bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant chemoradiation for rectal cancer: A 5-year institutional experience at Sparrow Hospital
Authors: Srkalovic G. , Miranda R. A. , Maier M. , DiCarlo L. , Chamarthy U. , Herman J. 
Published: March 2020

14601 Continued efforts to improve local control and to maximize sphincter preservation in patients with rectal carcinoma led to consideration of preoperative chemoradiation. The purpose of this retrospective study is to examine clinical outcomes and find out which prognostic factors are related to survival in patients treated with neoadjuvant chemoradiation in Sparrow Hospital from 1998–2003. Forty two patients with biopsy proven rectal carcinoma without evidence of extra pelvic spread were treated in this fashion. Radiation therapy was administered for a total dose of 5.00 cGy. Chemotherapy used was 5-FU in 37 patients, and in combination with leucovorin in additional 5 patients. Surgical treatments performed were abdominoperineal resection (23 pts), low anterior resection in 13 pts., transanal excisions (2 pts), 2 patients had only exploratory laparotomy and for 2 patients records were not available. Cox proportional hazards regression techniques were used to estimate survival rates. Univariate and multivariate Cox proportional hazards analyses were used to evaluate relationship between risk factors and the survival. The SAS system (V9.1.3, Cary NC) was used for all analyses. Out of 42 patients analyzed 25 were males and 17 females. Mean age was 65 years (range 31 - 85). Median follow-up time was 57 months with a range from 7 to 98 months. After the surgery 4 patients had complete response, 12 were stage I, 10 stage II, 12 patients stage III, one patient had metastatic disease and for 2 patients records were inadequate. Analysis of disease free survival showed actuarial 5-year disease free survival to be 59%. Actuarial 5-year overall survival was 67%. Median overall survival was still not reached, while median disease-free survival is 78 months . Univariate and multivariate analyses showed that only postoperative stage was associated significantly with overall survival. Specifically, there was an increase in the risk of mortality of just over 3-fold for each increment in post-operative stage. In conclusion, in the community settings preoperative chemoradiation seem to provide good overall and disease free survival for patients with rectal cancer. Postoperative stage appears to be the most important prognostic factor for the survival. No significant financial relationships to disclose.
Phase I-II trial of weekly bicalutamide in men with high PSA and negative biopsy
Authors: Decensi A. , Zanardi S. , Puntoni M. , Bandelloni R. , Branchi D. , Argusti A. , Campodonico F. , Turbino L. , Mori M. , Maffezzini M. 
Published: March 2020

1500 Background: Men with persistent PSA elevation after non-cancer findings are at high risk of prostate cancer (PC). Bicalutamide (Bic) is an androgen receptor antagonist, which, unlike finasteride, is not associated with testosterone (T) escape. Given its long half-life (6–8 days), allowing for a weekly administration with potentially reduced side effects, Bic may be a suitable chemopreventive agent. We assessed the activity and safety of a weekly low-dose Bic in a phase I-II study in subjects with PSA >4 ng/ml and no PC at initial biopsies (10- 12 cores). Methods: Eligible subjects were sequentially assigned to either Bic 50 mg/week (group A), or 100 mg/week (group B), or no treatment (group C) for 6 mos. The outcome measures were the 6 mos changes in tissue Ki67 (primary endpoint), topoisomerase-IIa, Bcl- 2, and COX-2 by IHC, morphology and circulating PSA, prostatic acid phosphatase (PAP) and hormones. Results: From May, 2004 to June, 2006, 107 subjects were screened and 80 were enrolled: 26 in group A, 28 in group B, and 26 in group C. High-grade (HG) PIN decreased from 32% to 23% in the treated group and increased from 24% to 34% in controls; proliferative inflammatory atrophia (PIA) decreased from 41% to 32% in the treated group and increased from 14% to 19% in the controls. Complete remission of HG-PIN was found in 10/14 treated subjects versus 1/5 controls. Cancer or HG-PIN were found in 11 control subjects (52%) versus 16 subjects (36%) in the treated arms at 6 mos. Ki67 expression was significantly higher in HG-PIN lesions than in normal tissue (12% vs. 3%, p<0.01), but it was not modulated by Bic. Bcl-2 expression in normal tissue was 0/1+ in most subjects, and increased in 36% of treated subjects versus 20% of controls. Total and free PSA, as well as PAP, decreased by >30% on Bic. T, LH, estradiol and SHBG increased on Bic by 50–60%. There was no dose-related modulation in any biomarker. Treatment was well tolerated, mild (G1) breast pain and gynecomastia being recorded in 40% of treated subjects. Conclusions: Weekly Bic is active and safe in subjects with high PSA and negative biopsy. It seems to be associated with HG- PIN remission, Bcl-2 overexpression and a favorable modulation of PSA. The dose of 50 mg/week should be selected for future chemoprevention trials. No significant financial relationships to disclose.
A phase II study to establish a referential arm for treatment of gastric cancer patients with intraperitoneal micrometastases
Authors: Kodera Y. , Ito S. , Mochizuki Y. , Kondo K. , Suzuki N. , Matsui T. , Kojima H. , Kanyama Y. , Fujiwara M. , Nakao A. 
Published: March 2020

15002 Background: Gastric cancer patients with free cancer cells in the peritoneal cavity as detected by cytologic examination of the peritoneal washes (CY1) are known to have dismal prognosis. In vivo studies by the authors suggest prognostic impact of early postoperative treatment with S-1 (Nakanishi H, et al. Cancer Sci 2003;94:112–8) . No standard treatment for this population has been proposed to date. Methods: A phase II study was conducted to evaluate the efficacy of S-1, a new oral fluoropyrimidine, given postoperatively to patients with CY1 disease. Eligibility criteria included histologically confirmed adenocarcinoma of the stomach without distant metastasis (peritoneal seeding allowed if completely resected), curatively resected with negative margins, <80 years of age with adequate organ functions and preoperative PS of 0∼2, and written informed consent. The primary endpoint was 2-year survival rate and secondary endpoints were time to treatment failure and safety. By referring to the historical control (2-year survival rate: 13.3%, 90% CI 3.1∼23.5%), the target 2- year survival rate was set at 36 % with estimated 90% CI>23.5%, and the sample size was calculated as 50. Results: Forty eight patients were accrued before the study was closed, and one patients was found to be ineligible (negative for the cytologic examination). Of 47 patients, 32 were men. Median age was 66 years (range: 39∼79 years). Serosal invasion was confirmed in 44 patients (94%) and node metastasis in 42 (89%). Seven patients had macroscopic but resectable peritoneal deposits. D2 dissection was encouraged and performed in 33 patients (70%). To date, median survival time was 21.7 months with 2-year survival rate of 43.5%. One patient died of ischemic heart disease 5 days after the initiation of treatment, and treatment for 7 other patients was discontinued due to toxicity. Time to treatment failure was 9.8 months and progression-free survival was 12.9 months. The most frequent >G3 toxicity was neutropenia (n=6), followed by anorexia/nausea (n=4). Conclusions: Although further period of observation is required, postoperative S-1 is likely to overwhelm the survival data obtained in the pre-S-1 era. Toxicity was manageable and 80% of the patients tolerated the treatment. No significant financial relationships to disclose.
ERCC1 Codon 118 polymorphism is a useful prognostic marker in patients with pancreatic cancer treated with platinum-based chemotherapy
Authors: Kamikozuru H. , Kuramochi H. , Hayashi K. , Uchida K. , Yamamoto M. 
Published: March 2020

15012 Background: Excision repair cross-complementation 1 (ERCC1) has been reported to play a major role in the response to platinum-based therapies. A synonymous polymorphism at codon 118 converting a common codon usage (AAC) to an infrequent one (AAT) has recently been proposed to impair ERCC1 translation and to affect the response to cisplatin chemotherapy. This polymorphism has been reported in lung, colorectal and ovarian cancer, but not in pancreatic cancer. The aim of our study was to assess whether this polymorphism had an effect on tumor response and survival time in patients with relapsed pancreatic cancer treated with cisplatin and S-1. Methods: Fifty-eight patients with relapsed pancreatic cancer were analyzed in our study. Twenty-eight patients out of 58 were treated with cisplatin and S- 1, and 30 patients were treated with S-1 alone. Genomic DNA was extracted from a formalin-fixed paraffin-embedded tumor specimen and the ERCC1 codon 118 polymorphism was analyzed by PCR-RFLP method. Results: Thirty-one (53%) were homozygous for AAC codon, 6 (10%) were homozygous for AAT codon, and 21 (36%) were heterozygous. Among the patients treated with cisplatin and S-1, no significant difference in objective response rate was observed between each genotype. However, the patients with one or two AAT codon had a significantly longer progression free survival (PFS) and overall survival (OS) than those with homozygous for AAC allele (PFS: 12.7 months vs 2.4 months, p=0.0022, OS: 25.4 months vs 13.8 months, p=0.029). In contrast, no significant difference in PFS or OS was observed between each genotype among the patients treated with S-1 alone. No differences in the frequency of toxicity were found between each genotype in both treatment groups. Conclusions: ERCC1 polymorphism is a useful prognostic marker in patients with pancreatic cancer treated with platinum-based chemotherapy. No significant financial relationships to disclose.
Phase II study of a fixed dose-rate infusion of gemcitabine associated with erlotinib in advanced pancreatic carcinoma
Authors: Espinosa E. , Feliu J. , de Castro J. , Belda C. , Casado E. , Herrero A. , Sereno M. , Pinto A. , Gomez C. , Gonzalez Baron M. 
Published: March 2020

15013 Background: The efficacy of gemcitabine in pancreatic cancer can be improved by its combination with erlotinib. Likewise, a fixed dose-rate infusion of gemcitabine seems to be superior to the conventional 30-minute infusion. Our objective was to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with erlotinib in patients with advanced adenocarcinoma of the pancreas. Methods: From May 2005 to October 2006, 21 chemotherapy-naïve patients were included, median age 62 years (range 47 - 78), male/female 12/9. Five patients (24%) had locally advanced disease and 16 (76%) distant metastases. The Karnofsky score was 80–100 in 11 (52%), and 60–70 in 10 (48%). Treatment consisted of gemcitabine 1200 mg/m2 given as a 120-minute infusion on days 1, 8, 15, plus erlotinib 100 mg p.o daily. Cycles were repeated every 4 weeks. Results: A total of 80 cycles of chemotherapy were delivered with a median of 3.8 per patient (range 1- 8). There were five partial responses (24%, 95% CI: 8.4 - 47.6%), whereas seven patients had stable disease (33%) and 9 had a progression (43%). The median time to progression was 4 months. After a median follow-up of 6 months (1–14 months), the median overall survival has not been achieved. Toxicity was low. Grade 3- 4 WHO toxicities per patient were as follows: neutropenia in 5 (24%), thrombocytopenia in 1 (5%) and anaemia in 3 (14%). Grade 1–2 rash appeared in 8 (38%) and grade 3 in 3 (14%). Four patients (19%) had diarrhoea grade 1–2. Conclusions: These preliminary results suggest that a fixed dose-rate infusion of gemcitabine associated with erlotinib is active and well tolerated in patients with advanced pancreatic carcinoma. No significant financial relationships to disclose.
A phase 2 study of ARQ 501 in combination with gemcitabine in adult patients with treatment naïve, unresectable pancreatic adenocarcinoma
Authors: Khong H. T. , Dreisbach L. , Kindler H. L. , Trent D. F. , Jeziorski K. G. , Bonderenko I. , Popiela T. , Yagovane D. M. , Dombal G. 
Published: March 2020

15017 Background: ARQ 501 is a DNA damage checkpoint pathway activator whose effect is to induce selective cell death in cancer cells, independent of the tumor cell’s p53 status. Current evidence implicates a rapid and sustained increase of the pro-apoptotic protein E2F-1 by ARQ 501 as the mechanism of action. Cancer cells are selectively affected due to their pre-existing DNA damage. Induction of E2F-1 in combination with gemcitabine demonstrated potent anti-tumor activity in xenografts of human pancreatic cancer (PACA-2). A recommended phase 2 dose of 400 mg/m2 of ARQ 501 and 800 mg/m2 gemcitabine was identified. Methods: A Phase 2 study in adult patients with treatment naïve, non-resectable adenocarcinoma of the pancreas was initiated to assess the effect of ARQ 501 and gemcitabine on ORR in approximately 66 patients. Cycles consisting of weekly ARQ 501 (400mg/m2) and gemcitabine (800 mg/m2 were repeated every 4 weeks until progression, unacceptable toxicity, or another discontinuation criterion was met. Results: 73 patients were enrolled, with 58 treated to date with at least one infusion. Data is available for 27 patients (16M/11F, median age, 63 years). Of these 27, 5 did not reach a post baseline assessment (3 deaths, 2 PD prior to week 8), 20 are evaluable for response at eight weeks (1 PR, 12 SD of 8–24+ weeks), 7 PD) and 2 have yet to be assessed but are active. Tumor regressions have been observed in 6/20 patients assessed to date. This includes 1 PR, 4 MR (14.3% - 24%) and 1 patient with significant reduction (29.6%) in pancreatic lesions although new superficial liver lesions were observed. Adverse events (N=235) the most common being: anemia (54, 22%), hemolysis (17, 7%), fatigue (15, 6%), edema (7, 3%), and nausea (5, 2%). Conclusions: ARQ 501 has been administered to 58 patients with treatment-naïve, non-resectable adenocarcinoma of the pancreas. Enrollment is complete and early efficacy data is encouraging. A high proportion of patients (13/20) have achieved a minimum SD at the first tumor evaluation. In addition, objective tumor regressions has been observed in this study, providing preliminary confirmation of the utility of induction of E2F-1 in combination with gemcitabine. [Table: see text]
Prospective assessment of short-term quality of life after total, distal or proximal gastrectomy for gastric cancer
Authors: Graham D. , Zucker E. , Ishmil N. , Coit D. , Brennan M. , Brennan M. 
Published: March 2020

15020 Background: Few studies have systematically examined the short-term quality of life (QOL) of patients undergoing gastrectomy for gastric cancer. This is due to a lack of consistent prospectively acquired baseline and early outcome measures. The purpose of the current study is to assess differences in QOL scores among patients within a year of curative distal (DG), proximal (PG) or total (TG) gastrectomy, using validated gastric cancer specific questionnaires. Methods: Patients undergoing curative gastrectomy were asked to prospectively complete preoperative, postoperative, 3, 6, and 12 month EORTC QLQ-C30 and STO22 questionnaires. We used analysis of covariance to compare differences in scores based on type of operation while adjusting for potential differences in baseline scores. Results: Patients undergoing DG (n=101), PG (n=20) or TG (n=49) were consented and interviewed. Data collection is complete on all patients through twelve months. In the immediate postoperative period, patients in all three surgical groups demonstrated worse scores in about half of the 23 function and symptom scales, compared to their preoperative scores. However, DG and TG patients had mostly returned to baseline by three to six months, while PG patients continued to remain below the baseline scores for many function and symptom scales over the entire twelve month period following surgery. PG patients had significantly poorer scores than DG and TG patients in reflux, nausea/vomiting, eating restrictions and anxiety scales, among others ( Table 1 ). Conclusion: This prospective study indicates that patients fared better after DG or TG than after PG in most function and symptom scales throughout the twelve month period following gastrectomy. Long term follow-up studies are required to see if these differences persist over time. Table 1 Mean change in score from preoperative baseline score (a negative value means return to baseline or better). [Table: see text] No significant financial relationships to disclose.
Economic evaluation of the cost of treating advanced gastric cancer (AGC) with capecitabine/cisplatin (XP) vs. 5-FU/cisplatin (FP) regimens in an Italian setting
Authors: Giuliani G. , Falcone A. , Garrison L. 
Published: March 2020

15022 Background: A recent randomized phase III trial of XP vs. continuous infusion of FP as first-line therapy in patients with AGC met its primary endpoint of non-inferior progression-free survival (PFS) [Kang et al. ASCO 2006]. There was a trend toward superior efficacy with XP in terms of both PFS (median 5.6 months for XP vs. 5.0 months for FP) and response rates. An economic evaluation was conducted to compare the costs of the two therapies from an Italian perspective. Methods: Direct medical costs during the study period were estimated from the perspective of the Italian health system. The costs of the 2 regimens were estimated based on the trial results on actual dose and the number of administrations, and unit costs in an Italian setting. The adverse event (AE) profiles were used to estimate the costs of treating AEs. An expert panel estimated typical treatment patterns and costs of treating major AEs. Indirect costs for time and travel for study drug administration were estimated. Results: Patients in the XP arm received 5.2 cycles of therapy vs. 4.6 cycles of FP. The substitution of oral capecitabine for infusional 5-FU reduced the number of hospital clinic visits by 17.6 (22.8 for FP vs. 5.2 for XP). Chemotherapy drug costs were estimated to be €1200 greater in the XP arm, but drug administration costs were €2900 lower, yielding a net cost saving of €1700 per patient. The AE profiles were similar: associated costs to treat major (grade 3/4) AEs were less than €170 per patient and were lower in the XP arm. Due to the additional 17.6 visits for infusion of 5-FU, FP patients incurred substantially greater indirect costs in terms of lost time and travel expenses. Conclusion: Oral capecitabine benefits AGC patients by reducing the number of infusion visits and time spent receiving treatment, and would produce significant direct medical cost savings in an Italian setting. AE costs are similar with the 2 regimens. Given the trend to superior efficacy, the projected direct and indirect cost savings, and the convenience of oral treatment, XP would be considered a dominant (less costly and more effective) regimen for AGC from both a health system and societal perspective. No significant financial relationships to disclose.
Retrospective analyses of m-RNA gene expression profile from formalin fixed paraffin embedded (FFPE) specimens in colorectal cancer (CRC) and correlation with chemoresponsiveness
Authors: Ghi M. G. , Paccagnella A. , Stanta G. , Murer B. , Petrera F. , Busato S. , Bonin S. , Medici M. , Carnuccio R. , Biason R. 
Published: March 2020

15039 Background: Patients with chemoresponsive tumors are more likely to have a survival advantage, consequently a great interest is being placed on the identification of predictive markers. Currently, the improving in the extraction techniques allow the detection of gene profile at the mRNA level from FFPE materials. The purpose of the study was to analyse the m-RNA level of specific genes from FFPE (Stanta et al, BioTechniques 1998), both primary tumor (T) and locoregional lymphnodes (N) in CRC patients treated with chemotherapy (CT), and to relate it with chemoresponsiveness. Material and Methods: RNA was extract from FFPE tumor specimen both in T and N. RNA was reversing transcribed to cDNA. From the cDNA sample, BRCA1, ERCC1, CES2 and TS gene transcripts were specifically amplified by PCR. ERCC1 and BRCA1 are involved in platinum-compound resistance; TS is involved in responses to 5Fluorouracil (5FU) and CES2 level expression was recently related to Irinotecan pro-drug activation. Eligible patients included metastatic CRC patients treated from March 2000 to December 2003 as first line CT with Oxaliplatin/5FU or Irinotecan/5FU or 5FU alone. Results: Forty-five consecutive patients were retrospectively analysed. 15 of them received Oxaliplatin/5FU, 15 Irinotecan/5FU and the other 15 5FU alone. Median age was 64 (range 46–75). 13 patients (28%) had received adjuvant CT. 32 patients (72%) had metastatic disease at the time of surgery. Global Response Rate was 44%. All 45 patients received 5FU and they were analysed for the level of TS expression. With Multiple Regression Analysis, no statistical significant relation between TS level expression and response to 5FU was observed (P=0.36). A strong relation was observed between ERCC1 and response to Oxaliplatin (P=0.006) and a possible correlation of BRCA1-exon11 level expression and response to Irinotecan (P=0.06). The analyses of CES2 and the relation between gene expression and survival are ongoing. Conclusions: The analyses of mRNA gene expression profile from FFPE could be use to predicting response to CT in CRC patients. To test this hypothesis, a randomized phase II-III prospective study of tailored therapy in metastatic CRC is planned. No significant financial relationships to disclose.
HER2 positivity in advanced gastric cancer is comparable to breast cancer
Authors: León-Chong J. , Lordick F. , Kang Y. K. , Park S. R. , Bang Y. J. , Sawaki A. , Van Cutsem E. , Stoss O. , Jordan B. W. , Feyereislova A. 
Published: March 2020

15057 Background: Accurate HER2 testing is required to identify patients eligible for treatment with trastuzumab (Herceptin®). HER2 positivity is reported as 6–35% in gastric cancer (GC). This range is due to small sample sets and differing methods of evaluation or scoring. A specific HER2-testing process was established for the Phase III ToGA trial, which is evaluating trastuzumab added to chemotherapy in HER2-positive advanced GC. Methods: A validation study was completed to standardise IHC (HercepTest™) and FISH (PharmDx™) protocols, and to establish a scoring system specific for GC (M Hofmann et al. ASCO Gastrointestinal Cancers Symposium 2006. Abstract no. 24). Tumour samples for ToGA were then centrally tested by both IHC and FISH to identify patients eligible for enrolment. Results: To date, 1024 tumour samples have been assessed (243 HER2 positive and 781 HER2 negative) giving an overall HER2-positivity rate of 23.7%. Both IHC and FISH results are available for 960 patients, with 87% concordance. Differences were largely due to FISH-positive cases that were IHC 0/1+. HER2 positivity differed significantly by histological subtype: 36% in intestinal, 7% in diffuse and 23% in mixed. HER2 positivity also varied according to the site of the tumour: 36% (8/22) for gastro-oesophageal junction tumours and 21% (60/291) for gastric tumours. Sample numbers were very small so these results must be treated with caution. The HER2- positivity rate was similar in specimens obtained by biopsy (168/689; 24%) and surgery (71/322; 22%). Conclusions: Using validated methodology and based on the large sample set from the ongoing ToGA trial, the HER2-positivity rate observed in advanced GC is as high as in breast cancer: ∼24%. The first efficacy data from ToGA are expected in 2009. No significant financial relationships to disclose.