bluuebunny/crossref_metadata_2025 huggingface dataset:
Colon cancer epidemiology in United Arab Emirates
Authors: Maarraoui A. M. , Uttamchandani A. , Abdulatif H. , Attia N. M. , Gausia Q. U. , Rubina M. H. , Daud N.
Published: March 2020

14597

Background: Mafraq Hospital is the largest tertiary hospital in United Arab Emirates (UAE). The exact charecterstics of colon cancer in this country are not yet documented. Methods: This is a retrospective study of colo-rectal cancer. Files of all patients with the diagnosis of colo-rectal cancer between 1/99 and 12/05 at the department of Oncology at Mafraq Hospital were reviewed. Intent to treat analysis was used. Total of 176 patients were seen. The youngest was age 18 and the oldest was 79 Results: Mean age of patients at initial presentation was 48.5. Gender was as follows: males 121 patients (68.7%) and females 55 patients (31.3%). Mean male age at initial presentation was 49.5, and mean female age was 46.4. UAE Citizens represented 34 patients (19.3%) of cohort and non-citizens 137 patients (80.7%). Cancer stages were as follows: stage I: 7 patients (4.7%), stage II: 41 patients (27.5%), stage III: 48 patients (32.2%), stage IV: 53 patients (35.6%). 27 patient elected to do staging work-up and further care elsewhere. Conclusions: 1- Colon cancer screening is needed in order to diagnose cancer at earlier stages. 2- As our patients are younger than patients in the West. Colon cancer screening should be done at an earlier age.

No significant financial relationships to disclose.
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.
A phase I/II study of docetaxel /S-1 with radiation for esophageal cancer patients
Authors: Hirai T. , Matsumoto H. , Hirabayashi Y. , Urakami A. , Yamashita K. , Hiratsuka J. , Imajyo Y. , Tsunoda T.
Published: March 2020

15061

Background: The combined therapy of CDDP/5-FU with radiation is the standard therapy for esophageal cancer patients. However, this therapy is associated with a comparatively high incidence of gastrointestinal disorders resulting in therapy interruptions and long hospital stays. Herein, we propose a new regimen of Docetaxel / S-1 combined with radiation to improve the success rate and outcome. The clinical phase Istudy was conducted from May, 2004 until June, 2006. and we report on the results in this paper. Methods: Patients were given S-1 (60mg/m2/day) orally from days 1 to 14, and Docetaxel (20mg/m2 in level 1, 25mg/m2 in level 2, and 30 mg/m2 in level 3) intravenously on days 1 and 8. Patients received radiation in 2.0 Gy daily fractions from days 1 to 21, for a total of 30 Gy. Patients were given a seven-day rest after the first course, and then treated with the same regimen from days 28 to 49.P The phase I study was completed for 10 cases. Results: All patients completed the treatment schedule, with no treatment-related deaths and no grade 4 adverse events were observed. As for hematotoxicity, one case revealed leucopenia of grade 3 and neutropenia of grade 2. A non-hematotoxic adverse event (grade 3 anorexia) was observed in one patient. The response rate evaluated by RECIST was 66 % (CR in 2 cases, PR in 4 cases). We assumed that the recommended dosage of TXT and S-1 was 30mg/m2 and 60mg/m2, respectively, combined with a radiotherapy dose of 60Gy. Conclusions: This combination therapy may be superior to other treatments because of its lower rate of adverse events and higher response rates. We continue this study to Phase II in order to generate data on the response rate and adverse effect rate in a greater number of patients with esophageal cancer.

No significant financial relationships to disclose.
Predicting risk of estrogen receptor positive breast cancers in postmenopausal women
Authors: Chlebowski R. T. , Anderson G. L. , Lane D. S. , Aragaki A. , Rohan T. , Yasmeen S. , Sato G. , Rosenberg C. A. , Hubbell F. A.
Published: March 2020

1507

Background: Chemoprevention strategies for estrogen receptor positive (ER+) breast cancers are emerging, especially for postmenopausal women, but require methods of targeting appropriate populations. Our objective was to improve the Breast Cancer Risk Assessment Tool [Gail Model (GM)] for estimating ER+ breast cancer risk. Methods: A prospective cohort involving 161,809 postmenopausal women aged 50–79 years, (93,676 in the observational study (OS) and 68,132 in clinical trials (CT)) at Women’s Health Initiative (WHI) Clinical Centers had comprehensive assessment of lifestyle, medication use and breast cancer risk factors. Breast cancer risk from the GM and other models incorporating additional or fewer risk factors and five year incidence of ER + and ER negative (ER-) invasive breast cancers were determined. Main outcome measures were concordance statistics for models predicting breast cancer risk. Results: Of 148,266 women meeting eligibility criteria, (no prior breast cancer and/or mastectomy), 3,236 developed breast cancer. Chronological age and age at menopause, both GM components, were significantly associated with only ER+ but not ER- breast cancer risk (p<0.05 for heterogeneity test). The GM predicted population-based ER+ cancer risk with reasonable accuracy (concordance statistic 0.60, 95% confidence interval (CI) 0.58 to 0.62) but for ER- cancers, the results were equivalent to chance allocation (concordance statistic 0.49, 95% CI 0.45 to 0.54). For ER+ cancers, no additional risk factors improved the GM prediction. However, a simpler model, developed in the OS and tested in the CT population, including only age, family history, and benign breast biopsy was comparable to GM in ER+ breast cancer prediction (concordance statistics 0.58, 95% CI 0.56 to 0.60). Using this model, all women ≥ 55 years old (or ≥ 60 year old if African American) with either a prior breast biopsy or first degree breast cancer family history had five year breast cancer risk of ≥ 1.8%. Conclusions: In postmenopausal women with comprehensive mammography use, the GM identifies populations at increased risk for ER+ breast cancer but not for ER- cancer. A model with fewer variables provides a simpler alternative for identifying populations appropriate for breast cancer chemoprevention interventions.

No significant financial relationships to disclose.
A phase II study of docetaxel in combination with ZD1839 (gefitinib) in previously treated patients with metastatic pancreatic cancer
Authors: Blaszkowsky L. S. , Ryan D. P. , Earle C. , Kwak E. , Fuchs C. , Meyerhardt J. A. , Stuart K. , Zhu A. X. , Enzinger P. , Kulke M. H.
Published: March 2020

15080

Background: The reported activity of docetaxel in pancreatic cancer and high level of EGFR expression in pancreatic carcinomas led us to examine the efficacy of combination docetaxel and gefitinib in patients with metastatic pancreatic cancer. Methods: Eligibility criteria included PS = 1, failed prior adjuvant ot metastatic gemcitabine-containing regimen, = 1 prior regimen for metastatic disease, no prior taxane or EGFR inhibitor, and adequate organ function. Patients received docetaxel 40 mg/m2 intravenously weekly for 2 of every 3 weeks and daily oral gefitinib 250 mg. The primary endpoint was CA19–9 response (>50% decrease in tumor marker CA19–9 levels). Additional endpoints included radiologic response, toxicity, and survival. Results: Fifteen patients received docetaxel and gefitinib between 11/2/04 and 11/26/05. The median age of patients was 60 (46–76), and included 7 women and 8 men. The regimen was generally well tolerated, and there were no unanticipated toxicities. Grade 3 or 4 toxicities included lymphopenia (6 pts), hyperglycemia (3 pts), leucopenia (3 pts), infection (2 pts), fatigue (2 pts), elevated transaminases (2 pts), neutropenia (2 pts), pleural effusion (2 pts), irregular menses (1 pt), anorexia (1 pt), dysphagia/esophagitis (1 pt), diarrhea (1 pt), alkaline phosphatase (1 pt), and sensory neuropathy (1 pt). No treatment-related deaths occurred. No patient experienced a biochemical (CA 19–9) response to treatment. All 15 patients were evaluable for radiologic response, of which 9 experienced stable disease and 6 progressive disease as their best response to therapy. The trial was stopped due to lack of efficacy, in accordance with an early stopping rule incorporated into the trial design. Conclusions: In the doses and schedule used in this trial, the combination of docetaxel and gefitinib does not appear to be active in patients with pancreatic cancer who have failed prior gemcitabine-based chemotherapy.

No significant financial relationships to disclose.
Interferon-based chemoradiation as primary therapy for locally advanced pancreatic cancer: A phase II trial
Authors: Picozzi V. J. , Boone-Hill N. , Traverso L. W. , Kozarek R. A.
Published: March 2020

15082

Background: Locally advanced pancreas cancer (LAPD) is a therapeutic challenge for clinicians worldwide. Chemoradiation and chemotherapy-only approaches are used, typically producing overall survival (OS) of only 9–14 months (mo). In 1995, we developed a unique chemoradiation method using cisplatin (C), 5-FU (F), and alpha-interferon (IFN) , followed by post-chemoradiation (F). As adjuvant therapy to resected pancreas cancer; this method has produced 5-yr OS of 40%-50% in our institution.We report here a phase II trial assessing the efficacy of this regimen in LAPD. Methods: Patients with LAPD ( non-laparascopy-staged), ECOG performance score 0–1, were treated with XRT 5000cGy/25 fractions simultaneous with (C) 30mg/m2 d 1,8,15,22,29, (F) 200mg/m2 IVCI d 1–35, and (IFN) 3million U SQ qod d 1–35 .(F) 200mg/m2 IVCI was given for 2 additional 6 week cycles (weeks 9–14 and 17–22) . Therapy post- progression was given at the discretion of the treating physician. Results: From 7/1995 and 7/2002, 20 patients(pts) (median age 62) were accrued. 19/20 pts (95%) completed >95% of specified XRT dose; 17/20 pts (85%) received >80% of specified chemotherapy doses during XRT. 12/20 pts (60%) completed >80% of specified (F) post chemoradiation. 10/20 pts (50%) experienced grade 3 toxicity during chemoradiation, and 10/20 pts (50%) required hospitalization including 4-GI symptoms (e.g.diarrhea/dehydration), 2-GI bleeding, 2-fever, 1-hyponatremia and 1-anorexia. No grade 4 toxicities and no toxic deaths occurred. All 20 pts have now expired. Initial site of disease progression was liver 8 pts, abdominal cavity 4 pts, local 4 pts, unknown 4 pts. Median time to progression was 7 mo; median OS was 12.5 mo (range 3–51 mo). 1-and 2-yr OS were 55% and 20%, respectively. 7/20 pts. received gemcitabine-based regimens following tumor progression; median OS of these pts was 17 mo. Conclusions: 1) The IFN-based chemoradiation described above is moderately severe in toxicity, but can be successfully applied to LAPD. 2) This chemoradiation method may be a sucessful platform for the treatment of LAPD with gemcitabine-based chemotherapy. Studies investigating this approach are presently underway at our institution.

No significant financial relationships to disclose.
The correlation of perfusion-weighted MRI with VEGF in resected pancreatic cancer
Authors: Ueno M. , Ohkawa S. , Niwa T. , Yoshida T. , Morinaga S. , Sugimasa Y.
Published: March 2020

15092

Background: Perfusion-weighted magnetic resonance imaging (MRI) can detect angiogenesis in brain malignant tumors, and as angiogenesis increases in various carcinomas the prognosis becomes worse. We evaluated the usefulness of perfusion-weighted MRI as a prognostic predictor in pancreatic cancer patients in ASCO 2005. This time, we examined the correlation of perfusion-weighted MRI with vascular endothelial growth factor (VEGF) and microvessel density (MVD) immunohistochemically in resected pancreatic cancer patients. Methods: Perfusion-weighted MRI was performed on 14 consecutive resected pancreatic cancer cases. Imaging acquisition was continually repeated with echo-planar sequence every 2 sec for 2 min with bolus injection of gadolinium. We made the time intensity curve of perfusion-weighted images and calculated the signal ratio (SR). We investigated the expressions of VEGF and CD34 (for calculating MVD) immunohistochemically. MVD was assessed per 200x field. We compared SR with VEGF expression and MVD. The correlations were evaluated with t-test. Results: All cases showed transient decreases in tumor signal intensity (SR range: 18.2–66.0%) in perfusion-weighted MRI. The expressions of VEGF were divided into two groups (high and low expression). MVD ranged from 6 to 34 and was divided into two groups at the median value. The correlation of SR in perfusion-weighted MRI with VEGF expression was significant (p=0.002). High SR correlated with high VEGF expression. The correlation of SR in perfusion-weighted MRI with MVD was not significant. Conclusions: Perfusion- weighted MRI correlated with VEGF expression in pancreatic cancer.

No significant financial relationships to disclose.
A randomized study of arterial infusion chemotherapy for hepatocellular carcinoma: Low-dose 5-fluorouracil/cisplatin versus low-dose 5-fluorouracil/cisplatin/Interferon beta
Authors: Ueda H. , Tanaka H. , Kida Y. , Fukuchi H. , Ichinose M.
Published: March 2020

15098

Background: Recently, efficacy of intraarterial infusion chemotherapy for advanced hepatocellular carcinoma (HCC) have been improved by combination with interferon(IFN)-alpha and 5-fluorouracil (5-FU) or 5-FU and cisplatin (FP). However, there is no report about combination chemotherapy with 5-FU, cisplatin and IFNbeta. Therefore, we examined to evaluate the efficacy and safety of combination intraarterial infusion chemotherapy with IFN-beta, 5-FU and cisplatin in patients with advanced HCC in comparison with a chemotherapy using 5- FU and cisplatin. Methods: Twelve HCC patients in advanced stage were enrolled in the study after informed consent was performed. Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with platelet less 80 x 109/l were not eligible. They were randomly assigned to FP group (n=6) and FP-IFN group (n=6). One cycle of both regimens lasted for 4 wk. 5-FU (500 mg/day) and cisplatin (10mg/day) were administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. IFNbeta (1 x 106 units) was injected via the proper hepatic artery twice a week for 3 wk. Primary and secondary end points are efficacy and safety, respectively. The effect of combination chemotherapy was evaluated in each patient after one cycle based on the reduction of tumor volume. Adverse event was based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Results: The reduction rates in the FP group and FPI group were 16.5% and 36.2%, respectively. The response rates in the FP group and FPI group were 16.7%(CR:n=0, PR:n=1) and 66.7%(CR:n=0, PR:n=4), respectively. The efficacy in FPI group was significantly higher than that in FP group. As for safety, any severe adverse event was not observed in this study although neutropenia and thrombocytopenia were more common in FPI group than in FP group. Conclusions: These data indicate that arterial infusion chemotherapy with 5-FU/cisplatin/IFNbeta may be a promising treatment modality for advanced HCC.

No significant financial relationships to disclose.
A phase II trial of high-dose calcitriol and docetaxel in patients with untreated, incurable pancreatic adenocarcinoma
Authors: Lopez C. D. , Beer T. , Todd K. , Blanke C. D.
Published: March 2020

15099

Background: Taxanes have activity in patients with advanced pancreatic adenocarcinoma. In preclinical studies, calcitriol, the active form of vitamin D, potentiates docetaxel-induced cell death in pancreatic and prostatic cancer cell lines. Clinically, single institution and randomized prostate cancer trials using weekly high-dose calcitriol with docetaxel have demonstrated high PSA response rates (J Clin Oncol 2003, 2007). Herein we report results from a phase II study of the identical regimen in patients with incurable pancreatic adenocarcinoma. Methods: Patients with a histologic diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, Zubrod PS 0–2, and adequate organ function were eligible. Previous non-docetaxel adjuvant chemotherapy and radiation were permissible. Patients received calcitriol 0.5 mcg/kg orally day 1, followed by docetaxel 36 mg/m2 on day 2. Therapy was given weekly for 3 weeks, followed by a 1 week break, and patients were treated until progression. The primary endpoint was time-to-progression (TTP). Results: 24 patients with metastatic and 1 with locally advanced (25 total) were enrolled, treated and are evaluable for efficacy and toxicity. Median age and PS were 60 (range 30 to 79) and 1, respectively. 68% were males, and all were white. Three patients are alive and 22 have died. The median number of cycles was 1 (range 0 to 12). 3 patients (12%, 95% CI 3 to 31) achieved a partial response, and 7 (28%) stable disease for at least 7 weeks. Median TTP and median overall survival were 2.2 and 5 months respectively. Potentially treatment-related common grade 3/4 toxicities included: thrombosis -12%, abnormal LFTs-16%, nausea-8%, fatigue-16%, infection-12%, neutropenia/leucopenia-16%, effusion-8%, abnormal electrolytes-24%, and infusion reaction-4%. Conclusions: The combination of docetaxel and high-dose calcitriol has activity in pts with advanced pancreatic cancer, but the regimen offers no apparent advantage over historical results achieved with standard gemcitabine.

No significant financial relationships to disclose.
Feasibility of sequential fixed S-1 followed by paclitaxel for the treatment of advanced or recurrent gastric cancer
Authors: Ohashi M. , Kanda T. , Yajima K. , Honma H. , Kosugi S. , Hatakeyama K. , Kobayashi T. , Hayami M.
Published: March 2020

15113

Background: First-line chemotherapy for advanced/recurrent gastric cancer has limited efficacy, achieving a median survival time (MST) of about 7 months, while addition of second-line and subsequent chemotherapy may prolong MST to about 11.5 months. In practice, however, about half of patients failing with first-line chemotherapy are unable to receive second-line chemotherapy because of worsening of their performance status (PS), disease progression, or toxicities during protracted first-line chemotherapy. We studied the feasibility of a sequential fixed regimen devised to ensure prompt initiation of second-line chemotherapy after first-line failure. Methods: Between December 2002 and December 2006, patients with advanced or recurrent gastric cancer were enrolled who met the following requirements: 1) major organ function preserved; 2) PS 0–2; 3) presence of at least one evaluable lesion; and 4) written informed consent. The treatment regimen consisted of 3 courses of single-agent S-1 or S-1/cisplatin combination followed by weekly paclitaxel (wPTX). The endpoints of the study were entry to the second-line treatment, time to failure (TTF), and MST. Results: Of 39 patients enrolled, 37 completed first- line S-1. Twenty-eight patients (76%) then received wPTX, 2 non-wPTX chemotherapy, and 6 surgery; only 1 received no additional treatments. Second-line wPTX was followed by a third-line treatment in 23/28 patients (82%). The TTF with the sequential fixed regimen was 7 months. The MST and the 1- and 2-year survival rates in the 37 completing first-line treatment were 14.6 months, 61% and 25%, while those in the 28 switched over to wPTX were 12.5 months, 51% and 17%. Conclusions: Patients with advanced/recurrent gastric cancer treated sequentially with a fixed number of courses of S-1 followed by wPTX may have a good chance of treatment continuation. A sequential fixed regimen may further improve survival of patients with advanced/recurrent gastric cancer only with combinations of currently available drugs.

No significant financial relationships to disclose.
Adenocarcinoma (AC) small intestine (SI). Review of prognostic factors and treatment outcomes
Authors: Chalchal H. I. , Tonita J. , Alvi R. , Sirdar J. , Salim M. , Aboo I. Y. , Zarkovic M.
Published: March 2020

15117

Background: AC of SI is a rare disease. Review of 123 cases was done for prognostic factors and treatment outcomes. Methods: Total of 123 cases identified using Saskatchewan Cancer Agency registry. A data collection sheet was generated and chart review was performed. Cause specific survival (CSS) was based on primary cause of death from AC of SI. Survival was calculated using Kaplan Meyer survival curves. P values were calculated using log rank test. Results: CSS of the whole group was 565 days. CSS with no metastatic disease (MD) at presentation was 792 days. 30 patients presented with MD. Patient with MD at presentation who did not receive chemotherapy had a CSS of 83 days. 13 out of 30 patients with MD received 5 flurouracil based chemotherapy. CSS of patients with MD who received chemotherapy was 363 days compared to 83 days who did not receive chemotherapy (p. 0.0036). 11 patients with stage I to III received adjuvant fluropyramidine based chemotherapy. CSS of patients who did not receive adjuvant chemotherapy was 617 days and 52% of patients who received chemotherapy had a survival of 1307 days. There were no further events till 3788 days. CSS for grade 1 tumor was 37.5%, for grade 2 it was 28.9% and 26.4% for Grade 3 tumors. (P value 0.571). 5 year CSS was 15.8% for patients with duodenal involvement 10% for patients with ileal disease and 23.5% for patients with jejunal involvement. (P value 0.415). 5 year CSS with T4 lesions was 18.6% compared to 35% for patients with T3 lesions. (P value 0.077). Patient with node positive disease had 5 years CSS of 11.6% compared to 44.1% with node negative disease. (P value 0.004). Median age at diagnosis was 71 years. CSS of patients with age more than 71 years was 15.3% compared to 19% for less than 71 years of age. (P value .078). Conclusions: Patients who received 5 flurouracil based chemotherapy for MD and in adjuvant setting seems to have better survival outcome. However this may be related to selection bias. Nodal Involvement was associated with poor outcome. Factors as grade of tumor, T stage, age and site of disease involvement were not found to have independent prognostic significance.

No significant financial relationships to disclose.
Increased risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers after breast-conserving therapy compared to mastectomy
Authors: Schmutzler R. K. , Graeser M. K. , Rhiem K. , Schlehe B. , Hofmann W. , Jonat W. , Schönbuchner I. , Kiechle-Bahat M. , Strunz K. , Engel C.
Published: March 2020

1512

Background: BRCA mutation carriers affected by breast cancer face an elevated risk of contralateral breast cancer (clBrCa). We here aimed at estimating the influence of breast conserving therapy (BCT) versus mastectomy (MXT) on the rik of clBrCa. Methods: We conducted a retrospective cohort study in 3810 index patients (pts) collected within the CHBOC. Deleterious BRCA1 or BRCA2 mutations were detected in 921 pts and medical records were obtained from 532 pts (344 BRCA1, 184 BRCA2 mutation carriers, 4 both) of whom 261 (49%) underwent BCT and 271 (51%) MXT. Pts were followed from the initial diagnosis of breast cancer until clBrCa or censored at time of prophylactic contralateral mastectomy, oophorectomy, death, or date of last visit. Median age at first diagnosis was 39.9 years (range 17.5 to 79.0) and median follow up 48.84 months (3413 person years). The hazard ratio (HR) was estimated using multivariate Cox regression analysis adjusting for conduct of radiotherapy, age at first breast cancer, and affected BRCA gene. Results: In the univariate analysis the risk of clBrCa was 12.2% (95% CI 7.6 to 16.8) at 5 years and 24.9% (95% CI 18.0 to 31.9) at 10 years for pts treated with MXT and 25.9% (95% CI 18.8 to 33.1) at 5 years and 45.7% (95% CI 35.0 to 56.5) at 10 years for pts treated with BCT. In the multivariate analysis, the HR was 1.8 for BCT versus MXT (95% CI 1.2 to 2.7). Neither age at diagnosis of the first primary nor BRCA mutation status were significantly predictive. A subgroup analysis comparing BCT plus radiotherapy with MXT minus radiotherapy revealed a HR of 1.6 (95% CI 1.02 to 2.56) for the BCT group. Conclusions: We report for the first time a 1.8-fold increased risk of clBrCa in BRCA mutation carriers undergoing BCT versus MXT. Scattered radiation is the most probable causation. Although results from further studies such as the WECARE study should be awaited, our results provide evidence that recommendations for primary brCa treatment of BRCA mutation carriers must to be reconsidered.

No significant financial relationships to disclose.