bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.