bluuebunny/crossref_metadata_2025_split huggingface dataset:
Esophageal squamous cell carcinoma in the VA population: What is the optimal treatment modality
Authors: Safa M. M. , Beg M. S. , Atiq M. , Ali S. , Komrokji R. 
Published: March 2020

15042 Introduction: Surgery for esophageal squamous cell carcinoma (SCC) has been the mainstay of treatment despite dismal outcome and significant surgical complications. There is no standard treatment modality for esophageal SCC. Methods: The VA (veteran affairs) Central Cancer Registry (VACCR) is a function of the Chief, Program Office for Oncology at VA Headquarters in Washington DC. We queried the VACCR database for all diagnosed squamous cell esophageal cancer cases between 1995 and 2005 using ICD codes 150–159. The data was transformed, entered and analyzed using SPSS v.13.0. We analyzed, in a retrospective fashion, survival in VA patients with early disease (stages 1–2), and locally advanced (stage 3) SCC comparing the treatment modality: chemoradiation alone (CRT), surgical resection alone (SUR) or trimodality therapy (TMT) which includes all three treatment options. Results: Out of a total of 6874 patients diagnosed with esophageal carcinoma, 2894 patients had SCC. A total of 433 patients were included in this study that were staged as 1–3 and had complete treatment information available. Baseline characteristics were not different between the three groups and are summarized in table 1 . Out of those, 57 (13.2%) received SUR, 323 (74.6%) CRT, and 53 (12.2%) TMT. Kaplan Meier analysis for median survival in early disease was 14 mo for SUR, 17 mo in CR, and 79 mo in TMT (p = 0.0288). There was no difference in survival among patients with locally advanced disease between the treatment groups (p = 0.7079) Conclusion: In VA patients with early esophageal SCC, TMT confers better survival than SUR or CRT. However, in patients with advanced disease, SUR, CRT and TMT groups showed comparable outcome. [Table: see text] No significant financial relationships to disclose.
A phase II trial of weekly gemcitabine and bevacizumab in combination with abdominal radiation therapy in patients with localized pancreatic cancer
Authors: Small W. , Mulcahy M. , Benson A. , Gold S. , Bredesen R. , Rademaker F. , Talamonti M. 
Published: March 2020

15043 Purpose: To evaluate the response rate, survival and toxicity of non-metastatic pancreatic cancer patients treated with a combination of, Gemcitabine, Bevacizumab and Radiotherapy. Materials and Methods: Eligibility included patients with non- metastatic pancreatic cancer, standard organ function and ECOG performance status of 0 or 1. The patients received three cycles of therapy. Cycle one was 21 days and consisted of Gemcitabine days 1 and 8 and Bevacizumab days 1 and 15. Cycle 2 was 28 days and consisted of Gemcitabine days 1, 8, and 15, Bevacizumab days 8 and 22 and Radiotherapy days 1–5, 8–12, and 15–19. Cycle three was 21 days and delivered Gemcitabine days 1 and 8, and Bevacizumab day 8. The Gemcitabine dose was 1,000 mg/m2, Bevacizumab at 10 mg/kg and Radiotherapy was delivered to the gross tumor volume only for a total dose of 36 Gy at 2.4 Gy/fraction. Response was determined on week ten with cross sectional imaging and CA 19–9. Toxicities were scored utilizing CTC version 3.0. Resectable patients were to undergo surgery 8 (currently amended to 6) weeks after the last dose of Bevacizumab. Results: Ninteen patients have been enrolled on study from 10/10/05 - 1/4/07. Twelve patients are evaluable for toxicity and response. Ten (83%) had a grade 3 toxicity. The grade 3 toxicities included cytopenias (9), DVT (2), Dehydration (2), hypotension (1), mucositis (1), increased LFT’s (2), Anorexia (1), nausea (1) and fatigue (1).There were no Grade 4 or 5 toxicities. All but one patient completed all three cycles. Radiographic response at 10 weeks was noted to be stable in 10 (83%) patients. Two patients progressed distantly (liver and abdomen). The mean CA 19–9 pre and post treatment CA 19–9 was 1519.56 and 356.09 respectively. One patient underwent surgical resection. The mean follow up is 4.83 months. At last follow up nine patients were alive. Conclusions: The combination of full dose Gemcitabine, Bevacizumab and Radiotherapy was generally well tolerated with no Grade 4 toxicities and the majority of Grade 3 toxicities hematologic. All but one patient completed all three cycles. Responses were limited to a reduction in CA 19–9. Nine patients remain alive. Accrual to the trial continues. No significant financial relationships to disclose.
Results of semimonthly 5-florouracil/leucovorin combined with paclitaxel and oxaliplatin in treatment of advanced gastric cancer (AGC)
Authors: Lin R. , Fan N. , Guo Z. , Wang X. , Chen Q. , Liu J. , Lin J. 
Published: March 2020

15045 Background: At present there is still no standard chemotherapy regimen for AGC, the progress of AGC exhibits a pessimistic result with a median survival of less than 9 months. The purpose of this trial was designed to enhance the treatment efficacy for AGC by using semimonthly FU/LV combined with paclitaxel and oxaliplatin. Methods: Patients chosen with histologically proven diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, locally advanced (i.e., unresectable) or metastatic and measurable disease. The chemotherapy regimen was comprised of a 3-hour infusion of 135 mg/m2 of paclitaxel followed by oxaliplatin 85 mg/m2 and LV 400 mg/m2, administered simultaneously as a 2-hour infusion, then continued a 46-hour infusion of FU 2.4 g/m2 using an ambulatory pump. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. The primary endpoint was response rate. Results: Twenty-seven patients were enrolled onto this study in our center between September 19, 2005 and December 25, 2006. The median patient age was 51 years (range, 28 to 66 years), 21 were males and 6 were females. All patients received the chemotherapy between at least two cycles and maximum eight cycles with a median of three. Four CRs of 27 enrolled patients, fifteen PRs and eight SDs were observed. Nineteen patients were chemonaive within enrolled patients: Four CRs, eleven PRs. At a median follow-up of 8.7 months, the median survival was 6.8 months. Frequent grade 3 to 4 toxicities were: neutropenia (37.0%), stomatitis (7.4%), nausea (7.4%), vomiting (7.4%), hepatic dysfunction (3.7%), paresthesia (18.5%). No treatment-related death occurred. Conclusion: Semimonthly FU/LV combined with paclitaxel and oxaliplatin appears to be of well efficacy and is well tolerated in patients with AGC. Currently, this regimen is being tested in the phase III trial involving patients with AGC on the basis of well result. No significant financial relationships to disclose.
HER2/neu overexpression/amplification in advanced gastric cancer (AGC) patients (pts): Correlation with clinicopathological parameters
Authors: Ballestín C. , López-Rios F. , Vicioso L. , Burgos F. , Adrados M. , Nieto S. , López García-Asenjo J. A. , Mayorga M. , Luna S. , Gómez-Martín C. 
Published: March 2020

15046 Background: HER2/neu protein is overexpressed in several types of human cancers. Its amplification is associated with poor prognosis and constitutes a predictive factor of response to therapy. In this phase II study, we investigate the correlation between the HER2/neu overexpression/amplification and clinicopathological characteristics of AGC pts. Objective: To prospectively determine the frequency of HER2/neu expression and to evaluate the relationship with clinicopathological characteristics in AGC pts. Methods: HER2/neu expression/amplification has been examined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). HER2/neu has been considered overexpressed if: IHC=3; IHC=2 and FISH+ or FISH+. Clinical stage, prior therapies, tumor localization and histological characteristics have been also recorded. Results: Between Feb/2004 and Dec/2006, 181 pts have been tested for HER2/neu status. 132 (73%) males, median age 66 yrs (r-29–83). 24 (13.5%) pts were HER2/neu +. At screening, metastatic disease was the most frequent clinical stage (163, 91.1% vs 16, 8.9% locoregional advanced), being mainly localized in liver (45.3%), lymph nodes (41.4%), peritoneum (28.2%). 88 pts underwent prior surgery, 19 pts received adjuvant irradiation and 24 prior chemotherapy (21 pts adjuvant, 4 neoadjuvant). Primary tumor localization was 140 (79.5%) gastric and 33 (18.8%) gastroesophageal junction (GEJ). HER2/neu overexpression was found in 10.9% of tumors with gastric localization and in 24.2% of GEJ tumors (p=0.084). Adenocarcinoma was the histological type in 98% cases (34.9% diffuse, 43.2% intestinal, 0.6% mucoid, 21.3% unknown subtype). No statistically significant relationship was found between HER2/neu expression and histological subtype (7% type diffuse, 18.1% type intestinal, 13.9% unknown; p=0.186). Conclusions: HER2/neu overexpression/amplification was found in 13.5%. There were no significant correlation of HER2/neu overexpression/amplification with both tumor localization and histological subtype. The study is ongoing. No significant financial relationships to disclose.
Weekly high-dose 5-FU as a 24h-infusion and sodium folinic acid (AIO regimen) plus Irinotecan in patients with locally advanced non-resectable and metastatic adenocarcinoma or squamous epithelial carcinoma of the esophagus: Analysis of a phase II trial
Authors: Boxberger F. , Wolff K. , Brueckl V. , Brueckl W. M. , Albrecht H. , Engel M. , Maennlein G. , Mach K. , Hohenberger W. , Hahn E. G. , Wein A. 
Published: March 2020

15051 Background: In the majority of patients with esophageal carcinoma curative treatment proves to be impossible when establishing the diagnosis. While adenocarcinomas (ac) of the oesophago-gastric junction are increasingly treated in the same way as gastric carcinomas, the most frequently applied palliative chemotherapy regimen for both advanced squamous epithelial carcinomas (sec) of the oesophagus and gastric carcinomas is a combination of 5-FU and cisplatin. The question should be answered whether the AIO regimen plus irinotecan may achieve similarly positive results in esophageal carcinomas such as in gastric carcinomas (median survival (ms) up to 11 months). Methods: Prospective phase II trial, patients: n=25, trial start: 11/2002, chemotherapy: Irinotecan (80 mg/m2 i.v. as 1h-infusion; d 1, 8, 15, 22, 29, 36, qd 57) as well as sodium folinic acid (500 mg/m2 i.v.) together with 5-FU (2000 mg/m2 i.v.; d 1, 8, 15, 22, 29, 36, qd 57) as 24h-infusion via a miniature pump system. Results: Last date of evaluation: 31/12/2006: n=25; ac: n=13, sec: n=12; UICC III: n=3, UICC IV: n =22; grading G1/G2/G3/G4: 0/10/10/5; median age: 58 (44- 77) years; men/women: 20/5; ECOG 0/1/2/3: 3/17/4/1; chemotherapeutic applications: 429. Evaluable in terms of toxicity: n=25. Higher grade toxicity: grade (g) III diarrhea: n=2, g III hyponatremia: n=1, g III stomatitis: n=1, g III fatigue: n=1, g III vomiting: n=1, g IV nausea: n=1, g IV elevation of creatinine: n=1, thrombosis of the vena subclavia: n=1, ischemic lesion of the brain stem: n=1. 4 patients died after 2 chemotherapeutic applications due to known peritoneal carcinomatosis and high tumour burden. Evaluable in terms of response: n=25. PR: n=7 (28%), SD: n=10 (40%), PD: n=2 (8%), not evaluable: n=6 (24%). Cases of death: n=18. Total ms: 13 months (95% CI 3,9–22,1). ms of ac: 20 months (95% CI 8,6–31,4). ms of sec: 8 months (95% CI 0,0–17). Secondary resection (R0): n=2. Conclusion: In oesophageal carcinomas the AIO regimen plus irinotecan is excellently manageable on an outpatient basis and shows high efficacy in both adenocarcinomas and squamous epithelial carcinomas of the oesophagus. No significant financial relationships to disclose.
DCC is a potential methylation marker in human cancers
Authors: Yamashita K. , Park H. L. , Sidransky D. , Watanabe M. 
Published: March 2020

15054 Background: DCC (deleted in colorectal cancer) is a tumor suppressor gene, and known to be inactivated by mutation in human cancers. In this study, we revealed DCC gene promoter methylation in primary human esophageal and breast cancers and refer to its excellence as a cancer-prone marker. Methods: Quantititative TaqMan real time polymerase chain reaction; 20 esophageal squamous cell carcinoma (ESCC) and the corresponding non-cancerous esophageal mucosal tissues, 58 breast cancer tissues, and ESCC cell lines. Results: (1) In ESCC tissues, DCC hypermethylation is detected in 18/20 cases (sensitivity=90%), while it is detected in only 2/20 normal cases (specificity=90%). (2) In breast cancer tissues, DCC hypermethylation is detected in 29/58 cases (50%), and patients with higher methylation of DCC showed size larger than 6 cm (100%) as compared with those less than 6 cm (45.3%)(p<0.025). (3) DCC is silenced in cancer cell lines, and found to be reactivated by demethylating agent in several cell lines, while still silenced in other cell lines. Conclusions: In ESCC, DCC hypermethylation could be an excellent potential marker. DCC inactivation is partially explained by methylation, however other mechanism could be involved like p53. The accurate mechanism of DCC requires further elucidation, but its potential as a tumor marker in SCC is considered excellent to apply for cancer detection using human body fluid. No significant financial relationships to disclose.
Predictive factors for metastasis in patients (pts) with gastric cancer
Authors: Kilickap S. , Dizdar O. , Harputluoglu H. , Aksoy S. , Yalcin S. 
Published: March 2020

15056 Background: Determination of patients (pts) with early stage disease who have a high risk for developing metastatic disease is crucial. We investigated the risk factors associated with metastases development in pts with operable gastric cancer. Patients and Methods: In this retrospective study, pts with stage I-III and non-metastatic stage IV gastric cancer diagnosed between 1990 and 2006 were evaluated. The medical records of all pts including patient characteristics, laboratory results, histopathological examinations, were reviewed. Logistic regression methods were used to determine the risk factors for developing metastasis and to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: 184 pts (70% male, 30% female) were analyzed. The mean age ± standard deviation was 56.5±11.9. The mean age of female were higher than male (p=0.014). At the time of diagnosis, 13.6% of the pts had stage I, 19.0% had stage II, 53.3% had stage III, and 14.1% had non-metastatic stage IV disease. The tumors were distally localized in 80% of the cases. Median follow-up period was 35 months. During follow up, 51 pts developed metastases. Median time to metastases development was 14 months. Overall survival was shorter in pts who developed metastasis than those who did not. (20 months vs. not reached, respectively, p=0.002). In univariate analyses, stage (p=0.020), tumor localization (p=0.006), extracapsular lymphatic extension (ELE) (p<0.001), the number of metastatic lymph nodes (p=0.001), CEA level (p<0.001), lymphovascular invasion (LVI) (p=0.001), and perineural invasion (p=0.007) were associated with metastasis development. In multivariate analysis, elevated CEA levels (p=0.009; OR: 2.8; CI 95%: 1.29–6.19), LVI (p=0.041; OR: 2.2; CI 95%: 1.03–4.64) and ELE (p=0.029; OR: 2.3; CI 95%: 1.09–4.78) were associated with increased risk of metastasis development while distal localization (p=0.038; OR: 0.42; CI%: 0.18–0.95) was associated with decreased risk in pts with gastric cancer. Discussion: In pts with early stage or locally advanced gastric cancer, elevated CEA levels, LVI, proximal localization and ELE were associated with increased risk of developing metastasis. Aggressive treatment options and closer follow up should be considered for pts with these risk factors. No significant financial relationships to disclose.
Phase I trial of imexon, Inj. plus gemcitabine in patients with advanced previously untreated pancreatic adenocarcinoma
Authors: Cohen S. J. , Zalupski M. , Modiano M. , Conkling P. , Mahadevan D. , Wong L. , Smith D. , Dorr R. T. , Boytim M. , Hersh E. M. 
Published: March 2020

15058 Background: Imexon for inj. (Amplimexon®, AMP) is an aziridine-containing iminopyrrolidone which causes G2 arrest, accumulation of reactive oxygen species, and induction of apoptosis in pancreatic cancer cells. AMP demonstrated synergy with gemcitabine (GEM) in preclinical pancreatic cancer models. This phase I study of AMP plus GEM was undertaken to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). Secondary endpoints were pharmacokinetics for both agents (PK) and tumor response. Methods: Patients (pts) with previously untreated advanced pancreatic adenocarcinoma received one of two dosing regimens. The first 19 received 30 minute AMP IV days 1–5 and 15–19 followed by 30 minute GEM IV days 1, 8 and 15 Q4 wks (Regimen A). Dosing was modified after 19 pts to administer both AMP and GEM over 30 minutes days 1, 8 and 15 every 4 weeks (Regimen B). Dose levels (AMP/GEM, in mg/m2) for Regimen A: 200/800, 280/800, 200/1000, and 280/1000, and for Regimen B: 280/1000, 335/1000, 390/1000, 540/1000, and 750/1000. The current cohort is 1000/1000. Pts were assessed for response after cycles 2, 5 and 8. PK and pharmacodynamic (plasma thiol depletion) measurements were obtained during cycle one. Results: Forty-six pts have been treated to date, with 36 having complete toxicity data and evaluable. Pt characteristics: M/F (24/12), Age (mean 60.4 years, range 43–75), ECOG PS 0/1 (56%, 44%), metastatic/locally advanced (91%, 9%). The 36 pts have completed 122.5 cycles of therapy (median 2, range 0.5–12). Common toxicities: anemia (77%), fatigue (71%), nausea (60%), fever (54%), and leukopenia (54%). DLT were 1/6 at 280/1000 (Regimen A - febrile neutropenia), 1/6 at 280/1000 (Regimen B - gr 3 hypotension, gr 4 renal failure), and 1/9 at 390/1000 (gr 3 hyperbilirubinemia). Accrual continues at 1000/1000. Of 36 pts, 4 have had partial responses and 14 stable disease. PK and plasma thiol analysis are ongoing. Conclusions: Imexon can be administered safely with full dose gemcitabine. Accrual continues to define the combination MTD. The response rate in this phase I study compares favorably with historical gemcitabine monotherapy, and further phase II evaluation of this combination in advanced pancreatic cancer is warranted. No significant financial relationships to disclose.
Esophageal cancer at the VA: Does histology matter?
Authors: Gupta A. K. , Beg M. S. , Komrokji R. , Atiq M. , Mekan S. , Safa M. 
Published: March 2020

15069 Introduction: In recent years esophageal cancer has shown a shift from largely squamous cell carcinoma (SCC) histology to adenocarcinoma (AC). This is felt to be due to changing risk factor profiles among the American population. Methods: The VA Central Cancer Registry is a function of the Chief, Program Office for Oncology at VA Headquarters in Washington DC. We queried the VACCR database for all diagnosed esophageal cancer cases between 1995 and 2005 using ICD codes 150–159. The data was transformed, entered and analyzed using SPSS v.13.0. Results: There were a total of 6874 cases diagnosed between 1995 and 2005. Out of those, 2968 (43.2%) were diagnosed with AC and 2894 (42.1%) with SCC. Black patients were more likely to have SCC than AC. Baseline characteristics are summarized in table 1 . Staging information was available in 2823 (48.1%) patients. Patients with AC were more likely to present with metastatic disease than those with SCC (52.7% vs. 44.3%). Median survival in AC was better than SCC for non-metastatic disease (12.3 mo vs. 8.6 mo, p=0.0009). No difference in survival was seen in metastatic disease between the two histologies (AC 4.2 mo vs. SCC 3.97 mo p=0.537). In Cox- regression analysis using variables including race, histology, stage, grade and treatment, only histology, stage, grade and treatment were significant predictors of survival. Conclusions: In non-metastatic esophageal cancer at the VA, SCC has worse outcome compared to AC. However, in metastatic disease, SCC and AC have similar outcome. We recommend further studies to determine if the differences in histology are determined by biological or lifestyle differences. [Table: see text] No significant financial relationships to disclose.
Thalidomide in patients with advanced hepatocellular carcinoma: A clinical/biological study
Authors: Fazio N. , Petralia G. , Mancuso P. , Lorizzo K. , Jemos C. , Boselli S. , Porcu C. , Bertolini F. , Bellomi M. , de Braud F. 
Published: March 2020

15076 Background: thalidomide has been reported to have anti-angiogenic properties and therefore has been studied in several hypervascularized cancers. We evaluated the effect of thalidomide on progression-free survival (PFS) and several surrogate markers of angiogenesis in patients (pts) with advanced hepatocellular carcinoma (HCC). Methods: from June 2005 to November 2006, 19 out of the foreseen 24 HCC pts were treated with oral thalidomide 200 mg/day continuously. All of them had cytological/histological diagnosis of HCC, with no indication for curative treatment. Prior treatment was allowed. Six-month PFS was the main clinical endpoint. Perfusion parameters (Blood Flow -BF-, Blood Volume -BV-, Permeability Surface -PS-, and Mean Transit Time -MTT-) were measured with perfusion Computed Tomography (CTp). Circulating endothelial cells (CEC), progenitor cells (CEP), and apoptotic CECs, were measured by flow cytometry. Results: Eleven pts were HCV-positive and 4 HBV-positive. Eighteen had cirrhosis (80% Child-Pugh A). Five pts had extra-hepatic metastases. The maximum CLIP value was 3, in 5 pts. Six-month PFS was 41%. Constipation and somnolence were the most common G2–3 toxicities, occurring in 50% and 18% of pts, respectively. Three pts stopped treatment because of toxicity (one oedema, one neurotoxicity, and one suspect intratumoral bleeding). Baseline BF and BV of HCC were significantly higher (p<.05) for the background liver in 18 evaluable pts. BF and BV remained quite stable at six months in the 7 pts free of progression, whereas they increased at the time of progression in the 9 pts with progression within 6 months. The baseline BV in the 7 pts free of progression at 6 months was significantly lower compared with that of pts progressive within 6 months (p=0.03). Seven out of 9 pts who underwent both perfusional and circulating evaluations are currently evaluable at 2 months (2 too early). BF and BV showed an inverse trend with respect to CECs in the 4 pts with PD. Pharmacokinetics and QoL evaluation is ongoing. Conclusions: thalidomide may prolong PFS in pts with advanced HCC, with manageable toxicity. CTp and CECs detection could be used to assess the antiangiogenic drug activity, but it requires further studies to be confirmed. The BV grade could be studied as a predictive factor No significant financial relationships to disclose.