bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of modified Glasgow Prognostic Scale as a predictor of survival advantage by FOLFIRINOX in metastatic pancreatic cancer.
Authors: Yamada Ikuhiro , Ozaka Masato , Kanata Ryo , Saito Kei , Sasaki Takashi , Matsuyama Masato , Takano Kouichi , Sasahira Naoki 
Published: February 2017

440 Background: The superiority of FOLFIRINOX (FFX) therapy over gemcitabine (Gem) alone in patients with metastatic pancreatic cancer (mPC) has been demonstrated in ACCORD11. However, this combination regimen is associated with relevant toxicity and predictors for response to therapy are warranted. The aim of this study is to determine the prognostic factors associated with an indication for FFX therapy in patients with mPC. Methods: The current study included data from all consecutive patients who were diagnosed as mPC at our hospital between September 2007 and December 2014. Selection criteria were as follows: patients who 1) had histologically confirmed pancreatic adenocarcinoma, 2) were diagnosed as having metastatic disease, and 3) received first-line chemotherapy with Gem alone or FFX. We examined the prognostic markers, such as derived neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, modified Glasgow prognostic scale (mGPS), ECOG Performance Status (PS), CA19-9 level and number of metastatic sites from the medical records and analyzed their survival data by chemotherapy regimen subgroups. Results: There were 187 patients who met the selection criteria. 159 (85%) received Gem alone, 28 (15%) received FFX. Univariate and multivariate regression analyses revealed that mGPS (1≦), number of metastatic sites (2≦) and high level of CA19-9 level (1000 U/ml≦) were significantly associated with worse prognosis in Gem group. PS (1≦) and mGPS (1≦) were significantly associated with worse prognosis in FFX group. Since mGPS was the only significant prognostic marker in both groups, we analyzed survival data stratified by regimen in both mGPS 0 or 1≦ cohort. In mGPS 0 cohort, the median survival time was 17.9 months in the FFX group as compared with 8.5 months in the Gem group (hazard ratio, 0.27; 95% CI, 0.11 to 0.55; P = 0.004). However there was no significant difference in mGPS 1≦ cohort (P = 0.4). Conclusions: This data suggests that mGPS 0 is associated with better survival time, and suggests it may also be predictive of benefit for FFX in Japanese patients with mPC. Incorporating mGPS into the clinical context may better inform prognosis and chemotherapy decisions in mPC patients.
Randomized, multicenter phase II trial of CAP7.1 in patients with advanced biliary tract cancers.
Authors: Pape Ulrich-Frank , Kasper Stefan , Sinn Marianne , Caca Karel , Kuhlmann Jan , Keilholz Ulrich , Vogel Arndt , Utku Nalan 
Published: February 2017

441 Background: Non-resectable biliary tract cancers (BTC) have poor prognosis, but are chemosensitive. CAP7.1 is a new chemical entity that releases etoposide in the presence of carboxylesterases, leading to higher intra-tumor etoposide (E) with improved safety and efficacy. Methods: The primary objective of this trial is to determine the rate of disease control (DCR) (stable disease, SD; partial response, PR and complete response, CR) according to Recist 1.1. of CAP7.1 in patients (pts) with BTC. Secondary objectives are progression free survival (PFS), overall survival (OS) and safety. Pts with adenocarcinoma arising from bile ducts or gallbladder were randomized (1:1) to either CAP7.1 or best supportive care (BSC) group (institutional palliative treatment). Pts in CAP7.1 arm subjected to a 3-week cyle (cy) with CAP7.1 on days 1-5 in 3-week cy was given with either 200 or 150mg/m2. until progression. At progression BSC pts were allowed to cross over to CAP7.1. Safety was assessed with CTCAE v 3.0 and efficacy after 2 cy of treatment. 18 /50 pts (9 in each study arm) finalized 1st stage and analyzed for efficacy and safety. Results: DCR in the CAP7.1 arm was 56%, with 5/9 of pts with SD (including tumor shrinkages), while all pts in the BSC arm progressed. The median PFS time was 3.5 months (95% CI, 1.9 to 8.4 months) in the CAP7.1 arm. 5 pts crossed over to the CAP7.1 arm. 2/3 pts continued CAP7.1 treatment up to 5 and 8 cycles as SD, respectively, while one pts achieved PR. The median OS time from first treatment with CAP7.1 was 5.9 months (95% CI, 2.6 to 15.3 months) over all evaluable pts, including BSC after crossing to CAP7.1. Commonly observed drug related adverse events (AE) are hematoxicity/myeolosuppression, various events of infection, alopecia, fatigue, nausea and abdominal pain, which were in general well managed. G3-4 neutropenia occurred in 4/10 pt at a dose of 150 mg/m²/d and in 6/11 pts at 200 mg/ m2/d; uncomplicated g 3-4 thrombocytopenia occurred in 2/11 pt at 200 and in 1/10 at 150 mg/ m2/d. Non-hematological AE were mainly mild or moderate e.g. abdominal pain and alopecia as most frequent AEs. Conclusions: CAP7.1 showed promising activity in therapy refractory advanced BTC patients.
Can response to treatment predict outcome in patients with metastatic pancreatic adenocarcinoma (MPAC)?
Authors: Pattali Jayavalsan Shinoj , Schmidt Shannon Leah , Durkal Vipal , Ritch Paul S. , Thomas James P. , Erickson Beth , Christians Kathleen K. , Tsai Susan , Evans Douglas B. , George Ben 
Published: February 2017

443 Background: Front-line (FL) chemotherapy regimens for MPAC include FOLFIRINOX (FFX)/FOLFOX (FX) and Nab-paclitaxel plus Gemcitabine (NabG). We examined our hypothesis that objective response (OR) to these regimens can influence clinical outcome when employed sequentially. Methods: All MPAC patients treated with FFX/FX or NabG from 1/1/2011 to 12/31/2014 at the Froedtert and Medical College of Wisconsin (MCW) Clinical Cancer Center were reviewed. This study was approved by the MCW Institutional Review Board. Results: 64 patients were evaluated and the baseline characteristics are summarized in the table below. OR to FL chemotherapy included partial response(PR) - 23/64 (35.9%), stable disease (SD) - 14/64 (21.9%) and disease control rate (DCR) of 57.8%; OR to second line (SL) therapy included PR - 7/37 (18.9%), SD - 14/37 (37.8%) and DCR of 56.7%. Only 57.8% patients received SL chemotherapy. Among patients who demonstrated PR to FL chemotherapy, 64% were refractory to SL chemotherapy, while 33% of patients who were refractory to FL chemotherapy demonstrated a PR to SL chemotherapy. 3/64 patients who demonstrated PR to both FL and SL chemotherapy had excellent outcomes with overall survival (OS) of 20.9 months, 37 months and not met (PFS of 11 months to FL chemo and ongoing response of > 4 months to SL chemo). Median OS of patients who demonstrated a PR/SD to FL and SL chemotherapy (15/64; 23.4 %) was 20.9 months. The patients who demonstrated progressive disease(PD) to both FL and SL chemotherapy (5/64; 7.8%) had a median OS of 3.8 months. Conclusions: Patients with MPAC who are refractory to FL chemotherapy may demonstrate a response to SL chemotherapy. Patients who are able to undergo sequential therapy with FFX/FX and NabG (in either sequence) and demonstrate either a PR or SD with both treatment regimens have an excellent clinical outcome. The minority of patients who demonstrate PR to both sequential regimens have a distinctly different outcome compared to patients who demonstrate PD to both regimens; tumors from these two subsets of patients need to be better characterized to improve our understanding of pancreatic cancer biology. [Table: see text]
Perioperative calculator to predict complications for patients with hepatocellular carcinoma resection.
Authors: Ostapoff Katherine , Attwood Kristopher , Kurenov Sergei , Kuvshinoff Boris W. , Hochwald Steven N. , Kukar Moshim , Nurkin Steven J. 
Published: February 2017

446 Background: Hepatocellular carcinoma (HCC) is a common cancer worldwide, but few patients are optimal surgical candidates due to liver disease. Current prediction models (Childs-Pugh and MELD) poorly estimate serious morbidity risks for those patients considering resection. Methods: Using ACS-NSQIP database, patients with HCC were selected from 2006-2013. Patients included had a curative resection (partial hepatectomy or formal lobectomy) and were excluded if they had emergency surgery or disseminated cancer. Outcomes included 30 day morbidity and serious morbidity. Data was randomly divided into testing (n=1764) and validation (n=441) cohorts. Regression analyses of the testing cohorts were used to construct prediction models, then optimized using the validation cohort. Results: We identified 2,205 patients. Major morbidity or serious morbidity occurred in 34% (n=745) and 21% (n=456). Patient demographics are shown in Table 1. Factors significant for morbidity include age, surgical procedure, BMI, ASA class, hypertension, alkaline phosphatase (AP), bilirubin (Bili), BUN, AST, albumin and MELD score. Factors included in risk score for morbidity included MELD, ASA class, surgical procedure, platelet count, smoking and AP. The model predicts morbidity AUC 0.616 vs 0.597 for model and validation cohort respectively. Factors significant for serious morbidity included age, race, procedure, BMI, diabetes, ASA class, hypertension, AP, Bili, AST and albumin. Serious morbidity score included MELD, surgical procedure, platelet count, diabetes and AST. The model predicts serious morbidity AUC 0.566 vs 0.592 for model and validation cohort respectively. Conclusions: Our calculator predicts morbidity based on surgical procedure for patients undergoing HCC curative intent surgery. Risk prediction can assist in appropriately selecting patients for surgical vs medial therapy. [Table: see text]
Perioperative management of pancreatoduodenectomy patients: Are North American practices any different? A survey involving IHPBA/AHPBA members.
Authors: Anantha Sandeep , Macedo Fransisco Igor , Race Alice J , Singh Awinderpreet , Parikh Janak A , Mittal Vijay K , Jacobs Michael J 
Published: February 2017

447 Background: Pancreatoduodenectomy is performed worldwide with significant variations in the perioperative management. The aim of this study is to evaluate the practice patterns across regions of the world. Methods: A pilot cross-sectional 25-item survey questionnaire was electronically distributed using Survey Monkey to IHPBA and AHPBA members between May and August 2015 regarding practice patterns and perioperative care of patients undergoing pancreatoduodenectomy. Results: A total of 285 responses were obtained. The majority of participants were from United States (34.7%), Europe (28.1%) and Asia (14.3%). North American (NA) surgeons are less likely to culture intraoperative bile (36.5% vs. 53.1%, p<0.02), routinely check postoperative drain amylase (80.5% vs. 91.3%, p<0.03) or irrigate the wound with Betadine solution (7.7% vs. 29.1%, p<0.001) as compared to European members. Overall, NA surgeons are more likely to use 1 drain (46.3% vs. 88.7% other regions (2 drains), p<0.001), limit the prophylactic antibiotic use within 24 hours of surgery (70.1% vs. 68.5%, p<0.001) and do not culture drain fluid routinely (91.5% vs. 67.1%, p<0.001). Conclusions: Our survey evaluated a wide range of practice patterns globally amongst surgeons performing pancreatoduodenectomy. North American surgeons do not routinely check for amylase rich fluid in the drains, utilize one drain routinely when compared to European surgeons. Further studies are warranted to evaluate if these variations translate into impacts upon surgical outcomes on patients undergoing Whipple operation.
Randomized, open-label trial of gemcitabine/nab-paclitaxel (G/NP) ±FG-3019 as neoadjuvant chemotherapy in locally advanced, unresectable pancreatic cancer (LAPC).
Authors: Picozzi Vincent J. , Rocha Flavio G. , Helton Scott , Mody Kabir , Asbun Horacio , Pishvaian Michael J. , Jackson Patrick G , Etheridge Tina , Carney Mairead , Neff Thomas B , Porter Seth , Crans Gerald , Valone Frank , Shi Wen 
Published: February 2017

457 Background: Curative therapy for PDAC is currently achievable through resection only, but ≤ 15% of patients are candidates for surgery. FG-3019, a recombinant human mAb to connective tissue growth factor (CTGF), plus gemcitabine (G) significantly reduced tumor growth, increased apoptosis and improved survival vs G alone in the KPC mouse model. Higher FG-3019 exposure and lower baseline (BL) CTGF were independently and significantly associated with improved overall median and 1-year survival (OS) in a Ph2a trial with G and erlotinib in stage 3 or 4 PDAC. Neoadjuvant treatment of LAPC with FG-3019 combined with multidrug therapy may change the fibrotic character of LAPC and thus may make it amenable to surgical resection and potentially improve OS. Methods: Patients with unresectable LAPC (confirmed by laparoscopy) are randomized to G/NP ±FG-3019 for 6-cycle/24-week treatment. Safety, efficacy, PK and changes in CT, PET, & CA19.9 from BL through end of treatment (EOT) are assessed. Up to 4 endoscopic ultrasound (EUS) guided core biopsies are collected at BL. Protein microarrays of pre- and post-treatment biopsies are prepared from tumor and stromal cells isolated by laser capture microdissection. Surgical exploration is performed in subjects who achieved the protocol-defined criteria for possible resection. Results: To date, 11 subjects were enrolled with 5 randomized to +FG-3019 arm. There were no complications from laparoscopy or EUS core biopsies that were clinically significant or delayed dosing. Per investigator assessment, no FG-3019-related SAEs were reported, nor any identified toxicity suspected from combination of FG-3019 with chemotherapy. Overall, CA19.9 mean change from BL was −62.7% at Week 8 (n = 8), and target lesions were reduced by 20.6% (n = 6) at Week 16. Three out of 4 subjects had PET SUVmax reductions of ≥ 30% at EOT. Additional data from protein microarrays will be presented. Conclusions: Based on the limited data collected so far, this trial design is feasible and the G/NP +FG-3019 combination is well-tolerated and appears to be active. Summary results on surgical exploration of subjects will be provided later. Clinical trial information: NCT02210559.
The effects of HOXB7 in the promotion of migration, invasion and anti-apoptosis in gastric cancer.
Authors: Joo Moon Kyung , Park Jong-Jae , Yoo Hyo Soon , Lee Beom Jae , Chun Hoon Jai , Lee Sang Woo , Oh Sang Cheul , Bak Young-Tae 
Published: February 2017

46 Background: HOX genes, a subset of the homeobox gene family, are known to be aberrantly expressed in various types of cancers. Among them, HOXB7 recently has been reported to be highly expressed in esophageal or colorectal cancers. We aimed in this study to demonstrate the critical roles of HOXB7 in development and progression of gastric cancer. Methods: We screened gene and protein expression of HOXB7 in various gastric cancer cell lines, and also compared gene expression level of HOXB7 among chronic gastritis, intestinal metaplasia and gastric cancer tissues. To figure out the oncogenic effects of HOXB7 in vitro, we performed annexin-V assay, wound closure assay and Matrigel invasion assay. We performed Western blot analysis to examine the impact of HOXB7 on AKT pathway. Results: Both mRNA and protein was substantially expressed in stomach cancer cell lines (SNU-638, SNU-719, MKN-28, MKN-45, AGS, KATO-III, NCI-N87), however, they were nearly abolished in normal gastric tissues. Gene expression was significantly higher in primary or metastatic stomach cancer, compared with chronic gastritis or intestinal metaplasia. Knockdown of HOXB7 by transfection with siRNA in AGS and SNU-638 cells significantly inhibited migration and invasion, and showed anti-apoptotic effect. Because a previous study demonstrated that enforced expression of HOXB7 could enhance PI3K/AKT pathway activity in colon cancer cells (Liao W.T. et al, Clin Cancer Res; 17(11) June 1, 2011), we investigated the modulation of AKT/PTEN pathway by HOXB7 and observed that knockdown of HOXB7 significantly downregulated phospho-AKT and upregulated PTEN in both cell lines. Furthermore, target gene products of AKT pathway including cyclin D1, survivin, Bcl-xL and MMP-9 were significantly downregulated by siHOXB7. Conclusions: Our findings suggest that HOXB7 might play a crucial role in migration, invasion and anti-apoptotic effect via modulating AKT/PTEN pathway.
The impact of the multiple types of treatments on OS and the decline of liver function in patients with advanced stage of HCC.
Authors: Prins Petra , Bhardwaj Prarthna , Fishbein Thomas , Johnson Lynt B. , Smith Coleman , Satoskar Rohits , Kim Alexander Y. , Jha Reena , Wang Hongkun , Sullivan David , Taher Salha , Zhang Tiger , Zhu J , Pishvaian Michael J. , Smaglo Brandon George , Salem Mohamed E. , Hartley Marion L. , Marshall John , He Aiwu Ruth 
Published: February 2017

461 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death worldwide. Most HCCs develop in severely damaged liver. Methods: The effect of multiple treatment options on liver function (LF) and disease outcome of patients (pts) with HCC (n = 185) were examined retrospectively. Pt tumor burden (using Barcelona clinic liver cancer [BCLC] classification) and LF (Child Pugh [CP]) were assessed at time of diagnosis and then after treatment. Using Kaplan Meier with log rank and T tests, BCLC and CP scores were correlated with overall survival (OS) following individual treatment regimens. Results: We show that better BCLC and LF scores at time of diagnosis predict a better outcome (median OS; p < 0.05). Pts received one or more of the following: no treatment, experimental treatment, TACE, Y90 radioembolization, radiofrequency ablation, resection, radiation, and sorafenib (SFB). Considering all treatment scenarios, LF improved in 9.5%, did not change in 33%, and worsened in 57% of pts. Sixty percent of untreated pts experienced LF decline, compared with 33, 54, 48 and 50% of pts receiving TACE, SFB, TACE/SFB, and Y90/SFB, respectively (no significant differences [NS]); 72% of pts receiving TACE/Y90/SFB (NS); and 85% of pts receiving other Y90/SFB combinations (p = 0.006). In general, pts who saw no change or an improvement in LF from baseline had longer median OS versus pts who had declining LF (p < 0.002). However, pts receiving TACE/Y90/SFB (n = 29) had similar OS to those receiving TACE/SFB (n = 35), despite the toxicity difference (72% [TACE/Y90/SFB] vs. 48% [TACE/SFB] of pts had declining LF). TACE/SFB or TACE/Y90/SFB led to longer median OS than any other treatment group (p = 0.017). Conclusions: The outcome of pts with HCC depends on disease stage and LF. Most pts experience LF decline during treatment. Despite LF decline in 48% of pts receiving a SFB/TACE, these pts experienced longer median OS than pts on any other treatment. Balancing survival benefit with liver toxicities is critical to the successful treatment of pts with advanced HCC. Agents with good antitumor activity and minimal liver toxicity are desperately needed for these pts.
Outcomes of perioperative systemic therapy (ST) in patients with R0 resection of metastatic colorectal cancer (mCRC).
Authors: Lee-Ying Richard M. , Renouf Daniel John , Lim Howard John , Speers Caroline , Cheung Winson Y. 
Published: February 2017

496 Background: Adjuvant fluoropyrimidine (FP) +/- oxaliplatin (OX) ST improves overall survival (OS) following curative resection of stage II or III CRC, while other regimens do not. Utility of pseudo-adjuvant ST in mCRC patients who achieved R0 resection of their metastases remains controversial. We aim to describe population-based outcomes based on choice of ST. Methods: Patients diagnosed with mCRC from 2003 to 2010 and referred to any 1 of 5 cancer centers in British Columbia, Canada were reviewed. We categorized patients who underwent a successful R0 resection of their metastases into 3 groups based on receipt of peri-operative ST: 1) FP alone; 2) OX-based; and 3) non-standard or no ST. We compared OS using multivariate Cox regression models that adjusted for potential confounders. Results: We identified and reviewed 1,641 patients with mCRC among whom 225 achieved R0 resection of their metastases. In this cohort, median age was 63 years (Interquartile range (IQR) 55-70), 118 (52%) were men, 196 (87%) reported ECOG 0/1, 149 (66%) had a colonic primary, and 103 (46%) presented with de novo metastatic disease. The site of metastatic resection was hepatic in 144 (64%), pulmonary in 34 (15%), locoregional in 11(5%), and other in 36 (16%). A total of 122 (54%) received standard ST. Regimens included 28 (12%) FP alone, 94 (42%) OX-based, 25 (11%) irinotecan and 38 (17%) including bevacizumab. The median duration of ST was 10 cycles (IQR 7-12), with 56% and 44% delivered pre- and post-operatively, respectively. In multivariate analyses, liver or lung involvement (HR 0.60, 95% CI 0.40-0.88, p=0.01) predicted for improved OS when compared to metastases affecting other organs or sites. Receipt of OX-based ST was the only regimen associated with better OS, while the rest were not (Table). Conclusions: Findings from this population-based cohort of mCRC suggest that use of a defined course of OX-based ST for pseudo-adjuvant intent around the time of R0 resection of liver or lung metastases is correlated with improved OS. [Table: see text]
Objective sleep duration (SD) and overall survival (OS) in patients (pts) with metastatic colorectal cancer (MCC).
Authors: Spiegel David , Levi Francis , Bjarnason Georg A. , Ulusakarya Ayhan , Palesh Oxana , Innominato Pasquale F. 
Published: February 2017

511 Background: Sleep is often altered in patients with cancer, with clinical repercussions. Short sleep duration (SD) has been associated with increased risk of earlier death in the general population. The prognostic relevance of SD in cancer pts is unknown. We explored the effect of short ( < 7 hours) SD on the clinical outcomes of pts with MCC before chemotherapy. Methods: Participants were 236 pts with MCC: M/F ratio: 1.66; median age: 60.4 years; range: 21-78; WHO Performance Status (PS) = 0/1/2: 60/34/6%; synchronous metastases: 63%; 2 or more metastatic sites: 55%; prior chemotherapy for metastatic disease: 35%. Pts wore an actigraph for 72 hours before receiving the initial course of an oxaliplatin-based chemotherapy; objective night-time SD was estimated from actigraphy recordings using the Cole-Kripke algorithm. SD was considered short if < 7 hours, based on previous studies. Multivariate Cox proportional Hazard models were built to assess the prognostic value of short SD on OS and progression-free survival (PFS); Binary logistic regression was used to assess the predictive value of short SD for an objective response (OR) or grade 3-4 Toxicity (Tox). Results: Median night SD was 7.4 hours (range: 1.5-10.5). Short SD was observed in 105 (44.5%) pts. Median OS and 3-year survival rate were 14.6 months (mo) [95% C.I.: 11.8-17.4 mo] and 16% [9-23], respectively, in patients with short SD as compared to 16.4 mo [13.0-19.8] and 27% [20-36%] in those with longer SD (p = 0.04). There was no significant difference in PFS (p = 0.25), OR (p = 0.1) or Tox (p = 0.43) rates according to SD. The negative prognostic value of short SD on OS remained significant even after adjustment for age, sex, body mass index, PS, number of metastatic sites, prior chemotherapy and stage at diagnosis (multivariate hazard ratio: 1.45 [1.08-1.93]; p = 0.013). Conclusions: We observed that sleep duration of less than 7 hours before chemotherapy was associated with a significantly shorter survival, independently from other prognostic factors, in pts with MCC. Sufficiently long restorative sleep should be promoted in cancer pts. More research is needed to understand the relationship and mechanisms behind shorter sleep duration and prognosis.