bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis of gastric cancer (GC) patients with positive peritoneal cytology.
Authors: Shiozaki Hironori , Elimova Elena , Slack Rebecca , Chen Hsiang-Chun , Staerkel Gregg A , Sneige Nour , Planjery Venkatram , Charalampakis Nikolaos , Wadhwa Roopma , Sudo Kazuki , Matamoros Aurelio , Lee Jeffrey H. , Weston Brian , Bhutani Manoop S. , Blum Mariela A. , Estrella Jeannelyn , Das Prajnan , Mansfield Paul F. , Badgwell Brian D. , Ajani Jaffer A. 
Published: February 2017

41 Background: Laparoscopic staging of patients with GC can disclose peritoneal metastases. Although this finding is associated with a poor prognosis, some patients achieve a long-term survival. In an attempt to provide explanation we compared the overall survival (OS) of patients with GC peritoneal metastases from two settings: cytology positive only (Cy+) and grossly positive (Gross+). Methods: 146 GC patients with peritoneal metastases were identified between 2000 and 2014. Cox-model regression was used for overall survival (OS) analyses. Results: Patient/treatment characteristics were as follows: males (66%), good ECOG scores (0-1; 89%), metastases confirmed by a diagnostic laparoscopy (84%), poorly differentiated histology(92%), received chemotherapy (89%), received chemoradiation (22%), and received surgery (10%). The median follow-up time for all patients was 12.9 months and median OS was 15 months. Patients with Gross+ were at higher risk of death compared to Cy+ patients (50% vs. 83%1-year OS, respectively). Only diagnostic laparoscopy and metastasis type (Gross+ vs. Cy+) were significant in both univariate and multivariate OS models. With both factors in the same model, patients with Gross+ were more than twice as likely to die when compared to those with Cy+ (HR=2.23; p=0.001) while patients having a diagnostic laparoscopy were half as likely to die (HR=0.52; p=0.01). Conclusions: The one-year OS of patients with Cy+ peritoneal metastases is significantly longer than those with Gross+ findings. As such, novel strategies for Cy+ patients may further prolong their survival. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI).
Impact of FOLFOXIRI regimen on early “conversion” and long-term outcome in patients with initially unresectable colorectal liver metastases.
Authors: Shimada Mitsuo , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Arakawa Yusuke , Iwahashi Shuichi , Saito Yu , Yamada Shinichiro , Higashijima Jun , Takasu Chie 
Published: February 2017

416 Background: In our principle, hepatectomy is the first choice for liver metastases (mets) from colorectal cancer whenever future remnant liver is over 40% in volume. Recently, FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab (Bev) regimen was reported to be high rates of pathologic responses and necrosis of colorectal liver metastases (CLMs) without increasing liver toxicity (Br J Cancer 2013). The aim of this retrospective study is to clarify impact of FOLFXIRI plus molecular targeted drugs on initially unresectable CLMs. Methods: Among 81 patients with initially unresectable liver mets, 59 had chemotherapy (CTx), including 10 old CTx (-2003) and 49 new CTx (2004- ) using new drugs such as oxaliplatin. Regimen of FOLFOXIRI + molecular target drugs, consisting of Bev in 12 and C/P-mab in 2, was applied to 14 patients. “Conversion” rate and the period until “Conversion”, and overall survival (OS) were compared between FOLOFOXIRI group and other regimen group. Pathological and morphological responses were also examined. Results: “Conversion” was not obtained in old CTx group. In new CTx group, “Conversion” was achieved in 21 patients (43%). OS in “Convresion” group was better than “non-conversion” group (3-year survival: 70 % vs. 15 %). “Conversion” rate in FOLFOXIRI group was higher than that in other regimen group (64% vs. 34%). The period until “Conversion” in FOLFOXIRI group was shorter than that in other regimen group (6.2 cycles vs. 16.1 cycles). Furthermore, tumor necrosis rate in FOLFOXIRI group (80 %) was higher than that in other regimen group (47 %), and morphologic response (optimal/partial) in FOLFOXIRI group (33 % / 44 %) was higher than in other regimen group (8 % / 33 %). Prognosis after “Conversion” in FOLFOXIRI group was better than that in other regimen group (3-year survival: 80 % vs. 33 %). In addition, time to surgical failure (TSF) in FOLFOXIRI group tended to be better than that in other regimen group. Conclusions: FOLFOXIRI + molecular target drugs is highly effective in order to obtain early conversion and better long-term outcome after ”Conversion” for initially unresectable CLMs.
Nab-paclitaxel as second-line treatment in advanced biliary cancer.
Authors: Prager Gerald W. , Kornek Gabriela , Scheithauer Werner , Steger Guenther G. , Zielinski Christoph , Unseld Matthias 
Published: February 2017

463 Background: Addition of nab-paclitaxel to gemcitabine has recently been demonstrated in the clinical phase III trial MPACT to be beneficial for progression free survival, overall response rate, and overall survival in advanced pancreatic cancer patients. Any potential biologic activity of nab-paclitaxel in biliary cancer is hitherto unknown. Methods: A retrospective analysis of patients with advanced biliary cancer was undertaken to determine the disease control rate (CR+PR+SD), progression-free survival and overall survival in patients who had received nab-paclitaxel-based chemotherapy after failure of a platinum-containing first-line combination chemotherapy. Results: Eleven patients were identified. 4 of 11 patients received nab-paclitaxel as second line, 7 of 11 patients as a third-line treatment. 7 of 11 patients received nab-paclitaxel in combination with gemcitabine, while in 4 of 11 patients nab-paclitaxel was combined with fluoropyrimidine. The disease control rate seen with nab-paclitaxel was 81% (nine of eleven patients). Disease was progressive in one patient, and in one patient the response status is unknown yet. One patient received partial remission and 8 patients had stable disease. As of September 13th, 2014, three patients are still undergoing nab-paclitaxel combination therapy, but were censored by this date for analysis. The median time to progression was 4.9 months (2.3 – 18.9 months) for all patients (11/11 pts.), and 9.5 months for patients completed nab-paclitaxel treatment (8/11 pts.). Median overall survival for all eleven patients after initiation of nab-paclitaxel treatment was 7.3 month (2.6 – 21.8 month). The mean time of survival after diagnosis of advanced disease was 21.3 month, whereby 5 patients were alive at date of censoring. Conclusions: Nab-paclitaxel based chemotherapy can be an effective second-line regimen after platinum-failure in patients with advanced biliary cancer. In this small series, nab-paclitaxel appears to have a biological activity by controlling the disease and positively affecting survival. Randomized trials in this group of patients are urged.
Investigation of the tolerability of FOLFIRINOX in patients with unresectable advanced pancreatic cancer: Single-institution experience in Japan.
Authors: Miyashita Kouichirou , Sekikawa Takashi , Shimada Ken , Yamamoto Taikan , Kaga Yasuhiro , Nunoue Toshikazu , Uto Yu , Kitahara Yu , Hisamatsu Atsushi , Saito Yusuke , Kobayashi Kouji , Takinishi Yasutaka , Kinugasa Eriko 
Published: February 2017

487 Background: FOLFIRINOX therapy has contributed to the overall survival extension of unresectable advanced pancreatic cancer. This regimen is however associated with significant toxicity. And doing the treatment, while careful to toxicity at our institution. We investigated the tolerability of FOLFIRINOX for the treatment of unresectable advanced pancreatic cancer in clinical practice. Methods: We conducted a retrospective analysis of patients with unresectable advanced pancreatic cancer who received FOLFIRINOX between November 2012 and August 2014. FOLFIRINOX is as follows: irinotecan at 150 mg/m2; oxaliplatin at 85 mg/m2; 5-fluorouracil (5FU) at 400mg/m2 bolus, 2,400mg/m2 continuous infusion. Patients' characteristics, objective response, survival and toxicities were collected. Response were evaluated with RECIST version 1.1 and toxicities with NCI-CTCAE version 4.0. Results: 13 patients were includes (8 males and 5 females). Treatment eligibility criteria in our institution were Performance Status 0 or 1, and UGT1A1 polymorphisms were excluded. Median age was 58.6 years (41-74). Clinical stage IVa/IVb was 3/10. The mean number therapy was 7.7 (3-15) cycles. The toxicity of all grade was 100% and grade 3 was 80%. The non-hematological toxicities included nausea in 8 patients (61.5%) and anorexia in 9 (69.2%). The hematological toxicities included neutropenia in 12 patients (92.3%), of which 11 (84.6%) presented a grade 3/4 neutropenia. In patients who developed grade 3 neutropenia, the treatment of FOLFIRINOX could be continued once every three weeks (triweekly) without reducing the dose. Response rate was 38.5% (CR: 0, PR: 5, SD: 6, PD: 2) and disease control rate was 84.6%. Time to treatment failure was 175 days. Relative dose intensity was 95.0% for oxaliplatin, 88.9% for irinotecan, 81.9% for 5FU (bolus), and 95.6% for 5FU (continuous). Conclusions: In clinical practice, it is expected that FOLFIRINOX is an effective, well-tolerated regimen by reducing the dose or determining the appropriate dosing interval.
Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy.
Authors: Smith Jesse Joshua , Chow Oliver S , Eaton Anne , Widmar Maria , Nash Garrett Michael , Temple Larissa K. F. , Guillem Jose G. , Weiser Martin R. , Goodman Karyn A. , Cercek Andrea , Saltz Leonard , Gollub Marc J. , Gonen Mithat , Garcia-Aguilar Julio , Paty Philip 
Published: February 2017

509 Background: Nonoperative management (NOM) of rectal cancer following a clinical complete response (cCR) to neoadjuvant therapy is a non-standard approach. We review our experience with NOM to evaluate safety and efficacy. Methods: A retrospective review of prospectively collected data between 2006 and 2014 was conducted. We compared patients completing neoadjuvant therapy for stage I to III rectal cancers who: a) achieved cCR and were treated with NOM, or b) underwent standard total mesorectal excision (TME) and achieved a pathologic complete response (pCR). Kaplan-Meier estimates and the log-rank test were used. Results: Seventy-three patients underwent NOM after cCR. From 369 rectal resections performed, 72 (20%) achieved pCR and form the comparison group. Median follow-up across both groups was 3.3 years. Rectal preservation was achieved in 56 (77%) of the patients treated with NOM. Of the 19 NOM patients with local regrowth, 18 were salvaged successfully with standard TME (n=16) or local excision (n=2), with one patient pending a salvage operation (n=1). No significant differences were noted in the number of distant recurrences between the NOM and pCR groups. Four-year disease-specific survival and overall survival between the two groups were not significantly different. Conclusions: In this highly selected group of patients with cCR to neoadjuvant treatment, NOM with surgical salvage of local tumor regrowth achieved local control in all patients. The oncologic outcome for NOM patients at 4 years was comparable to patients with pCR after rectal resection. These data continue to suggest that NOM does not compromise oncologic outcome, and that preservation of the rectum is achieved in a majority of patients. [Table: see text]
RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab (RAM) or placebo (PBO) in patients (pts) with metastatic colorectal carcinoma (CRC) progressive during or following first-line combination therapy with bevacizumab (bev), oxaliplatin (ox), and a fluoropyrimidine (fp).
Authors: Tabernero Josep , Cohn Allen Lee , Obermannova Radka , Bodoky Gyorgy , Garcia-Carbonero Rocio , Ciuleanu Tudor-Eliade , Portnoy David Craig , Van Cutsem Eric , Grothey Axel , Prausová Jana , Garcia-Alfonso Pilar , Yamazaki Kentaro , Clingan Philip R. , Zagonel Vittorina , Kim Tae Won , Simms Lorinda , Chang Shao-Chun , Nasroulah Federico , Yoshino Takayuki ,   The RAISE Study Investigators
Published: February 2017

512 Background: Angiogenesis is an important therapeutic target in CRC; VEGF plays a key role in angiogenesis. RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The RAISE study evaluated the efficacy and safety of adding RAM to standard second-line treatment FOLFIRI. Methods: Eligible pts with mCRC who progressed on or after first-line combination therapy with bev, ox, and fp, had an ECOG PS of 0 or 1, and adequate organ function were randomized 1:1 (stratified by region, KRAS mutation status, and time to progressive disease [PD] after beginning first-line treatment) to receive RAM (8 mg/kg IV) plus FOLFIRI or PBO plus FOLFIRI every 2 weeks until PD, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Planned sample size of 1,050 pts ensured 85% power to demonstrate statistical significance at an overall two-sided alpha of 0.05, assuming a hazard ratio (HR) of 0.8. Results: Between Dec 2010 and Aug 2013, 1,072 eligible pts were randomized (RAM 536; PBO 536). Baseline pt characteristics were similar between treatment arms. The OS HR was 0.84 (95% CI: 0.73, 0.98; log-rank p=0.0219). Median OS was 13.3months (m) for RAM vs 11.7m for PBO. The PFS HR was 0.79 (95% CI: 0.70, 0.90; log-rank p = 0.0005). Median PFS with RAM was 5.7m and 4.5m for PBO. ORR was 13.4% RAM; 12.5% PBO (p = 0.6336). Subgroup results were consistent with the OS and PFS results. Grade ≥3 adverse events (AEs) occurring in >5% of pts in RAM+FOLFIRI were: neutropenia (RAM 38.4% vs PBO 23.3% ), hypertension (11.2% vs 2.8%), diarrhea (10.8% vs 9.7%), and fatigue (11.5% vs 7.8%). Conclusions: RAISE met its primary end-point, demonstrating a statistically significant improvement in OS for RAM and FOLFIRI vs PBO and FOLFIRI in second-line mCRC pts. Benefits were similar across important clinical subgroups and no unexpected AEs were identified. Clinical trial information: NCT01183780.
A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer.
Authors: Xu Rui-hua , Shen Lin , Wang Keming , Wu Gang , Shi Chunmei , Ding Kefeng , Lin Lizhu , Wang Jinwan , Xiong Jianping , Wu Changping , Li Jin , Liu Yunpeng , Wang Dong , Ba Yi , Feng Jueping , Bai Yuxian , Bi JingWang , MA Liwen , Lei Jian , Yu Hao 
Published: February 2017

513 Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and is the fifth leading cause of cancer death in China. No standard care is available for patients with advanced CRC who failed the second-line treatment. Famitinib is a small-molecular, multi-target receptor tyrosine kinase inhibitor which primarily acts against angiogenesis. This phase II study was designed to evaluate the efficacy and safety of famitinib in the treatment of advanced colorectal cancer. Methods: This is a multi-center, randomized, double-blind, placebo-controlled, phase II clinical study (ClinicalTrials.gov Registration No.: NCT01762293). Totally 154 patients with advanced colorectal cancer who failed second or later-line treatments were randomized in a 2:1 ratio to receive either famitinib or placebo at 25 mg each day in each treatment cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and safety. The statistical analyses of endpoints were using intent-to-treat population. Results: Of 154 patients randomized, the mPFS was 2.8 and 1.5 months in the treatment group and control group, respectively (p=0.0034; HR=0.58). The ORR was 2.02% and 0.00% (p=0.54) and the DCR was 57.58% and 30.91% (p=0.0023) in the treatment group and control group, respectively. Analysis of OS data is ongoing. The frequently reported adverse events (AEs) include neutropenia, thrombocytopenia, hypertension, proteinuria, and hand-foot syndrome and were most grade 1/2. The incidences of serious adverse events (SAEs) for the famitinib and placebo groups were 11.11% and 9.09%, respectively (p=0.7884). Overall, famitinib was well tolerated and toxicities were manageable. Conclusions: Famitinib improved the PFS in patients with advanced metastatic colorectal cancer resulting in higher ORR and DCR in the treatment group with good safety and tolerability. Clinical trial information: NCT01762293.
MicroRNA targeting for the therapy of colitis-associated colon cancer.
Authors: Polytarchou Christos , Hommes Daniel W. , Palumbo Tiziana , Hatziapostolou Maria , Koukos Georgios , van der Meulen-de Jong Andrea E. , Oikonomopoulos Angelos , van Deen Welmoed K. , Vorvis Christina , Koutsioumpa Marina , Birli Eleni , Choi Jennifer , Chang Lin , Anton Peter A. , Pothoulakis Charalabos , Verspaget Hein W. , Iliopoulos Dimitrios 
Published: February 2017

571 Background: Inflammatory Bowel Diseases (IBD) consist of ulcerative colitis (UC) and Crohn’s Disease (CD), which are characterized by activation of inflammatory responses. Patients with longstanding UC are at high risk of developing colorectal cancer. The identification of novel molecular targets with therapeutic potential for UC and UC-related dysplasia are of major importance. Methods: Using a high throughput functional suppressor screen of the human microRNAome, we identified microRNAs involved in the regulation nuclear factor kappa beta (NF-κB). We correlated microRNA expression levels with different clinicopathological parameters in 401 colonic specimens derived from patients with UC, CD, irritable bowel syndrome (IBS), sporadic colon cancer (CRC), colitis-associated cancer (CAC) and control subjects. Bioinformatic and molecular analyses were employed for the study of micoRNA-regulated signaling pathways. A microRNA specific chemical inhibitor was used to treat colonic biopsies ex vivo and murine CAC development in vivo. Results: The microRNA screen identified miR-214 as master regulator of NF-κB. MiR-214 levels are increased in colonic tissues from UC and CAC, but not from CD, IBS and CRC patients and positively correlate with UC disease activity and duration. STAT3 regulates miR-214 expression in colonocytes in vitro and STAT3 and miR-214 levels positively correlate in UC and CAC. MiR-214 regulates the expression of phosphatase and tensin homolog (PTEN) and PDZ and LIM domain 2 (PDLIM2) and both are decreased in colonic tissues of UC and CAC patients. MiR-214 is amplified through a feedback loop circuit and its overexpression increases the tumorigenic and invasive phenotype of colon cancer cells. A chemical miR-214 inhibitor perturbs this circuit in colonic biopsies from UC patients ex vivo while intracolonic delivery suppresses CAC growth in mice. Conclusions: Our findings demonstrate a gene controlling the inflammatory response specifically in UC and CAC. The miR-214 molecular circuit activity correlates with UC disease activity and duration. Activation of this circuit contributes to colitis-associated colon carcinogenesis, and its suppression has therapeutic potential for patients with UC-related dysplasia.
Clinical impact of expanded BRAF mutational status on the outcome for metastatic colorectal cancer patients with anti-EGFR antibody: An analysis of the BREAC trial (Biomarker Research for Anti-EGFR Monoclonal Antibodies by Comprehensive Cancer Genomics).
Authors: Yamazaki Kentaro , Yoshino Takayuki , Tsuchihara Katsuya , Shinozaki Eiji , Muro Kei , Nishina Tomohiro , Yamaguchi Kensei , Akagi Kiwamu , Yuki Satoshi , Yamanaka Takeharu , Nomura Shogo , Fujii Satoshi , Esumi Hiroyasu , Abe Yukiko , Ohtsu Atsushi 
Published: February 2017

573 Background: BRAFV600E mutation has been recognized as a prognostic marker in patients (pts) with metastatic colorectal cancer (mCRC). Several studies have consistently shown a significant association between the presence of BRAFV600E mutation and resistance to anti-EGFR antibody therapy in pts with previously treated mCRC while there are few reports on the clinical impact of minor BRAF mutations. Methods: The BREAC trial was a multicenter, retrospective study to investigate the novel biomarkers of anti-EGFR antibody therapy. RAS and BRAF mutations were detected by targeted sequencing using FFPE materials of mCRC pts who received anti-EGFR antibody after a failure to standard therapies. Progression-free survival (PFS), overall survival (OS), and response rate (RR) were evaluated according to expanded RAS/BRAF mutational status. Results: Of 184 pts enrolled in the study, RAS/BRAF testing was succeeded in 150 pts. Patients characteristics were as follows; male/female 87/63, median age 63.5 years (range, 28-85), PS 0/1/2 81/65/4. Median PFS, OS, and RR were 4.0 months, 12.4 months, and 21%, respectively. Expanded RAS and BRAF mutations were detected in 40 pts (26.7%, KRAS/NRAS 29/11) and in 16 pts (10.7%, BRAFV600E/other 9/7), respectively. Observed BRAF mutations other than BRAFV600E were located at kinase domain. The clinical outcomes of other BRAF mutations were worse similar to those of BRAFV600E and expanded RAS mutations (Table). Conclusions: Expanded BRAF mutations might predict a lack of response for mCRC pts who received anti-EGFR antibody. Further investigation is warranted to confirm the clinical impact of expanded BRAF mutations. [Table: see text]
Regional variation in physicians’ awareness, understanding, and use of personalized medicine in the treatment of cancer and perception of patient (pt) education.
Authors: Ciardiello Fortunato , Seufferlein Thomas , Tabernero Josep , Taieb Julien , Moiseyenko Vladimir , Ma Brigette , Lopez Gustavo A. , Esser Regina , Adams Richard A. 
Published: February 2017

574 Background: A multinational survey of oncologists was conducted to assess the awareness and use of biomarkers in clinical practice (Ciardiello et al, ESMO 2014). These data explore regional variations as well as perceived level of “cancer literacy” among pts. Methods: Ten-minute online interviews were conducted with practicing oncology specialists (3 to 35 years of experience, treating > 15 pts/month) from 12 representative countries in Europe, South America, and Asia. Results: In total, 895 interviews were completed; numerous regional differences were observed. While most physicians use biomarkers (90%), there were marked regional variations. KRAS was the most frequent test. Among the 10% of physicians not using biomarkers, local availability of testing, speed of obtaining results, and cost were cited as the main reasons. The majority of Chinese doctors indicated that physician training (82%) and better biomarker information for pts (83%) would enable them to use biomarkers more often (global averages: 38% and 34%, respectively). Striking variation was seen in physicians’ assessment of pts’ knowledge of cancer biology, treatment options, use of biomarkers, and involvement in their own treatment plans. Only 38% of German physicians believed their pts know that tumors can be tested to help decide which treatment to give (global average: 73%). Only 21% of Saudi Arabian physicians believed the treatment decision process is shared between the doctor and/or multidisciplinary team and pt (global average: 82%). While physicians felt specialist nurses were the best source of information for pts, only 45% globally believed pts had access to these nurses (ranging from 19% in Russia to 83% in the UK). Conclusions: These data demonstrate wide global use of biomarkers but with regional variations reflecting cultural and local practice. Perception of pt cancer literacy and pt access to information also differs widely. Most physicians agree, however, that pts require more information to understand their disease better and become involved in treatment decisions.