bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a cell viability assay based on cultures of CTICs to identify treatment options in third-line pancreatic cancer.
Authors: Ricigliano Mark , Isacoff William H. , Ocean Allyson J. , Cooper Brandon , Welkie Mary , Bartlett Andrew , Yu Kenneth H. 
Published: March 2017

338 Background: Standard of care treatment for pancreatic adenocarcinoma (PDAC) includes FOLFIRINOX or gemcitabine with nab-paclitaxel used in either the front-line or 2nd line treatment setting. There is no consensus for 3rd line treatment for this cohort of poor prognosis patients with clinical trials being the only viable option. We evaluated a cell viability assay using cultures of circulating tumor and invasive cells (CTICs) to identify effective 3rdline PDAC treatment options. Methods: CTICs were isolated from peripheral blood samples of 17 PDAC patients who previously had received one of the two standard of care regimens using an immunomagnetic separation for EPCAM epitope Ber-EP4 and cultured in enriched DMEM-F12 medium. After 14 days, seven chemotherapeutics (gemcitabine (G), oxaliplatin (O), fluorouracil (F), irinotecan (I), mitomycin C (M), cisplatin (C) and paclitaxel (P)) were added to the cultures and response to treatment was measured 48 hr. after treatment by immunofluorescence using a live-cell resazurin assay. Response to treatment was determined by a reduction of fluorescence in the treated cultures compared to control and the mean florescence (Fm) was calculated for each chemotherapeutic. A one-sample t-test was used to measure the variance between Fm control and treated samples. (p-value <0.005). Sensitivity to treatment was determined using linear regression based on Fm values and the sensitivity of each chemotherapeutic was interpolated from a standard curve (range 1.0-5.0, sensitive <2, intermediate 2-3, resistant >3). Results: m (Fm=1.6) demonstrated the most effective treatment option with marked resistance to treatment for G, I, P and O. (Fm=3.4, 3.7, 3.4 and 3.7). Intermediate response was observed for F and C (Fm=2.8 and 2.8). Patient treatment response to m will be described. Conclusions: CTICs can be routinely isolated and cultured for cell viability assays. m based regimens with C and F should be considered for 3rd line PDAC patients.
CA19-9-low and Lewis(+) pancreatic cancer: A unique subtype.
Authors: Luo Guopei , Yu Xian Jun 
Published: March 2017

339 Background: Pancreatic cancer is a lethal malignancy and patients often survive within one year. CA19-9 is the most important biomarker for pancreatic cancer and Lewis (-) individuals have no or scarce CA19-9 secretion. We have met several patients with low CA19-9 and metastatic disease survived over one year without major treatments, prompted us to examine the characteristics of CA19-9-Low subgroup (Lewis (+)&CA19-9 ≤ 37 U/mL). Methods: Medical record of 1484 patients was retrieved from a prospectively maintained database. Lewis genotypes were determined by Sanger sequencing. Characteristics of CA19-9-Low pancreatic cancers were examined. Results: No significant difference was found between Lewis (-) (8.4%) and CA19-9-High (77.8%) patients in survival (HR = 1.16, P = 0.216). CA19-9-Low patients (13.8%) had strikingly better survival than CA19-9-High&Lewis (-) patients (HR = 0.52, P < 0.001). The 5-year survival rate of stage III, IV CA19-9-Low patients (28.2%) was even higher than that of stage I, II CA19-9-High&Lewis (-) patients (21.5%). Compared with CA19-9-High&Lewis (-) patients, CA19-9-Low patients had a lower proportion of nerve invasion (74.7% vs. 84.2%, P = 0.044), EGFR expression (37.5% vs. 51.2%, P = 0.047), a lower level of serum glucose (6.3 ± 1.9 vs. 7.4 ± 3.1, P = 0.001) and neutrophil-lymphocyte ratio (2.6 ± 2.4 vs.3.0 ± 3.1, P = 0.027), and poor response to Gemcitabine-based chemotherapy (stage I, II, HR = 0.73, P = 0.446; stage III, IV, HR = 0.70, P = 0.244). Conclusions: CA19-9-Low pancreatic cancer is a unique subtype with poor response to Gemcitabine-based chemotherapy.
Adjuvant chemoradiation for node-positive pancreatic adenocarcinoma: A propensity-matched analysis.
Authors: Raoof Mustafa , Melstrom Laleh Golkar , Warner Susanne , Woo Yanghee , Singh Gagandeep , Chen Yi-Jen , Fong Yuman 
Published: March 2017

347 Background: American Society of Clinical Oncology guidelines recommend adjuvant chemoradiation (ACR) for margin-positive(R1) and/or node-positive (N+) pancreatic cancers. However, randomized trials and meta-analyses have have not shown superiority of ACR over AC. Methods: National Cancer Database (NCDB) was used to analyze patients with N+ and/or R1 pancreatic adenocarcinoma who underwent ACR or AC over a ten-year period (2004-2014). Patients who received neoadjuvant radiation, no adjuvant treatment or adjuvant radiation alone were excluded. Propensity score nearest-neighbor 1:1 matching (PSM) was performed between ACR and AC groups based on age, sex, race, insurance, comorbidities, T-stage, nodal status, margin status, grade, and neoadjuvant chemotherapy. Primary outcome was overall survival (OS). Results: A total of 9,732 patients were eligible. After PSM two well-balanced groups of 4000 patients each were analyzed. ACR resulted in superior OS in patients with N+ and/or R1 disease as compared to AC alone (HR: 0.83, 95% CI 0.78-0.87; Median OS 22 vs. 19 months, p<0.001). Subset analyses demonstrated overall survival benefit of ACR compared to AC in N+, margin-negative patients (HR: 0.82, 95% CI 0.77-0.88; Median OS 24 vs. 20 months, p<0.001), as well as N+, R1 patients (HR: 0.77, 95% CI 0.68-0.87; Median OS 17 vs. 15 months, p<0.001); but no benefit in node-negative, R1 patients (HR: 1.12, 95% CI 0.84-1.48; Median OS 18 vs. 22 months, p = 0.43). Conclusions: This is the largest study to date that shows superiority of ACR over AC in N+ patients irrespective of margin status. The study failed to show a survival benefit in R1, node-negative patients.
Quality-of-life findings in patients with midgut neuroendocrine tumors: Results of the NETTER-1 phase III trial.
Authors: Strosberg Jonathan R. , Wolin Edward M. , Chasen Beth , Kulke Matthew H. , Bushnell David L , Caplin Martyn E. , Baum Richard P. , Kunz Pamela L. , Hobday Timothy J. , Hendifar Andrew Eugene , Oberg Kjell E. , Lopera Sierra Maribel , Kwekkeboom Dik J. , Ruszniewski Philippe B. , Krenning Eric 
Published: March 2017

348 Background: Neuroendocrine tumor progression is associated with decline in quality of life, both due to tumor and hormone-related symptoms. The Phase III NETTER-1 trial randomized patients with advanced, progressive midgut NETs to receive treatment with 177Lu-DOTATATE (177Lu; Lutathera) versus high-dose (60 mg) Octreotide LAR (Oct). EORTC questionnaires C30 and GINET21 were assessed during the trial in order to determine the impact of treatment on health-related quality of life (HRQoL). Methods: Patients completed EORTC QLQ-30 and QLQ-G.I.NET21 questionnaires at baseline and every 12 weeks thereafter until disease progression. Raw scores were converted to a 100-point scale and individual changes from baseline scores were assessed. Clinically relevant ( ≥ 10 point) deterioration/improvement was considered clinically significant. Results: Clinically and statistically significant improvements in QoL were observed in the 177Lu arm versus the Oct arm at certain time points in key domains of HRQoL including global health status and diarrhea. In mean, global health status improved in 28% of patients on 177Lu arm vs. 15% on Oct, and worsened in 18% of patients on 177Lu vs. 26% on Oct. Diarrhea improved in 39% of patients on 177Lu vs. 23% on Oct, and worsened in 19% of patients on 177Lu vs. 23% on Oct. There was a trend towards improvement in pain that was not statistically significant. Flushing appeared to improve compared to baseline in both arms of the study with no clear advantage to treatment with 177Lu vs. Oct. Conclusions: QoL analysis suggests benefit in important domains associated with 177Lu treatment compared to high-dose octreotide in patients with advanced midgut NETs, and confirms the treatment value of 177Lu on patient QoL, in addition to the meaningful increase in progression-free survival already reported. Clinical trial information: NCT01578239.
Two-stage hepatectomy for colorectal liver metastases: A multi-institutional retrospective review.
Authors: Berger Nicholas G , Kim Bradford , Gholami Sepideh , Margonis Georgios A , Ethun Cecilia , Silva Jack P , Tsai Susan , Christians Kathleen K. , Mogal Harveshp , Clarke Callisia , Maithel Shishir Kumar , Pawlik Timothy , D'Angelica Michael Ian , Aloia Thomas A. , Gamblin T. Clark 
Published: March 2017

351 Background: A significant number of patients with colorectal liver metastases (CRLM) present with unresectable bilobar disease. Two-stage hepatectomy with portal vein embolization (PVE) have been described as a treatment for CRLM allowing for volume regeneration of a functional liver remnant. No large-scale multi-institutional studies exist. The aim of this project was to describe outcomes following two-stage hepatectomy, including overall survival (OS), recurrence-free survival (RFS), and complications. Methods: Patients completing two-stage hepatectomy for CRLM at five US institutions were identified and retrospectively analyzed (2000-2015). Overall survival and recurrence-free survival following second-stage surgery, short-term mortality, Clavien-Dindo complications, and readmission rates were examined. Results: A total of 209 patients were identified. Mean age was 52 (SD +/-11.4), 59.8% were male, and 87.0% had synchronous disease. A total of 65.1% of patients underwent PVE, and 27.3% underwent hepatic artery infusion pump placement. 88.3% of cases underwent neoadjuvant chemotherapy. Following the first stage, 30-day morbidity was 24.4%, with 4.8% major (Clavien-Dindo grade ≥3) complications, and 30-day readmission was 6.7%. Mean time between first and second stage was 4.1 months (S.D. +/-3.1), and 57.5% received systemic chemotherapy between the two resections. Following the second stage, overall complications were 47.4% with 23.9% major complications, and 30-day readmission was 9.7%. Mortality following second stage was 3.8% at 30 days, and 5.3% at 90-days. Following the second stage, RFS at 1-, 3-, and 5-years was 80%, 46%, and 29% respectively. OS at 1-, 3-, and 5-years was 87%, 64%, and 45% respectively. Conclusions: Two-stage hepatectomy for CRLM provides acceptable recurrence-free and overall survival in the context of advanced bilobar disease. Major complications and readmission following the first stage are rare. Following the second stage, short-term major morbidity, mortality, and readmissions are also acceptable. For well-selected patients, two-stage hepatectomy remains a safe and effective treatment for CRLM, with potential for more widespread adoption.
Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer.
Authors: Park Joseph Junyong , Hajj Carla , Reyngold Marsha , Shi Weiji , Zhang Zhigang , Cuaron John J , Crane Christopher H , O'Reilly Eileen Mary , Lowery Maeve Aine , Yu Kenneth H. , Goodman Karyn A. , Wu Abraham Jing-Ching 
Published: March 2017

353 Background: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for unresectable pancreatic cancer, and may be more effective and less toxic than intensity modulated radiation therapy (IMRT). Methods: We retrospectively reviewed unresectable stage I-III pancreatic adenocarcinoma treated with SBRT (5 fractions, 30-33Gy) or IMRT (25-28 fractions, 45-56Gy with concurrent chemotherapy) between 2008-2016 at our institution. The groups were compared with respect to overall survival (OS), local failure (LF), distant failure (DF), any failure (AF), proportion of patients becoming resectable, and incidence of acute toxicity. Competing risks methods were used for univariate (UVA) and multivariate analysis (MVA) for LF, DF and AF. All endpoints were calculated from end of RT. Results: Median follow-up for surviving patients was 12.9 months. 44 patients received SBRT and 226 patients received IMRT. Patients who received SBRT were older (45% vs 29% > 70 years old, p = 0.05). Otherwise there was no significant difference in baseline characteristics, including stage and duration of induction chemotherapy. On MVA, there was no significant difference in OS, LF, DF, or AF between IMRT and SBRT (p = 0.73, 0.81, 0.44, and 0.39 respectively). Median OS was 15.7 months, and the 1-year rate of LF was 34.4% for SBRT and 30.2% for IMRT. Response to induction chemotherapy was associated with longer OS (p = 0.03). There was no significant difference in the proportion of patients who were subsequently resected between IMRT (17%) and SBRT (7%; p = 0.11). Significantly more IMRT patients experienced acute G2+ GI toxicity (24% vs. 7%, p = 0.008), G2+ fatigue (42% vs. 7%, p < 0.0001), and G3+ hematologic toxicity (26% vs. 5%, p = 0.001) compared to SBRT. Conclusions: SBRT achieves similar disease control outcomes as IMRT, and is associated with less acute toxicity. This data suggests SBRT is an attractive technique for pancreatic radiotherapy because of improved convenience and tolerability with equivalent efficacy. However, the lack of observed advantages in disease control with this moderate-dose SBRT regimen suggests a role for increasing SBRT dose, if this can be accomplished without significant increase in toxicity.
Initial gemcitabine/nab-paclitaxel (GA) followed by sequential (S) mFOLFIRINOX or alternating (A) mFOLFIRI in metastatic pancreatic cancer (mPC): The SEENA-1 study.
Authors: Picozzi Vincent J. , Leach Joseph W. , Seng John E. , Anthony Stephen Patrick , Mena Raul , Larson Tim , Borazanci Erkut Hasan , Weiss Glen J. , Lin Shih-Li Bruce , Jameson Gayle S. , Bolejack Vanessa , Stoll Amy C. , Von Hoff Daniel D. , Ramanathan Ramesh K. 
Published: March 2017

359 Background: GA, FOLFIRINOX and FOLFIRI are standard chemotherapy (CTX) regimens for mPC.The optimal introduction of these regimens following GA is not known. This phase II study evaluated 2 different approaches to this question. Methods: Eligibility criteria included 1) untreated mPC, 2) ECOG PS 0/1, 3) organ function adequate for Rx. Patients (pts) were treated according to one of 2 methods following GA given per standard dose/schedule: FOLFIRINOX (bolus 5-FU omitted) for up to 12 cycles at 24 weeks or at time of disease progression (S); or GA alternating with FOLFIRI q8 weeks up to 48 weeks total Rx (A). Results: 54 evaluable pts (28S, 26A) were enrolled . Pt characteristics included median age 65, M/F 48/52% , liver involvement 89%. 17/53 pts (31%) did not achieve disease control at 8 weeks (8 toxicity/complications , 6 disease progression, 3 declined further protocol therapy). Of the remaining 37 pts, 24/13 were treated with S/A regimens, respectively. Grade ≥ 3 treatment toxicities reported while on study with frequency ≥ 10% included anemia 21%, neutropenia 43%, thrombocytopenia 15%, and fatigue 22%. Grade ≥ 3 neuropathy occurred in 8% of pts. For all 54 pts using RECIST 1.0, CR/PR/SD/DC was 2 (4%)/20 (37%)/19 (35%)/41(76%). Ca19.9 response ≥ 90% was seen in 20/37 (54%). For all pts, median OS was 12.3 months ( 95% CI 8.6-14.5 mo); 12 and 24 mo OS was 51% and 11%, respectively. For the 37 pts with DC on GA at 8 weeks (calculated from start Rx) median OS was 13.5 mo (95% CI 10.7-15.4 mo); 12 and 24 mo OS was 55% and 16% , respectively. No statistically significant differences were seen between S and A with respect to toxicity, response or survival. Conclusions: 1) As opposed to introduction of 5FU-based CTX at the time of disease progression/prohibitive toxicity, introduction prior to that time may be at least comparable regarding both toxicity and OS. 2) This approach may further enhance OS in pts who achieve DC on GA at 8 weeks. 3) Neither S nor A method of 5FU-based CTX introduction following GA was clearly superior in this study. 4) How best to combine 5FU-based combination CTX following GA in mPC merits further study. Supported by the Seena Magowitz Foundation.
Neoadjuvant therapy versus upfront surgery for pancreatic adenocarcinoma: A propensity score matched analysis of short-term outcomes.
Authors: Kasumova Gyulnara G. , de Geus Susanna W.L. , Tabatabaie Omidreza , Fadayomi Ayotunde B. , Miksad Rebecca A. , Ng Sing Chau , Moser Arthur J. , Hidalgo Manuel M. , Tseng Jennifer F. 
Published: March 2017

361 Background: Neoadjuvant therapy is increasingly utilized and has demonstrated a survival advantage in borderline and locally advanced pancreatic cancer. However, many have feared that preoperative chemotherapy and radiation result in a more challenging operative field and consequently increased morbidity. Methods: ACS-NSQIP targeted pancreas database was queried for patients with adenocarcinoma who underwent PD in 2014. Propensity score matching was used to account for potential selection bias in pre-operative and intra-operative characteristics. Sensitivity analysis assessed the impact of neoadjuvant radiation. Results: 1,313 patients were identified, of whom 338 (25.7%) received neoadjuvant therapy. Patients who received neoadjuvant therapy vs upfront surgery were more likely to be: female (53.6% vs 47.2%; p=0.04), < 65 years of age (53.0% vs 39.2%; p < 0.0001), have BMI <25.0 (43.5% vs 36.6%; p = 0.03), and require vascular resection (37.6% vs 19.6%; p < 0.0001). Patients receiving neoadjuvant therapy were less likely to develop pancreatic fistulae (9.2% vs 14.0%; p = 0.02), more likely to require transfusion (27.8% vs 22.4%; p = 0.04), and had longer operative time (median: 405 vs 371 mins; p < 0.0001). After matching, there were no differences in baseline characteristics, approach, biliary stenting, and vascular resection. The only significant difference in outcomes between the two groups was longer operative time (median 405 vs 377, p = 0.006; Table). These results were robust on sensitivity analysis for use of radiation. Conclusions: Neoadjuvant therapy is safe and, despite prolonging operative time, does not affect 30-day outcomes. Concern for increased morbidity should no longer preclude treatment with neoadjuvant chemotherapy and/or radiation in borderline, locally advanced, and resectable pancreatic tumors. [Table: see text]
Curative treatment in gallbladder cancer: Adjuvant or multimodal concepts—Evidence from data of 975 cases of The German Registry of Incidental Gallbladder Carcinoma.
Authors: Goetze Thorsten Oliver , Al-Batran Salah-Eddin , Paolucci Vittorio 
Published: March 2017

367 Background: Incidental gallbladder cancer (IGBC) in T1b-3 stage do profit from radical cholecystectomy but nevertheless the cure rate in T2-3 carcinomas is disappointing. For improvement, following questions are of interest. What is significant regarding adjuvant or multimodal aspects? Which technique of liver resection (LR) and lymph- node dissection (LAD) is meaningful? Role of lymph node ratio (LNR)? Answers based on the data of 975 IGBC of the GR- platform. Methods: For data analysis we used the German- Registry- platform (GR). The GR is a network of more than 300 clinics in Germany. More than 1000 cases of IGBC are registered and to the knowledge of the authors the largest prospective gallbladder registry worldwide. Results: To date more than 1000 IGBC in the GR have been registered, n = 975 analyzed. In 44 of 119 T1b cases there was an IRR, with a significant survival benefit for T1b after IRR. There was also a significant survival benefit for the 244 T2 and 86 T3 with IRR of the 492 T2 and 228 T3 tumors. Comparison of LR showed good results for the wedge resection technique (WRT) in T1b and T2. For T3 more radical techniques showed better results. In 233 patients the LNR could be calculated. Statistic indicates that LNR has a significant influence on prognosis. The results show that the referral of patients from a LV to a HV has no practical relevance. In n = 433 T2 / T3 patients there are data calculated about adjuvant therapy, with a highly significant survival benefit after adjuvant therapy in T2 and a trend for a survival benefit in T3 carcinomas. Positive effect of adjuvant therapy exists in the subgroup with and without re- resection but was more evident in patients without radical resection. Conclusions: IGBC's up to T1b needs radical surgery. The WRT is attractive for T1b / T2 IGBC. LAD and LNR are of prognostic relevance. In 433 T2-3 IGBC's, adjuvant therapy has a positive effect, especially in cases without radical surgery. Regimen will be discussed at the meeting. For further improvement in T2-3 IGBC a multimodal therapy (GAIN-) trial has already been planned by the investigator of the GR under the support of the GR- platform with more than 300 clinics in Germany.
FOLFIRINOX (F-NOX) followed by individualized radiation for borderline-resectable pancreatic cancer: Preliminary toxicity and R0 resection rates from a prospective phase II study.
Authors: Murphy Janet E. , Wo Jennifer Yon-Li , Ryan David P. , Jiang Wenqing , Yeap Beow Y. , Blaszkowsky Lawrence Scott , Kwak Eunice Lee , Allen Jill N. , Clark Jeffrey W. , Faris Jason Edward , Zhu Andrew X. , Goyal Lipika , Mamon Harvey J. , Lillemoe Keith D , DeLaney Thomas F. , Fernandez-del Castillo Carlos , Ferrone Cristina , Hong Theodore S. 
Published: March 2017

368 Background: F-NOX has been increasingly utilized in borderline resectable pancreatic cancer (BRPC) due to the improved response rate compared to gemcitabine. However, prospective data remains limited, with the largest series being a 22 patient (pt) cooperative group trial (Alliance A021101), in which 14 pts had R0 resection. In this study, we evaluate neoadjuvant F-NOX followed by individualized chemoradiation (CRT) for BRPC. Methods: Pts ECOG PS 0-1 with biopsy-proven BRPC as defined by NCCN criteria (SMV/PV involvement with suitable flow, abutment of SMA < 180 degrees or of hepatic artery) were enrolled in a single institution, NCI-sponsored phase II study (NCT01591733). Pts received F-NOX for 8 cycles. If after chemotherapy, the tumor was radiographically resectable, pts received short course CRT in 5 (protons 25 GyE) or 10 fractions (photons 30 Gy) with capecitabine 825 mg/m2 bid. If the tumor was still abutting vasculature, pts received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. The primary endpoint of the study was R0 resection rate. Results: 50 pts were enrolled from 8/2012 to 8/2016. One pt was ineligible (lung metastases) and 1 pt is still on treatment, thus 48 patients were evaluable for this analysis. Median age was 62y (46-74). Median tumor size was 37 mm (21-56). Tumor location was in the head of pancreas for 36 (75%) pts. Of the evaluable pts, 40 (83%) completed therapy. Reasons for not completing therapy included pt withdrawal (3), physician decision (3), unacceptable toxicity (1) and progression (1). Grade 3 or greater toxicity occurred in 21 (44%) pts, including diarrhea (6, 12%), febrile neutropenia (4, 8.5%), neutropenia (4, 8.5%), elevated AST/ALT (3, 6.2%), thrombocytopenia (2, 4.2%), anemia (2, 4.2%), elevated alkaline phosphatase (2, 4.2%). 27 (56%) had short course CRT, while 13 (27%) had long course CRT. In evaluable pts, R0 resection rate was 28/40 (58%). Conclusions: Preoperative F-NOX followed by individualized chemoradiation results in a high R0 resection rate. Final results including PFS outcomes on the entire cohort will be presented at the meeting. Clinical trial information: NCT01591733.