bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of preoperation mFOLFIRINOX and chemoradiation for high-risk resectable and borderline resectable pancreatic adenocarcinoma.
Authors: Varadhachary Gauri R. , Fleming Jason B. , Crane Christopher H. , Fogelman David R. , Shroff Rachna T. , Lee Jeffrey Edwin , Lee Jeffrey H. , Tamm Eric P. , Bhosale Priya , Das Prajnan , Krishnan Sunil , Javle Milind M. , Weston Brian , Wang Huamin , Wolff Robert A. , Katz Matthew H. G. 
Published: February 2017

362 Background: Patients with high risk resectable and borderline resectable pancreatic adenocarcinoma (BRPC) are at a high risk for R1/R2 resection, early relapse with upfront surgery and poor OS. Preop therapy has a sound rationale and current retrospective data suggest resection rates of 40-60% with a possible impact on OS. Methods: We planned a prospective study of 33 pts. Eligibility includes diagnosis of pancreatic ductal carcinoma (PC) and >=1 criteria of BRPC (radiographic) A: (i) PC involves SMV with vein deformity or segmental occlusion; (ii) PC involves <=1800 SMA, CA or its branches (iii) abutment or encased short segment of CHA and/or BRPC (high-risk) B: (iv) CA19-9 >=500 mg/dl (v) malignant peripancreatic nodes outside planned surgical field (vi) indeterminate liver or peritoneal lesions. Enrolled pts receive mFOLFIRINOX (oxaliplatin 75 mg/m2 d1+ irinotecan 150 mg/m2 d1+ 5-FU 2000mg/m2 46h CI) for 6 cycles. Those without progression & good PS undergo EBRT 50.4Gy with weekly Gemcitabine 350 mg/m2. Surgery is planned 4-6 weeks after CRT in pts without progression. Results: 24/33 pts accrued. 18(75%) with A criteria alone; 1(4%) with B criteria alone and 5 (21%) with both. Median age is 66 yrs; ECOG PS0 42%, PS1 58%. Median CA19-9 is 219 (1-1185) mg/dl. 20/24 have completed all preop therapy and 10 underwent surgery (50%).10 patients did not proceed to surgery due to disease progression (5), poor PS (3) or withdrawal of consent (2). Grade ¾ hematologic and non-hematologic toxicity noted in 8/21 (38%). Of the 10 resected pts, all underwent vein reconstruction and R0 rate is 80%. Major pathologic response rate (>50 % tumor kill) was 30%. One (bleeding) major complication occurred within 90 d of surgery. 5/10 resected pts relapsed <1yr after surgery with a median TTP from surgery of 5mo (3-7mo). SMAD4 and CTC analysis pending. Conclusions: Although the sample size is limited, using strict criteria, resection rates with preop FOLFIRINOX and Gem-RT mirror retrospective data (50%). Half of the resected pts have recurred early suggesting aggressive preop therapy does not rescue aggressive biology. Further analysis may allow identification of pts who are poor candidates for an aggressive preop approach. Clinical trial information: NCT01560949.
Effects of lanreotide autogel/depot (LAN) in patients with neuroendocrine tumors (NETs) age 65 or younger versus older than age 65: Subgroup analyses from the CLARINET study.
Authors: Phan Alexandria T. , Caplin Martyn E. , Pavel Marianne E. , Cwikla Jaroslaw B , Raderer Markus , Sedláčková Eva , Cadiot Guillaume , Wolin Edward M. , Capdevila Jaume , Wall Lucy , Rindi Guido , Langley Alison , Gomez-Panzani Edda , Ruszniewski Philippe B. ,   on behalf of the CLARINET Study Group
Published: February 2017

367 Background: The somatostatin analog lanreotide Autogel 120 mg significantly prolonged progression-free survival (PFS) vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67 <10%) non-functioning enteropancreatic NETs (hazard ratio [HR] for progressive disease [PD]/death: 0.47 [95% CI: 0.30, 0.73]). The large size of the trial (n=204) affords an opportunity to examine treatment effects within subgroups of particular interest. Here, we compare PFS and safety data for patients aged ≤65 years vs. aged >65 years. Methods: In this 96-week randomized double-blind trial, patients received LAN 120 mg or PBO every 4 weeks by deep s.c. injection (NCT00353496). Subgroup analyses were undertaken to investigate only the consistency of treatment effects as the study was not otherwise designed or powered for such analyses. Results: Median age (range) was 57 years (30, 65) for thegroup aged ≤65 years and 71 years (66, 92) for the group aged >65 years. Other baseline characteristics were similar between age groups, including tumor origins (≤65 years: pancreatic 43%, midgut 34%; >65 years: pancreatic 46%, midgut 38%) and hepatic tumor loads (>25%: 30% and 37% for ≤65 and >65 years, respectively). Disease was predominantly stable at baseline (94% vs. 98%, respectively). Therapeutic effects of LAN on PFS were similar for the age groups and there were no consistent differences in tolerabilities between age groups (Table). The most common AE was diarrhea irrespective of age and treatment (≤65 years: LAN 36%, PBO 32%; >65 years: LAN 33%, PBO 40%). Conclusions: The treatment effect with LAN in terms of PFS was consistent across age groups and LAN tolerability/safety was favorable in both cases. Clinical trial information: NCT00353496. [Table: see text]
Effect of coadministration of propranolol and etodolac (VT-122) plus sorafenib for patients with advanced hepatocellular carcinoma (HCC).
Authors: de la Torre Andrew N , Castaneda Ismael , Hezel Aram F. , Bascomb Newell F. , Bhattacharyya Gouri Shankar , Abou-Alfa Ghassan K. 
Published: February 2017

390 Background: Propranolol and etodolac (designated VT-122) target the adrenergic and prostaglandin stress systems activated in HCC. These stress-induced systems are proposed to induce changes in the tumor microenvironment and immune system leading to tumor promotion and immune tolerance. In a separate study, administration of VT-122 prior to sorafenib showed an increase in median overall survival (OS) of 21 months when VT-122 is administered before sorafenib compared to 10 months OS for sorafenib alone. The aim of the current study was to evaluate the effect of administering VT-122 at least 30 days after starting sorafenib. Methods: Patients with HCC receiving sorafenib for at least 30 days were eligible for this double-blind, placebo-controlled study. Patients were randomized to receive sorafenib with either VT-122 or placebo. Patients received therapy for up to 12 months or until treatment failure. VT-122 was administered twice daily. The primary endpoint was duration of therapy (DoT) and the secondary endpoint was OS. Results: Twenty patients were randomized, 11 and 9 patients to the VT122 and placebo arm, respectively. Each arm was balanced with regards to age (mean of 60.4 years), Child Pugh status (9 Child Pugh A, 11 Child Pugh B7), hepatitis virus status (6 HBV and 1 HCV positive) and C-reactive protein (CRP) (20.4 mg/L). VT122 with sorafenib was well tolerated with no unexpected serious adverse events reported. Mean OS was 13.9 months and 9.6 months in the VT-122 and placebo arms, respectively. Mean DoT (unvalidated) was 10.1 months and 7.5 months in the VT-122 and placebo arms, respectively. Conclusions: Co-administration of VT-122 with sorafenib was well tolerated and showed an increase in duration of therapy and OS versus sorafenib alone. The small sample size and number of events precludes the ability to make any significant efficacy conclusions. The increase in survival was not as great as that seen in a separate study in which VT122 was started prior to sorafenib. A further Phase 3 study of VT122 administered prior to sorafenib in patients with HCC is warranted. Clinical trial information: NCT01265576.
Morbidity and mortality after laparoscopy-assisted and open distal gastrectomy for stage I gastric cancer: Results from a multicenter randomized controlled trial (KLASS-01).
Authors: Lee Hyuk-Joon , Kim Hyung-Ho , Han Sang Uk , Kim Min-Chan , Hyung Woo Jin , Ryu Seung Wan , Cho Gyu Seok , Kim Chan Young , Yang Han-Kwang , Park Do Joong , Song Kyo Young , Lee Sang Il , Ryu Seung Yub , Lee Joo-Ho , Kim Wook ,   Korean Laparo-endoscopic Gastrointestinal Surgery Study Group (KLASS)
Published: February 2017

4 Background: Laparoscopy assisted distal gastrectomy (LADG) is widely performed for gastric cancer in Eastern countries, although large scale prospective data are still lacking. We conducted a phase III, multicenter randomized controlled trial (KLASS-01) to compare the short and long term outcomes of LADG versus open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea. Methods: The primary end point was 5-year overall survival. The morbidity within 30 postoperative days and the surgical mortality were compared to evaluate the safety of LADG as a secondary end point. A total of 1,416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between Feb 1, 2006 and Aug 31, 2010. Results: 1,256 were eligible for per protocol (PP) analysis (644 and 612, respectively). The overall complication rate was significantly lower in the LADG group (LADG vs. ODG; 13.0% vs. 19.9%, P =.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs. 7.7%, P <.001). The major intra-abdominal complication (7.6% vs. 10.3%, P =.095) and mortality rates (0.6% vs. 0.3%, P =.450) were similar between groups. Modified intention-to-treat analysis showed similar results with PP analysis. Conclusions: LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG. Clinical trial information: NCT00452751.
Impact of postoperative complications on pancreatic cancer survival and recurrence.
Authors: Asari Masahiro , Aoyama Toru , Katayama Yusuke , Murakawa Masaaki , Yamaoku Koichiro , Kanazawa Amane , Higuchi Akio , Shiozawa Manabu , Ueno Makoto , Morimoto Manabu , Akaike Makoto , Hayashi Tsutomu , Yamamoto Naoto , Oshima Takashi , Yoshikawa Takaki , Rino Yasushi , Masuda Munetaka , Morinaga Soichiro 
Published: February 2017

446 Background: We investigated the impact of postoperative complications on pancreatic cancer survival and recurrence after curative surgery. Methods: This study included 164 patients who underwent curative surgery for pancreatic cancer between 2005 and 2014. The patients were classified into those with postoperative complications (C group) and those without postoperative complications (NC group). The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. Results: Postoperative complications were found in 61 of the 164 patients (37.2%). The RFS rate at five years after surgery was 10.6% in the C group patients and was 21.0% in the NC group patients. The RFS tended to be worse in the C group than in the NC group (p=0.1756). The OS rate at five years after surgery was 7.4% in the C group and 22.8% in the NC group, which was significantly different (p=0.0189). The multivariate analysis demonstrated that postoperative complications and lymphatic invasion were significant independent risk factors for the RFS and OS. Conclusions: The development of postoperative complications was a risk factor for a decreased overall survival and for disease recurrence in patients who underwent curative surgery for pancreatic cancer. The surgical procedure, perioperative care and the surgical strategy should be carefully planned to avoid complications.
Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma.
Authors: Alessandretti Matheus Bongers , Moreira Raphael Brandao , Brandao Erika Pereira , Gomes Jessica Ribeiro , Amarante Marcus Paulo Fernandes , Lino Aline Da Rocha , Martins Junior Rodnei Merlrina , Abrahao Carina Mina , Sousa Tarcia Tarciane Soares de , Peixoto Renata D'Alpino , Cruz Marcelo Rocha , Maluf Fernando C. , Buzaid Antonio C. 
Published: February 2017

468 Background: There is only limited data regarding efficacy and safety of FOLFIRINOX in elderly patients with advanced pancreatic adenocarcinoma. We aim to evaluate our experience with dose-reduced FOLFIRINOX in patients > 65 years-old. Methods: All patients > 65 years-old with biopsy-proven advanced pancreatic adenocarcinoma who received at least one cycle of modified dose-attenuatedFOLFIRINOX (no bolus FU and reduced dose of oxaliplatin and/or irinotecan) at our institution were identified. Results: Twenty-one consecutive patients (62% males) were reviewed. Median age was 67 (range 65-79). Grade 3/4 toxicities were reported in 7 (33%) patients ; the most common toxicities were anemia (62%), and nausea/vomiting (45%). Elevations in AST and/or ALT above the upper limit of normality were identified in 38%. No deaths due to toxicities were reported. Prophylactic granulocyte colony stimulator factor (G-CSF) was given in 16 (70 %) patients. Dose reductions were substantial with median reductions of 27,8 % (range 15 - 50%) for 5-FU, 27,1% (range 6-50%) for oxaliplatin and 25% (range 12-75%) for irinotecan. Median overall survival (OS) was 11,8 months (95% CI 10,2 - 13,3). Median progression free survival (PFS) was 6,9 months (95% CI 5,3 - 8,5). Conclusions: Modified dose-attenuated FOLFIRINOX is a reasonable option for elderly patients with advanced pancreatic adenocarcinoma. Adverse events were manageable and no deaths due to toxicity were reported. Median OS and PFS were similar to the pivotal phase III trial, demonstrating that dose-attenuated FOLFIRINOX may be beneficial to elderly patients.
Phase I study of chemoradiation therapy (nab-paclitaxel/Gemcitabine) in 15 patients with unresectable locally advanced pancreatic cancer (UR-LAPC).
Authors: Sueyoshi Hironari , Ioka Tatsuya , Tamura Takeshi , Takada Ryoji , Fukutake Nobuyasu , Ashida Reiko , Ohkawa Kazuyoshi , Takahashi Hidenori , Teshima Teruki , Katayama Kazuhiro 
Published: February 2017

475 Background: Pancreatic cancer (PC) is one of the most difficult cancers to treat. Over 90% of cases, they are UR-LAPC or metastatic PC (mPC) at the first time of diagnosis. To prolong survival time, radiation therapy is considered to be promising with strong local control. Some papers reported that RT with 5-FU is effective to LAPC, but they are far from standard regimen. Gemcitabine (Gem) has enhancing effect of sensibility to RT. Gem and nab-paclitaxel (G+NP) showed priority compared with Gem monotherapy in mPC patients with Phase III study. So, we performed Phase I study to decide recommended dose of G+NP when we administer for concurrent CRT in URPC patients. Methods: From Aug 2013, we have registered patients who were examined as UR-LAPC because of cancer invasion to major artery. Dose of G+NP are classified by each level. At Level 1, Gem 600mg/m2 and NP 50mg/m2. At Level 2, Gem 600mg/m2 and NP 75mg/m2. At Level 3, Gem 600mg/m2 and NP 100mg/m2. At each level, patients accepted RT (50.4Gy/28fr). During performing RT period, we prescribed G + NP weekly. So, G+NP are prescribed 4-5 times if pts accomplish the study.We evaluate effectiveness and side effect of the regimen, and try to decide maximum tolerated dose. Results: Until July 2014, 14 pts (11 males and 3 females) have been registered in this trial. 6 cases were performed at Level 1, 7cases at Level 2, 1 cases at Level 3. 13 cases accomplish the prescription. 1 case at Level 1 dropped out because the patient suffered liver abscess. Effectiveness of the regimen is as follows; 4cases are PD (progressive disease), 6cases are SD (stable disease), and 2cases are PR (partial response). Conclusions: Now we prescribe the regimen at Level 3. We have not yet decided MDT. But, CRT with G + NP may be promising regimen for LAPC. When we accumulate more cases, and decide MDT, we will report later. Clinical trial information: UMIN000012254.
Association of gemcitabine (GEM) efficacy on unresectable invasive pancreatic carcinoma with intraductal papillary mucinous neoplasms.
Authors: Hashimoto Yusuke , Shimizu Satoshi , Watanabe Kazuo , Umemoto Kumiko , Okuyama Hiroyuki , Takahashi Hideaki , Ohno Izumi , Mitsunaga Shuichi , Ikeda Masafumi 
Published: February 2017

478 Background: Invasive pancreatic carcinoma associated with intraductal papillary mucinous neoplasms (IC-IPMN) has showed more favorable prognosis than invasive pancreatic ductal carcinoma (IPDC) following surgical resection in some studies. IC-IPMN differs from IPDC in clinical manifestation and biology profile and is mostly surgically resectable in initial presentation. Chemotherapeutic effect on unresectable IC-IPMN is not described in the literature yet. Methods: Our pancreatic cancer database was reviewed to identify 43 patients with IC-IPMN between 2006-2013. IC-IPMN was determined with surgical pathology or with radiological diagnosis and biopsy evidence of adenocarcinoma. Of 43 patients, 14 unresectable IC-IPMN patients received GEM as first-line chemotherapy regimen. We investigated GEM efficacy, Overall Survival (OS), Progression Free Survival (PFS) and 1-year survival rate. Results: Characteristic baseline included gender (male: 9, female: 5), age (median: 73 years old), ECOG performance status (0-1, 92%), location (head 7, body/tail 6, diffuse 1), prior surgical resection (8), biliary intervention (5), metastasis (11), CRP (median: 0.15mg/dl, 0.1-1.0), CA19-9 (median: 29U/ml, 8-20820), CEA (median: 3.1ng/ml, 0.1-237). Median OS, PFS and 1-year survival rate were 24.0 months, 8.0 months and 86%. Gemcitabine therapy demonstrated 14% (2/14) response rate and 79% (11/14) disease control rate. Conclusions: UnresectableIC-IPMN indicates favorable survival and fair response to GEM in our study. Limitations are retrospective study at single center and small population due to its disease rarity.
Hybrid minimally invasive versus open oesophagectomy for patients with oesophageal cancer: A multicenter, open-label, randomized phase III controlled trial, the MIRO trial.
Authors: Mariette Christophe , Meunier Bernard , Pezet Denis , Dalban Cecile , Collet Denis , Thomas Pascal-Alexandre , Brigand Cecile , Perniceni Thierry , Carrere Nicolas , Bonnetain Franck , Piessen Guillaume 
Published: February 2017

5 Background: Surgical resection is regarded as the only curative option for resectable oesophageal cancer. Postoperative morbidity, in particular pulmonary complications, continues to be of great concern and occurs in more than half of patients after open oesophagectomy (OO). We assessed whether hybrid minimally invasive oesophagectomy (HMIO) reduces morbidity compared with OO. Methods: We performed a multicentre, open-label, randomised controlled trial at 12 study centres between October 2009 and April 2012. Patients aged 18-75 years old with resectable cancers of the middle or lower third of the oesophagus were assigned by a computer-generated randomisation sequence to undergo either transthoracic OO or HMIO. Surgical technique was standardised by both on site visits and the use of videos, and was based on an Ivor Lewis procedure with laparoscopic gastric mobilisation and open right thoracotomy. Randomisation was stratified by centre. The primary outcome was 30 day grade II-IV postoperative morbidity as defined by the Dindo-Clavien classification. Analysis was by intention to treat. Results: We randomly assigned 104 patients to the OO group and 103 to the HMIO group. Sixty-seven (64.4%) patients in the OO group had major postoperative morbidity compared with 37 (35.9%) in the HMIO group (OR 0·31, 95% CI 0·18-0·55; p=0·0001). Thirty-one (30.1%) patients in the OO had major pulmonary complications compared with 18 (17.7%) in the minimally invasive group p=0·037), whereas 30-day mortality was 5 (4.9%) vs. 5 (4.9%), respectively. Conclusions: These findings provide evidence for the short-term benefits of HMIO for patients with resectable oesophageal cancer (NCT00937456 ClinicalTrials.gov). Clinical trial information: NCT00937456.
Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).
Authors: Ng Kimmie , Venook Alan P. , Sato Kaori , Hollis Bruce W. , Niedzwiecki Donna , Ye Cynthia , Chang I-Wen , O'Neil Bert H. , Innocenti Federico , Lenz Heinz-Josef , Blanke Charles David , Mayer Robert J. , Fuchs Charles S. , Meyerhardt Jeffrey A. 
Published: February 2017

507 Background: Prospective epidemiologic data suggest that higher levels of 25-hydroxyvitamin D [25(OH)D] are associated with improved survival in patients with colorectal cancer (CRC), however, the relationship between 25(OH)D and outcome in metastatic CRC, specifically, is unknown. Methods: We prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated metastatic CRC patients enrolled in CALGB 80405, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS WT amendment. Progression-free survival (PFS) was a secondary endpoint. Plasma 25(OH)D levels were measured at baseline by radioimmunoassay, and dietary and lifestyle behaviors collected from self-administered questionnaires. Cox proportional hazards models were used to calculate hazard ratios adjusted for other prognostic factors. In sensitivity analyses, patients who died within 3 or 6 months of blood draw were excluded to address the possibility of reverse causation. Results: Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL (range 2.2-72.7). Older and black patients, those with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (vs. 0), higher body-mass index, lower physical activity, and blood draws during the winter and spring had significantly lower levels of 25(OH)D. Patients in the highest quintile of 25(OH)D had significantly improved OS compared to those in the lowest after adjusting for pathologic and clinical prognostic factors (median 32.6 vs. 24.5 months; HR 0.67, 95% CI, 0.53-0.86; p trend 0.002). Increasing concentrations of 25(OH)D were also associated with improved PFS (median 12.2 vs. 10.1 months; HR 0.80, 95% CI, 0.64-1.01; p trend = 0.02). The results were consistent across subgroups of patient characteristics, including KRAS status, and remained unchanged after excluding patients who died within 3 or 6 months of blood draw. Conclusions: Higher concentrations of plasma 25(OH)D are associated with significantly improved survival in metastatic CRC patients treated with chemotherapy + biologics. Randomized trials of vitamin D supplementation are warranted and are currently underway.