bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive model for microvascular invasion of hepatocellular carcinoma among candidates for either hepatectomy or liver transplantation.
Authors: Nitta Hidetoshi , Allard Marc Antoine , Sebagh Mylene , Pittau Gabriella , Ciacio Oriana , Vibert Eric , Sa Cunha Antonio , Cherqui Daniel , Castaing Denis , Bismuth Henri , Guettier Catherine , Samuel Didier , Baba Hideo , Adam Rene 
Published: September 2018

4079 Background: Microvascular invasion (MVI) is the strongest prognostic factor following surgery of hepatocellular carcinoma (HCC). However, it is usually not available on the preoperative setting. A predictive model of MVI in patients scheduled for hepatic resection (HR) or liver transplantation (LT) would thus help guiding treatment strategy. The aim of this study was to develop a predictive model for MVI of HCC before either HR or LT. Methods: HCC patients who consecutively performed HR or LT from January 1994 to June 2016 at a single institution were subdivided into a training and validation cohort. Risk factors for MVI in the training cohort were used to develop a predictive model for MVI, to be validated in the validation cohort. The outcomes of the HR and LT patients with high or low MVI probability based on the model, were compared using propensity score matching (PSM). Cut-off values for continuous factors were determined based on ROC curve analysis. Results: A total of 910 patients (425 HR, 485 LT) were included in the training (n = 637) and validation (n = 273) cohorts. In the training cohort, multivariate analysis demonstrated that alpha-fetoprotein ≥100ng/ml ( p < 0.0001), largest tumor size ≥40mm ( p = 0.0002), non-boundary HCC type on contrast-enhanced CT ( p = 0.001), neutrophils-to-lymphocytes ratio ≥3.2 ( p = 0.002), aspartate aminotransferase ≥62U/l ( p = 0.02) were independently associated with MVI. Combinations of these 5 factors varied the MVI probability from 15.5% to 91.1%. This predictive model achieved a good c-index of 0.76 in the validation cohort. In PSM (109 HR, 109 LT), there was no difference in survival between HR and LT patients among the high MVI probability (≥50%) patients, (5y-OS; 46.3% vs 42.2%, p = 0.77, 5y-RFS; 54.0% vs 28.8%, p = 0.21). Among the low probability ( < 50%), survival was significantly decreased following HR compared with LT (5y-OS; 54.1% vs 78.8%, p = 0.007, 5y-RFS; 17.3% vs 86.1%, p< 0.0001). Conclusions: This model developed from preoperative data allows reliable prediction of MVI, and may thus help with preoperative decisions about the suitability of HR or LT in patients with HCC.
Stereotactic body radiation therapy to generate comparable survival to surgery in treating hepatocellular carcinoma (HCC): Results of 756 patients.
Authors: Kong Feng Ming , Zang Yong , Pi Wenhu , Long David , Ellsworth Susannah , Saito Naoyuki , Ghabril Marwan , Lacerda Marco A , Agarwal David M , O’Neil Bert , Tann Mark , Zellars Richard C. , Maluccio Mary A. 
Published: September 2018

4080 Background: Stereotactic Body Radiation Therapy (SBRT) has emerged as a viable treatment option in patients with hepatocellular carcinoma (HCC). This study aimed to compare survival outcomes after SBRT with other front line local treatments for HCC. Methods: This is a retrospective analysis of patients identified through our cancer registry from 2000 to 2016. Patients treated with any local therapy alone were eligible: SBRT, surgery, conventional external beam radiation (CEBRT), and other local therapies including brachytherapy. Patients treated with combined therapies such as SBRT plus liver transplant were excluded. The primary endpoint was overall survival which was estimated from the time of diagnosis. Differences between the groups were compared using log-rank test. The data are presented as median (95%CI). Results: A total of 756 patients with a median follow-up of 45 months (mo) met the selection criteria: 116, 380, 43, and 217 patients received SBRT, surgery, CEBRT, and other local treatment, respectively. Median age was 61, 60, 61 and 60 years, respectively. The median overall survival/3 year overall survival rate were 49 (32-66) mo /53% (44-65%) for patients treated with SBRT, which were not significantly different from 75 (57-94) mo /63% (58-69%) of surgery (p = 0.27), non-significantly better than 22 (13-31) mo /41% (27-60%) of CEBRT (p = 0.13), significantly better than 15 (13-20) mo /26% (20-34%) of other local treatments (p = 3×10-7). After adjusting for significant prognostic factors including age, race, status of tobacco abuse, history of alcohol use, tumor size, histology grade and stage, the survival outcomes of SBRT remained to be insignificantly different from surgery (HR = 0.8, p = 0.2), have a trend of significant difference from CEBRT (HR = 1.4, p = 0.1) and remarkably superior to that of other local treatments (HR = 1.8, p = 2×10-4). Conclusions: This study suggests that SBRT is an excellent front line option for HCC, potentially comparable to surgical resection and associated with longer survival than other front line local treatments. Randomized studies are needed to validate these findings.
Lanreotide depot (LAN) for symptomatic control of carcinoid syndrome (CS) in neuroendocrine tumor (NET) patients previously responsive to octreotide (OCT): Subanalysis of patient-reported symptoms from the phase III elect study.
Authors: Fisher George A. , Pommier Rodney F. , Wolin Edward M. , Kunz Pamela L. , Liyanage Nilani , Pitman Lowenthal Susan W. , Mirakhur Beloo , Shaheen Montaser F. , Vinik Aaron 
Published: September 2018

4088 Background: In ELECT, LAN significantly reduced the need for short-acting OCT rescue therapy 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 ELECT. Methods: Adults with histopathologically-confirmed NET and history of stable 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 SC OCT if needed and recorded daily 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) and plasma chromogranin A (CgA) were assessed at baseline and wk 12. Results: Of 115 pts randomized, 51 were OCT-naive and 64 received prior OCT. The least squares (LS) mean percentages of days with moderate/severe diarrhea and/or flushing were lower in both naive and prior OCT LAN pts vs naive and prior OCT PBO pts; LS mean difference (LAN-PBO) was significant in the naive group (Table). By week 12, 5HIAA and CgA levels dropped by ≥30% to normal in 35.3% and 15.8% of naive LAN pts and 28.6% and 4.5% of prior OCT LAN pts; 5HIAA and CgA reductions were seen in 15.4% and 21.4% of naive PBO pts and 5HIAA in 7.1% of prior OCT PBO pts. Conclusions: Pts showed improvement in CS symptoms of flushing and diarrhea and reduction in 5HIAA levels with LAN treatment, indicating efficacy of LAN regardless of prior OCT use. Transition from OCT to LAN was well tolerated among prior OCT pts in ELECT. Clinical trial information: NCT00774930. [Table: see text]
68Ga-DOTATATE PET/CT to predict response to peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumours (NETs).
Authors: Sharma Rohini , Wang Wai Meng , Evans Joanne , Yusuf Siraj , Al-Nahhas Adil , Mauri Francesco , Barwick Tara , Aboagye Eric 
Published: September 2018

4093 Background: PRRT represents a step change in NET management, significantly improving survival. However, objective response to PRRT, approximately 20%, is poor. There are no predictive biomarkers of response. Uptake on 68Ga-DOTATATE PET/CT imaging is used to assess patient suitability for PRRT, highlighting the presence of somatostatin receptors (SSTR) to which PRRT selectively binds. We hypothesise that the density of SSTRs, as defined by a minimum SUV uptake, predicts for response to PRRT. Methods: 54 patients underwent PRRT. Modified PERCIST assessment was performed: up to 2 target lesions per organ were identified and volume of interest drawn. Maximum 5 targets were counted. Average SUV (SUVave) was calculated by dividing sum of SUVmax of target lesions by number of lesions. Response was determined by RECIST 1.1. Ki67 and SSTR2 expression were assessed on tumour samples and compared with SUVave. Results: Response to PRRT: partial response (PR) 26%, stable disease (SD) 40% progressive disease (PD) 12%. Response to PRRT predicted progression free survival (PFS) with patients experiencing PR having a PFS 2.5x that of those with SD, and almost 20x as long as PD. Using ROC curve analysis, SUVave of 21.6 predicted for tumour response with high sensitivity (0.74) and specificity (1.0), p = 0.15, 95% CI 0.71-3.96. No association between baseline SUVave and SSTR2 or Ki-67 was observed. SUVave > 21.6 was an independent predictor of clinical outcome. Conclusions: Objective response to PRRT defines a subset of patients with markedly improved PFS. SUVave 21.6 defines a threshold below which patients have a poor response to PRRT. This threshold should be taken forward into prospective study.
Effect of lanreotide depot (LAN) on 5-hydroxyindoleacetic acid (5HIAA) and chromogranin A (CgA) in gastroenteropancreatic neuroendocrine (GEP NET) tumors: Correlation with tumor response and progression-free survival (PFS) from the phase III CLARINET study.
Authors: Phan Alexandria T. , Wolin Edward M. , Liyanage Nilani , Mirakhur Beloo , Pitman Lowenthal Susan W. , Vinik Aaron , Fisher George A. , Pavel Marianne 
Published: September 2018

4095 Background: 5HIAA or CgA are biomarkers in some GEP NETs. We present posthoc analyses using prospectively collected urinary 5HIAA and serum CgA data from CLARINET. Methods: Adults with moderately or well differentiated, nonfunctioning (no symptoms of carcinoid syndrome), locally advanced or metastatic GEP NETs were randomized to LAN 120mg or placebo (PBO) every 4 weeks (wks) for 96 wks. Tumor response evaluated centrally (RECIST 1.0) and PFS were assessed by treatment. Biochemical response was defined as baseline > upper limit of normal (ULN, 41.6µmol/d 5HIAA; 98.1µg/L CgA) and ≥50% decrease from baseline to ≤ULN value on study. CgA analyses excluded gastrinoma patients (pts). Results: 48% (82/171) (45LAN; 37PBO) and 66% (129/195) (65LAN, 64PBO) of pts had > ULN baseline 5HIAA and CgA. In those pts with no radiologic progression, significantly greater reductions in 5HIAA (Table) and CgA were observed in LAN vs PBO pts at all assessments (all P< 0.05). PFS was significantly prolonged in LAN 5HIAA responders vs nonresponders (median not reached vs 22.1 months, P= 0.0076) but was not significantly different in PBO 5HIAA responders vs nonresponders. There were no significant differences in PFS by CgA response (responders vs nonresponders) in either LAN or PBO pts. Conclusions: These data suggest that serotonin is secreted by nonfunctioning tumors, but does not reach the threshold required for clinical carcinoid symptoms. Monitoring 5HIAA and CgA may be useful during LAN treatment of nonfunctional GEP NETs. Clinical trial information: NCT00353496. [Table: see text]
A novel scoring system to predict survival in patients with advanced pancreatic adenocarcinoma: The Memorial Sloan Kettering Cancer Center (MSKCC) Prognostic Score (MPS).
Authors: Yang Andrew Chung , Wiesenthal Alison , Epstein Andrew S. , Goldberg Jessica , Meadows Jason , O'Reilly Eileen Mary , Glare Paul A. 
Published: September 2018

4105 Background: A major limitation of several common prognostic tools, e.g. the Eastern Cooperative Oncology Group (ECOG), Karnofsky, and Palliative Performance Scales, is a reliance on subjective clinical assessment. An objective tool, the Glasgow Prognostic Score (GPS) derived from C-reactive Protein (CRP) and albumin levels, has been validated in patients with operable and inoperable malignancies but has the disadvantage that CRP is not routinely measured in the United States. We examined if the Neutrophil-Lymphocyte Ratios (NLR) (Ahn, H.K., et al., Neutrophil-Lymphocyte Ratio Predicts Survival in Terminal Cancer Patients. J Palliat Med, 2016) could be substituted for CRP in the GPS to predict survival in patients with advanced pancreatic adenocarcinoma. Methods: A retrospective review chart identified patients at MSKCC with pathology-confirmed stage IV pancreatic adenocarcinoma diagnosed between 2011 to 2014. Pre-treatment absolute neutrophil count, absolute lymphocyte count, and albumin were extracted. The NLR for each patient was calculated and assigned NLR ≤ 4 a value of 0; NLRs > 4 a value of 1, serum albumin > 4 g/dl assigned a value of 0; and serum albumin < 4 g/dl assigned a value of 1. Combining NLR and albumin scores results in a composite MPS score of 0-2, similar to GPS. We evaluated the association of the MPS with overall survival. Results: N = 833 patients were identified with median survivals in the table below. A log-rank test showed statistically significant differences in survival between MPS groups (p < 0.00005). The MPS on univariate analysis had a HR of 1.36 (95% CI 1.23 – 1.50, p < 0.0005) associated with overall survival. Conclusions: The MPS, a composite of NLR and albumin, is an objective prognostic tool that divided this sample of patients into three clinically and statistically significant subgroups. Further interrogation will control for performance status, disease characteristics and therapy. [Table: see text]
Phase II trial of neoadjuvant S-1 and concurrent radiotherapy for borderline resectable pancreatic cancer: Interim results of JASPAC05.
Authors: Takahashi Shinichiro , Ohno Izumi , Ikeda Masafumi , Konishi Masaru , Kobayashi Tatsushi , Akimoto Tetsuo , Kojima Motohiro , Morinaga Soichiro , Ku Yonson , Shimizu Yasuhiro , Nakamori Shoji , Hishinuma Shoichi , Takakura Norihisa , Kainuma Osamu , Hirano Satoshi , Otsubo Takehito , Nagino Masato , Kimura Wataru , Yamashita Yoichi , Uesaka Katsuhiko 
Published: September 2018

4107 Background: Borderline resectable pancreatic cancer (BRPC) has a high probability of a positive surgical margin and poor prognosis because the tumor interacts with surrounding arteries or veins. Chemoradiotherapy (CRT) with S-1 has shown favorable activity in locally advanced pancreatic cancer. This study was designed to assess S-1 and concurrent radiotherapy in a neoadjuvant setting to determine whether it increases R0 resection rate for BRPC. Methods: This was a multicenter, single-arm phase II study. Patients with BRPC received S-1 (40 mg/m2 BID) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery if they fulfilled any of the following: (1) bilateral impingement of superior mesenteric vein or portal vein; (2) tumor contact with superior mesenteric artery ≤180°; or (3) tumor contact with common hepatic artery or celiac axis ≤180°. Primary endpoint was R0 resection rate in BRPC confirmed by central review. At least 40 patients were required, with one-sided α = 0.05 and β = 0.05, with an expected and a threshold values for primary endpoint of 30% and 10%. Results: Fifty-two patients were eligible between December 2012 and May 2016. CRT was completed in 50 patients (96%) and was safe, with mostly grade 1 or 2 adverse events. Protocol treatment was withdrawn before surgery in 12 patients because of progressive disease diagnosed by computed tomography, and in one because of treatment refusal. Ten patients received exploratory laparotomy, or palliative/noncurative resection. In the rest of 29, R0 resection was conducted in 27, and R1 and RX in 1 patient each. This gave an R0 resection rate of 52% in all 52 eligible patients. In the 41 cases of BRPC confirmed by central review, R0 was confirmed in 26 (63%). Destruction of > 50% of tumor cells was confirmed pathologically in 10 (32%). Postoperative grade III/IV adverse events according to Clavien–Dindo classification were observed in 6 (15%). Conclusions: S-1 and concurrent radiotherapy were well tolerated and found to be effective in BRPC. A randomized controlled trial comparing neoadjuvant CRT and chemotherapy, including gemcitabine+nab-paclitaxel, for BRPC is under planning. Clinical trial information: NCT02459652.
Characterization of germline genomic alterations in familial pancreas cancer.
Authors: Goldstein Jennifer Brooke , Zhao Li , Javle Milind M. , Overman Michael J. , Shroff Rachna T. , Varadhachary Gauri R. , Wolff Robert A. , Futreal Phillip Andrew , Fogelman David R. 
Published: September 2018

4116 Background: Family history of BRCA-related tumors may correlate with response to chemotherapy and overall survival in patients with pancreatic cancer (PC). We retrospectively compared family history of such cancers with clinical outcomes and underlying molecular aberrations. Methods: A retrospective chart review was conducted of 350 metastatic PC patients treated with first line FOLFIRINOX and Gem/Abraxane at MDACC from 1/2010 -1/2016. Family history was defined as 1st through 3rdgeneration relatives with breast, ovarian, or pancreas cancer. Germline DNA was collected and sequenced using a familial cancer panel using an Illumina 2500. Average coverage was 200X. Platypus calls were analyzed for germline mutations. We assessed mutations in BRCA1, BRCA2, PALB2, MMR genes, ATM, and PolE. Results: Average age was 61. 60% of patients were male. We sequenced blood and tissue samples where available. We found at lease one mutation in 47 of 129 patients tested. There were 56 mutations identified among the 47 patients. Of patients with 0-1,2, or 3 or more affected family members we found mutations in 44%, 47%, and 29%, respectively. Patients with 3+ family members affected tended to have mutations in BRCA1 or PolE. Among the subset of patients with possible deleterious mutations, there were trends towards improved survival in pts with BRCA or PALB aberrations (307d vs 271d, p = ns) but worse outcomes in those with MMR gene defects (181d vs 387d, p = .126). Table 1 indicates outcomes based on number of family members with cancer and their associated mutations. Conclusions: Approximately one third of all patients tested had at least one germline mutation in previously described familial pancreas cancer genes. Screening for inherited cancer susceptibility genes may have prognostic value. [Table: see text]
Neutrophil count and efficacy of chemoradiation in patients with locally advanced unresectable pancreatic carcinoma: An ancillary study of in the LAP 07 trial.
Authors: Schernberg Antoine , Vernerey Dewi , Goldstein David , Van Laethem Jean Luc , Glimelius Bengt , Van Houtte Paul , Bonnetain Franck , Louvet Christophe , Hammel Pascal , Huguet Florence 
Published: September 2018

4120 Background: Predictive biomarkers of Overall Survival (OS) and Progression Free Survival (PFS) in locally advanced pancreatic cancer (LAPC) pts are mandatory. Baseline leukocyte, neutrophil and monocyte counts in addition to lymphocyte ratio (NLR) may predict OS in LAPC pts. Efficacy of chemoradiation (CRT) depending on neutrophil count was retrospectively analyzed in the largest Phase III cohort of LAPC. Methods: The international multicenter randomized LAP07 phase III trial (NCT00634725) has recruited 442 LAPC pts. We have studied the predictive and prognostic value of systemic inflammation, as defined: (i) baseline neutrophilia (neutrophil count > 7 G/L at first randomization) or (ii)increased absolute neutrophil count (IANC) after induction chemotherapy vs baseline. Univariate and multivariate Cox analysis evaluated the benefit of CRT for OS, PFS and Local Control (LC) in pts without systemic inflammation. Results: Patients with baseline neutrophilia (11%) had a worse OS (median 8.9 vs 13.3 months, p = 0.01). At 2nd randomization, 9% and 29% pts had baseline neutrophilia or IANC, respectively. Both neutrophilia (median OS 10.6 vs 16.1 months, p = 0.03) and IANC (median OS 14.6 vs 17.4 months, p = 0.02) predicted poor OS. Systemic inflammation predicted local resistance to CRT (p = 0.02, interaction = 0.015). After excluding pts with systemic inflammation, 1-year local control was 80% in CRT vs 54% in chemotherapy arms (p < 0.001). Pts without systemic inflammation in CRT arm had improved PFS vs chemotherapy arm (median 10.3 vs 8.3 months, p = 0.04). In multivariate analysis in this population, CRT increased PFS (HR = 0.66, 95%CI: 0.45 - 0.97, p = 0.03), after adjusting on age, tumor size, pain at enrollment, albumin, and CA 19.9 according to PROLAP nomogram parameters. Conclusions: In LAPC pts with tumor controlled after induction chemotherapy, systemic inflammation may help to better predict those who will benefit from CRT. This result may impact clinical management and the design of future clinical trials for LAPC. An external validation with a cohort from the ARCAD pancreas meta-analysis is under consideration. Clinical trial information: NCT00634725.
Selective benefit of adjuvant chemoradiation in resectable pancreatic cancer.
Authors: Wright Jesse P , Schlegel Cameron , Snyder Rebecca A , Du Liping , Shyr Yu , Cardin Dana Backlund , Merchant Nipun B. , Parikh Alexander A. 
Published: September 2018

4122 Background: Although level 1 data supports the use of adjuvant chemotherapy (ACT) in resected pancreatic adenocarcinoma (PDAC), the role of adjuvant chemoradiation (ACRT) remains controversial. The objective of this study is to investigate the impact of adding ACRT to ACT on overall survival (OS), based on lymph node (LN) and margin status. Methods: Resected AJCC Stage I and II PDAC patients from 2004-2013 identified within the National Cancer Database were classified into groups based on treatment: surgery alone (SX), ACT alone, ACT+ACRT, and ACRT only. Kaplan-Meier analyses were performed to determine median OS. Multivariable (MV) Cox regression models with interactions of treatment with LN and margin status were constructed to examine the independent effects of ACT and ACT+ACRT in these subgroups. Results: Of 31,348 patients, 30% were treated with SX, 30% with ACT, 38% with ACT+ACRT, and 2% with ACRT alone. Median OS (mos.) for ACT (22.5, 95% CI 21.9-23.1) and ACT+ACRT (23.7, 23.3-24.2) were significantly longer than SX (14, 13.4-14.5) or ACRT (11.2, 9.8-12.9). MV analysis confirmed a significant OS benefit of both ACT and ACT+ACRT controlling for patient and tumor related factors. ACRT+ACT was associated with improved OS compared to ACT in patients with positive margins and/or LN. Those with negative margins and LN did not benefit from the additional use of ACRT (Table). Conclusions: This large hospital-based study demonstrates that ACT and ACRT are associated with improved OS when compared to SX. The addition of ACRT to ACT, however, was only beneficial in high-risk patients with positive margins and/or LN. ACT+ACRT in patients with both margin and LN negative disease may not be warranted. Future clinical trials should stratify patients based on LN and margin status in order to determine which patients are most likely to benefit from the use of ACRT. [Table: see text]