bluuebunny/crossref_metadata_2025_split huggingface dataset:
Did neoadjuvant chemotherapy provide better long term outcomes in borderline resectable with arterial involvement (BR-A PC)?
Authors: Saito Kei , Nakai Yousuke , Sakamoto Yoshihiro , Ishigaki Kazunaga , Takahara Naminatsu , Arita Junichi , Watadani Takeyuki , Isayama Hiroyuki , Koike Kazuhiko 
Published: January 2019

434 Background: Recently high rates of conversion (or adjuvant) surgery were reported after neoadjuvant chemo(radiation)therapy (NAC) for borderline or locally advanced pancreatic cancer (BR/LA PC) including our phase II trial of gemcitabine, S-1 and leucovorin (GSL) combination therapy for BR PC with arterial involvement (BR-A PC) and LA PC. In our phase II trial, a high recurrence rate of 78% was noted despite a high R0 resection of 76%. Herein, we conducted a retrospective analysis of BR-A PC who underwent NAC, upfront surgery and palliative chemotherapy to evaluate the long term outcomes of NAC. Methods: Consecutive patients with BR-A PC at the University of Tokyo Hospital were retrospectively studied. Clinical outcomes in patients who underwent (NAC group) were compared with those in patients who underwent upfront surgery or palliative chemotherapy (non-NAC group). NAC was introduced in our institution from January 2014. Results: A total of 45 patients (22 non-NAC and 23 NAC group) were diagnosed with BR-A PC between January 2008 and December 2016. There were no significant differences in patient characteristics between non-NAC group and NAC group: Median age of 63 vs. 64, male in 72% vs. 52%, Performance status of 0 in 63% vs. 65%, median pretreatment CA19-9 of 175 vs. 205 U/ml. In non-NAC group, 17 underwent palliative chemotherapy as follows 8 gemcitabine alone, 3 gemcitabine and S-1 combination chemotherapy and 6 other regimens. The remaining 5 patients underwent upfront surgery with an R0 resection rate of 80%. In NAC group, a median duration of neoadjuvant chemotherapy was 4 months. A total of 14 patients underwent surgical resection with an R0 resection rate of 76%. The remaining 9 patients had disease progression during NAC and received 2nd line chemotherapy. The median follow-up time was 16.5 months in non-NAC group and 15.3 months in NAC group. The median overall survival (OS) were 19.3 vs. 21.9 months (p = 0.25). Conclusions: Both R0 resection rate and the median OS were comparable between non-NAC group and NAC group. An ideal regimen of NAC or its duration needs further investigation to prolong OS in BR-A PC.
A retrospective review of borderline resectable-locally advanced pancreatic adenocarcinoma (BR-LAPC) undergoing neoadjuvant chemotherapy followed by stereotactic body radiation therapy (SBRT) at the University of Colorado Cancer Center.
Authors: Cuny Claymore Joey , Hoyle John , O'Bryant Cindy L. , Meguid Cheryl Lauren , Lieu Christopher Hanyoung , Davis Sarah Lindsey , Messersmith Wells A. , Leong Stephen 
Published: January 2019

436 Background: Metastatic pancreatic chemotherapy regimens are often used as neoadjuvant treatment in the LAPC setting. The University of Colorado has a treatment paradigm for BR-LAPC which consists of 2-4 months of chemotherapy followed by SBRT then reevaluated for surgical resection. Methods: Retrospective analysis of patients with pathologically confirmed BR-LAPC who received all neoadjuvant treatment (chemotherapy and SBRT) with intention of undergoing surgical resection at the University of Colorado Cancer Center from 2012 to 2017. Baseline data collected includes demographics, comorbidities, disease characteristics and chemotherapy regimen FOLFIRINOX or Gemcitabine/Nab-Paclitaxel (GNP). The objective of the study is to describe the correlation of neoadjuvant regimens and clinical outcomes. Results: A total of 100 patients were identified with 40 patients collected for the interim analysis. Of these patients 82.5% (N = 33) received FOLFIRINOX and 17.5% (N = 7) received GNP. Patients who received FOLFIRINOX, 78.8% went for surgical resection compared to 85.7% in the GNP group. The number of patients who had a reported College of American Pathology (CAP) grade ≤1, representing no or minimal residual disease, was 3 for the FOLFIRINOX group and no patients in the GNP group. The percent of patients in the FOLFIRINOX group who achieved R0 resections was 90% compared to 83% for the GNP group. Mean initial CA 19-9 was 38.5U/ml, 386.7U/ml, and 1799.8U/ml in CAP grade 1, 2, 3 respectively, while percent reduction in CA 19-9 level during neoadjuvant was 33.3%, 69.7%, and 72.4% respectively. Assessment of the impact of relative dose intensity for each neoadjuvant regimen on clinical outcomes is ongoing. Conclusions: FOLFIRINOX neoadjuvant treatment was associated with improved surgical outcomes including an increased rate of R0 and CAP grade ≤1 resections. Low initial CA 19-9 levels were associated with favorable surgical and pathologic outcomes whereas absolute or relative CA 19-9 reductions with neoadjuvant were not. Final analysis of all 100 patients will be reported.
Prediction of pancreatic cancer surgical outcomes and prognosis based on an objective resectability scoring system.
Authors: Toesca Diego Augusto Santos , Jeffrey Brooke , von Eyben Rie , Poullos Peter D. , Poultsides George A. , Fisher George A. , Visser Brendan C. , Koong Albert , Chang Daniel Tandel 
Published: January 2019

446 Background: There is no consensus on the best radiographic criteria to define pancreatic cancer (PCA) resectability. We undertook this study to objectively assess the probability of tumor resection based on quantitative measures of tumor abutment from the main peripancreatic vessels. Methods: Measurements of the circumferential degree and length of solid tumor contact with the superior mesenteric artery, the celiac artery/common hepatic artery, and superior mesenteric vein/portal vein were obtained through curved planar reformations from diagnostic CT images of PCA patients treated at our institution between 2001 and 2015. Results: A total of 399 patients were identified, of which 294 were used for the analysis. Of them, 113 (38.4%) were resected, 71 (62.8%) with negative margins (R0). Based on the individual measurements of vascular involvement, a resectability scoring system (RSS) was created (table), and used in a classification and regression tree model that correlated strongly with resection (p < 0.0001) and R0 resection (p < 0.0001) probabilities. The RSS demonstrated a higher PPV, NPV and accuracy (94.3%; 98.6%; 97%) to predict resection compared to the NCCN (90.8%; 96.7%; 94.5%) and MDACC resectability criteria (87.1%; 97.9%; 93.5%). Moreover, the RSS correlated with overall survival (OS) (p < 0.0001) and metastasis-free survival (p < 0.0001). Conclusions: We developed a PCA resectability scoring system that is objective, reproducible, and highly correlated with surgical outcomes and prognosis. External validation is warranted. [Table: see text]
A SEER-based multiethnic picture of cholangiocarcinoma in the United States pre and post the advent of gemcitabine/cisplatin.
Authors: Mody Kabir , Antwi Samuel O , Hodge David O , Meghji Zahara , Ailawadhi Sikander , Bekaii-Saab Tanios S. , Roberts Lewis R. 
Published: January 2019

448 Background: Cholangiocarcinoma (CCA) is a rare, lethal cancer with five-year survival of less than 10%. Although incidence rates have been increasing in the United States, ethnic variations in survival have not been investigated. We examined multi-ethnic variation in overall survival (OS) and CCA-specific survival (CSS) using data from the population-based Surveillance Epidemiology and End Results (SEER) program in the four year periods before and after introduction of gemcitabine/cisplatin as treatment for CCA. Methods: The study included data from 9,975 CCA cases reported in SEER between 2006 and 2013. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated to examine overall and cholangiocarcinoma-specific survival by ethnicity, age, gender and in the pre- and post- gemcitabine/cisplatin era (2006-2009 vs. 2010-2013). Results: Compared to non-Hispanic Whites, Hispanics had poorer 3-year OS (HR = 1.18, 95% CI = 1.10-1.26) and 3-year CCA-specific survival (HR = 1.25, 95% CI = 1.16-1.35). Similarly, non-Hispanic Blacks had 3-year OS (HR = 1.22, 95% CI = 1.12-1.30) and 3-year CCA-specific survival (HR = 1.24, 95% CI = 1.13-1.37). Males and older patients also were found to have shorter survival compared to females and younger patients. Also noted was an increase in CCA incidence rate over time (2006-2013) of 5.93%. Among those < 50 versus ≥50 years old, a 23% higher rate of incidence in those < 50 was noted. Overall survival and CSS were both significantly improved for patients post-advent of Gemcitabine/Cisplatin. Statistically significant improvement in CSS pre- and post-advent of Gemcitabine/Cisplatin was noted in non-hispanic whites (p < 0.001) and Hispanics (p = 0.02). Conclusions: Hispanics and non-Hispanic Blacks have worse survival after diagnosis with CCA. Further studies are needed to determine the determinants of poor survival among these groups toward targeted intervention. Significant improvements in OS and CSS have been seen after the advent of Gemcitabine/Cisplatin. The incidence of CCA is rising faster in young persons, under the age of 50, compared with older patients.
Role of adjuvant therapy in resected gallbladder cancer.
Authors: Hassan Mohamed Abdelrahim Muddathir , Wongjarupong Nicha , Sanhueza Cristobal T. , Hartgers Mindy L. , Hassan Fatima , Roberts Lewis R. , Mahipal Amit 
Published: January 2019

452 Background: Surgical resection is the only curative treatment for patients with gallbladder cancer, despite surgical advances many patients ultimately develop recurrent disease. Management of resected gallbladder cancer mostly relies on single-arm trials and retrospective observations. The purpose of our study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer patients who have undergone surgical resection. Methods: Clinical data were collected on 251 patients who underwent surgical resection for stage I-III gallbladder cancer and presented to Mayo clinic from January 2000-December 2015. Patients were then classified into adjuvant treatment group and surveillance only group. Overall survival and recurrence were compared between the two groups. Results: 78 (31.1%) patients received adjuvant therapy while 173 patients were observed only. Patients who received adjuvant tended to be younger (63.0[SD 11] vs 66.2 [SD 13.1]), have higher stage, and underwent extended surgery. Most patients received chemoradiotherapy (55) with 5-Fluorouracil (67.3%) and capecitabine (25.5%) as radiosensitizing agents. 21 patients received additional adjuvant chemotherapy. 27% of patients received chemotherapy as the sole adjuvant treatment. The most common chemo regimens included gemcitabine (52.3%) and gemcitabine plus cisplatin combination (23.8%). On multivariate analysis patients > 65 years(HR 1.53 [1.07-2.19], p = 0.02), males (HR 1.7 [1.2-2.4], p = 0.003), positive margins (2.77 [1.69-4.38], p < 0.01), and stage III (HR 1.91 [1.35-2.70], p < 0.01) had worse overall survival. Patients who underwent extended radical resection (HR 0.73 [0.51-1.05], p = 0.09) had better overall survival. Adjuvant therapy had no statistical significant effect on overall survival (HR 1.10 [0.75-1.59], p = 0.63 or disease free survival (HR 1.05 [0.69-1.59], p = 0.81) on overall population. However, in stage IIIB, patients receiving adjuvant therapy had better overall survival (HR 0.51 [0.25-1.01], p = 0.05) and disease free survival (HR 0.45 [0.19-1.09], p = 0.06). Conclusions: In our study, adjuvant treatment, especially chemoradiation therapy, was only beneficial in patients with stage IIIb gallbladder cancer patients.
The effect of socioeconomic factors on the outcome of intrahepatic cholangiocarcinoma.
Authors: Sellers Cortlandt , Ludwig Johannes M , Uhlig Johannes , Stein Stacey , Lacy Jill , Kim Hyun S 
Published: January 2019

465 Background: To investigate the impact of socioeconomic factors on overall survival (OS) for patients with intrahepatic cholangiocarcinoma (ICC) at an inner-city tertiary care hospital. Methods: Consecutive patients treated for ICC diagnosed between 2005 and 2016 in the cancer registry were studied. Patients were stratified by demographic, socioeconomic variables, and treatment course. Kaplan-Meier curves and Cox proportional hazard modeling were performed. Results: Patients were 52% male (95 pts) and 74% white (136 pts) with mean age of 65.7 yrs (SD 10.7 yrs). 82% of patients were married or had been previously married (148 pts). 11% of patients had Medicaid as their primary insurance (20 pts), 45% of patients had Medicare (78 pts) and 44% of patients had private insurance (77 pts). Patients with private insurance (66 pts, 87%) and Medicare (64 pts, 83%) were more likely to have been married than Medicaid (12 pts, 60%) (p = 0.036). Patients with Medicare (mean 72.0 yrs, SD 6.9 yrs) were older than private insurance patients (mean 60.3 yrs, SD 10.3 yrs) and Medicaid patients (mean 61.8 yrs, SD 12.4 yrs) (p < 0.001). Gender and ethnicity were similarly distributed by primary insurance. Median OS stratified by primary insurance demonstrated median OS in private insurance of 13.2 mo (95% CI: 8.2–18.7 mo) vs 7.3 mo (95% CI: 3.8–10.6 mo) for Medicare (HR 1.3, p = 0.11) vs 4.7 mo (95% CI: 1.7–11.3 mo) for Medicaid (HR 1.8, p = 0.0488), (p = 0.0465). Cancer-directed treatments were utilized by 81% in private insurance vs. 67% in Medicare vs 67% in Medicaid (p = 0.18). Median OS stratified by main treatment demonstrated 43.3 mo in resection (37 pts, 21%), 17.3 mo in locoregional therapy (LRT) (22 pts, 13%), 10.0 mo in chemotherapy or radiation (79 pts, 45%), and 1.4 mo in palliative or no treatment (37 pts, 21%) (p < 0.0001). Increased age was associated with decreased median OS (correlation -0.23, p = 0.0019). No differences in median OS were seen with ethnicity, gender, or marital status. Conclusions: Screening and early treatments appear to affect the OS of patients with ICC. Further investigations for preventive care for vulnerable populations to enhance survivals are warranted.
A phase 2 study of s-1 plus leucovorin in patients with untreated advanced cholangiocarcinoma (CCA).
Authors: Tanasanvimon Suebpong , Ungtrakul Teerapat , Poovorawan Nattaya , Parinyanitikul Napa , Vinayanuwattikun Chanida , Mingmalairak Siyamol , Luangdilok Sutima , Lamlertthon Wisut , Sriuranpong Virote 
Published: January 2019

467 Background: Patients with CCA usually present with advanced disease leading to the grave prognosis. Currently, cisplatin and gemcitabine is the standard treatment in advanced CCA. However, the CCA treatment outcomes are still poor and the options of treatment are quite limited. This study aimed to explore the efficacy and safety of S-1 plus leucovorin in patients with untreated advanced CCA. Methods: This single-arm two-center phase 2 study evaluated the efficacy and safety of S-1 40, 50 and 60 mg according to body surface area and leucovorin 15 mg , both given orally twice daily for one week, repeated every two weeks. Treatment was continued until complete 12 cycles, disease progression or unacceptable toxicity. The primary endpoints were overall response rate (ORR) and disease control rate (DCR) per RECIST version 1.1. The secondary endpoints were progression free survival (PFS), overall survival (OS) and toxicity. Results: Of total 32 patients and a median follow up time of 9.5 months, the ORR was 25% (95%CI 9.1-40.9) and the DCR was 62.5% (95% CI 44.8-80.2). In 25 response evaluable patients, the ORR was 32% (95% CI 12.4-51.7). The PFS was 8.0 (95%CI 5.59-10.4) months. The OS was 11.0 (95%CI 9.47-12.53). The most common grade 3 or 4 toxicities were anemia, mucositis and diarrhea. There was one patient discontinuing treatment due to treatment related toxicity. Conclusions: S-1 plus leucovorin was active and tolerable in patients with advanced CCA. Clinical trial information: TCTR20160313001.
Impact of antitumor activity on survival outcomes, and nonconventional benefit, with nivolumab (NIVO) in patients with advanced hepatocellular carcinoma (aHCC): Subanalyses of CheckMate-040.
Authors: El-Khoueiry Anthony B. , Melero Ignacio , Yau Thomas Cheung , Crocenzi Todd S. , Kudo Masatoshi , Hsu Chiun , Choo SuPin , Trojan Jorg , Welling Theodore , Meyer Tim , Kang Yoon-Koo , Yeo Winnie , Chopra Akhil , Zhao Huanyu , Baakili Adyb , Dela Cruz Christine Marie , Sangro Bruno 
Published: January 2019

475 Background: NIVO (anti–PD-1 mAb) has demonstrated durable responses, long-term OS, and manageable safety in pts with aHCC in CheckMate-040 (El-Khoueiry, Sangro et al. 2017). With anti–PD-1 therapies, meaningful OS benefit may be seen even in pts who do not achieve a conventional response by RECIST v1.1. Here we report nonconventional benefit with NIVO and effect of antitumor activity on OS in sorafenib-experienced (sor-exp) pts with aHCC, including pts with a best overall response (BOR) of progressive disease (PD). Methods: Sor-exp pts received NIVO (3 mg/kg Q2W) in a phase 1/2 dose-expansion cohort regardless of PD-L1 status. Impact of antitumor activity on median OS (mOS) was determined by calculating change in target lesion size from baseline using quartile analyses (25% cutoff). Nonconventional benefit was analyzed by reductions or stabilizations in target lesion size after progression in pts with a BOR of PD. Results: Sor-exp pts (N=145) had a median follow-up of 14.9 mo. The ORR (RECIST v1.1) was 14% and the DCR was 56%. Median duration of stable disease (SD) was 4.3 mo and the DCR with SD ≥6 mo was 27%. Overall, mOS was 15.6 mo. Degree of OS benefit corresponded with antitumor activity in pts with decreases (≥25%, mOS not reached; 0–25%, mOS 17.7 mo) or increases (0–25%, mOS 11.7 mo; ≥25%, mOS 8.9 mo) in target lesion size (Table). In non-responders (n=124; including pts with BOR of SD or PD), mOS was 13.4 mo. Nonconventional benefit was observed in 11 of 56 pts (20%) with a BOR of PD. Updated clinical data with additional follow-up will be presented. Conclusions: In sor-exp pts, mOS with NIVO corresponded to degree of antitumor activity, with OS benefit not limited to RECIST v1.1 responders. Improved OS in non-responders is likely due to nonconventional benefit, supported by disease reduction or stabilization even in pts with a BOR of PD. Clinical trial information: NCT01658878. [Table: see text]
Risk stratification of gastrointestinal stromal tumors by CtBP2 and CD44 analysis.
Authors: Gopie Priya , Rosca Oana C. , Chawla Ayesha , Mei Lin , Almenara Jorge , Glass Edmund , Dozmorov Mikhail , Grossman Steven R. , Idowu Michael , Boikos Sosipatros Alexandros 
Published: January 2019

48 Background: C-terminal binding protein 2 (CtBP2) is an oncogenic transcription factor that promotes cancer stem cell (CSC) growth and self-renewal, and controls pathways for tumor initiation, progression, and response to therapy. Expression of CtBP2 is linked to aggressive behavior in ovarian cancer, while genetic or pharmacologic targeting of CtBP2 disrupts CSC growth and self-renewal. CD44 is a cell surface marker that has been linked to CSC populations in many solid tumors, though data is conflicting on its role as tumor suppressor or oncogene. Gastrointestinal stromal tumors (GIST) is an increasingly common malignancy where risk stratification is essential for guiding post-surgical adjuvant therapy. We hypothesized that CtBP2 and CD44 staining would enhance risk stratification of GIST which currently relies on purely non-molecular clinicopathologic criteria. Methods: We identified 149 GIST cases from 1990 to 2016 in the Virginia Commonwealth University Medical Center pathology archive. Clinical data for 121 patients was available. The Armed Forces Institute of Pathology (AFIP) criteria (Miettinen's criteria) was used to risk stratify GISTs using the size, site, and mitotic index of the primary tumor. Immunohistochemistry for CtBP2 and CD44 was then performed on GIST samples with adequate tumor (86, CD44; 87, CtBP2). Stains were scored 0 (negative) to 3 (maximum) by two independent pathologists. Statistical analysis (χ2) correlating AFIP risk category with CD44 and CtBP2 staining was performed using PRISM6. Results: Moderate and high risk GISTs, based on AFIP criteria, significantly correlated with high CtBP2 expression (score = 3, p = 0.046) and low CD44 expression (score = 0-2, p = 0.034). Conclusions: CD44 and CtBP2 staining can be used to risk stratify GIST, and may enhance and complement current clinical risk stratification systems. Our data also suggests a potential tumor suppressive role of CD44 in GIST. Additionally, based on our findings, investigation of therapeutics that target CtBP2 in GISTs should be pursued.
FOLFIRINOX in advanced pancreatic cancer patients with the double-variant type of UGT1A1 polymorphism: A multicenter, retrospective study.
Authors: Umemoto Kumiko , Takahashi Hideaki , Morizane Chigusa , Yamada Ikuhiro , Shimizu Satoshi , Shioji Kazuhiko , Yoshida Yukio , Motoya Masayo , Mizuno Nobumasa , Kojima Yasushi , Terashima Takeshi , Uesugi Kazuhiro , Ikeda Masafumi , Ueno Makoto , Furuse Junji 
Published: January 2019

484 Background: UGT1A1 *28 or *6 polymorphism is associated with reduced enzyme activity and severe toxicity of irinotecan, especially in patients homozygous for UGT1A1*28 or *6 and heterozygous for both UGT1A1*28 and *6 (double-variant-type: DV). FOLFIRINOX (FFX) is one of the standard treatments in patients with advanced pancreatic cancer (APC). In Japanese guideline for FFX in patients with APC, full-dose regimen of FFX is not recommended in patients with DV, but dose adjustment for patients with DV is not established yet. The purpose of this study was to evaluate the safety and efficacy of FFX in Japanese APC patients with DV. Methods: APC patient of DV treated with FFX from December 2013 to March 2016 in 16 hospitals in Japan were enrolled. Results: A total of 31 patients were enrolled. Irinotecan were variously administered at the first cycle of dose ranged from 70 to 180mg/m2. The proportion of the patients receiving standard dose of oxaliplatin, 5-FU infusion and 5-FU continuous infusion at the first cycle of FFX were 97%, 19% and 97%, respectively. Severe adverse events were observed 8 of 31 patients. Main grade 3 or 4 adverse events were included neutropenia (65%), febrile neutropenia (13%) and diarrhea (6%). Response rate (RR) and overall survival (OS) receiving FFX as first-line treatment were 23% and 13.5 months, respectively. In this study, patients receiving irinotecan 150mg/m2 was high frequency of 80% (4/5), otherwise, grade 4 neutropenia in all patients was observed in 29% (9/31) Conclusions: The results of neutropenia in this study indicated that irinotecan 150mg/m2 may not be tolerable in DV patients. RR and OS were almost the same as previous reports. We are planning the dose finding study of FFX in APC patients with DV.