bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thiazolidinedione (TZD) exposure and risk of squamous cell carcinoma of head and neck (SCCHN)
Authors: Govindarajan R. , Siegel E. R. , Simmons D. L. , Lang N. P. 
Published: March 2020

1511 Background: Peroxisome proliferator-activated receptor γ (PPARγ), a nucleic acid receptor, heterodimerizes with retinoic acid X receptor (RXR). Ligand activation of RXR leads to decreased proliferation of SCCHN cell lines. TZDs (syn: glitazones), used to treat diabetes mellitus (DM), are ligands for the RXR:PPARγ heterodimer. A retrospective study of diabetics attending the Veterans Affairs (VA) health care system was undertaken to assess the association between TZD exposure and the risk of developing SCCHN. Methods: Data were obtained from the electronic patient database VISN 16 (covering 10 VA institutions) for males aged ≥40 presenting with DM and no prior SCCHN between 10/01/96 and 12/31/03. DM and SCCHN diagnoses were identified using ICD9 codes. Subjects were followed until 12/31/05, and analyzed for SCCHN risk via Cox regression, using time-dependent covariates to model exposure to TZDs, insulin and other anti-DM agents. Results: 130,406 subjects met the study criteria. Median (quartiles) age at DM presentation was 64 (55–72).18.5% were African-American, 61.3% were Caucasian, and 20.2% were other/unknown. The table shows TZD exposure, SCCHN incidence and hazard ratios for SCCHN with exposure to TZD alone or in combination with insulin and other anti-DM agents after adjusting for age, race, BMI, and HbA1C. Conclusions: A 41%-55% reduction in the risk of SCCHN was observed in diabetic subjects treated with TZD alone, with insulin, and with other anti-DM agents. The decrease was statistically significant (P<0.05) for TZD alone and TZD with other agents, but not for TZD with insulin. These findings suggest a protective effect of TZD on the development of SCCHN. The mechanism is not clearly known but possibly mediated through RXR:PPARγ pathway. [Table: see text] No significant financial relationships to disclose.
Is there a role for neoadjuvant chemotherapy in the management of non-carcinoid epithelial neoplasms of the appendix?
Authors: Katz M. H. , Mansfield P. F. , Eng C. , Wolff R. A. , Diaz P. , Ng C. , Lambert L. 
Published: March 2020

15115 Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) are considered the standard of care for patients with pseudomyxoma peritonei (PMP) and carcinomatosis of appendiceal origin. The role of neoadjuvant chemotherapy (CTX) in the management of these patients is unknown. Methods: Retrospective analysis of all patients evaluated for the treatment of appendiceal epithelial neoplasms at a tertiary center between 1992 and August 2006. All diagnoses were confirmed pathologically and classified by a single group of pathologists. Patients with carcinoid tumors or metastases to the appendix were excluded. Tumor histology, stage, peritoneal-based disease, and the potential for complete cytoreduction dictated treatment. Results: 250 consecutive patients were evaluated, 140 of whom had low grade disease. 114 underwent CRS and HIPEC. Median follow-up was 24 mos from referral. Average time to referral was 13 mos after diagnosis (range 0–243); 85% had undergone prior surgical therapy (median 1.3 operations, range 1–4); 22% had previous CTX consisting of many different regimens. 5- and 10-year survival for patients with low grade tumors treated with CRS and HIPEC alone (n=80) were 84% and 68%, respectively. 21 patients with low grade tumors had CTX prior to CRS and HIPEC. There was no effect on overall survival (p = 0.61). 5-and 10-year survival of 39 patients with low grade histology who did not receive CRS and HIPEC was 55% and 30%, respectively (p = 0.009). 83 patients with intermediate and high-grade disease who received CTX but not CRS and HIPEC had a 5- year survival of 27%. 5-year survival for patients with intermediate or high grade disease who underwent CRS and HIPEC (n=13) was 67%. Conclusions: Patients with peritoneal-based disease from non-carcinoid epithelial neoplasms of the appendix who undergo CRS and HIPEC have a more favorable survival. Currently there is no survival advantage to the use of CTX before CRS and HIPEC for low grade appendiceal neoplasms. The role of neoadjuvant CTX and biologic agents for patients with high grade neoplasms needs to be determined. Early referral to a peritoneal malignancy center will help standardized treatment for these patients. No significant financial relationships to disclose.
Synergistic activity of PHY906 with capecitabine in pancreatic carcinoma
Authors: Saif M. W. , Liu S. , Elfiky A. , Jiang Z. , Cheng Y. 
Published: March 2020

15116 Background: Preclinical data indicates that PHY906, a traditional Chinese botanical formulation, can reduce chemo-induced gastrointestinal toxicity while simultaneously enhancing therapeutic efficacy of a broad-spectrum of common anticancer agents. Methods: Male NCR athymic nude mice were transplanted with human PANC-1 cells. To determine the best dose of combinational regimen, two dose ranges of capecitabine, 60 and 180 mg/kg bid for 14 consecutive days with two dose ranges of PHY906, 300 and 900 mg/kg bid on days 1–4 and days 8–11 were administered by gavage in the first experiment. In the second experiment, PHY906 was fixed at 500 mg/kg bid at days 1–4 and 8–11 while dose of capecitabine was increased to 360 mg/kg bid for 14 consecutive days. A dose of 180 mg/kg of capecitabine was also included for comparison with previous experiments. In the third experiment, capecitabine at 360 mg/kg was selected to evaluate effect of different doses of PHY906 ranging from 100 mg/kg to 500 mg/kg on enhancement of antitumor activity of capecitabine. PHY906 was always administered 30 minutes prior to capecitabine. Tumor size, body weight and mortality were monitored daily and mice were sacrificed when tumor size reached 10% of body weight or on Day 21. Results: PHY906 showed enhancement of antitumor activity of capecitabine when both doses of PHY906 were co-administered with both doses of capecitabine in first experiment. In second experiment, increase of capecitabine dose from 180 mg/kg to 360 mg/kg significantly increased disparity of tumor growth rates between capecitabine alone and concomitant use of both PHY906 and capecitabine. Similar results were obtained in third experiment using a dose of 360 mg/kg of capecitabine and 500 mg/kg of PHY906 (p= 0.0018) as compared with control, capecitabine or PHY906 alone. Similar observation was found in mice bearing PAN-2 murine pancreatic cancer. Conclusions: The studies demonstrate that PHY906 potentiates antitumor activity of capecitabine in human pancreatic carcinoma xenograft mouse model in all capecitabine and PHY906 dosing regimens examined. Observed effect appeared to be dependant on dosage of capecitabine. Therefore, we are employing a dose intense weekly schedule for capecitabine with PHY906 in a phase I/II study in patients with advanced pancreatic cancer. No significant financial relationships to disclose.
Treatment of unresectable or metastatic pancreatic cancer in the VA population: Does it improve survival?
Authors: Mekan S. F. , Komrokji R. S. , Beg M. S. , Nahleh Z. A. , Safa M. M. 
Published: March 2020

15121 Background: Locally advanced and metastatic pancreatic adenocarcinoma present as a treatment challenge because of poor outcomes with current treatment modalities. Therapy of unresectable or metastatic disease has not been studied in the VA population. Methods: We reviewed all cases of pancreatic cancer presenting to the system from 1995–2005. Cases were extracted from the VA Cancer Registry (VACCR). Results: There were 5522 cases identified; 5218 were adenocarcinomas. Out of these, there were 263 (5.1%) patients with unresectable locally advanced disease and 2778 (53.2%) patients with metastatic disease. Median survival for patients with unresectable disease was 5.6 months. Chemotherapy was administered to 94 patients and chemoradiation to 31 patients. No difference in survival was noted between the two groups (8.4 vs. 7.9 months, P = 0.434). In patients with metastatic disease, median survival was 2.2 months. Chemotherapy was administered to 760 (27%) patients in this group and showed improved survival as compared to patients who did not receive chemotherapy (5.3 vs. 1.5 months, p = 0.000). Conclusions: In VA patients with locally advanced unresectable disease, there is no difference in survival in patients treated with chemoradiation versus chemotherapy alone. In patients with metastatic disease, chemotherapy conferred a survival advantage. No significant financial relationships to disclose.
Pancreatic cancer and diabetes: Is diabetes a risk factor or the outcome?
Authors: Garg P. , Gupta R. 
Published: March 2020

15123 Background: Though pancreatic cancer ranks eighth among all major forms of cancer related deaths, it accounts for only 3% of all cancers worldwide. Diabetes mellitus type 2 and pancreatic cancer are known to be associated but this relationship decreases inversely with an increasing duration of diabetes. The aim of the present study is to assess whether new onset type 2 diabetes is a risk factor for pancreatic cancer or it results as an outcome of pancreatic cancer. Methods: We conducted a meta-analysis of all available studies to examine this association. Using PUBMED, EMBASE & MEDLINE we searched the literature for studies from 1980 to present. All published studies with quantitative estimates and standard errors, or confidence limits, of the association between type 2 diabetes and pancreatic cancer were included. Studies having patients with an un-defined period of diabetes or diabetes for greater than 5 years before the development of pancreatic cancer were excluded. 14 case control and 11 cohort trials with information on 5807 individuals with pancreatic cancer met the above criteria. Each study was independently reviewed by 2 reviewers. Results: The pooled odds ratio for case control studies for patients with diabetes and pancreatic cancer was 1.98 (95% CI - 1.58–2.42) while that for cohort studies was 1.88 (95% CI - 1.72–2.16). The combined odds ratio was 1.92 (95% CI - 1.62 - 2.38). However in patients who developed pancreatic cancer with in 2 years of diagnosis of diabetes the odd’s ratio was significantly higher (OR- 3.2, 95% CI - 2.24- 4.02). Conclusions: On the basis of above data pancreatic cancer is more likely to occur in new onset diabetes mellitus type 2 than the general population. However, the evidence above is insufficient to conclude that diabetes mellitus is indeed a risk factor for pancreatic cancer. Since the relative risk of developing pancreatic cancer was higher in patients with new onset type 2 diabetes in the first two years, it further supports the hypothesis that the development of diabetes may be a manifestation of early but yet undiagnosed pancreatic cancer. Large population based studies are needed to truly determine this relationship. No significant financial relationships to disclose.
Epirubicin, cisplatin, oral UFT (ECU) combination chemotherapy in metastatic gastric carcinoma
Authors: Kaya S. , Aliustaoglu M. , Dane F. , Gumus M. , Seker M. , Ozturk A. , Salepci T. , Yaylaci M. , Mayadagli A. 
Published: March 2020

15126 Background: Chemotherapy significantly improves survival in comparison to best supportive care in patients with metastatic gastric cancer. In patients for whom a three-drug-combination is considered as the treatment of choice, ECF (epirubicin, cisplatin and 5-FU as a continuous infusion) should be regarded as standard of care. Continuous 5-FU infusion may be replaced by oral fluoropyrimidines. Here, we aimed to evaluate treatment with epirubicin and cisplatin combined with oral UFT with leucovorin (ECU), replacing intravenous 5-FU infusion Methods: Fifty-three patients (17 female, 36 male) with metastatic gastric carcinoma received epirubicin, cisplatin, and oral UFT plus leucovorin in two outpatient chemotherapy clinics, in Istanbul. Epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were administered on day 1; and UFT 300 mg/m2/day was administered in conjunction with oral calcium folinate at a fixed dose of either 45 or 90 mg/day in divided daily doses for 21 days continuously. The treatment was repeated every 3 weeks. The patients were evaluated radiologically for response after each three-cycle period. Age, gender, ECOG performance score (PS), primary cancer localization, and presence of primary curative surgery were analyzed for prognostic factors. Results: Median follow-up was 6 (range 1–12) months. Median age was 57 years (range 27–76). Patients received a median of three courses of treatment (range: 1–6). Over 86% of the patients had PS =1, whereas remaining 13% had PS 2. Forty-three percent of the patients were undergone curative surgery at the time of cancer diagnosis, while 57% presented as metastatic disease. The most frequent site of metastases was liver (42%). Twenty-five percent of the patients showed partial responses, while none showed a complete response. Over 28% of the patients had stable disease resulting in a tumor control rate of 53%, and 47% had progressive disease. Median TTP and OS were 6 and 8.6 months, respectively. In univariate analysis; having PS =1, and presence of primary curative surgery were independent prognostic factors (p:0.042, and p:0.019, respectively) Conclusion: ECU regimen has a significant activity in metastatic gastric cancer. It does not require an infusion pump and intravenous catheter. No significant financial relationships to disclose.
Phase II study of irinotecan plus leucovorin and bolus 5 fluorouracil as first or second line chemotherapy in patients with advanced gastric or esophageal-gastric junction adenocarcinoma
Authors: Gerolymos M. , Koutras A. , Kontogeorgou E. , Iconomou G. , Vourli G. , Tsiata E. , Makatsoris T. , Chrysanthopoulos C. , Kalofonos H. 
Published: March 2020

15128 Background: The aim of this study was to evaluate the activity and safety of 5-fluorouracil (5-FU) / leucovorin (LV) and irinotecan as first- or second-line treatment in patients with advanced gastric adenocarcinoma. Methods: Treatment consisted of irinotecan 80 mg/m2 intravenously (i.v.), followed by LV 200 mg/m2 (i.v.) and 5- FU 450 mg/m2 as an i.v. bolus. Treatment was administered weekly for 6 weeks, followed by a 2-week rest period. Results: Thirty-one patients (23 chemo-naïve, 8 chemo-exposed) were enrolled. The overall response rate was 22.6% and the disease control rate was 38.7%. Among the patients who received the regimen as first-line treatment, objective response rate was 30.4% and the disease control rate was 52.1%. However, progression of the disease was recorded in all the patients receiving the combination as second-line chemotherapy. The median time to disease progression (TTP) was 4 months and the median duration of survival was 7 months. The median TTP was 6 months for patients treated with first-line chemotherapy and 2.5 for those who received study treatment as second line. Furthermore, the median survival duration was 8 months and 6 months, respectively. The most frequent grade 4 toxicity was febrile neutropenia. Grade 3 or 4 non-hematological toxicities were rare. There were no treatment-related deaths. Conclusions: The combination of 5-FU/LV and irinotecan as first-line treatment was found to be well tolerated, with efficacy comparable to that of other regimens in advanced gastric cancer. Accordingly, this regimen can be regarded as one of first-line options, particularly in patients who can not tolerate aggressive chemotherapy. No significant financial relationships to disclose.
Assessment of intra and interfractional organ motion during adjuvant radiochemotherapy in gastric cancer
Authors: Wysocka B. A. , Kassam Z. , Lockwood G. , Brierley J. , Dawson L. , Ringash J. 
Published: March 2020

15132 Background: Adjuvant combined chemotherapy and radiotherapy (RT) in gastric cancer improves survival, however acute toxicity is substantial. Toxicity may be improved with three-dimensional (3D) RT, but organ motion must be considered in planning target volume (PTV) delineation. Methods: Participants (n=22) had baseline free breathing planning CT (CT0) with BodyFix immobilization. Abdominal CTs in free breathing (FB), inhale (I) and exhale (E) states were obtained in weeks 1, 3 and 5 of RT. Datasets were fused to CT0 in Pinnacle3 6.2 planning system using bone registration. Volumes of interest (VOIs) [right (R) and left (L) kidney, liver, stomach, pancreas, celiac axis and porta hepatis] were contoured and points of interest (POIs) were placed at each centre of mass. POIs were manually placed at the left dome of diaphragm and splenic hilum. Organ motion was determined by the difference between POI positions in cranial-caudal (CC), anterior-posterior (AP) and right-left (RL) directions. Maximal respiratory motion was determined from the difference between I and E positions. Interfractional displacement in organs relative to bones at weeks 1, 3 and 5 was determined on FB scans as compared to baseline. Results: Interfractional organ motion was maximal in CC direction with median absolute displacements (range) in mm of: splenic hilum 10 (0–52), stomach 8 (0.4–27.2), liver 7.4 (0.5–23.6), diaphragm 6 (0–28), L kidney 5.7 (0–37.3), R kidney 5.3 (0.2–35.3), pancreas 5.7 (0.3–29.1), porta hepatis 4 (0–14) and celiac axis 1.7 (0–9.1). Median interfraction displacement (range) in CC, AP and RL in mm for all organs was: 5.7 (0- 52), 2.1 (0–23.1), 2.3 (0–15.9). Positional difference between I and E state (median for all organs) was: 16 mm CC, 5.9 mm AP, and 1.7 mm RL with maximal individual breathing excursions of 59.9, 30.2 and 21.1 mm, respectively. Conclusions: Interfraction organ displacement relative to bones can be quantified and used in the safe design of 3D conformal radiotherapy. Respiratory motion can be substantial in some individuals. Accounting for organ motion in 3D RT planning is necessary and may reduce the toxicity of treatment. No significant financial relationships to disclose.
An individual patient data meta-analysis of the immunochemotherapy using lentinan in patients with advanced gastric cancer
Authors: Oba K. , Morita S. , Matsui T. , Kobayashi M. , Kondo K. , Sakamoto J. 
Published: March 2020

15136 Background: An anti-tumor effect of lentinan (LNT), a non-specific immunomodulator, via an immunological response has been reported and combination immunochemotherapy has been examined. However, the survival benefit of LNT for patients with advanced or recurrent gastric cancer (AGC) was unclear in the world. We performed an individual patient data (IPD) meta-analysis in order to evaluate the survival effect of immunochemotherapy using LNT. Methods: A computerized and a manual search procedure were performed to identify all randomized clinical trial (RCT) for chemotherapy in patients (pts) with AGC. Inclusion criteria were RCTs for AGC and to compare any chemotherapy (control group) with the same plus LNT (LNT group). The primary endpoint was overall survival, secondary endpoints includes objective tumor response and toxicity. All analyses were based on IPD. Treatment effects were displayed as hazard ratios estimated by Cox proportional hazard model. A ratio less than unity indicated benefit from LNT. Results: We analyzed IPD of 5 randomized clinical trials for AGC, which met the predetermined inclusion criteria. These 5 trials had a combined total of 650 pts (LNT: 339 pts median age=63, control: 311 pts median age=63). The number of deaths was 83.8% (286/334) in LNT group and 84.8% (262/309) in control group. The overall hazard ratio was 0.83 (95%CI, 0.70–0.98; p=0.03) with no significant heterogeneity between the treatment effects in different trials (χ2 for heterogeneity=3.69; p=0.45). Three hundred and fifty five pts were evaluable for objective tumor response and the response rate was 18.4% (21/185) in LNT group (CR, 0 pts; PR, 21 pts) and 6.3% (5/173) in control (CR, 0 pts; PR, 5 pts). There were no significant differences in the toxicity. Conclusions: This IPD meta-analysis demonstrated that LNT significantly improves both OS and tumor response in pts with AGC. No significant financial relationships to disclose.
Prognostic relevance of the novel TNM-classification system for neuroendocrine tumors of foregut origin
Authors: Pape U. , Jann H. , Berndt U. , Wiedenmann B. 
Published: March 2020

15147 Background: Until recently no TNM-classification existed for neuroendocrine tumors (NET) of the gastroenteropancreatic system. In 2006 Rindi et al. proposed a new TNM-classification system for foregut-NET of gastric, duodenal and pancreatic origin. The present study validates prognostic significance of the new TNM-classification in a cohort from a German referral center. Methods: The case files of 193 patients with histologically proven foregut NET were analyzed retrospectively. Patients were classified according to Capella (1995) and the WHO (2000) and to the new TNM-classification. Uni- and multivariate analysis was performed using log-rank and Cox regression methods. Results: Primary tumors localization was gastric (n=48), duodenal (23) and pancreatic (122); 35 patients (18%) died during the observation period. Overall 5- and 10-year survival rates (YSR) were 76% and 65% resp., while 5- and 10-YSR according to NET-related deaths (74% of all deaths, 26/35) were 83% and 74% resp.. The classifications by Capella and the WHO significantly discriminated between low and high grade malignant NET (p<0,001 and 0,002 resp.), but did not allow further prognostic differentiation. In contrast, the newly proposed TNM-classification system was able to significantly differentiate stage IV NET from all other stages (I vs. IV p=0,001; II vs. IV p=0,001; III vs. IV p=0,008) as well as stage III from stage I NET (p=0,038). Furthermore, the new classification system which includes a grading system according to the mitotic index (Ki67-index; G1 <3%, G2 3–20%, G3 >20%) was also able to significantly distinguish all three groups from each other (G1 vs. G3 p<0,001; G2 vs. G3 p<0,001). On multivariate analysis stage I and II as well as stage III-NET had a decreased hazard ratio (HR) when compared to stage IV-NET (I/II: HR 0,094, p=0,003; III: HR 0,38, p=0,096). In the same model G1 and G2-NET were associated with an decreased HR as compared to G3-NET (G1: HR 0,05, p=0,01; G2: HR 0,20, p=0,002). Conclusions: Here we demonstrate prognostic relevance of the newly proposed TNM-classification system for foregut-NET with statistical significance which therefore provides a new and powerful tool for future classification of NET. No significant financial relationships to disclose.