bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic endocrine tumors (PETs): Incidence and recent trend toward improved survival
Authors: Halfdanarson T. R. , Rabe K. , Rubin J. , Petersen G. M. 
Published: March 2020

4584 Background: PETs (islet cell tumors) are uncommon and often indolent tumors, but little is known about the incidence of PETs in the US and trends in survival. Methods: The SEER registry was used to identify cases of functional PETs (fPETs) and non-functional PETs (nfPETs) diagnosed from 1973–2000. Benign insulinomas were excluded. Incidence rates were age adjusted to the standard US population for 2000. Results: Of 971 patients with PETs, 824 (85%) were nfPETs, 37 (4%) were malignant insulinomas, 88 (9%) were fPETs other than insulinoma, and data were missing for 22 (2%). The crude annual incidence of PETs (per 100,000) for all ages was 0.1 in females and 0.2 in males. The incidence was highest in the age group >70 years (0.4, Table ). Tumors were localized in 109 (11%), regionally advanced in 228 (23%), and distant metastases were present in 545 (56%). Patients with fPETs were younger than patients with nfPETs (mean age 54.2 vs. 57.6, p=0.038) and had a longer median survival (MS) (47 vs. 30 months (mos), p=0.001) but were as likely to have advanced disease (p=0.50). The 5 and 10 year overall survival was 45.3% vs. 32.7% and 31.7% vs. 18.1% for fPETs vs. nfPETs, respectively. MS was 95 mos for localized PETs, 66 mos in regionally advanced PETs and 19 mos for distant metastases (p<0.001). Race did not influence incidence and survival. On multivariate analysis, only age (p<0.0001) and stage (<0.0001) were independently associated with prognosis but the functional status of the tumor approached significance (p=0.053). Survival has improved over time with longer MS in patients diagnosed in later quartiles of the observation period (p<0.001, Table). This difference is not explained by stage migration, as patients in all four quartiles had a similar stage distribution (p=0.79). Conclusions: PETs are uncommon tumors and the prognosis is highly dependent on the stage and the age of the patients. Patients with fPETs may have a better prognosis than nfPETs. Survival has improved over time. [Table: see text] No significant financial relationships to disclose.
PET scanning and patient reported dysphagia before and after chemotherapy (CT) for prediction of pathological response after CT and chemoradiotherapy (CRT) in patients with locally advanced esophageal cancer (EC): A multicenter phase ll trial of the Swiss
Authors: Ribi K. , Nitzsche E. , Schuller J. , Klaeser B. , Hany T. , Roth A. , Hess V. , Zuend M. , Lombriser N. , Ruhstaller T. 
Published: March 2020

4587 Background: Only responding patients (pts) ultimately benefit from preoperative therapy for locally advanced EC. To predict response quality after CRT and detect non-responders earlier, we evaluated changes from baseline in FDG uptake by PET scans and patient reported dysphagia after two cycles of CT. Methods: Pts with resectable, locally advanced squamous cell carcinoma or adenocarcinoma of the esophagus were treated with 2 cycles of CT with docetaxel/cisplatin (DC) q3w followed by CRT (DC weekly x5 with concomitant 45 Gy RT) and surgery. PET imaging using [F]-deoxyglucose (FDG) uptake and subjective dysphagia assessment using a quality of life module specific to EC (EORTC QLQ-OES24) were performed at baseline and after the 2nd cycle of CT. 40% decrease of FDG uptake was prospectively hypothesized to be an early predictor for a pathological complete remission (tumor regression grade 1, TRG) and subtotal regression (TRG 2) after the CRT. The predictive value of improvement in dysphagia was tested by analysis of covariance with baseline dysphagia as covariate. Results: Out of included 66 pts, 56 completed preoperative therapy and surgery. Dysphagia scores (range 0–100) were available in 51 pts, mean changes were 14 (n=13), 12 (n=16) and 12 (n=22) for pts with TRG 1, 2 or >2, respectively, lacking any significance. 44 pts had two PET scans (5: centers not participating, 3: no FDG-uptake at baseline, 4: second scan too late or not done). Mean FDG-decrease was 49% (n=7), 44% (n=17), 15% (n=20) for pts with TRG 1, 2 or >2, respectively. Less than 40% reduction in FDG uptake predicted non-response (TRG>2) with sensitivity 70%, specificity 50%, negative predictive value 70% and positive predictive value 50%. FDG- uptake reduction indicated reduced risk of TRG>2 in a logistic regression model (p<0.01, 95%-CI 2–273). Conclusions: Decreased FDG uptake in sequential PET scans strongly correlates with tumor response, but is not accurate enough to early identify non- responders. Early improvement of dysphagia after 2 cycles CT did not predict TRG after CRT. No significant financial relationships to disclose.
Prognosis of hepatocellular carcinoma (HCC): Comparison of four staging systems in two French clinical trials
Authors: Collette S. , Bonnetain F. , Paoletti X. , Doffoel M. , Bouche O. , Raoul J. L. , Rougier P. , Masskouri F. , Bedenne L. , Barbare J. C. 
Published: March 2020

4589 Background: The aims of our study were to compare performances of 4 staging systems and to explore how to improve prognostic classification among French patients with HCC whose main aetiology is alcoholic cirrhosis. Methods: We have pooled 2 RCTs in palliative condition from Federation Francophone de Cancerologie Digestive (FFCD): - FFCD 9403 comparing tamoxifen vs symptomatic treatment and - FFCD 9402 comparing chemoembolization + tamoxifen vs tamoxifen alone. They had respectively included 416 and 122 patients. Performance of Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer group (BCLC) and GRoupe d’Etude et de Traitement du Carcinome Hépatocellulaire scores have been compared using: Akaike information criteria (AIC), discriminatory ability (Harrell’s c and the Royston’s D statistics), monocity of gradients and predictive accuracy (Schemper statistics Vs). To explore how to improve classifications univariate and multivariate Cox model were performed. Variables with univariate p< 0.10 have been retained for multivariate analyses. A forward selection procedure has then been implemented. Bootstraps validation was performed to test the robustness of our results. Analyses were done for each trial and for the pooled database with trial stratification. Results: Median OS was 5,3 months (IC 95%: [4,6; 6,2]), 402 patients had (75%) an alcoholic cirrhosis aetiology . As shown in Table 1 , CLIP staging had the best properties, followed by Okuda and BCLC. Performances of all staging systems were rather disappointing. WHO staging for CLIP or alphafetoprotein for BCLC allowed a significant improvement of prognostic information. Conclusions: Our results suggest that CLIP staging seems to be most adapted to french patients, it could be better by associating WHO PS. An external validation of our result will be performed on another trial in palliative condition. [Table: see text] No significant financial relationships to disclose.
A phase II study of weekly paclitaxel and doxifluridine (an intermediate metabolite of capecitabine) combination chemotherapy for advanced/recurrent gastric cancer
Authors: Takeyoshi I. , Makita F. , Tanahashi Y. , Iwazaki S. , Nakamura S. , Ishikawa H. , Ogawa T. , Ohya T. , Kawate S. , Horiguchi J. , Morishita Y. 
Published: March 2020

4593 Background: Paclitaxel and doxifluridine (5’-DFUR; an intermediate metabolite of capecitabine), which have distinct mechanisms of action and toxicity profiles, each have considerable single-agent activity in gastric cancer. A synergistic interaction between these two drugs was suggested from the taxane-induced upregulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. Therefore, this study evaluated the antitumor activity and toxicities of paclitaxel and 5’-DFUR in combination in patients with advanced/recurrent gastric cancer (AGC) Methods: Patients with histologically confirmed AGC, which was unresectable or metastatic, PS 0–2, and over 20 years old were eligible for this study. The treatment included paclitaxel 80 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and doxifluridine 533 mg/m2 p.o. on days 1–5/week until there was disease progression or the appearance of unacceptable toxicity. Results: Between April 2003 and May 2006,104 patients were enrolled in this study. Their median age was 67.0 years (range: 36–82) and 87 patients were male. Forty-three patients had advanced gastric cancer and 61 had recurrent gastric cancer. After a median of 3 (range: 1- 21) cycles of chemotherapy, 104 patients were evaluated for toxicity and 93 patients were evaluated for response. In the intention-to-treat analysis, the overall response rate was 32.3% (95% C.I., 22.8–41.8%), including 2 CR, 28 PRs, 37 SDs, 16 PDs, and 10 NEs. The first-line therapy involved 48 patients (primary advanced or surgery alone) in whom the response rate was 41.7% (95% C.I., 27.7–55.6%). The second-line therapy involved 40 patients (72.5% TS-1 failure) in whom the response rate was 22.5% (95% C.I., 9.6–35.4%). The median overall survival was 287 days. The actual dose intensity was 81.7% (85/104) of the planned dose during the first two cycles for both drugs. Commonly observed grade 3/4 adverse events were leukopenia (13.5%), anorexia (3.8%), fatigue (3.8%), and diarrhea (2.9%).There was no neutropenic fever or treatment-related death. Conclusions: These data suggest that Paclitaxel and 5’-DFUR combination chemotherapy is a well tolerated convenient out-patient combination with very promising efficacy for AGC. No significant financial relationships to disclose.
Low expression of bax predicts poor prognosis in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy
Authors: Kang S. , Han J. , Lee K. , Choi J. , Park J. , Lee H. , Kim H. , Kim J. , Kang S. , Oh Y. , Sheen S. 
Published: March 2020

4597 Background: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, bcl-2, bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Sixty-three patients with locally advanced esophageal cancer (stage II-IV) were treated with definitive CRT using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, bcl-2, bax, and galectin-3 expression by immunohistochemistry. Results: High expression of bax, p53, bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, bcl- 2, and galectin-3 did not demonstrate correlation with clinicopathologic characteristics, including patient outcome. Low expression of bax was significantly correlated with clinical complete response (p=0.023). Low expression of bax was also associated with poor OS (median, 8 months vs. 16 months; P=0.0008) in univariate analysis. In multivariate analysis, low expression of bax was the most significant independent predictor of poor OS (p=0.01) followed by clinical complete response and low radiation dose. Conclusions: Low expression of bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with CRT using 5-fluorouracil and cisplatin. Immunohistochemical staining for bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients. No significant financial relationships to disclose.
Pharmacogenetic profiling and clinical outcome of patients (pts) with advanced gastric cancer (AGC) treated with S-1 monotherapy
Authors: Ichikawa W. , Takahashi T. , Sasaki Y. 
Published: March 2020

4600 Background: Intra-tumor gene expressions of thymidylate synthase (TS) and orotate phosphoribosyltranseferase (OPRT) have been indicated to be positive predictive markers for the clinical outcome of pts treated by S-1 monotherapy for AGC (Int J Cancer 119:1245,2006). The aim of this study is to investigate whether polymorphisms with putative influence on S-1 activity are associated with clinical outcomes of pts with AGC. Patients and Methods: The study population consisted of consecutive 55 pts with AGC from 01/1999 to 03/2002 in our institute. All patients homogenously received the S-1 monotherapy (80mg/sqm/day, 4 wks with 2-wks drug holiday) as a first line treatment. The overall response rate was 40% and the median overall survival (OS) was 8.0 months (range, 2.1 to 23.0 months). Genomic DNA obtained before starting chemotherapy was used for genotyping 8 polymorphisms in 5 genes (DPD, TS, OPRT, MTHFR, CYP2A6). Results: No alleles of DPYD*2 were found in this Japanese cohort. There were no association among the clinical outcome, such as tumor response and OS, and genotypes including tandem repeat (VNTR) in TS 5’UTR, G/C polymorphism with in the 3R VNTR, OPRT G638C, MTHFR C677T, CYP2A6*4, and CYP2A6*9. Even if TS 5’UTR and G/C polymorphism were combined, TS 5’UTR 3G genotype (2R/3G, 3C/3G, 3G/3G) was not associated with the clinical outcome. Only 6-bp insertion/deletion (ins/del) in the TS 3’UTR was closely related to both tumor response and OS. The response rates were 23% and 55% in pts with del/del genotype and pts with ins/ins or ins/del, respectively, with a statistical significance (P=0.015). The median OS was 9.5 months in pts with the ins allele versus 6.2 months in pts with del homozygote (P=0.0345). Conclusion: This exploratory study shows that polymorphism in TS 3’UTR may influence clinical outcomes of AGC pts treated by S-1. No significant financial relationships to disclose.
A phase II trial of perioperative chemotherapy with folinic acid, 5-fluorouracil, and oxaliplatin in potentially resectable gastric cancer with regional lymph node metastasis
Authors: Im S. , Kim S. , Kim J. , Lee H. , Kim M. , Kim S. , Kang W. , Yang H. , Song I. , Bang Y. 
Published: March 2020

4602 Background: Peri-operative chemotherapy in operable advanced gastric cancer (AGC) is still in a controversial area. Results from MAGIC trial suggest that a peri-operative regimen of ECF (epirubicin, cisplatin, 5-FU) decreased tumor size and significantly improved PFS and OS in patients with operable AGC (NEJM 355: 11, 2006). The aim of this study was to evaluate the efficacy and toxicity of folinic acid (FA), infusional 5-fluorouracil (5-FU), and oxaliplatin (modified FOLFOX6), administered every 2 wks in potentially operable AGC with regional lymph node (LN) metastasis. Methods: Previously untreated gastric adenocarcinoma patients with measurable LN on CT scan (clinical stage: cT2 or cT3, N+) were eligible. Staging also included a PET-CT and endoscopic ultrasonography (EUS). Patients received 4 cycles of neoadjuvant therapy with FA 100 mg/m2 (2-hr i.v.), 5-FU 2.4 g/m2 (46-hr continuous infusion), and oxaliplatin 100 mg/m2 (2-hr i.v.), followed by curative radical surgery including D2 dissection and 4 cycles of adjuvant modified FOLFOX6. Clinical responses were assessed by RECIST using CT scan before surgery and early metabolic responses were assessed by PET-CT after 2 cycles of chemotherapy. Results: Thirty-one patients were enrolled from Oct. 2004 to Nov. 2006 and currently, 29 of them are evaluable for response. Median age was 56 yrs (range, 35–69). Most patients had EUS T3N1or2 designation. Of 29 evaluable patients, PR were observed in 19 (66%), SD in 9 (31%), and PD in 1 (3%) patient. Early metabolic responses (SUV decrement = 35% by PET-CT) were significantly correlated with conventional radiographic response (p=0.037). The R0 resection rate was 90% and pathologic CR was 7%. Median follow-up duration was 11.8 mo. and median PFS has not been reached yet. Total 219 cycles were administered. G3/4 neutropenia occurred in 6 cycles (3.0%). Nausea G3/4 occurred in 1 cycle (0.5%) and diarrhea in 1 cycle (0.5%). There were no cases of peripheral neuropathy G3/4 or febrile neutropenia G3/4. Conclusions: Peri-operative chemotherapy with modified FOLFOX6 is very effective and feasible in patients with potentially resectable AGC with regional LN metastasis. Early response can be predicted by PET-CT. No significant financial relationships to disclose.
A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for advanced gastric cancer
Authors: Yan T. D. , Black D. , Sugarbaker P. H. , Yonemura Y. , Zhu J. , Morris D. L. 
Published: March 2020

4614 Objectives: Despite the use of adjuvant systemic chemotherapy or radiotherapy, the long-term survival in patients with stage III and IV gastric cancer remains limited. The purpose of this systematic review and meta-analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with advanced gastric cancer. Methods: Studies eligible for this systematic review included those in which patients with gastric cancer were randomly assigned to receive surgery combined with intraperitoneal chemotherapy versus surgery without intraperitoneal chemotherapy. All forms of intraperitoneal chemotherapy in addition to surgery were included. There were no language restrictions. Quality of the trials was assessed by a predetermined checklist. The primary end-point of the meta-analysis was overall survival, defined as the time from random assignment to the last follow-up or death. Secondary end-points were the differences in the incidence of recurrence, morbidity and mortality. Results: Thirteen reports of randomised controlled trials (RCTs) were included for appraisal and data extraction. Ten reports were judged fair-quality and subjected to the meta-analysis. A significant improvement in survival was associated with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) alone (HR = 0.60; 95% CI = 0.43 to 0.83; p = 0.002) or combined with early postoperative intraperitoneal chemotherapy (EPIC) (HR = 0.45; 95% CI = 0.29 to 0.68; p = 0.0002). Survival improvement was marginally significant (HR = 0.67; 95% CI = 0.44 to 1.01; p = 0.06) with normothermic intraoperative intraperitoneal chemotherapy, but not significant with EPIC alone or delayed postoperative intraperitoneal chemotherapy. Intraperitoneal chemotherapy was also found to be associated with higher risks for intra-abdominal abscess (RR = 2.37; 95% CI = 1.32 to 4.26; p = 0.003) and neutropenia (RR = 4.33; 95% CI = 1.49 to 12.61; p = 0.007). Conclusion: The present meta-analysis indicates that HIIC with or without EPIC after resection of advanced gastric primary cancer is associated with an improved overall survival. However, increased risks of intra-abdominal abscess and neutropenia are demonstrated. No significant financial relationships to disclose.
Phase 2 study of talabostat/gemcitabine in Stage IV pancreatic cancer
Authors: Nugent F. W. , Cunningham C. , Barve M. A. , Fisher W. , Patel H. , Meiri E. , Oza Y. V. , Yang Z. , Jurkowski E. C. , Uprichard M. J. 
Published: March 2020

4616 Background: Talabostat is an oral small molecule inhibitor of fibroblast activation protein (FAP), a stromal enzyme with collagenase and dipeptidyl peptidase activity. Talabostat also upregulates cytokine and chemokine production, resulting in immune stimulation. Talabostat is active in pancreatic tumor xenograft models and enhances the activity of gemcitabine in mice. Therefore, a clinical trial in patients with metastatic pancreatic cancer was initiated. Methods: Open-label, single-arm, Phase 2 study in 60 evaluable patients with Stage IV pancreatic cancer. Study treatment is administered in 4 x 4-week cycles; gemcitabine 1g/m2 weekly for 4 weeks in Cycle 1, then once weekly for 3 of 4 weeks. Talabostat 200mcg tablets are given BID for 6 days following each gemcitabine infusion; dose-escalation to 300mcg BID is allowed post-Cycle 1. Either agent alone or in combination can be continued beyond 4 cycles depending on tolerability. Eligible patients have measureable Stage IV pancreatic adenocarcinoma (per RECIST) are chemotherapy-naive, have a KPS ≥50, no CNS metastases, transaminases < 3 X ULN, and total bilirubin < 1.5 X ULN. Primary endpoint is 6-month survival with secondary endpoints of overall survival, PFS, pain, and quality-of-life. Tumor response or PD is assessed per RECIST. Results: As of the cut-off date, 46 patients (30 men, 16 women, median age 66 [range 43–88 years]) have received study treatment. Most patients (76%) were Stage IV at original diagnosis, and 72% have a KPS of 80 or higher. Ten of 21 evaluable patients treated as of June 30, 2006 meet 6-month survival. Median overall survival is currently estimated at 4.8 months (95% CI: 2.9, NE) in all 46 patients, and median PFS at 3.5 months (95% CI: 2.0, 4.9). Tumor responses have been reported in 3 patients: one CR and 2 PRs. Pain and QOL have not yet been analyzed. AEs are consistent with those of gemcitabine, with the exception of edema in 28.3% of patients. Grade 3 anemia, neutropenia, hyponatremia hyperbilirubinemia, and increased alk phos are reported in 2 patients each. No Grade 4 AEs have been reported in more than one patient. Conclusions: Talabostat/gemcitabine shows activity in metastatic pancreatic cancer and can be safety administered. Enrollment completed in early January 2007, and final results will be presented at the annual meeting. No significant financial relationships to disclose.
Simplified LV5FU2-irinotecan (FOLFIRI) in the first-line therapy of well-differentiated endocrine carcinomas of the duodeno- pancreatic area: Preliminary results of the FFCD 0302 phase II trial with GTE participation
Authors: Cadiot G. , Bonnetain F. , Landi B. , Bouché O. , Mitry E. , Bedenne L. , Ruszniewski P. , Ricard F. , Vitry F. , Jouve J. L. 
Published: March 2020

4620 Introduction: Few chemotherapies have been tested in the first-line treatment of endocrine carcinomas. The aim of the study was to evaluate the efficacy of FOLFIRI in the first-line therapy of evolutive, metastatic or locally invasive, well-differentiated endocrine carcinomas of the duodeno-pancreatic area. Methods: To show a 6-month tumoral non-progression (RECIST) rate ≥ 60% (a = 5%), 20 pts had to be included in a phase II, prospective, multicentric trial. Inclusion criteria were : well-differentiated endocrine carcinoma of the duodeno-pancreatic area, functioning or non functioning, with hepatic or extra-hepatic metastases or locally invasive tumor > 50 mm, not resectable; tumoral growth within 6 months; no previous antitumoral therapy except interferon ( = 3 months) or somatostatin analogs; PS 0–2. Treatment administration every 14 days : D1 : irinotecan 180 mg/m2, folinic acid 400 mg/m2, 5 FU 400 mg/m2 bolus; D1-D2 : 5 FU 2,400 mg/m2 in 46 hrs. Evaluation (clinical, radiological, biological) every 3 months. In case of progression during a chemotherapy free-interval following an objective tumoral response, treatment was reintroduced. All analyses were performed in intent to treat. Data cut off was done at July 1st 2006. Results: Between May 2004 and July 2005, 20 pts (13 M, 7 F) were included with median age 57 yrs (37–82). 19 pts had liver metastases and 1 pt had metastatic lymph nodes. 5 tumors were functioning; 2 pts had MEN 1. Median proliferation index was 7% (0–58). All pts were treated and evaluation at 6 months for the primary endpoint was available in 19 pts. The 6-month non-progression rate was 75% (CI 95% = 51–91%,), including 14 stabilization (70%) and 1 partial response (5%). 4 pts had 1 chemotherapy free-interval and 2 pts had 2 with reintroduction of the same chemotherapy regimen. Median number of cycles was 11.5 (1–28). 80% had at least 1 grade 3–4 toxicity and 25% had grade 3–4 hematological toxicity. 10% had grade 3 diarrhoea.. Conclusion: FOLFIRI has an antitumoral effect in the first-line therapy of evolutive well-differentiated pancreatic endocrine carcinomas. Frequency of grade 3–4 toxicities can be explained by length of therapy. No significant financial relationships to disclose.