bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of gemcitabine in combination with oxaliplatin and capecitabine in previously untreated metastatic or recurrent pancreatic cancer.
Authors: Sym Sun Jin , Hong Junsik , Jung Minkyu , Koo Yang Seo , Park Yeon Ho , Kim Koen Kook , Park Jinny , Cho Eun Kyung , Lee Jae Hoon , Shin Dongbok 
Published: February 2017

344 Background: Treatment with single agent gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. This study was performed to determine the efficacy of gemcitabine in combination with oxaliplatin and capecitabine in patient with recurrent or metastatic pancreatic adenocarcinoma. Methods: This was a prospective, single-arm, single center study in patients with chemotherapy-naive metastatic or recurrent pancreatic adenocarcinoma. The primary endpoint was objective response. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 18 patients. If at least two objective responses were obtained, then a further 25 patients would be enrolled into the study. If no more than two responses were obtained among these 18 patients, the study would be halted. The study patients received gemcitabine 800 mg/m2, plus oxaliplatin 100 mg/m2 and capecitabine 800 mg/m2/day on days 1-7 every 14 days. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Results: Eighteen patients were enrolled. Median age was 63 years (range, 39-73 years). Among these 18 patients, only one patient (5.5%) achieved an objective response. Therefore, the accrual terminated. The median time to disease progression was 2.1 months, and the median overall survival duration was 4.9 months. One-year overall survival rates were 35.3%. The most frequently reported grade 3 or 4 adverse events were asthenia (16.6%), and nausea (5.5%). There were no unexpected toxicities. Conclusions: The addition of oxaliplatin and capecitabine to gemcitabine did not improve objective response in the first-line treatment of advanced pancreatic cancer patients.
Transarterial infusion chemotherapy with cisplatin plus S-1 for treating hepatocellular carcinoma: Results of a phase I trial.
Authors: Terazawa Tetsuji , Kondo Shunsuke , Morizane Chigusa , Yamaguchi Tomohiro , Shimizu Satoshi , Mitsunaga Shuichi , Ikeda Masafumi , Ueno Hideki , Okusaka Takuji 
Published: February 2017

357 Background: In Japan, transarterial infusion chemotherapy (TAI) with cisplatin (CDDP) is used for advanced hepatocellular carcinoma (HCC) patients (pts), and the response rate (RR) was 33.8% in previous phase (P) II study. S-1, oral systematic chemotherapy, is also promised for advanced HCC pts, and achieved 23.1% RR in previous P-II study. The clinical feasibility and efficacy of CDDP for TAI plus S-1 in pts with advanced HCC has not yet been investigated. Thus, we performed this trial to determine the recommended dose (RD). Methods: Although 13 Child–Pugh class A or B pts with advanced HCC entered themselves for this P-I trial, 1 pts of them was excluded from this trial due to the breach of criteria. The pts received TAI with CDDP (infusion on day 1 of the courses) plus S-1 (daily oral administration on days 1–21 of the courses), every 5 weeks until disease progression. The dose-escalation scheme is provided in the table below. Results: Three dose levels were used for the 12 pts. Dose-limiting toxicity was not observed in 3 pts at level 1, 3 pts at level 2, and 7 pts at level 3; therefore, the RDs for CDDP and S-1 were considered to be 65 mg/m2 and 80–120 mg/day, respectively (level 3). Grade 3 adverse events were reported for 10 pts and were considered to be related to the study drugs for 6 pts: 2 pts, increased alanine aminotransferase level; 2 pts, increased aspartate aminotransferase level; 1 pt, anemia; and 1 pt, decreased platelet count. The total number of treatment courses was 25, with a mean of 1.5 courses per pt (range, 1–6 courses). The median progression-free survivaltime was 73 days. The disease control rate was 58% (7/12) ; 2 pts (16%) achieved partial response and 5 (42%) had stable disease. Conclusions: TAI with CDDP plus S-1 can be used safely with promising tumor control for treating advanced HCC. The RD to be used for a P-II study of this regimen was determined to be level 3. [Table: see text]
Retrospective analysis of treatment effects and prognostic factors associated with overall survival in patients with resected adenocarcinoma of the pancreas.
Authors: Luu Dai Chu Nguyen , Li Xiaobai , Ojcius Julia , Muscarella Peter , Ellison Edwin Christopher , Malhotra Lavina , Bloomston Mark , Bekaii-Saab Tanios S. 
Published: February 2017

359 Background: The role of adjuvant chemotherapy in pancreas cancer has been well established. The role of radiation therapy however remains controversial. The ESPAC-1 study showed a possible deleterious effect for radiation on survival of patients with resected pancreas cancer, although the study was limited by lack of compliance and quality control. Methods: We performed a retrospective analysis of patients who underwent curative resection of their cancer of the pancreas over the last 2 decades at the Ohio State University. 333 patients with adenocarcinoma of the pancreas were identified from our database and 148 subjects were found with complete treatment information available. Thirty patients had no treatment after resection. Log-rank test was used to compare the overall survival (OS) of two groups of patients: treated with chemotherapy (C, N=68) or fluoropyrimidine-based chemoradiation (CRT, N=50). Demographics of the CT and CRT groups were balanced. Patient characteristics including age, sex, tumor size, tumor location, tumor grade, nodal status, margins (R0 vs. R1) and number of hospitalizations within a six-month period of discharge from the hospital after surgery were compared across all groups. The effect of these variables on OS was assessed using log-rank test. Results: The mOS for C (21.5 months, 95% CI; 13.5, 24.6) and CRT (16.8 months, 95% CI; 13.9, 23.1) were similar. There was no statistically significant difference observed for C vs. CRT (p>0.8). Out of all the characteristic variables tested (N= 148), only the presence of at least one positive lymph node vs. none had a statistically significant negative effect on survival (mOS of 12.20 months vs. 23.10 months; p=0.0053). Conclusions: In patients with resected adenocarcinoma of the pancreas, the addition of radiation does not seem to add benefit. The presence of positive lymph nodes is an adverse prognostic factor on overall survival.
Combination of antiangiogenic therapy using the mTOR inhibitor RAD001 (everolimus) and low-dose chemotherapy for locally advanced and/or metastatic pancreatic cancer: Dose-finding study.
Authors: Joka Mareile , Boeck Stefan Hubert , Hosius Christian , Decroix Laetitia , May Christoph , Alberter Barbara , Pustowka Anette , Heinemann Volker , Bruns Christiane 
Published: February 2017

360 Background: This was an open-label, multicenter two-arm combined phase I (dose finding, cohort 1-5)/II (dose expansion) study of continuous doses of RAD001 every 2nd day or every day in combination with escalating low dose gemcitabine in patients (pts) with locally advanced and/or metastatic pancreatic cancer. The primary objective was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). The secondary objectives were to characterize safety and tolerability and to evaluate preliminary efficacy (ORR). Methods: A total of 27 pts were enrolled in phase I. All of these were analyzed in the safety population and 23 pts in the MTD-determining population. In total, 21 pts completed the study. Results: The MTD was determined to be 500mg/m2/week gemcitabine and 5mg/d RAD001 (cohort 4, 7 pts treated). In total, 3 DLTs occured: hepatic toxicity and unknown DLT as worsed case assumption in cohort 5 and hepatic toxicity in cohort 4. Overall, 25 of 27 pts (92.59%) reported at least one AE. Thrombocytopenia was most frequent AE, followed by leukopenia and nausea. In the individual dose groups, thrombocytopenia was most common in cohorts 1, 2 and 5, leukopenia in cohort 3 and nausea in cohort 4. The majority of pts experienced AEs with suspected relation to study drug (81.48%), AEs leading to dose adjustments or temporary interruption (77.78%) or required concomitant medication (66.67%). A total of 11 pts (40.74%) experienced SAEs. Two pts died during the study (not related to study drug). 4 pts were dicontinued permanently due to 2 AEs and 2 SAEs. ORR was 13%. None of the pts reported complete response (CR), the progressive disease rate was 13%. The clinical benefit rate was 78.3%. Conclusions: The present study was prematurely terminated due to slow recruitment and the dose expansion phase (phase II) was not started. In phase I, the MTD was determined to be 500mg/m2/week Gemcitabine and 5mg/d RAD001. No new safety concerns were identified for combination of antiangiogenic therapy using the mTOR- inhibitor RAD001 (Everolimus) and low dose chemotherapy for locally advanced and/or metastatic pancreatic cancer.
Characteristics and outcomes of patients with gallbladder cancer and cholangiocarcinoma referred to a phase I clinic.
Authors: Subbiah Ishwaria Mohan , Subbiah Vivek , Kaseb Ahmed Omar , Janku Filip , Wheler Jennifer J. , Naing Aung , Fu Siqing , Piha-Paul Sarina Anne , Hong David S. , Falchook Gerald Steven , Tsimberidou Apostolia Maria , Kurzrock Razelle 
Published: February 2017

364 Background: The prognosis of cholangiocarcinoma (CC) and gallbladder carcinoma (GC) remains grim. The purpose of this study was to report the presenting characteristics and outcomes of patients with CC and GC treated on phase 1 clinical trials focused on targeted agents at a major cancer center. Methods: We reviewed the records of consecutive patients with GC and CC in the Phase I Clinical Trials Program at the M. D. Anderson Cancer Center from Nov 2004. We assessed the relationship between overall survival, patients' tumor types, and mutations, demographic and clinical characteristics. Results: Fifty-two patients were identified (7 with GC, 45 with CC). The median age was 58 yrs (range, 20-75 yrs). ECOG performance status (PS) was 0, 1, 2, and 3 in 9 (17%), 30 (58%), 7 (13%), and 6 (12%) pts, respectively. Median number of prior therapies was 3 (range 0-17). The median time from diagnosis of metastatic disease to primary Phase I clinic evaluation was 14.6 months. Of 52 patients, 17 (33%) were not enrolled on a Phase I trial due to decline in PS (n=13) or decision to pursue other treatments (n=4). Of 35 patients evaluable for response, 2 (6%) had a partial response (PR), and 3 (9%) had stable disease > 4 months. Prognostic factors analyzed include Hg < 10.5 g/dL, elevated CA 19-9 (>47 ng/mL), ECOG PS > 3, LDH > 618 IU/L, albumin < 3.5 g/dL, platelets < 150 K/UL, and number of metastatic sites. Full analysis including the mutational analysis for PIK3CA, KRAS, BRAF, TP53 is in progress. Median survival since presentation to the Phase I clinic was 4.1 months (range 2.3 - 30.8 months). Median overall survival from diagnosis was 23.9 months. The median survival since enrollment in a Phase I trial was 4.6 months w the median time to disease progression on Phase I treatment was 2.2 months (range 0.6 - 25.6 months). Conclusions: Prognosis of pts with CC and GC referred for phase I studies remains poor. Further analysis including complete mutational profiles of CC and GC patients will be reported.
Identification of distinct phenotypes of locally advanced pancreas cancer.
Authors: Teo MinYuen , Crotty Grace Frances , O'Suilleabhain Criostoir , Power Derek Gerard , McDermott Raymond S. 
Published: February 2017

369 Background: A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease (LAPC). Optimal treatment remains controversial. There is no consensus on timing of chemotherapy and radiotherapy. We sought to analyse the clinical course of LAPC in order to identify potential distinct clinical phenotypes. Methods: Patients (pts) diagnosed with LAPC who survived >2 months were identified from prospectively maintained databases from two medical oncology departments in teaching hospitals. Demographics and clinical details were collected. Sequential restaging scans were reviewed for each pts to identify date and pattern of progression. Time to progression (TTP), time from progression to death (TTD) and overall survival (OS) were defined as time from histologic diagnosis to time of radiographic progression, time from radiographic progression to death and the summation of TTP and TTD, respectively. Survival was estimated with Kaplan-Meier method and compared with log-rank test. Results: Between Mar 2005 and Apr 2011, a total of 40 pts were identified. Median age was 66yrs (range: 43 – 74) and 60%(n=24) were males. Median OS for entire cohort was 11.3mos. Of 40 pts, 20(50%) had local only progression (LP) and 16(40%) had metastatic progression (MP) at first documentation of disease progression, while 4 pts (10%) had stable disease (2 died with no evidence of progression and 2 remain on treatment). TTP was 4.0 vs 5.6mos HR 0.97 (95% CI 0.49 – 1.93, p=.94) for LP and MP, respectively. Three of the pts with LP (15%) eventually developed metastatic disease after a median of 4.2 mths (3.7 – 9.6). For MP pts, five had concurrent local progression. Sites of disease were lungs(8), peritoneum(5), liver(3) and bone(1). TTD for LP and MP was 5.6 vs 1.4mos HR 0.62 (95% CI 0.28 – 1.39, p=.24), and OS was 13.2 vs 8.0mos, HR 0.59 (95% CI 0.28 – 1.25, p=.17) respectively. Conclusions: We identified two subgroups of LAPC with clinically distinctive behaviour, one local-dominant progression with low predilection for distant metastases, and another with rapid metastatic development and worse survival. Early recognition of these phenotypes might allow a more tailored treatment approach to improve outcome.
Clinical results at 3 years of the ACCORD 12 randomized trial in rectal cancer.
Authors: Gérard Jean-Pierre , Azria David , Gourgou-Bourgade Sophie , Conroy Thierry , Bedenne Laurent 
Published: February 2017

389 Background: The main end point of this trial was pathological response and published in 2010. We present the main clinical outcome after 3 years follow up. Methods: A total of 598 patients were included by 56 different French institutions between 2005 and 2008. Inclusion criteria were: resectable rectal adenocarcinoma accessible to digital examination and staged T3,4 Nx M0. Low anterior T2 were also eligible.Two neoadjuvant treatments were compared: CAP 45 (Radiotherapy 45 Gy/5 weeks with concurrent chemotherapy: capecitabine 1 600 mg/m2/day) versus CAPOX 50 (RT 50 Gy/5weeks with the same capecitabine plus oxaliplatin 50 mg/m2 /q week). Adjuvant chemotherapy was given to 253 patients and well balanced between both arms. All patients were analysed according to the intent to treat principle. Results: With a median follow up time of 36 months the main clinical results are presented in the table . There was no significant difference in local control, survival, toxicity and functional results. In an exploratory analysis, clinical complete response (24 pts) before surgery and pathological complete response (92 pts) were associated with an excellent disease free survival at 3 years respectively 92% and 90%. These results must be interpreted in reference with 3 other recent randomized trials involving the same patients: STAR 01 (Italy) NSABP R 04 (USA) (Table) CAO/ARO 04 (Germany). Conclusions: It is possible to conclude from this trial and the 3 other trials that: (1) oxaliplatin should not be included in the protocol (increased early toxicity and no effect on the pCR rate) (2) capecitabine is as efficient as fluorouracil (3) RT dose escalation to 50 Gy is improving pCR without increasing toxicity. A “CAP 50” regimen appears as safe and efficient in this neoadjuvant situation. [Table: see text]
Detector-C 2.0: A highly accurate blood-based IVD test for early detection of colorectal cancer with sensitivity and specificity over 90%.
Authors: Rosenthal Andre , Mayr Tobias , Koeppen Hartmut , Musikowski Reiner , Berendt Johannes , Goebel Uwe , Pross Matthias , Pertschy Jörg , Nartschik Peter , Wehnisch Hubertus J.C. , Manger Thomas , Mantke Rene , Steinmueller Thomas , Ridwelski Karsten , Buthut Thomas , Hinzmann Bernd , Nuernberg Dieter , Pommerien Wilfried , Adams Hans-Peter 
Published: February 2017

393 Background: We previously reported on the discovery and prospective validation of a blood based test (Detector C) for early detection of colorectal cancer (CRC). Detector C measures 202 RNA markers in white blood cells as a response of the host to tumor formation and growth. Detector C was validated using a prospective, multicenter case-control study with 343 patients (pts), 210 cases with confirmed CRC and 133 controls undergoing a complete screening colonoscopy. Detector C has a validated sensitivity (S+) of 90% (95% CI 0.851-0.937) and specificity (S-) of 88% (95% CI 0.812-0.930) (Rosental A. et al, J Clin Oncol 28:7s, 2010 (suppl; abstr 3580)). We now present the discovery of Detector C 2.0 based on 445 samples representing most of the pts previously used in the discovery and validation sets of Detector C. Methods: We used Affymetrix U133 plus 2.0 expression data of 291 CRC cases and 154 controls for discovery of Detector C 2.0. Random forest was used for feature (gene) selection and the support vector machine algorithm was employed as classifier in 600 repetitions of double-nested bootstraps to discriminate between cases and controls. Within each repetition, randomly chosen 23 controls and 160 CRC cases served as prospective validation set. The most frequent chosen genes for discrimination between cases and controls formed the consensus signature, namely Detector C 2.0. Results: Choosing a signature length of 1000 genes resulted in the following second order unbiased prospective performance estimates: S+=0.916 (95% CI 0.863-0.954) and S-= 0.948 (95% CI 0.773-0.994). S+ for UICC stage I and stage II cases were 0.93 and 0.94. S+ for high-grade intraepithelial neoplasia was ∼ 0.67 and S+ for adenoma ≥ 10 mm was ∼ 0.45. Conclusions: Using a three times larger discovery set for Detector C 2.0 than for Detector C we improved S+ (cancer detection rate) by 1.6% to 91.6%. The most important enhancement is the high S- of 94.8% of Detector C 2.0 which is six percent higher than the S- of Detector C. Detector C 2.0 is based on a much larger pts set and should be even more robust than Detector C. We will prospectively validate this test in the largest case-control study ever performed in early detection of CRC.
Changes in management and survival outcomes for patients receiving gene-expression-based tissue-of-origin test results for difficult-to-diagnose primary cancers.
Authors: Hornberger John C. , Varadhachary Gauri R. , Gutierrez Hialy R , Henner William David , Becker Shawn , Amin Mahul , Nystrom J. Scott 
Published: February 2017

397 Background: An important step for a novel test is assessing its clinical utility and real-world effect on diagnosis and patient management. This report describes completed results of a cohort of physicians who have ordered a gene expression profile assay for identification of tumor tissue of origin (Pathwork Tissue of Origin Test) for patients with difficult-to-diagnose primary cancers and their subsequent treatment and survival. Methods: The IRB-approved registry collected data from participating physicians who have ordered the Tissue of Origin test. A detailed interview was conducted using both a web-based questionnaire and a confirmatory telephone interview with the physicians. Chart survey included collection of data on patient demographics, diagnostic procedures including imaging and immunohistochemistry as well as therapy. The physicians were queried regarding their working diagnoses and treatment recommendations prior to and after Tissue of Origin Test result availability. Date of death was also obtained with a minimum of one year follow-up from date of biopsy. Results: One hundred seven patients (61 women) have been studied and 65 participating physicians have completed the interview. Results indicate that most patients underwent extensive evaluation (≥ 10 IHC) prior to gene expression analysis. After receiving test results, physicians changed the primary site diagnosis for 53 patients (50%, CI [43,58%]; p<.001) and changed the treatment management for 72 patients (65%, CI [58%,73%]; p<.0001). At last follow-up, 69 patients had died with a median survival of 426 days. More than 30% of patients were alive at 1000 days. Conclusions: This registry study confirms that in patients with difficult-to-diagnose primary cancers, extensive baseline diagnostics are common and less than half of the patients have an established working diagnosis. Results indicate that the Tissue of Origin Test led to a change in working diagnosis and changed treatment recommendations in over half the patients. Survival outcomes compare favorably to historical controls in treatment trials where median survival is generally less than one year.
Interval colorectal cancer despite screening colonoscopy: A single-center experience.
Authors: Resch Gudrun , Mallinger Christian , Schauer Walter , Thaler Josef , Knoflach Peter 
Published: February 2017

401 Background: Colonoscopy is recommended as the primary screening method for colorectal cancer (CRC) and polypectomy is considered effective for preventing cancer. CRCs which occur within 5 years of screening colonoscopy are defined as interval cancer. Despite regular colonoscopy and complete polypectomy interval colorectal cancer may occur. Methods: All patients undergoing a colonoscopy were recorded in a colonoscopy registry, all CRC-patients who underwent colectomy were recorded in a surgery registry and all patients with newly diagnosed CRC were recorded in a tumor registry at the Klinikum Wels-Grieskirchen. In this retrospective analysis all patients with newly diagnosed CRC since the year 2000 were evaluated if a screening colonoscopy was done before the diagnosis of CRC at our institution. Results: Overall, 1.102 patients with CRC were evaluated. 939 patients underwent tumorectomy/colectomy at our department of surgery. In 65.8% (n=725) CRC was detected by colonoscopy at our institution and 85 out of these patients had a previous screening colonoscopy (range 14-176 months, median 55 months) at our institution. Interval cancers, which occur within 5 years since screening colonoscopy, were detected in 45 patients. Six patients could be identified with complete negative colonoscopy, 2 patients had inadequate bowel preparation, in 7 patients colonoscopy was not complete because of technical problems, 26 patients had a history of colorectal adenomas and 4 patients had inflammatory bowel disease. In 16 out of 26 patients with adenomas a CRC was detected distant from the side of the previous polypectomy. Conclusions: More emphasis and short-term control of incomplete and inadequately prepared colonoscopies, as well as a re-call system for post-polypectomy controls could reduce the number of so called interval CRSs.