bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population based study of prognostic factors in stage II colon cancer
Authors: Morris M. J. , Iacopetta B. , Platell C. 
Published: March 2020

3619 Background: Guidelines for the use of adjuvant chemotherapy in stage II colorectal cancer state this treatment may be considered to patients whose tumours show features of poor prognosis. The aim of the current study was to evaluate the prognostic significance of commonly reported clinical and pathological features of this disease. Methods: A population-based observational study encompassing all stage II colon cancer patients diagnosed in the state of Western Australia from 1993–2003 inclusive. A total of 1306 cases treated by surgery alone were identified and had a median follow-up of 59 months (range 0–145). Results: Multivariate analysis revealed the only independent prognostic factors for disease-specific survival were T4 stage (HR=1.75, 95%CI [1.32–2.32], P<0.0001) and vascular invasion (HR=1.63, 95%CI [1.15–2.30], P<0.0001). In the younger patient group (≤75 yrs) who are more likely to be considered for chemotherapy, the same two features showed independent prognostic significance but with higher HR values (1.96 and 2.73 respectively). T4 and/or the presence of vascular invasion identified a “poor” prognosis group comprising 26% of younger cases and having a 5-year survival rate of 71%. The remaining “good” prognosis group showed 84% survival at 5 years follow-up. Conclusion: This study highlights the importance of accurate pathological assessment of T stage and vascular invasion for the prognostic stratification of stage II colon cancer and their subsequent consideration for adjuvant chemotherapy. No significant financial relationships to disclose.
QoL and resource use analysis of tegafur-uracil/LV or 5-FU/LV in first-line metastatic colorectal cancer (mCRC): Final results of a multicenter phase II study
Authors: Sizer B. , Makris A. , Barone C. , Mainwaring P. , Eggleton P. 
Published: March 2020

3631 Background: Tegafur-uracil (UFT) is an effective oral fluoropyrimidine for patients with mCRC. Aims of this prospective phase II study were to evaluate quality of life (QoL), patient preference and healthcare resource use in patients receiving oral UFT/LV or i.v. 5-FU/LV as first-line therapy for mCRC. Safety and efficacy were also assessed. Methods: 243 patients in 3 countries (Austria, Italy and UK) were randomized in a 2:1 ratio to receive either UFT 300mg/m2/d + LV 90mg/d for 28d q5w, or i.v. 5-FU 425mg/m2/d + LV 20mg/m2/d for 5d q4w. Patients were assessed at baseline and every cycle for symptoms, adverse events (AEs), and overall response rate (ORR). QoL was evaluated using EORTC QLQ-C30, and patients completed a preference questionnaire at baseline, end of cycle 1, and end of study. Data on hospital attendances (in- and out-patient), physician visits, concomitant medication use and other healthcare resources were collected for every cycle and during study follow up. Results: 162 patients received UFT/LV (median 3 cycles) and 81 i.v. bolus 5-FU/LV (median 4 cycles). Patient demographics were similar in both groups: median age was 70y (range 39–83) for UFT/LV and 69y (41–80) for 5-FU/LV; 92% of patients were ECOG PS ≤1. QoL was maintained in the UFT/LV group with little variation across time whereas QoL deteriorated with 5-FU/LV. Most patients in the UFT/LV (85–95%) and 5-FU/LV (49–66%) groups stated a preference for oral treatment with the most common reason being ‘taken at home’ (83%). Fewer UFT/LV patients had one or more hospitalizations for AEs (21% vs. 36%). Clinical benefit (ORR+SD) was 32% with UFT/LV (41% evaluable for response) and 32% with 5-FU/LV (45% evaluable). Median time to disease progression was 173d (95% CI 140–199) for UFT/LV and 168d (95% CI 133–205) for 5-FU/LV. Median overall survival was 385d (95% CI 296–472) for UFT/LV and 330d (95% CI 252–484) for 5-FU/LV. Conclusions: UFT with LV has comparable efficacy to i.v. 5-FU/LV in first-line mCRC, with the advantages of favorable QoL, patient preference for oral treatment, and fewer hospitalizations for managing AEs. [Table: see text]
Tissue factor, angiogenesis and thrombosis in pancreatic cancer
Authors: Khorana A. A. , Francis C. W. , Ryan C. K. , Taubman M. B. , Hu Y. C. , Ahrendt S. A. 
Published: March 2020

4001 Background: Coagulation proteins are commonly activated in pancreatic cancer and are closely linked to regulation of angiogenesis. We investigated tumor cell expression of tissue factor (TF), the prime initiator of coagulation, and its association with parameters of angiogenesis, venous thromboembolism (VTE) and survival. Methods: Tissue cores from a bi-institutional retrospective series of patients consecutively resected between January 1994 and February 2002 and followed for a median period of 16 months were used to build a pancreatic cancer tissue microarray. TF expression was graded semiquantitatively using immunohistochemistry (IHC)(grade 0:negative, grade 1: 1- 33% positive, grade 2: 34- 66% positive and grade 3: > 66% cells positive) in pancreatic intraductal dysplasia (n=5) and resected pancreatic cancer (n=122). Study endpoints included correlation of TF with VEGF expression by IHC, microvessel density (MVD), clinical VTE and survival in resected patients. Patients with history of VTE, on anticoagulation or with inadequate follow-up were excluded from analysis of VTE outcomes (n=33). Results: TF expression was observed in all specimens with intraductal dysplasia and 108 resected pancreatic cancers (89%) but not in uninvolved pancreas. Sixty-six patients (54%) with resected pancreatic cancer were found to have high TF expression (defined as ≥ grade 2, the median score), and 56 patients (46%) had low or no TF expression. Tumors with high TF expression were more likely to also express VEGF (80% versus 27% with low TF expression, p<0.0001). Tumors with high TF expression had a higher median MVD (8 versus 5/tissue core with low TF expression, p=0.01). Resected patients with high TF expression had a VTE rate of 20% compared to 5.5% in patients with low TF expression (p=0.04). Median survival in tumors with high TF was 17.9 months versus 12.6 months in those with low TF (p=0.16). Conclusions: TF expression appears to occur early in pancreatic cancer pathogenesis. This is the first report describing an association of TF expression with VEGF expression, increased MVD and clinical VTE in resected pancreatic cancer, confirming the linkage of thrombosis and angiogenesis. Targeting TF in pancreatic cancer could affect both neoplastic and thrombotic outcomes. No significant financial relationships to disclose.
Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase 1 and 2 (Her2/Neu) in patients (pts) with advanced biliary tree cancer (BTC) or hepatocellular cancer (HCC). A California Consortium (CCC-P) Trial
Authors: Ramanathan R. K. , Belani C. P. , Singh D. A. , Tanaka M. , Lenz H. J. , Yen Y. , Kindler H. L. , Iqbal S. , Longmate J. , Gandara D. R. 
Published: March 2020

4010 Background: Advanced BTC (gallbladder, bile duct) and HCC respond poorly to systemic chemotherapy. Lapatinib is an oral inhibitor of EGFR and Her/2-neu with evidence of activity in a number of tumor types. Both BTC and HCC overexpress EGFR 1 and 2. In addition, Her2/neu somatic mutations have been reported in HCC, and may predict response to EGFR targeted agents (Bekaii-Saab et al, A 4037, ASCO 2005). This trial conducted by the CCC-P and Univ. Chicago, is designed to determine the efficacy of lapatinib in BTC and HCC pts. Methods: A two-stage design is utilized and pts are stratified by tumor type (BTC or HCC); the study has a 90% power to detect a true response rate ≥20%. Two initial groups of 17 patients for BTC and HCC were accrued; one response from each was required to proceed with accrual to a total of 37 patients in each group. Adequate hematologic, renal, and hepatic function is required. Eligible pts are in Child A group and have ECOG PS of 0–2. One prior treatment regimen is allowed. Lapatinib dose is 1,500 mg/d orally without interruption. One cycle is 28 days and radiological assessment is done every 8 weeks. Results: 49 pts have been accrued (BTC 19 and HCC 30). Pt Characteristics: Male 59%, ECOG PS 0 (18 pts), ECOG PS 1 (22 pts). Median age 66 yrs (range19–82). Median cycles 2 (range 1–12). Grade 3/4 toxicity was noted in 19 pts and included fatigue in 4 pts, elevation of liver enzymes in 4 pts and diarrhea in 2 pts. Nausea, vomiting, rash, anemia and thrombocytopenia were noted in 1 pt each. There was no evidence of cardiac dysfunction. In 17 evaulable pts with BTC, no responses were observed, 5 had stable disease (SD). Among the first 17 pts with HCC, 2 confirmed partial responses have been recorded. In addition 8 pts have SD. The progression free survival is 1.8 mo for both BTC and HCC. Tumor and blood specimens are being analyzed for expression of EGFR, HER-2/neu, status of downstream signal pathway molecules, and correlation to response. Conclusions: Lapatinib is well-tolerated. No activity in BTC was noted and that cohort is closed. Lapatinib activity in HCC is encouraging, and study is close to completion. Source of support: NCI-NO1-CM-57018–16. [Table: see text]
Surgery plus ELFE (epirubicin, leucovorin, 5-fluorouracil and etoposide) vs surgery alone in radically resected gastric cancer (GC): Final results of a randomised phase III trial by the Gruppo Oncologico dell’ Italia Meridionale (GOIM)
Authors: De Vita F. , Giuliani F. , Gebbia V. , Galizia G. , Orditura M. , Maiello E. , Romito S. , Cartenì G. , Manzione L. , Catalano G. , Colucci G. 
Published: March 2020

4014 Background: In a previous phase II study the ELFE regimen resulted to be active and well tolerated for the treatment of advanced GC (Am J Clin Oncol 22:262;1999). Based on this background the G.O.I.M. conducted a randomised phase III study (trial 9602) to evaluate efficacy and toxicity of ELFE regimen as adjuvant therapy for radically resected GC patients (pts). Methods: All enrolled pts underwent total or subtotal gastrectomy with at least a D1 lymphoadenectomy. After stratification for nodal involvement (N+ vs N-) pts were randomised to follow-up alone (116 pts) or 6 cycles of ELFE regimen ( EPI 60mg/m2 d1, LV100 mg/m2 d 1–5, 5FU 375 mg/m2 d 1–5, VP-16 100 mg/m2 d1–3, every 3 weeks). Results: From June 1997 to June 2001, 228 pts with stage IB-IIIB GC were enrolled. Pts characteristics were: median age 63 yrs (29–70); total gastrectomy 148 pts; N+ 163 pts; PS 0–1 according ECOG scale 210. A total number of 638 cycles were delivered with a median number of 5/pt. During chemotherapy, the most frequent G3–4 side-effects graded according to NCI-CTC included alopecia (32%), neutropenia (26%), diarrhea (26%), nausea/emesis (17%), thrombocytopenia (12%) and stomatitis (11%). With a median follow-up of 60 months, the 5-years overall survival was 48% in the treatment arm and 43.5% in the control arm ( p=0.610); the 5-years disease-free survival was 44% in the treatment arm and 39% in the control arm ( p=0.305). Between patients with positive nodes the 5-years overall survival was 41% in the treatment arm and 34% in the control arm( p=0.068), while the 5-years disease-free survival was 39% in the treatment arm and 31% in the control arm (p=0.052). Multivariate analysis showed TNM stage as the only covariate that was independently associated with overall and disease-free survival. Conclusions: In radically resected GC adjuvantELFE chemotherapy produces an absolute difference in overall survival and disease-free survival at 5 years respectively of 4.5% and 5%, but this advantage was not statistically significant. No significant financial relationships to disclose.
Phase II trial of preoperative cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy: PET scan after induction therapy may identify early treatment failure
Authors: Ilson D. H. , Bains M. , Rizk N. , Shah M. , Rusch V. , Capanu M. , Flores R. , Kelsen D. , Park B. , Kepler S. , Minsky B. 
Published: March 2020

4023 Background: Response on PET scan during preoperative chemotherapy (chemo) for esophageal cancer (EC) has prognostic significance [JCO 19:3058;2001]. Induction chemo with weekly irinotecan(I)/cisplatin(C) relieves dysphagia, and weekly I/C administered with radiotherapy (RT) is well tolerated [ProcASCO 23:Abs 4017;2005]. We completed a Phase II trial of induction I/C followed by I/C/RT followed by surgery. Repeat PET scan was performed after induction chemo and prior to RT. Methods: Patients (pts) with resectable EC/GE junction carcinoma were staged with EUS, PET, and CT scan. Induction chemo consisted of I-65 mg/m2 and C-30 mg/m2 weeks 1,2,4,5, and weeks 7,8,10,11 with RT (180 cGy daily fractions to 5040 cGy). PET scan was repeated at week 6. Esophagectomy was planned 4–8 weeks after RT. Results: 60 pts were enrolled: 6 inevaluable, 54 evaluable, 3 await surgery; 49 male (91%), 5 female (9%), 41 adenocarcinoma (76%), 13 squamous (24%), median age 59, median PS 0, EUS T3N1 35 (65%), N1 40 (74%). Of 41 pts with dysphagia, 31 (76%) had resolution/improvement with induction chemo and 3/54 (6%) required a feeding tube. Of 51 pts, 3 clinical complete responders (CR) deferred surgery (1 refusal, 2 medically inoperable). Of 48 pts, 4 progressed during induction (8%), 9 progressed during RT (19%), and 35 underwent R0 resection (73%). 9/48 (19%) achieved pathologic CR. The median overall survival was 35.4 mos (median follow up 15 mos). In exploratory analysis in 54 pts, response after induction on the week 6 PET scan measured as a decline in SUV, correlated with time to tumor progression (TTP). The mean change in SUV was 43%. A set point of 22% or greater decline in SUV (PET responder) yielded the greatest distinction in TTP (PET responders TTP 18.5 mos, vs nonresponders 5.5 mos, p = 0.03). 4 pts with progression during induction crossed over to RT with paclitaxel: 3 (2 squamous, 1 adenocarcinoma) achieved durable disease control (one pathologic CR, one pathologic PR, one clinical CR). Conclusions: Response on PET scan during induction chemo for EC may identify early treatment failures, and may direct pts to successful salvage with alternative chemo during RT. Supported by a grant from Pfizer. [Table: see text]
Randomized phase II trial comparing gemcitabine/cisplatin-based chemoradiotherapy (CRT) to 5-FU-based CRT in patients with locally advanced pancreatic cancer
Authors: Wilkowski R. , Rau H. , Bruns C. , Wagner A. , Sauer R. , Hohenberger W. , Koelbl O. , Heinemann V. 
Published: March 2020

4038 Background: CRT is a relevant treatment option for patients with unresectable pancreatic cancer. Up to now, 5-FU has been the drug of choice for concurrent CRT. Based on evidence that also gemcitabine may improve the antitumor activity of radiation, a randomized phase II trial was undertaken. Methods: Patients with locally advanced, non-metastatic and histologically proven pancreatic cancer were included into a three-arm trial. In arm treatment arm A, radiation (CTV I up to 50.0 Gy, conventional fractionation) was applied concurrently with protracted venous infusion of 5-FU (350 mg/m2/irradiation day). In treatment arm B, patients received radiotherapy together with gemcitabine (300 mg/m2/d 30 minute infusion) and cisplatin (30 mg/m2/d 60 minute infusion) applied on days 1, 8, 22, and 29. In treatment arm C, patients received an identical regimen of CRT as described for arm B which was followed by 4 cycles of chemotherapy with gemcitabine (1000mg/m2, 30 min iv) plus cisplatin (50mg/m2) applied at 2-week intervals. Patients were stratified for Karnofsky performance status (KPS ≥80% vs. <80%). The primary end-point of the trial was the 9-months survival rate. Results: Ninety-six patients with a median age of 63.5 years (range 40–75 years) were included into the trial from 01/02 until 06/05 (arm A: 32 patients, arm B: 33 patients, arm C: 31 patients). Two patients did not complete CRT. At the time of evaluation, 66 patients (70.2%) had died. 9-months survival rate was 60%, 58%, and 46% in treatment arms A, B, and C, respectively. Median overall survival in arm A was 9.6 mo (95% CI, 8.7–10.5 mo), in arm B 9.6 mo (95%CI, 7.4–11.8 mo), and in arm C 6.1 mo (95% CI, 1.6–10 mo). Secondary end-points such as treatment-related toxicity, response rate, secondary resectability, and time to progression are under evaluation. Conclusions: CRT with gemcitabine plus cisplatin is not superior to 5-FU-based CRT with regard to the primary end-point of 9-months survival rate. Updated results will be presented at the meeting. No significant financial relationships to disclose.
Concomitant administration of weekly oxaliplatin, 5FU continuous infusion and radiotherapy in locally advanced pancreatic cancer (LAPC): A GERCOR phase II study
Authors: Moureau-Zabotto L. , Phélip J. , Afchain P. , Mineur L. , André T. , Vendrely V. , Lledo G. , Dupuis O. , Touboul E. , Balosso J. 
Published: March 2020

4039 Background: According to previous GERCOR studies in LAPC, concomitant chemoradiation therapy (CCRT) is indicated for non-progressive patients (pts) after systemic chemotherapy (CT). In order to improve the results of a classical 5FU-based CCRT, this study was designed to assess the efficacy and toxicity of weekly oxaliplatin (Ox), 5FU continuous infusion (c.i.) and radiation therapy (RT) in LAPC pts. Methods: Eligibility criteria included non resectable pathologically-proven LAPC, age > 18 yrs, PS < 2, and no prior CT or RT. All patients were first treated with 4 cycles of GEMOX (gemcitabine 1000 mg/m2, 100 min IV, d1; Ox 100 mg/m2, 2h IV, d2, every 2 wk). One month after cycle 4, non-progressive pts with PS < 2 received 45 Gy (25 fractions, 5 d/wk) + 10 Gy (concomitant boost in macroscopic tumor during wks 4 & 5, six hours apart large volume irradiation), combined with 250 mg/m2/d 5FU c.i. and weekly Ox. Initial 50 mg/m2 Ox dose was increased to 60 mg/m2 in absence of unacceptable toxicity after the 3 first included pts. Results: 60 pts were included (29 F/ 31 M, age 65.8 ± 9.6 yrs, range 37 - 80). 50 pts (83%) received CCRT, while 10 did not for the following reasons: metastatic progression (7 pts), OMS>2 (1), and CT toxicity (2). 44 pts (73 %) received the full planned CCRT dose-intensity. NCI-CTC grade 3–4 toxicities during CCRT and the following month (% of pts) were : neutropenia (14%), thrombocytopenia (10%), nausea-vomiting (20%), diarrhea (12%) and neuropathy (2%). 2 toxic deaths occurred during CCRT. With a median follow up of 15 mo, median progression-free survival (PFS) and overall survival (OS) of the whole population were 7.6 mo and 13.8 mo, respectively. For pts who received CCRT, median PFS and OS were 9.4 and 13.9 mo, respectively (2.6 and 9.9 mo, respectively, for pts who did not received CCRT). Conclusion: Chemotherapy before CCRT can identify pts who might potentially benefit of CCRT. Concomitant administration of weekly Ox, continuous IV FU and RT in LAPC is feasible with an acceptable toxicity. The results in terms of PFS and OS compare favourably with a classical 5FU-based CCRT. [Table: see text]
Changing patterns of prognosticators during long-term follow-up of gastric cancer after D2–3 resection and adjuvant chemotherapy: 15-year follow-up at one Korean institution
Authors: Jeung H. C. , Moon Y. W. , Rha S. Y. , Noh S. H. , Kim G. E. , Kim B. S. , Chung H. C. 
Published: March 2020

4050 Background: Clinical outcome of long-term follow-up after 5 years of gastrectomy, such as recurrence or survival rate, recurrence patterns, and prognosticators, have not been studied well. We evaluated long-term natural history of gastric cancer with a median follow up duration of 15 years after D2–3 resection and adjuvant chemotherapy at a single institution. Especially in survived patients after 5 years of surgery, we analyzed risk factors for recurrence or survival. Methods: A total of 525 patients with stage IB to IVM0 (AJCC 2002) were accrued between 1984 and 1996. As a standard surgery, radical gastrectomy with D2–3 lymphadenectomy was performed. All the patients had adjuvant 5-FU plus adriamycin chemotherapy and 160 of them had also immunotherapy with poly A:U. Results: The median follow-up duration was 191 months. 15 patients (2.9%) were lost to follow-up with median follow-up of 45 months. 15-year disease-free and overall survival rates were 49.5% and 42.9%, respectively. In survivors after 5 years, recurrence rate was 16.0% (11.3% between 5 and 10 years; 4.7% after 10 years). The dominant recurrence patterns were distant metastasis (29.0%) between 5 and 10 years and secondary cancer (53.9%) after 10 years of surgery. Stage (IB vs II vs IIIA vs IIIB vs IVM0) was a clear-cut prognosticator during 5 years of gastrectomy, but its significance was lost between 5 to 10 years. At this time, only stage IVM0 was a significant poor prognosticator for gastric cancer-specific recurrence (HR = 6.61; P = 0.000) and cancer-specific death (HR = 7.04, P = 0.000). However, stage did not represent any significance after 10 years of surgery. Conclusions: In gastric carcinoma with D2–3 resection and adjuvant treatment, late recurrences after 5 years of surgery were not rare. Prognosticators were different in survivors after 5-years, 5–10 years and more than 10 years of surgery. No significant financial relationships to disclose.
Thymidylate synthase polymorphisms and its mRNA expression levels as independent chemo-predictive markers in esophageal adenocarcinoma patients receiving 5-fluorouracil chemotherapy
Authors: Kuramochi H. , Tanaka K. , Lehman B. J. , Dunst C. M. , Oh D. S. , Demeester S. R. , Hagen J. A. , Danenberg K. D. , Demeester T. R. , Danenberg P. V. 
Published: March 2020

4063 Background: Thymidylate synthase (TS) has either a two or three 28bp tandemly repeated sequence in the 5’ untranslated (UTR) region. The triple repeat allele (3R) is classified into 2 subgroups (3RG, 3RC) according to a G/C polymorphism in the 3R sequences. Another polymorphism is a 6bp deletion in the 3’-UTR region. The genotype with either 3RG allele or 6bp insertion allele has been reported to be associated with high TS expression and chemoresistance to 5-FU. Methods: 83 patients with esophageal adenocarcinoma were assessed. Thirty-four had received 5-FU containing chemotherapy (16 adjuvant therapy, 12 upon recurrence, 3 both adjuvant and recurrence, 3 neoadjuvant) and 49 were treated with surgery alone. Surgically resected tumor tissues were analyzed for TS genotype and TS mRNA expression using a quantitative real-time RT-PCR method after microdissection. Results: No survival difference was seen between the patients with 3RG allele (3RG group) and non-3RG group among surgery-alone patients. However, among patients with a history of 5-FU-based chemotherapy, the non-3RG group showed significantly better overall survival compared to the 3RG group (p = 0.02). Moreover, whereas chemotherapy produced a significant increase in survival for the non-3RG group patients, those in the 3RG group obtained no survival benefit from chemotherapy. Patients with low TS mRNA levels had significantly better survival than the patients with high TS mRNA levels (p = 0.03) among chemotherapy-treated patients, despite the fact that there was no difference of median TS mRNA levels between 3RG and non-3RG group. Those who had both the non-3RG genotype and low TS mRNA levels obtained a significantly better survival benefit from chemotherapy than others (p = 0.02). The 3’-UTR polymorphism did not appeared to be associated with overall survival. Conclusions: The status of the TS 5’-UTR polymorphism and TS mRNA expression are independent predictive markers for survival benefit from 5-FU-based therapy in patients with esophageal adenocarcinoma. [Table: see text]