bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine and carboplatin in the treatment of metastatic cholangiocarcinoma and gallbladder cancer
Authors: Suresh R. , Picus J. , Sorscher S. , Fournier C. , Tan B. R. 
Published: March 2020

15102 Background: There is currently no standard therapy for patients with unresectable or metastatic biliary tract cancers. Gemcitabine has been shown to be active against these tumors with a 20–30% response in various phase II studies. Gemcitabine is also synergistic with platinum compounds. Aim: We conducted a Phase II study of gemcitabine plus carboplatin in patients with unresectable or metastatic choloangiocarcinoma or gallbladder cancer to assess the regimen’s safety and efficacy. Methods: Since 3/2002, 49 (48 evaluable) patients were treated with gemcitabine at 1000 mg/m2 IV over 30 minutes days 1 and 8 with carboplatin at AUC 5 IV on day 1 of a 21 day cycle. There were 34 women and 15 men enrolled. Ages ranged from 34 to 87 with a median age of 65 years. Results: Best radiologic responses - 5CR, 9 PR, 24 stable disease and 10 progression. CR+PR 14/48 (29.2%) and stable disease 24/48 (50%). Toxicity: Hematological toxicities: Grade 3 neutropenia 33%, febrile neutropenia 0.02%, anemia 12.5% and thrombocytopenia 14.6%. Grade 4 hematological toxicites were rare - neutropenia 0.04%, and thrombocytopenia 0.06%. Non-hematologic toxicities were generally mild (fatigue, edema, nausea, vomiting, elevated liver enzymes, electrolyte abnormalities). Except for one patient who had depression there were no grade 4 non-hematological toxicity. Grade 3 non- hematological toxicites were also rare occurring only in 1 to 3 patients. Conclusions: Gemcitabine and carboplatin is active against biliary cancer and is highly tolerable. This study is being supported by Eli Lilly & Co. No significant financial relationships to disclose.
Differential response of factor VIII and protein C expression following multimodal therapy for esophageal carcinoma
Authors: Byrne M. , M B. , O’ Donnell J. , White B. , Kennedy J. , Reynolds J. 
Published: March 2020

15106 Background: Tumour growth is associated with development of a hypercoaguable state and increased risk of thrombosis. Factor VIII plasma concentration has been shown to be an independent and dose-dependant risk factor for venous thromboembolism. Von Willebrand factor, the carrier molecule of circulating FVIII is expressed by vascular endothelial cells and in vitro observations indicate that chemotherapy induces endothelial damage with subsequent dysfunction. This study assessed FVIII, Protein C and Protein S response following multi modal therapy for oesophageal carcinoma. Methods: Fifty oesophageal cancer patients were studied, (multimodal n= 25, surgery only, n=25), at time points 0 (pre-operatively, following the first and final cycles of chemoradiation, and on days 1, 3, 7, 14, 21 and 28 days, and at 3 and 6 months postoperatively. Blood samples were collected and centrifuged at 3000g for 20 minutes to botain platelet poor plasmad. Factor VIII levels were measured by one stage clotting assay with factor VIII-deficient plasma. Automated functional assays for Protein C and Protein S in plasma were performed. Results: Factor FVIII levels were significantly elevated in the multimodal cohort following the 1st (p<0.008) and 2nd (p<0.001) cycles of chemoradiotherapy and at all time points following surgery, compared to baseline readings (p<0.001). Similar elevation was noted in the surgery only patients. No significant difference in factor FVIII levels between the multimodal group and surgery only patients was seen, except on day 21 (p < 0.04). Preliminary findings indicate a significant difference between the multimodal and surgery only cohorts in Protein C (0.74–1.32 IU/ml) levels (p < 0.05) at two timepoints. Conclusion: Factor VIII serum levels are significantly elevated following preoperative chemoradiotherapy. The pattern of response post oesophagectomy did not differ between the two cohorts. Elevated levels are a risk factor for both primary and recurrent venous thrombolism. The precise pathogenetic mechanism and cause of this elevation remains to be elucidated. Further studies investigating Protein C activity and, relating Factor VIII to thrombosis and inflammation in the oesophageal cancer patient are required. No significant financial relationships to disclose.
The utility of HCC screening among cirrhotics
Authors: Niravath P. , Hayes T. , Hilsenbeck S. 
Published: March 2020

15108 Background: Screening known cirrhotics for hepatocellular cancer (HCC) has long been a contentious topic. Studies to date have failed to conclusively prove or disprove the validity of AFP and hepatic ultrasound as screening mechanisms for HCC among cirrhotics, particularly in the American population. It is not clear whether these screening mechanisms provide any benefit in terms of reduced morbidity and mortality. Methods: The study examined all cirrhotics who developed HCC at the Houston Veterans Affairs Medical Center between 1999 and 2005. Those who were screened with AFP and/or imaging (either ultrasound, triphasic liver protocol CT, or MRI) were compared to those patients who were not screened at all. The screened and unscreened patients were compared in terms of Barcelona Clinic Liver Cancer Stage (BCLC) at the time of diagnosis. Results: Statistical analysis revealed a significant difference between the screened and unscreened groups in terms of BCLC stage at diagnosis, with the unscreened group being diagnosed at later stages than the screened group. Of the 155 patients observed, 26 were appropriately screened, and 129 were not. The BCLC stages at diagnosis for the two groups are shown in the table . The different trend in the two groups was found to be statistically significant with a p-value of 0.004. Furthermore, among the screened group, no particular method of screening (AFP vs. imaging vs. combination) was shown to be superior to another. Conclusions: Screening for HCC among cirrhotics using AFP and/or imaging every 6 months does correlate with HCC diagnosis at an earlier BCLC stage, thus portending better treatment options and improved prognosis. Therefore, screening all known cirrhotics for HCC may lead to decreased mortality. [Table: see text] No significant financial relationships to disclose.
Patterns of care and outcome of patients with gastroenteropancreatic neuroendocrine tumors (GNETs): Results from a Spanish multi-center hospital-based tumor registry
Authors: Garcia-Carbonero R. , Vilar E. , Alonso V. , Martínez del Prado M. , Sevilla I. , Crespo G. , Teulé A. , Llanos M. , Castellano D. , Salazar R. ,   Spanish Group of Neuroendocrine Tumors (GETNE)
Published: March 2020

15110 Background: GNET represent an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. To provide information regarding demographic characteristics, diagnostic procedures, tumor features, therapeutic interventions and outcomes of pts with GNETs, a national tumor registry was launched. We present here the results of this broad-based multi-institutional observational registry that comprises 41 sites representing all regions of Spain. Methods: Data was provided at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers. Results: The study cohort comprised 474 pts (57% male, median age: 59 years). 52% were carcinoids (C), 18% non-functioning pancreatic tumors (PT), 9% insulinomas and 6% gastrinomas. Most common primary tumor sites included midgut (19%), and head (14%) and body of the pancreas (9%). 10% were of unknown primary. Functioning symptoms led to diagnosis in 29% of cases. 5% were associated to MEN1. Diagnostic workup included serum hormone tests (60%), ultrasound (40%), CT scan (75%) and octreoscan (37%). 32% of pts presented with localized tumors (L), 14% with local-regional spread (LR) and 44% with advanced disease (Adv). Treatment for Adv disease consisted of somatostatin analogues (SA) (48%), surgery (45%), chemotherapy (CT) (42%), interferon (IFN) (23%), chemoembolization (9%) and radiofrequency ablation (5%). 5-year survival (5yS) for the whole group was 61.1% (SD:3.4%), 78.2% (SD:5.4%) for pts with L/LR disease and 47.1% (SD:5.6%) for Adv stages. 5yS rates were similar for C and PT tumors, also when stratifying according to tumor stage (84 and 76% for local-regional disease, and 51 and 49% for Adv disease). 1st line systemic therapy (n=175) consisted of CT (42%), SA (39%), IFN (5%), SA+IFN (10%) and SA+CT (3%), with 5yS rates of 59%, 36%, 42%, 46% and 38%, respectively (p=0.7). As second line systemic treatment (n=65) 45% received CT, 26% SA, 15% immunotherapy and 14% different drug combinations. Conclusions: This national database reveals relevant information regarding current Spanish practices and will provide valuable insights into the epidemiology and management of this heterogeneous uncommon disease No significant financial relationships to disclose.
Response to trans-arterial chemoembolization prior to orthotopic liver transplantation or hepatic resection in patients with hepatocellular carcinoma
Authors: Almhanna K. , Golshayan A. , Sands M. , Levitin A. , Kim R. , Pelley R. , Kalmadi S. 
Published: March 2020

15114 Background: Trans-arterial chemoembolization (TACE) is often used as pre-operative therapy for patients with hepatocellular carcinoma (HCC) prior to orthotopic liver transplantation (OLT) or hepatic resection (HR). However, the benefit of response to TACE on overall survival (OS) and progression free survival (PFS) remains unclear. Methods: Complete data was available for 24 patients with HCC who underwent TACE prior to either OLT or HR from 1998–2006. Known prognostic factors including tumor size, histology, number of nodules, Child-Pugh class, Okuda stage, MELD score, CLIP score were recorded. Clinical features before and after TACE were identified and tested by univariate analysis. Results: The mean patient age was age 51 years (range 31–65). Underlying diagnoses included: HBV (17%), HCV (54%), alcohol abuse (63%), cryptogenic (8%), nonalcoholic steotohepatitis (4%). The mean maximum tumor diameter was 6.2 cm (range 1.6–16.1 cm), with 13 tumors (54%) measuring >5 cm. The median number of lesions were 2 (range 1 - 7). The Milan criteria was met in 15 patients (63%). Eighteen subjects underwent OLT, while 6 had HR. Median PFS was 35 months (m) (95% C.I. 17–58 m). One- and three-year OS were 95.8% and 73%, respectively. TACE was performed within a mean time of 2.5 months from diagnosis (range 0.5–9 m). Post-TACE, eleven subjects demonstrated a biologic response, defined as decrease in serum alfa-fetoprotein (AFP) by >50%, or reduction in AFP level to <10 ng/mL. However, biologic response did not predict for improved PFS (p =0.41). Additionally, nine patients had a radiographic response to TACE as measured by RECIST criteria, but this also did not predict for improved PFS (p = 0.79). Only tumor size >5 cm (p = 0.04) and CLIP score (p = 0.01) were found to be independent predictors of improved PFS. Conclusions: Neither radiographic nor biologic responses to TACE appear to serve as selection criteria for OLT or HR. Those patients who fail to demonstrate response to TACE should not necessarily be denied surgical therapy. Larger, prospective trials are needed to better evaluate which patients will benefit most from TACE prior to OLT or HR. No significant financial relationships to disclose.
Maltodextrin supplemented diet prevents postoperative weight loss during the first months after gastrectomy for gastric cancer
Authors: Raida M. , Mestrom H. , Delbrück H. 
Published: March 2020

15127 Background: Postoperative nutritional status is a major factor determining the outcome after gastrectomy for gastric cancer. However, weight loss is a regular consequence after gastrectomy for gastric cancer. This weight reduction occurs during the first months, after which the weight curve seems to stabilize. Aim of this study was to determine the effect of maltodextrin supplemented diet on postgastrectomy weight loss. Methods: In 2005 we introduced a liquid supplementation of maltodextrin to the conventional solid dietary schedule of patients who had underwent gastrectomy for gastric cancer. Between 01/2005 and 6/2006 87 consecutive patients with gastric cancer were included in the study. They were admitted to our hospital for a 3–4 weeks period of oncological rehabilitation, median age was 70 years, gastrectomy had been carried out up to 8 months before study inclusion. Oral nutrition followed the recommended dietary guidelines to avoid postgastrectomy dumping syndrome. This diet was supplemented with 150 g of maltodextrin, dissolved in 1 litre of tea (600 kcal). Weight changes in this study population were compared to a control population of 65 consecutive patients with gastric cancer who had been admitted to our hospital between 01/1992 and 12/1993, matching the same inclusion criteria as the study population but fed without the supplementation of maltrodextrin. Results: During the 3–4 weeks rehabilitation period patients from the maltodextrin study group were able to reach an average weight gain of 407g while patients from the control group lost in average 352 g during the same time span. We observed that weight gain substantially improved the psychological condition of the patients. Postgastrectomy dumping syndrome was similar in both groups depending on strict control of the dietary schedule. Conclusions: We conclude that a maltodextrin supplemented diet can effectively prevent postoperative weight loss during the first months after gastrectomy for gastric cancer. No significant financial relationships to disclose.
The hormone replacement therapy opposed to low dose tamoxifen (HOT) study: safety data from an ongoing phase III trial
Authors: Bonanni B. , Santillo B. , Serrano D. , Rotmensz N. , Muraca M. , Vella A. , Belloni C. , Ponti A. , Veronesi U. , Decensi A. 
Published: March 2020

1514 Background: Primary prevention trials have shown that tamoxifen (T) lowers ER+ breast cancer (BC) incidence by 48%. While the IBIS I update showed mixed findings, the Italian trial showed an interesting positive risk/benefit ratio in T and hormone replacement therapy (HRT) users: fewer BC, endometrial cancer comparable to placebo, and no cardiovascular diseases (CVD) excess. In a phase II study, low dose T and HRT showed a safe gynecological profile and did not increase menopausal symptoms. Moreover low dose T maintains the same antiproliferative effects as the standard dose. To improve BC prevention and quality of life (QoL) in menopausal women we started a multicentric, phase III trial of low dose T in HRT users. Methods: current or de novo HRT users are randomized to T 5 mg/day or placebo for 5 yrs. The primary aim is the reduction of invasive or in situ BC. Secondary aims are: safety, gene polymorphisms (SNPs) correlated to BC risk and T activity. In a subgroup transvaginal ultrasound (TvUS) and endometrial biopsy is being performed after 3 years of treatment to monitor endometrial effects. Results: as of December 31 2006, 1870 women were enrolled, of which 21% were hysterectomized. Median age is 53 years (33–72), BMI is <25 in 66%, =25<30 in 26%, >30 in 8%. Current or de novo users are 80% and 20%. 84% participants have at least one follow-up visit. 128 subjects performed already the 3 years TvUS and endometrial biopsy: so far no atypical hyperplasia or cancer was found. A modest increase of menopausal symptoms was observed (hot flashes 42% vs 52%, night sweating 39% vs 44%). Drop-outs are 23%, of which 13% due to AE including: 21 cancers (12 invasive BC, 1 DCIS), 13 CVD (3 VTE), 9 gynecological (5 endometrial polyps). Conclusions: combination of low dose T and HRT has reasonable safety profile, we have reached almost 1,900 women on study and AE rate is very low. These unblinded findings support the safety of the association of HRT and T. No significant financial relationships to disclose.
Chemotherapy in gallbladder cancer: Improving survival
Authors: Gallardo J. , Rubio B. , Ahumada M. , Villanueva L. , Barajas O. 
Published: March 2020

15140 Background: Since 1999 we had been studying the effect of chemotherapy in gallbladder cancer, a disease frequent in low economical income area of the world, orphan of research, traditionally considered chemotherapy-resistant. Previous studies included 5- FU regimen and communicated response rate of 10–26 %, and no changes on survival. We first conducted a phase II study with gemcitabine (Gem), and later, another study (with support of GOCCHI) using Gem and cisplatin (C). Since 2001 we had treated patients out of clinical trial. We compare median survival observed in all series. Methods: Patients file of both 2 phase II studies and clinical record of all patients treated out of clinical trial were retrieved and median survival was calculated. The both phase two trials had a similar population, and inclusion criteria, both were multicenters. The third cohort is a one center experience. The regimens used were: Gem 1,000 mg/m2 on days 1,8 and 15 every 28 days (first trial), Gem 1,250 mg/m2+C 35 mg/m2 on the 1 and 8 days every 21 days (second trial), only maximum 6 courses were planned. The third group, most frequently, received Gem 1.000 mg/m2 (10mg/m2/min)+C 40 mg/m2 days 1 and 8 every 21 days, until disease progression and/or toxicity; second line chemotherapy was allowed. Among whole group 7 pts, who had significant response, underwent a surgical resection. Survival was also calculated and comparison is included. The toxicity was evaluated every 2 weeks and response was assessed every two cycles using CT scan. Overall survival was calculated from beginning of chemotherapy until death or last follow up. Survival analysis was also done using Kaplan Meier’s tables Results: For Gem monotherapy (26 pts) median survival was 30 weeks, for Gem+C (44 pts) median survival was 28 weeks. For third group (29 pts) median survival was 56 weeks. Until now, for the 7 pts who underwent a surgical resection median survival is 92 weeks, with one pt alive, without evidence of disease, at 112 weeks of follow up Conclusions: Both regimens showed better efficacy than 5-FU based chemotherapy, the combination did not show better survival. The third group has better median survival, probable due to the use of second line therapies. Combining chemotherapy + surgical resection may be a better treatment for some few, well selected patients. No significant financial relationships to disclose.
Taxane based neoadjuvant chemotherapy in locally advanced esophageal cancer: A single centre experience
Authors: Ambulkar I. B. 
Published: March 2020

15143 Background: Neoadjuvant taxane based chemotherapy may improve response rate in patients with locally advanced esophageal cancer. We have evaluated paclitaxel based induction chemotherapy in patients with locally advanced esophageal cancer to determine its feasibility, clinical response, radiological and endoscopic response. Methods: etween November 2004 to October 2006, 30 patients were enrolled in this study. All patients were categorized as locally advanced esophageal cancer. They underwent CT scan chest and upper GI endoscopy before chemotherapy and 3 cycles after the chemotherapy. Chemotherapy included 3 cycles of paclitaxel (135 mg/m2 on day 1),5FU (500 mg/m2 on day 1,2,3) and cisplatin (25 mg/m2 on day 1,2,3) every 21 days. The main endpoint was response evaluation. Twenty one (70%) had squamous cell carcinoma and 9(30%) had adenocarcinoma. Median age was 44 years (39–75), 22(73.3%) were males and 8 were(26.6%) females. Dysphagia was the predominant symptom in 28 (93.3%) patients. Results: All 30 patients were evaluable for response and toxicity. Radiological and endoscopic CR was seen in 6(20%), PR in 16(53.3%),5(16.6%) had SD and 3(10%) had PD. Twenty five (83.3%) patients underwent radiotherapy to a total dose of 4500 cGY,5(16.6%) underwent surgery, 2(6.6%) showed complete pathological response. Observed toxicity was predominantly hematologic and leucopenia grade III/IV in 10% of cycles, Hb grade III/IV in 6.6% and thrombocytopenia grade III/IV in 3% of cycles.6.6% patients developed grade III/IV oral mucositis. Conclusions: Addition of paclitaxel to cisplatin and 5FU as neoadjuvant chemotherapy in esophageal cancer appears to be highly effective with complete as well as partial response rates. It can be given safely with manageable side effects. It is predicted that combination of paclitaxel, cisplatin and 5FU having excellent response as neoadjuvant therapy will also produce long term benefits. No significant financial relationships to disclose.
Clinical outcome prediction in esophageal adenocarcinoma based on tumor and germ-line single nucleotide polymorphisms (SNP) in DNA-repair pathways
Authors: Yoon H. , Murphy K. M. , Gibson M. K. 
Published: March 2020

15144 Background: Germ-line SNPs in DNA repair enzymes are studied as predictive factors in various cancers. More rarely studied, however, is the presence of SNPs in tumor cells and how they relate to both germ-line SNPs as well as outcome. We explored the presence of and relationship between germ-line and tumor SNPs in esophageal adenocarcinoma using two systems: (1) Cell lines, to determine whether loss of heterozygosity (LOH) occurs near DNA repair genes, and for genotyping; (2) Patient samples, to determine whether SNPs differ between normal and tumor mucosa. Methods: (1) For LOH analysis, we examined three short tandem repeat (STR) loci on 19q13.2- 13.3 (near DNA-repair genes XPD, ERCC1, and XRCC1) in four esophageal adenocarcinoma cell lines. (The STR markers have a false positive rate of <10-3 for LOH when all three demonstrate homozygosity.) Then, using a real-time PCR allelic discrimination TaqMan assay (AB), we analyzed two SNPs of interest in these cell lines. (2) We performed SNP analysis on tumor and adjacent normal mucosa from paraffin-embedded esophageal specimens taken at resection in patients with T3N0–1 esophageal adenocarcinoma who received preoperative cisplatin, paclitaxel, gefitinib and radiotherapy followed by transhiatal resection. Results: (1) Cell lines: SEG1 and BiC1 were consistent with LOH, showing a single-allele pattern at XPD 751 (C allele) and XPD 312 (G allele). TE7 and SKGT4 did not have LOH. (2) Tumor and normal tissue: We obtained data on two patients for XPD 751. Genotypes in normal mucosa were heterozygous for one patient and homozygous at the minor allele (Q/Q) for the second patient. Genotypes in tumor were identical to those in normal tissue. Conclusions: Our cell line data shows that LOH occurs in esophageal tumor cells at DNA-repair genes of interest. Our data in two patients with esophageal adenocarcinoma did not demonstrate a difference at XPD 751 between tumor and normal tissue. Given the technical success and encouraging data from this work, we plan to evaluate tissue from ∼90 patients who underwent preoperative cisplatin-based chemoradiotherapy followed by surgery (as part of completed ECOG trial E1201). [Table: see text]