expressions of N-cadherin and E-cadherin in 62 normal esophageal epithelium specimens, 31 adjacent atypical hyperplasia epithelium specimens and 62 esophageal squamous cell carcinoma specimens, and to investigate the roles of N-cadherin in the invasiveness of esophageal squamous cell carcinoma cell line EC9706 transfected by N-cadherin shRNA.. Methods: PV immunohistochemistry was used to detect the expression pattern of N-cadherin and E-cadherin in 62 normal esophageal epithelium specimens, 31 adjacent atypical hyperplasia epithelium specimens and 62 esophageal squamous cell carcinoma specimens. The invasiveness of esophageal squamous cell carcinoma cell line EC9706 in vitro and in vivo was determined by transwell assay and nude mice experiments after EC9706 was transfected by N-cadherin shRNA. Results: The positive rates of N-cadherin decreased in the sequence of carcinoma, adjacent atypical hyperplasia and normal esophageal tissue, which were 75.8%, 61.3%, 29.0% (P < 0.05), respectively, while those of E-cadherin increased in sequence, which were 40.3%, 71.0% and 95.2% (P < 0.05). The increased expression of N-cadherin and decreased expression of E-cadherin were related to the invasion, differentiation, and lymph node metastasis (P < 0.05). The expression level of N-cadherin decreased in the N- cadherin knocked down cells, and the invasiveness of those cells decreased significantly as well in vitro and in vivo. Conclusions: These results suggest that N-cadherin is an important factor in the invasiveness of esophageal squamous cell carcinoma and N-cadherin may serves as a potential molecular target for biotherapy of esophageal squamous cell carcinoma. No significant financial relationships to disclose.
Survival predictors in second-line chemotherapy for metastatic gastric cancer
Authors: Bohanes P. O. , Courvoisier D. , Perneger T. , Morel P. , Huber O. , Roth A. D. 
Published: August 2020

e15575 Background: Many patients (pts) with metastatic gastric cancer (MGC) are in good condition after first line chemotherapy (chemo) and are offered further treatment. However there is no established predictor to select pts who will most likely benefit from second line chemotherapy (SLC). Methods: We conducted a retrospective review of all patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma who were treated until death at our institution and died between 01.1994 and 06.2008. Prognostic values of the tumour characteristics, pts characteristics at SLC, previous curative surgery (PCS) and sensitivity to previous chemo were analysed by Cox univariate and multivariate regression for overall survival (OS). Results: 65 pts with MGC were treated at our institution up to their death. Of these, 43 pts (65%) received SLC. 24 pts (55.8%) received CPT-11 based SLC. 4 pts (9.3%) docetaxel-platin, anthracyclines and fluoropyrimidine based SLC. 3 pts (7%) oxaliplatin and 3 pts (9.3 %) other chemo. Median OS from the start of SLC was 30.1 weeks. 25 pts (58.1%) had disease control (response and stable disease) lasting at least 12 weeks under SLC. Potential prognostic variables with their frequencies and prognostic values are listed in the Table . Multivariate analysis showed that PCS was significant predictor for OS (HR=0.46, p<.05). PFS1 of more than 26 weeks was a strong significant OS predictor (HR=0.41, p<.05). Interaction test between PFS1 and PCS was not significant (p=0.48). Conclusions: Benefit from a SLC in MGC is highly related to former sensitivity to first line chemo. This is of major importance in the design of trials in MGC in a second line setting. [Table: see text] No significant financial relationships to disclose.
Tolerability of sorafenib in the treatment of hepatocellular carcinoma (HCC) in patients with Child A and B liver cirrhosis
Authors: Schuette K. , Zimmermann L. , Bornschein J. , Huster D. , Csepregi A. , Malfertheiner P. 
Published: August 2020

e15593 Background: Sorafenib (S) is the only drug that prolongs overall survival in patients (pts) with advanced HCC by nearly 3 months in pts with Child A liver cirrhosis (LC). This study aims to evaluate tolerability of S in pts with Child B LC. Methods: Pts with HCC not suitable for curative therapy were treated with S since it became available for clinical use. 50 of 139 consecutive patients diagnosed with HCC were treated with S (8 f, 42 m; median age 67 (18–86) yrs). Initial dose was 400 mg/day and increased in case of good tolerability stepwise up to 800mg/day. Pts were stratified according to the stage of LC and analyzed for treatment toxicity based on the National Cancer Institute Common Toxicity System. Results: 41 pts with HCC had LC, 17 in Child A and 24 in Child B stadium. Due to side effects a dose escalation to 800mg was possible in 9 pts (22.0%) only, 3 with Child A and 6 with Child B LC. Grade 1/2 toxicity was observed in 15 pts with initial Child A (88.2%) and in 11 pts with initial Child B LC (45.8%), grade 3/4 toxicity occurred in 2 pts with Child A (11.8%) and 3 pts with Child B LC (12.5%). After 12 weeks of follow-up, 12 pts with Child A (70.6%) and 10 pts with Child B LC (41.7%) at entry were still under treatment. A deterioration of liver function from Child A to Child B was observed in 5 of 17 pts (29.4%) and from Child B to Child C in 1 patient (4.2%). In 5 pts (29.4%) with Child A LC and 14 pts with Child B LC at entry treatment had been discontinued in advance. Survival in patients with LC Child A was better than in patients with LC Child B (median overall survival 327 (60–495) vs 138 (10–560) days resp., ns). Conclusions: Systemic therapy of advanced HCC with S appears to be a safe treatment option in pts with Child B LC. However, tolerability is an important limitation in the use of S independently of the stage of LC. Whether pts with advanced HCC benefit from a systemic treatment with smaller doses than 800mg/day needs to be addressed in further studies. [Table: see text]
Reconsenting patients with cancer on clinical trials: Does added risk influence continued participation?
Authors: Elegbede A. , Andrei A. , Andrei A. , Holen K. D. 
Published: August 2020

e15610 Background: The general policy endorsed by multiple professional societies and cooperative groups regarding patients on cancer clinical trials states that subjects should be informed of new adverse events or significant developments during study participation and re-consented to continue on study. However, no information is known as to the effect of re-consenting on a patients’ decision to continue study participation. Our research question addresses how the severity of reported risk to other study participants will impact the subjects’ decision to continue participation in a clinical trial. Methods: We surveyed 34 patients with gastrointestinal (GI) tumors all of whom were currently enrolled in a clinical trial. The survey portrayed hypothetical adverse reactions affecting another study participant ranging from Grade 1 to Grade 5 according to the National Cancer Institutes Common Terminology Criteria for Adverse Effects v. 3.0. The survey asked about subjects’ opinions of the theoretical adverse event categorized as “would not be concerned,” “would be concerned, but would continue the study,” and “would discontinue the study.” Results: Patients willingness to continue the study was highest at Grade 1 with 97% of all participants. However, willingness to continue participation progressively declined as the severity of adverse events increased such that only 44% of participants would continue participation with a reported Grade 5 adverse event. Conclusions: Among surveyed GI cancer patients, willingness to continue participation in a clinical trial declined significantly as the severity of adverse events increased from Grade 1 to Grade 3 - 5 (p-value < 0.001. This could be due to multiple factors, including the terminal nature of the patients’ cancer, the side effects of study therapy and the patients’ response to study treatment. This data could produce a reasonable adverse event grade cut-off for re-consenting patients regarding new side effects. No significant financial relationships to disclose.
High-risk factors affecting survival after transcatheter therapy with doxorubicin-eluting beads for unresectable hepatocellular carcinoma
Authors: West J. K. , Dhanasekaran R. , Kooby D. A. , Staley C. A. , Kauh J. , Kim H. S. 
Published: August 2020

e15614 Background: Transcatheter therapy with drug eluting beads (DEB) with Doxorubicin is a relatively new modality of palliative treatment of patients with unresectable HCC. It is important to identify prognostic factors which affect survival after treatment with DEB to enable optimal patient selection and to ensure maximal survival benefit. Methods: Fifty consecutive patients with unresectable HCC who were treated with transcatheter therapy with DEB between the period of 2005 and 2008 were studied. Kaplan Meier test was used to study survival. Categorical variables were compared with Log rank test and continuous variable with Cox proportional hazards method. Results: The survival rates at one year from first transcatheter therapy in patients belonging to Okuda stage I, II and III were 67%, 35% and 27% (p=0.043). The survival rates at one year from the first transcatheter therapy in Child Pugh Class A, B and C were 60%, 39% and 13% (p=0.003). Portal vein thrombosis was present in 24%(12/50). Median survivals in patients with and without portal vein thrombosis were 335 days(31–638) and 610 days(482–738)(p=0.285). The median survival in patients with tumor thrombus and bland thrombus were 169 days and 335 days(p=0.69). The median survival in patients with main portal vein thrombosis and branch portal vein thromboses were 316 days(135–497) and 550 days(202–897)(p=0.89).Pre- procedure albumin, bilirubin and MELD score were found to be prognostic factors on univariate analysis ( Table 1 ).On multivariate analysis, pre-procedure serum albumin and Okuda staging were found to be independent prognostic factors. Conclusions: On multivariate analysis, serum albumin and Okuda staging were found to independently influence survival of patients treated with Doxorubicin eluting beads for unresectable hepatocellular carcinoma. The presence of portal vein thrombosis did not affect the long term survival. [Table: see text] No significant financial relationships to disclose.
Comparative efficacy of adjuvant chemoradiation versus chemotherapy in surgically resected adenocarcinoma of stomach
Authors: Aziz S. A. , Banday M. A. , Mir M. H. 
Published: August 2020

e15639 Background: Outcome of carcinoma of stomach has not changed over the past decades and surgery remains the time tested primary modality of treatment. Attempts to improve survival have been strengthened by recent studies of adjuvant chemoradiation in these patients. The present study focuses to compare the efficacy of adjuvant chemoradiation Vs Chemotherapy alone in surgically resected adenocarcinoma of stomach. Methods: Over a two years period (Nov. 2006 to Oct 2008) 60 patients were enrolled and randomized to two arms with 30 patients in each arm. ArmA received adjuvant chemoradiation and arm B received chemotherapy only. Chemoradiation protocol included Inj. 5 - FU 425mg/m2 and Inj. CLV 20mg/m2 I/V d1 - d5 followed by EBRT (45 GY) over 20 #s starting on d29. During first 4 days and last 3 days of radiation patients also received inj. 5 - FU 400mg/m2 I/V and CLV 20mg/m2 I/V bolus. Arm B received chemotherapy alone with Inj Cisplatin 100mg/m2 divided over 3 days, Inj 5- FU 500 mg/m2 I/V bolus d1 - d3 and Inj. CLV 20 mg/m2 /IV d1 - d3 q 21 days × 6 cycles. Results: All patients were followed post treatment for EFS and PFS for a maximum period of 24 months with a median followup of 19 months. EFS and PFS for two arms were; Arm A - 17.7 months and 19.0 months and Arm B - 16.0 months and 17.4 months respectively. Treatment related morbidity was significant in arm B. General well being and surrogate laboratory markers including hemogram were compared as well, favouring arm A. Conclusions: Although interim survival trends favour adjuvant chemoradiation, yet results are not statistically significant necessitating a longer followup of these patients to arrive at a definite conclusion as for as decision regarding efficacy of chemoradiation is established. Also these findings need to be reproduced by further studies. No significant financial relationships to disclose.