bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of ERCC1 and HER2 expression in human colon carcinomas
Authors: Kaskara A. V. , Antonacopoulou A. G. , Scopa C. D. , Rigopoulos A. G. , Iconomou G. , Georgoulias V. , Kalofonos H. 
Published: March 2020

14534 Background: Predictive and prognostic markers need to be established in colon cancer in order to tailor chemotherapy and, therefore, improve efficacy of adjuvant treatment. In this study, expression of the excision repair cross-complementing 1 (ERCC1) and HER2 tyrosine kinase receptor genes was evaluated in human colon carcinomas. Moreover, expression levels were associated with survival, time to disease progression and various clinicopathologic parameters. Methods: Fifty formalin fixed paraffin embedded tissues of primary colon carcinomas, resected from an equal number of patients at the University Hospital of Patras, Greece were studied. Forty four patients were treated with adjuvant chemotherapy and four patients with chemotherapy for advanced disease. Total RNA was extracted from tissues, quantified and reverse transcribed. Levels of ERCC1 and HER2 mRNA were quantified using Taqman probes in real time PCR and expressed relative to a calibrator. Results: ERCC1 and HER2 mRNA were detected in 92% and 82% of cases respectively, although overexpression was observed in 43.5% and 26.8%. Levels of expression were not related to age, stage, grade and overall survival. There was a significant association between overexpression of ERCC1 and time to disease progression (p<0.05) although this was not observed for HER2. There was a trend towards decreased relapse following adjuvant therapy in patients with low expression levels of ERCC1 and HER2 mRNA levels. However this difference failed to reach significance. Expression levels of ERCC1 and HER2 were not correlated with each other. Furthermore, coexpression of the two molecules was not related to time to disease progression. Additionally, 99.5% and 93.7% of patients with low expression of ERCC1 and HER2, respectively, having received adjuvant therapy were alive at the 36 months follow up. Conclusions: These data suggest that overexpression of ERCC1 is significantly associated with time to disease progression in colon cancer. Further studies of ERCC1 as a prognostic or predictive marker are warranted. No significant financial relationships to disclose.
Appropriate schedule of oral tegafur / uracil (UFT) in combination with irinotecan (CPT-11) and bolus 5-FU / l-leucovorin (LV) in patients (pts) with metastatic colorectal cancer (MCRC): A phase I study
Authors: Chayahara N. , Tamura T. , Miki I. , Okuno T. , Kamigaki T. , Nishisaki H. , Inoue Y. , Maeda T. , Sakaeda T. , Azuma T. 
Published: March 2020

14538 Background: FOLFIRI is one of the standard regimens for MCRC. Considering the burden of continuous 5-FU administration, oral fluoropyrimidine-based therapy has been proposed in several clinical trials; however, gastrointestinal toxicity makes it difficult to perform successive oral chemotherapy. Therefore, no previous study could confirm whether to replace FOLFIRI with oral regimen. In order to find an appropriate schedule of oral fluoropyrimidine with safety and efficacy instead of continuous infusion of 5-FU, clinical trial using CPT-11, bolus 5-FU / l-LV and oral UFT / LV was conducted in pts with MCRC. Methods: Pts with MCRC, age > 18 years, ECOG PS 0–2, adequate organ function, and no or 1 prior chemotherapy were eligible. Pts received CPT-11 (100mg/m2) / 5-FU (500mg/m2) / l-LV (15mg/m2) i.v. on day 1 and UFT (300mg/m2) / LV (75mg/body) p.o. on days 1–5 (level 1), days 1–7 (level 2), or days 1–10 (level 3). Each course was repeated every 14 days. After determining feasible UFT / LV schedule, CPT-11 was dose-escalated (level 4: 125 mg/m2; level 5: 150mg/m2). Results: Nineteen pts were enrolled. A dose-limiting toxicity (DLT) of grade 4 neutropenia lasting for > 4 days was observed in 1 pt at level 2. Additional 3 pts at this level showed no toxicity of grade 3 or 4. A DLT of treatment delay (>8 days) was observed in 1 pt at level 3 because of prolonged neutropenia. Other 2 pts at level 3 refused to continue treatment within 4 cycles because of prolonged grade 2 anorexia. Obvious difference in toxicity was observed between level 2 and level 3. Therefore, 7-day-administration of UFT / LV was recommended. No DLT was observed at level 4 and 5, and the recommended dose of CPT-11 was 150mg/m2. The overall response rate was 66.7%. The median time to disease progression was 8.0 months. Conclusions: This oral fluoropyrimidine-based regimen is considered feasible and effective. The treatment schedule of UFT might be a key to prevent an early dropout due to gastrointestinal toxicity. Further study will be needed to confirm toxicity and efficacy of this regimen compared to FOLFIRI profile. No significant financial relationships to disclose.
Prognostic factors in metastatic colorectal carcinoma at initial diagnosis, MCCID
Authors: Vallejo C. T. , Zwenger A. O. , Lacava J. A. , Iturbe J. , Perez J. E. , Machiavelli M. , Romero A. , Dominguez M. E. , Rodriguez R. , Leone B. 
Published: March 2020

14548 Background: Despite several studies have evaluated the role of prognostic factors (PF) in metastatic colorectal cancer, results are controversial. The aim of the present study was to assess PF in a homogeneous population with MCCID treated with biochemical modulation of 5- Fluorouracil-based regimens. Methods: Analyses were based on individual data of 318 patients (P) with MCCID treated in different prospective trials at GOCS Institutions since May 1984 to Jun 2001. The following variables (V) were considered: a) Clinical variables (CV): age, sex, family history of CC, hypertension, diabetes, tabaquism, weight loss, and performance status (PS), b) Tumor variables (TV): histologic grade, size and location of primary tumor; number of metastatic sites, number and size of liver metastases, uni- bilateral liver involvement; and c) Laboratory variables (LV): CEA, lactate dehydrogenase (LDH), alkaline phosphatase, ALT, AST, and hemoglobin. Overall survival (OS) was analyzed since date of diagnosis by means of Kaplan-Meier and the Log-rank test was used to assess the differences. A Cox’s proportional hazard modeling was used for multivariate analyses. Results: The OS for the entire group was 18.1 months (IC95, 15.0–22.7). Univariate analysis showed statistical significance in the following; a) CV: family history CC (p=0.001), PS (p=0.04), diabetes (P=0.003); b) TV: histologic grade (p=0.01), uni-bilateral liver involvement (p<0.0001), number of liver metastases (p<0.0001) and size of liver metastases (p<0.0001); and c) LV: hemoglobin (p=0.05), ALT (P=0.0006), AST (p<0.0001), alkaline phosphatase (p<0.0001), LDH (p=0.0004); Cox’s analyses showed statistical significance only for PS and alkaline phosphatase (p= 0.01 and p=0.0001, respectively). Conclusions: In this setting of P with MCCID the PS remains the most important PF for OS. High value of alkaline phosphatase may reflect liver involvement. No others PF considered in the analyses had prognostic influence. No significant financial relationships to disclose.
Safety of neoadjuvant oxaliplatin-based chemotherapy (N-FOLFOX) in patients undergoing resection of colorectal liver metastases (R-CLM). Interim results
Authors: Verghese M. , Pathak S. , Foster C. , Haqqani M. , Poston G. J. 
Published: March 2020

14550 Background: Oxaliplatin-5-fluorouracil-leucovorin (FOLFOX) has significant activity against CRC in both the metastatic and adjuvant settings. Consequently, neoadjuvant FOLFOX (N-FOLFOX) is being investigated in R-CLM. This has raised concerns regarding the safety and rate of post-operative complications (P-OCs) with N-FOLFOX, specifically, development of sinusoidal dilatation (SD), fibrosis and steatosis. This single-center cohort study was conducted to prospectively evaluate safety of N-FOLFOX in R-CLM patients. Methods: Planned total sample size is 40 patients [20 N-FOLFOX; 20 no chemotherapy (N-C)]. The N-C group consists of patients undergoing surgery for other hepatic pathology. Normal liver was examined by light (LM) and electron (EM) microscopy for SD, perisinusoidal fibrosis, and steatosis/necrosis; severity was graded from 0 (absent) to 2. The rate of P-OCs, hospital stays, and liver function tests (LFTs) were assessed. Results: At the time of this analysis, 20 patients (10 N-FOLFOX; 10 N-C) have undergone surgery. In the N- FOLFOX group, median number of cycles of N-FOLFOX was 6, with 2 patients receiving only 4 cycles. The median time between completion of N-FOLFOX and surgery was 6 weeks. There were no statistical differences between N-FOLFOX and N-C groups in potentially confounding factors, including previous chemotherapy, alcohol consumption, medical history, or concomitant medications. Number of patients with SD was 8 in each group (all were grade 1 except for 1 patient in N-C who had grade 2). Steatosis was seen in 7 and 6 patients in N-FOLFOX, and N-C groups, respectively (2 patients in each group were grade 2; remaining were grade 1). Fibrosis was noted in only 1 patient in N-C group. No nodular regeneration was observed in either group. There was a subjective loss on EM of mitochondria and Golgi apparatus/body with N-FOLFOX. Median post-operative hospital stay was 12 days in both groups. Conclusions: N-FOLFOX appears to have no clinically significant deleterious effects on normal liver architecture, function, or recovery post-surgery in R-CLM patients. The study is ongoing to accrue up to 40 patients; updated data will be presented. No significant financial relationships to disclose.
Identification of patients who most benefit from hepatic arterial infusion (HAI) combined or not with systemic chemotherapy for the treatment of unresectable colorectal liver metastases
Authors: Pilati P. , Mocellin S. , Lise M. , Nitti D. 
Published: March 2020

14565 Background: Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, there is substantial lack of evidence for benefit in terms of overall survival (OS). To test the hypothesis that systemic chemotherapy affects OS of patients with unresectable colorectal liver metastases treated with HAI. Furthermore, we investigated patient- and tumor-related predictive factors that might identify patients who most benefit from HAI regimen. Methods: In this retrospective study, 153 consecutive patients treated at our institution were considered. In group-A (n=72), patients were treated with HAI alone (floxuridine (FUDR) 0.2 mg/Kg + leucovorin (LV) 4 mg/m2 + desamethasone 20 mg 14 days/month) between 1994 and 1999. In group-B (n=81), patients were treated with the same HAI regimen combined with systemic chemotherapy (5-fluorouracil (5FU) 450 mg/m2 + LV 20 mg/m2) between 1999 and 2003. Results: No difference in OS was observed between group-A and group-B (median OS: 18.0 and 19.1 months, respectively). Considering all patients (group A + group B), low tumor load was associated with a better tumor response rate, but none of the traditional clinico-pathological prognostic factors correlated with OS. Median OS was better in patients with less than 50% of liver parenchyma involvement (21.3 vs 13.2 months; P<0.0001) as well as in responders (complete or partial response) versus non-responders (24.4 vs 13.4 months; P<0.0001). The combination of low tumor load with good tumor response to HAI was the only variable retained at multivariate analysis, and identified a subgroup of patients with a very favorable clinical outcome (median survival: 34.2 months; hazard ratio: 0.347, CI: 0.249–0.564, P< 0.0001). Conclusions: Combination with 5FU+LV systemic chemotherapy did not lead to an OS benefit over FUDR-based HAI alone. The identification of tumor response predictors is urgently needed, as it would lead to the tailored treatment of patients with low load but unresectable metastatic liver disease who most benefit from HAI therapy. No significant financial relationships to disclose.
Topoisomerase I expression in locally advanced rectal cancer as predictive marker for response to preoperative chemoradiation
Authors: Horisberger K. E. , Hofheinz R. D. , Muessle B. , Findeisen P. , Hochhaus A. , Post S. , Willeke F. 
Published: March 2020

14566 Background: In locally advanced rectal cancer combined modality treatment has become the standard therapeutical intervention. Preoperative downstaging is known as a predictor concerning lower local recurrence rate and probably better overall-survival. However, efficacy of neoadjuvant chemoradiation is compromised in some patients by so far unknown factors. The aim of the present study was to investigate topoisomerase I expression as a potential parameter for predicting response to irinotecan-based chemoradiation. Methods: 15 patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive weekly neoadjuvant irinotecan (1 hour before radiation) and capecitabine as well as cetuximab with a concurrent RT dose of 50.4 Gy (45+5.4 Gy). Surgery was scheduled 4–6 weeks after the completion of chemoradiation. Samples of normal and tumor tissues of all patients were collected before neoadjuvant treatment. Initially, RNA-oligonucleotid-array of three patients (one good responder and two non-responders) was accomplished to show qualitatively different gene expression. To quantify the differences, real-time PCR of topoisomerase I was performed. Results: The differences of gene expression in the RNA-oligonucletoidarray were correlated to the clinical response to neoadjuvant chemoradiation as topoisomerase I showed a significant higher expression in the tumor tissue of the good responder before treatment (p<0.0001). PCR-analysis showed a relatively higher median expression of topoisomerase I in normal tissue (1.7 vs. 0.9; p=0.85) and in tumor tissue (1.5 vs. 1.3; p=0.36) of the subsequent good responding patients (n=10). Conclusion: Patients respond differentially to chemoradiation in terms of clinical response and gene expression shifts. The oligonucleotidarray results leads us to assume that response may be predictable. The preliminary results of PCR demonstrate that TopoI expression describes a valuable parameter for prediction of efficiency of irinotecan in advanced rectal cancer. The small number of patients may have caused the missing of the statistical significance. We are intending an extension of the PCR analysis to more powerful series based on the achievements of the current investigation results. No significant financial relationships to disclose.
Cetuximab plus bevacizumab in patients (pts) with metastatic colorectal cancer (mCRC) who have failed on irinotecan, oxaliplatin and fluoropyrimidines-based chemotherapy
Authors: Souglakos J. , Kalbakis K. , Vamvakas N. , Kalykaki A. , Kotsakis A. , Agelaki S. , Karampeazis A. , Gioulbasanis J. , Georgoulias V. 
Published: March 2020

14576 Background: Bevacizumab (AVASTIN®) and Cetuximab (ERBITUX®) are IgG1 monoclonal antibodies targeting the Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR), respectively. Both are active in mCRC pts as first and/or second line treatment. Preclinical data suggest potentially synergistic effect for the combination of the two antibodies. This phase II trial evaluates the safety and efficacy of cetuximab combined with Bevacizumab in the treatment of mCRC pts who have failed on Irinotecan, Oxaliplatin and Fluoropyrimidines-based chemotherapy. Methods: mCRC pts with ECOG PS = 2 who had refractory disease to all three active chemotherapeutic drugs were enrolled. Determination of EGFR status was not mandatory. Cetuximab was given at an initial dose of 400mg/m2, then 250mg/m2 iv weekly; Bevacizumab was administered at a dose of 10 mg/kg on d1 every 2 weeks. Results: From June 2005 to November 2006, 14 pts were enrolled. Median age was 65 years, and median PS was 1. Treatment was 3rd-line in 5 pts, and = 4th-line for 7 patients. 12 pts had received prior treatment with Cetuximab and 6 were Bevacizumab. Thirty-nine cycles were administered with a median of 3 cycles/patient. All pts were evaluable for toxicity and response. No grade 3–4 hematological toxicity was observed. Non-hematological toxicities included grade 3 fatigue (7.1%), grade 2 diarrhea (7.1%), grade 2 allergic reactions (14.1%). Amongst the 14 patients evaluable for response, there was 1 objective PR (7.1%; 95% CI: 6- 24%), and 2 (14.2%) SD (tumor growth control rate, TGCR: 21.3%). The median time to progression was 2.4 months and the median survival has not yet been reached. The estimated probability for 1-year survival was 65.7%. Conclusions: The combination of Cetuximab plus Bevacizumab in patients with mCRC refractory or resistant all active chemotherapeutic drugs is safe and has promising activity. No significant financial relationships to disclose.
Correlation of bone marrow micrometastases with nodal status in gastrointestinal tumors
Authors: Chivu S. , Saha S. , Patel G. M. , Wiese D. , Bassily N. , Henke A. , Sankaran H. , Misra A. , Singh T. , Arora M. 
Published: March 2020

14577 Background: Presence of bone marrow micrometastases (BMM) is an important prognostic factor for patients (pts) with solid tumors. Sentinel lymph node (SLN) mapping (M) has been found to upstage pts with gastrointestinal (GI) malignancies. However, a direct correlation between the presence BMM and nodal metastases (mets) is lacking. Hence, a retrospective study was undertaken to determine the relationship between BMM and nodal status in various GI malignancies. Methods: A total of 159 consecutive pts with GI malignancies were analyzed. Of these, 6 pts with non-epithelial tumors were excluded. All pts underwent bilateral posterior-superior-iliac spine bone marrow (BM) aspiration. BM samples were examined for micrometastases by Automated Cellular Imaging System using ChromaVision Cytokeratin Detection Kit to detect cells expressing CK8 as defined by CAM 5.2 monoclonal antibody. When feasible, SLNM was performed followed by standard oncologic resection (n=105). The SLN were examined by H&E and immunohistochemical (IHC) staining. Results: A total of 153 pts were analyzed in the study. Of these 13.72% (21/153) were found to have BMM (CI 8.70–20.21, p=0.05). When analyzed by sites, the incidence of BMM was 33.3% (4/12) for stomach cancer, 9.1% (1/11) for pancreatic cancer, 12.36% (11/89) for colon cancer and 16.13% (5/31) for rectal cancer. No BMM were detected in pts with cancer of esophagus (n=7), small bowel (n=2) and liver (n=1). The BMM was positive bilaterally in 61.9% (13/21), and unilaterally in 38.1% (8/21). In pts who underwent SLNM (n=105), BMM were detected in 11.11% of SLN positive pts vs. 10.14% for SLN negative pts (p=0.87). For a subgroup of pts with colorectal cancer who underwent SLNM (n=97), BMM were detected in 9.67% of SLN positive pts vs. 9.09% for SLN negative pts (p=0.92) Conclusions: BMM did not correlate with nodal status for GI malignancies suggesting a possible different mechanism for metastases. Detection of BMM may have a significant clinical value in SLN negative pts who may benefit from adjuvant therapy. [Table: see text] No significant financial relationships to disclose.
Efficacy of FUFOX regimen in the treatment of a selected population with metastatic colorectal cancer (MCC)
Authors: Garassino M. C. , Borgonovo K. , La Verde N. , Sburlati P. , Bianchi C. , Cobelli S. , Rovej R. , Tomirotti M. , Torri V. , Farina G. 
Published: March 2020

14596 Background: FOLFOX is usually employed as first line treatment of MCC. Some patients (pts), for both clinical reasons and poor compliance, are not eligible for CVD insertion. At the moment, it is not clear if FUFOX (with 5-FU bolus) is less active than FOLFOX (with 5-FU infusion). We evaluated the outcome of MCC pts treated, as first line, with FUFOX. Primary end-point is efficacy. Secondary endpoints are time to progression (TTP) and overall survival (OS). Toxicity is also reported. Materials and Methods: We analysed all consecutive MCC patients who referred to our centre, without CVD, treated with the Hochster regimen: Oxaliplatin 85 mg/m2 days 1, 15; Leucovorin 20 mg/m2 and 5-FU 500 mg/m2 bolus days 1, 8, 15 - every 28 days. Response rate was evaluated with RECIST criteria. TTP and OS were analysed with Kaplan-Meier methods. Results: From July 2003 to October 2006 we treated 25 MCC pts. Main characteristics were: median age 71 years (range 46–79), 12 males, 13 females; PS 0–1; metastatic sites: liver 15 pts; lung 6; abdominal 10. 2 pts are early. A total of 128 courses were administered (5,4 median courses/pt, range 3–9). 5/23 pts (21.7% 90%CI: 9.0%-40.4%) had a PR and 2 achieved a secondary complete surgery. 15/23 pts (65.2%: 90%CI: 46.0%-81.4%) had a SD and 3 pts (13.0%: 90%CI: 3.7%- 30.4%) had a PD. At the moment of analysis 14 pts are still alive with a median follow up of 25 months; the median time to progression is 7.2 months. This combination was well tolerated with no grade 3–4 toxicities observed. G1-G2 peripheral neurotoxicity is reported in 15/25 pts (60%). Other common toxicities are: G1–2 haematological in 10 pts (40%); G1–2 gastrointestinal in 7 pts (28%); asthenia 5 pts (20%). Conclusions: We observed a low response rate, but high number of stable disease. Toxicity was acceptable. Although this is a not controlled study, this regimen seems to be less effective than infusional regimens but, due to the high control rate of disease (86.9%) we can consider it an alternative choice for patients that refuse or cannot receive continuous infusion. No significant financial relationships to disclose.
First-line chemotherapy with irinotecan plus capecitabine for advanced colorectal cancer
Authors: Michalaki V. , Gennatas C. , Gennatas S. , Vasiliou J. , Smyrniotis V. 
Published: March 2020

14602 Background: The effective, oral fluoropyrimidine capecitabine is increasingly replacing intravenous (IV) 5-FU/LV in colorectal cancer treatment. The aim of this study was to evaluate efficacy and safety of the combination chemotherapy with irinotecan plus capecitabine (XELIRI), in patients with advanced colorectal adenocarcinoma. Methods: Patients with advanced colorectal adenocarcinoma received a first-line chemotherapy with capecitabine (1000 mg/m2 twice daily) on days 1–14 and irinotecan (240 mg/m2) on day 1 of a 21-day cycle. Results: Twenty-eight patients were evaluable for response. Baseline characteristics: 18men, 10 women; median age 65.5 years (range, 49–73); colon cancer (71%), rectal cancer (29%). Most common metastatic sites were the liver (53.5%), lymph nodes (43%), lung (21%) and bones (18%). There were 7 partial responses (25%), 8 cases of stable disease (28.5%), and 13 cases of disease progression (46.5%). The median survival was 14 months (range, 2–28.8 months) and median progression-free survival was 7 months (range, 6- 26 months). The median number of cycles received was 7 (range, 3–15 cycles). Frequently encountered therapy-related events were leukopenia and gastrointestinal side effects including diarrhea. Conclusions: First-line capecitabine/ irinotecan is an active combination for the treatment of metastatic colorectal cancer achieving high efficacy with a good safety profile. No significant financial relationships to disclose.