bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure-response (ER) relationship of regorafenib (REG) in patients with hepatocellular carcinoma (HCC).
Authors: Solms Alexander , Ploeger Bart , Reinecke Isabel , Fiala-Buskies Sabine , Cleton Adriaan , Bruix Jordi , Meinhardt Gerold 
Published: March 2017

374 Background: In the phase 3 RESORCE trial (N = 573), REG (160 mg QD, 3 weeks on/1 week off) significantly (P < 0.001) improved overall survival (OS) versus placebo in patients with HCC who progressed during sorafenib treatment (HR 0.63; 95% CI 0.50‒0.79). This exploratory analysis evaluated the ER relationship between REG and both OS and time-to-progression (TTP). Methods: Exposure estimates were available for 327 and 315 patients for the OS and TTP analysis, respectively. A multivariate Cox proportional hazard analysis was used to evaluate differences between exposure quartiles and efficacy, taking into consideration all preselected baseline covariates. Subsequently, the functional form of the ER relationship within the REG group was evaluated. Results: The baseline risk factors ECOG status, AFP category, and AST/ALT baseline levels were significantly associated with OS (P < 0.01), with higher HRs for ECOG category ≥ 1, AFP levels ≥ 400 ng/mL, and AST/ALT levels > 3 x ULN. For TTP, a significant correlation (P < 0.01) with age was observed, with a higher HR for patients < 65 years of age. After adjusting for these baseline risk factors, the average exposure over the first 28 days grouped in exposure quartiles for REG was significantly associated with OS and TTP (P < 0.01), i.e. the HR in all exposure quartiles was < 1 versus placebo. By contrast, the difference in HR between exposure quartiles was found to be small and not significant. While no statistically significant ER relationship could be identified between (continuous) individual exposure and efficacy in the REG group, the analysis of the functional form of the ER relationship indicates that OS and TTP improved with an increase in exposure, under the assumption of a linear and a non-linear ER relationship. Conclusions: In addition to a significant difference in OS and TTP between REG and placebo, a trend towards improved efficacy was observed with an increase in REG exposure in HCC patients, which was not statistically significant when taking into consideration ECOG status, AFP level, and AST/ALT risk factors (OS) or age (TTP). Therefore, similar efficacy was observed in patients with HCC who started on REG 160 mg QD 3 weeks on/1 week off over the entire exposure range. Clinical trial information: NCT01774344.
Efficacy of lanreotide depot (LAN) for symptomatic control of carcinoid syndrome (CS) in patients with neuroendocrine tumor (NET) previously responsive to octreotide (OCT): Subanalysis of patient-reported symptoms from the phase III ELECT study.
Authors: Pommier Rodney F. , Fisher George A. , Wolin Edward M. , Kunz Pamela L. , Liyanage Nilani , Pitman Lowenthal Susan W. , Mirakhur Beloo , Shaheen Montaser F. , Vinik Aaron 
Published: March 2017

378 Background: In ELECT, LAN significantly reduced the need for short-acting OCT rescue medication for symptomatic control of CS in NET patients (pts) vs placebo (PBO) (primary result). Here we present flushing and diarrhea symptom data and biochemical response for pts with or without prior OCT use from the ELECT study. Methods: Adults with histopathologically confirmed NET and history of CS (diarrhea and/or flushing) who were OCT-naive or responsive to OCT long-acting release (LAR) (≤30 mg q4W) or short-acting OCT (≤600 μg daily) were randomized to LAN 120 mg (SC q4W) or PBO for 16 wks. Pts administered short-acting OCT if needed and recorded daily the frequency and severity of symptoms using Interactive Voice/Web Response System for 1 month pre-randomization and throughout the study. 24 hr urinary 5-hydroxindoleacetic acid (5HIAA) was assessed at baseline and wk 12. Results: Of 115 pts randomized, 51 (n=26 LAN; n=25 PBO) were OCT-naive and 64 (n=33 LAN; n=31 PBO) received prior OCT LAR (n=56) and/or short-acting OCT (n=24). The frequency of moderate or severe diarrhea and/or flushing decreased in both naive and prior OCT pts treated with LAN (Table). The least square mean percentage of days with moderate or severe diarrhea and/or flushing was significantly lower for pts treated with LAN (23.4%) vs PBO (35.8%) ( P=0.004, analysis of covariance adjusted for prior OCT use, region, and baseline values). By week 12, 5HIAA levels dropped by ≥30% to normal in 35% of OCT-naive pts and 29% of prior OCT pts treated with LAN. Among PBO pts, 5HIAA reductions were seen in 15% of OCT-naive pts and 7% of prior OCT pts. Conclusions: Pts showed improvement in CS symptoms of flushing and diarrhea and reduction in 5HIAA levels with LAN treatment, indicating efficacy of LAN in pts regardless of prior OCT use. Clinical trial information: NCT00774930; and EudraCT 2010-019066-92. [Table: see text]
A phase IB, multicenter, open-label study to assess the safety, tolerability, and efficacy of the pleiotropic pathway modifier CC122 administered orally to patients with advanced HCC.
Authors: Kelley Robin Kate , Shih Kent C. , Braiteh Fadi S. , Rasco Drew W. , Hollebecque Antoine , de Braud Filippo , Goncalves Anthony , Cervantes-Ruiperez Andres , Wei Xin , Hagner Patrick , Gandhi Anita K. , Hege Kristen , Pourdehnad Michael , Santoro Armando 
Published: March 2017

379 Background: CC122 is a novel cereblon-modulating agent with multiple biologic activities including potent immunomodulatory and antiangiogenic effects. CC-122 binding to cereblon promotes ubiquitination and subsequent degradation of lymphoid transcription factors Ikaros and Aiolos resulting in activation of T cells. Methods: Following establishment of oral CC122 3 mg daily (QD) as the MTD in phase 1a (Blood 122:2905 2013), an expansion cohort of advanced Hepatocellular Carcinoma (HCC) subjects was enrolled. All subjects had progressed on or were intolerant to sorafenib. Efficacy was assessed per RECIST 1.1 criteria. Results: As of Jan. 13, 2016, 25 advanced HCC subjects were enrolled. The median age was 59.6 years, median Child-Pugh score was 5 (range 5-8) and all were ECOG 0-1. Viral status was HBV 28%, HCV 28%, HBV/HCV 12% and non-viral 32%. 52% had alpha-fetoprotein ≥ 200. CC122 was well tolerated. Two subjects discontinued due to AEs. Dose reductions occurred in 32% (n = 8). The most common ( ≥ 5%) grade 3/4 AEs were neutropenia, ALT elevation (each n = 4, 16%), AST elevation (n = 3, 12%), asthenia, ascites, anemia, hyperbilirubinemia, pneumonia, and rash (each n = 2, 8%). Drugrelated serious AEs included vomiting and rash. 19 subjects were evaluable for efficacy. ORR was 10.5% (n = 2 PR, 1 confirmed) and Disease Control Rate (CR+PR+SD > 7 weeks) was 36.8%. The duration of response was 108 and 125 days in the 2 PRs. The median PFS was 57 days (MinMax: 28334, 95% CI: 45-135). CC122 treatment resulted in a median increase from baseline in peripheral blood activated and memory cytotoxic T cells by 64% (range: 17-213%, n = 6) and 78% (range: 30-111%, n = 6 (p < 0.05), respectively, and activated helper T cells by 106% (range: 62-218%, n = 7 (p < 0.05). CC122-activated T cells from the blood increased IFNg (2.73 fold; range: 0.45-26.1, n = 13) and IL2 (9.5 fold; range: 0.85-24.3, n = 11) production when compared to baseline (both P < 0.05) upon ex-vivo stimulation. Conclusions: CC122 3 mg QD appears to be well tolerated and activates cytotoxic T cells in HCC patients. Combination studies with sorafenib or nivolumab are recommended and underway. Clinical trial information: NCT01421524.
Tumor infiltrative pattern predicts sites of recurrence after curative gastrectomy for gastric cancer.
Authors: Kanda Mitsuro , Kobayashi Daisuke , Tanaka Chie , Yamada Suguru , Fujii Tsutomu , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: March 2017

38 Background: In East Asia, the tumor infiltrative pattern (INF) has been routinely evaluated by hematoxylin and eosin-stained sections as a pathologic characteristic of surgically resected specimens. Methods: The infiltrative pattern of gastric cancer (GC) has been histopathologically classified as INFa (expansive growth), INFb (intermediate type) and INFc (infiltrative growth) according to the Japanese Classification of Gastric Carcinoma. The prognostic value and characteristics of the disease recurrence pattern for each INF type were assessed in 785 patients with various stages of GC and also in 243 patients with stages 2 and 3 GC. Results: Comparison of the overall survival experienced by patients independently of stage showed that INF was significantly associated with prognosis. Specifically, peritoneal metastasis was present in 91 % of stage 4 patients in the INFc group, whereas hepatic metastasis was present in 39 % of stage 4 patients in the INFa and INFb group. After curative gastrectomy of patients with stages 2 or 3 GC, INF was not significantly associated with survival. The prevalence of peritoneal recurrence was significantly higher in the INFc group than in the INFa and INFb group, whereas the prevalence of hepatic recurrence was significantly higher in the INFa and INFb group than in the INFc group. Multivariate analysis identified INFc as an independent risk factor for peritoneal recurrence after curative gastrectomy. The association of the INF type with the incidence of peritoneal recurrence was observed with all disease stages regardless whether the patient was given adjuvant chemotherapy or not. Conclusions: Evaluation of the INF type shows promise for its role as a predictor of postoperative recurrence sites in patients with GC.
A nomogram to predict pathologic lymph node positivity in clinical stage I-II pancreatic adenocarcinoma.
Authors: Swords Douglas S. , Zhang Chong , Presson Angela P. , Firpo Matthew A. , Mulvihill Sean J. , Scaife Courtney L. 
Published: March 2017

382 Background: Clinical nodal staging in PDAC is inaccurate. Most pts are cN0, but > 70% are pN+. We hypothesize that preoperative variables are associated with pN+ and could be used to create a predictive nomogram. Methods: The NCDB was reviewed from 2010-13 for pts with clinical stage I-II PDAC. Exclusions were neoadjuvant therapy, < 12 nodes examined, and missing data for clinical/pathologic stage, size, and number of nodes examined/positive. Logistic regression assessed factors associated with pN+ and an interaction was included for extrapancreatic extension and cN stage. A logistic regression based nomogram was constructed and 10-fold cross validation evaluated model discrimination. Results: Of 7,475 pts, 28% were cN+ but 74% were pN+ (P < 0.001). Associations of preoperative factors with pN+ are shown. Size was pathology based. We recommend multiplying imaging based size estimates by 1.33 for use in the nomogram based on studies showing that imaging underestimates size by 25%. Interestingly, extrapancreatic extension was protective for cN0 pts but associated with increased odds of pN+ for cN1 relative to cN0 ps. A nomogram was created to predict pN+ using these variables. The 10-fold cross validated AUC was 0.77. Conclusions: Our nomogram has good discrimination to preoperatively predict lymph node positivity for patients with resectable PDAC. It could potentially be useful in identifying biologically aggressive resectable PDAC pts at higher risk of pN+ in order to select pts for neoadjuvant therapy. [Table: see text]
Survival analysis of yttrium-90 radioembolization for unresectable intrahepatic cholangiocarcinoma.
Authors: Gangi Alexandra , Shah Jehan , Shridhar Ravi , Kumar Ambuj , Hoffe Sarah E. , Choi Junsung , Frakes Jessica M. , Springett Gregory M. , El-Haddad Ghassan , Anaya Daniel A. , Sweeney Jennifer , Biebel Benjamin , Malafa Mokenge Peter , Kim Richard D. , Kis Bela 
Published: March 2017

383 Background: Intrahepatic cholangiocarcinoma (ICC) is a rapidly progressing malignancy that frequently presents at an advanced stage and is often chemorefractory. The median overall survival (OS) with best medical treatment is approximately 12 months. The current study examines survival and characterizes predictors of mortality for ICC patients treated with transarterial yttrium-90 radioembolization (TARE). Methods: All patients with unresectable ICC who underwent TARE between May 2009 and May 2016 at a single institution were included and clinicopathologic variables reviewed. Primary endpoint was OS from time of TARE. Secondary endpoints included OS from time of diagnosis, post procedure toxicities and predictors of mortality. Results: A total of 134 TARE were performed on 85 patients. Average age at treatment was 73.4 ± 9.3 years and most patients were female (52%). More than one third of patients had an ECOG of 2 and had no significant post procedure sequalae. Thirty-six patients (42%) had extrahepatic disease at time of treatment and 61 patients (72%) were treated with systemic chemotherapy prior to TARE. A majority of patients (92.9%) received treatment to one lobe with an average radiation dose of 180.1±127.1 Gy. The median OS from time of the first TARE was 12 months (95% CI 7.8–16.1). The median OS from time of diagnosis was 21.4 months (95% CI 14.9-27.8). 51.8% and 26% of treated patients were still alive at 1 and 3 years, respectively. On univariate analysis, age at treatment, ECOG score, presence of extrahepatic disease, baseline albumin, alkaline phosphatase and AST correlated with OS. On multivariate analysis only low ECOG score and higher baseline albumin predicted improved OS (p < 0.01). Conclusions: Y90 radioembolization demonstrates a survival benefit for patients with unresectable ICC compared to historic controls of best medical treatment and should be considered an effective therapy in select patients. A multi-institutional randomized control trial should be performed to evaluate efficacy of TARE in select patients as both 1st line and salvage therapy.
Survival outcomes of adjuvant chemotherapy combined with radiation versus chemotherapy alone following pancreatectomy for distal pancreatic adenocarcinoma: Single institution experience.
Authors: Batukbhai Bhavina D O , Herman Joseph M. , Zahurak Marianna , Laheru Daniel A. , Le Dung T. , Wolfgang Christopher Lee , Zheng Lei , De Jesus-Acosta Ana 
Published: March 2017

388 Background: There is limited data of survival following distal pancreatectomy and adjuvant therapy in patients with distal pancreatic adenocarcinoma. This study aimed to evaluate the survival following combined modality (chemo-radiation and chemotherapy) compared to chemotherapy alone following distal pancreatectomy (DP). Methods: Patients who underwent DP for adenocarcinoma of the body or tail of the pancreas between the years 2000 and 2015 at Johns Hopkins were included. Comparison analysis was performed between patients who received combined modality versus chemotherapy alone. Kaplan- Meier curve was used to estimate the median overall survival (OS) and the disease free survival (DFS) at 1, 3 and 5 years after pancreatectomy. Results: A total of 294 patients underwent DP at our institution. Patients were excluded if adjuvant therapy was not administered, developed metastasis prior to adjuvant therapy, had stage IV disease at the time of surgery, received neoadjuvant therapy or had inadequate follow up at our institution to assess survival outcomes. We included a total of 105 patients, of which 45 patients received chemotherapy alone and 60 patients received combined modality. The two groups were similar with respect to nodal and margin status. Patients treated with combined modality had larger > 3cm tumors (p = 0.02). Median OS with combined modality was 60.6 mo and 50.2 mo with chemotherapy only. DFS was 15.2 mo with combined modality and 17.6 mo with chemotherapy only. There was no significant difference between the groups for OS (p = 0.73) or DFS (p = 0.495). Further analysis showed a trend away from chemoradiation in the recent years. Thirty patients (29%) received multi-agent chemotherapy in the adjuvant setting. A tumor diameter > 3cm was a predictive factor for receiving chemoradiation (chi-square p value 0.02). Conclusions: There is no difference in survival with combined modality compared to chemotherapy alone as adjuvant therapy following DP. All patients in this study received adjuvant therapy. We report a higher survival than previously described which could suggest a different biology for distal tumors.
Gemcitabine/taxane adjuvant therapy in resected pancreatic cancer: A signal of improved survival?
Authors: Kanji Zaheer S , Edwards Alicia M , Mandelson Margaret T , Lin Bruce , Badiozamani Kasra , Song Goubin , Alseidi Adnan , Biehl Thomas , Kozarek Richard A. , Helton William Scott , Picozzi Vincent J. , Rocha Flavio G. 
Published: March 2017

392 Background: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit in metastatic pancreatic cancer (PC). We present our experience with gemcitabine/docetaxel (gem/tax) based adjuvant treatment (Rx) following curative intent surgery. Methods: Patients with upfront resectable PC from January 1, 2010 to December 31, 2015 were identified from our institutional database and tumor registry. We included resected patients who received gem/tax as initial Rx administered exclusively at our institution with or without chemoradiation (CRTx). Patients were excluded if they died or recurred prior to Rx or received neoadjuvant Rx. Survival was estimated by Kaplan-Meier methods and prognostic factors identified by Cox regression. Results: Of 185 eligible patients, 58 met study criteria. Characteristics included: median age of diagnosis 64.9 years, female gender 56.9%, Whipple procedure 69% and R1 resection in 55.2%%. Tumour characteristics included: median size 28.0mm, poor differentiation 53.5% and AJCC stage 2A/2B 27.6%/67.2%. Patients completing ≥ 80% of 24 week Rx was 89.7% (n = 52). Of those patients, 71.2% received post gem/tax CRTx. With a 51.2 month median follow-up (95%CI: 37.1-55.7), median disease-free survival (DFS) and overall survival (OS) were 35 months (95%CI: 20.7-NR) and 52.3 months (95%CI: 27.4-NR), respectively. Five year OS was 49.5% (95%CI: 33.7-63.4). Patients receiving CRTx (n = 37) had a superior OS compared to patients who only completed gem/tax Rx (n = 15)(61.5 vs. 26.7 months, p = 0.04). Prognostic variables impacting OS on multivariate analysis (HR, 95%CI) included: margin status (4.55, 1.46-14.2, p = 0.01), AJCC stage (10.9, 2.46-47.9, p = 0.002) and administration of CRTx (0.08, 0.03-0.24, p < 0.000). Variables impacting DFS included: AJCC stage (3.29, 1.15-9.41, p = 0.03), tumour size (2.59, 1.11-6.04, p = 0.03) and administration of CRTx (0.23, 0.09-0.56, p = 0.001). Conclusions: In this select cohort of resected PC patients with adverse pathologic features, adjuvant gem/tax with or without CRTx is feasible with favorable DFS and OS. These findings support further prospective studies of gem/taxane-based adjuvant Rx in PC.
Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high-volume referral centre.
Authors: Itchins Malinda , Arena Jennifer , Rabindran Joel , Christopher Nahm , Kim Sia , Gibbs Emma , Gill Anthony J. , Maher Richard , Schembri Geoffrey , Bailey Elizabeth , Mittal Anubhav , Bergamin Sarah , Wong Matthew , Hruby George , Kneebone Andrew , Pavlakis Nick , Samra Jaswinder S. , Clarke Stephen 
Published: March 2017

395 Background: The 5 year (yr) overall survival (OS) of pancreas cancer (PC) is < 5%. Surgical resection is the only curative treatment (tx), most relapse within 2yrs. Neoadjuvant (NA) tx can benefit by eradicating micro-metastases, avoids futile surgery if metastases develop, improves dose intensity and may down stage disease. Currently, there are no data that clearly demonstrate improved OS with NA tx. Randomised trials are in progress. Methods: A retrospective analysis of all patients (pts) who received NA therapy across campuses,in Sydney, was performed. Pt records were identified and all were discussed in a MDT by a panel of PC specialists. Results: 588 PC pts were treated between August 2011-July 2016. After consideration of anatomy, pt characteristics and preference 82 pts (14%) received NA tx, 30% were resected upfront. 26 pts were ‘borderline’ and received sequential chemo-radiotherapy (ctxRT). Median age at diagnosis (dx) was 73 yrs, 50% were men. Median follow up time was 31.2 months (m). 84% pts were resected. There was 1 death at 90 days. An R0 was achieved in 74%. A detailed tx overview will be provided. Most received gemcitabine/abraxane. For those who had PET, low SUV pre-operative correlated with high pathological regression score, 3 pts 0%. Median OS for all pts was 25.9 m (95% CI 21.2, 30.2). Survival by stage: 1- 21.2 mo (11.8, 29.5); 2- 25.2 m; stage 3-4 (not reached). Pts who received ctx alone OS 25.3mo (17.2,29.5); ctxRT 29.0 m (17.3, NA) (p = 0.03). R0 survival was 29.0 m (21.2, NA) and R1, 23 m. 30% were alive at 3 yrs. Time to recurrence was 22.3 m (14.3, NA). Weight > 74kg was predictive of survival; OS 23.0 m v 29.5m (p = 0.002). There was a trend to survival benefit in females (p = 0.099) and baseline LDH < 280 (IU/L) (p = 0.07). Age at dx, ECOG (0 v 1), baseline albumin, bilirubin, Ca 19.9, NLR ( < 3.1) and CRP and stage at dx were not predictive of survival. Conclusions: This pt cohort demonstrates superior survival with NA therapy in selected pts across stages in a high volume multi-disciplinary PC centre. Outside a clinical trial, NA therapy is evolving to be our standard of care in fit pts with any degree of vessel involvement.