bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of early vs. late onset gastroesophageal cancers.
Authors: Qureshi Sadaf , Xiu Joanne , Sarraf Yazdy Maryam , Shields Anthony Frank , Philip Philip Agop , Marshall John , Lenz Heinz-Josef , Salem Mohamed E. 
Published: March 2017

46 Background: Gastric and esophageal adenocarcinomas (GA and EA) in young patients (pts) are more likely driven by genetic factors than environmental carcinogens. Tumor molecular variations defining individual differences in age of onset have not been well elucidated. Methods: Protein expression (IHC), gene amplification (ISH), and next generation sequencing (NGS) were tested on GA and EA tumors. Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Chi-square and t-tests were used for comparative analyses. Results: In total, 1670 tumors were examined; older (age >60) vs. younger (<45)comparisons were made in 599 GA and 491 EA (Table). In GA, significantly higher TOPO2A and TOPO1 expression was seen in older vs. younger pts, while higher mutation rates of FGFR2, IDH1, and NRAS were seen in younger pts. In EA, EGFR expression was higher in the older pts, while ATM and BRCA1 mutations were higher in the younger pts. When only primary tumors were studied, younger GA had a higher NRAS mutation rate (4.5% vs. 0, p=0.02) than older GA, and younger EA had higher cMET amplification (10% vs. 0, p=0.002) and ATM mutations (25% vs. 0, p=0.01) than older EA. In metastatic EA, higher BRCA1mutations (1/2 [50%] vs. 0/12 [0%], p=0.01) and lower EGFR overexpression (81% vs. 29%, p = 0.004) were seen in younger vs. older pts. No differences were seen in the PD-1 or PD-L1 expression rates between the two groups. Mean TML was lower in young GA than old GA (6.2 mutation/megabase vs. 10.4, p=0.005) but was not different between young EA and old EA (5.3 vs. 6.9, p=0.1). Conclusions: Younger GA/EA has a molecular profile unique from older pts, suggesting molecular aberrations play a different part in early-onset disease. Prevalence of aberrations in the young, such as cMET amplification and FGFR2, IDH1, BRCA1mutations may indicate important therapeutic targets. [Table: see text]
A single institutional experience of carbon-ion radiotherapy for locally advanced pancreatic cancer.
Authors: Shinoto Makoto , Shioyama Yoshiyuki , Suefuji Hiroaki , Toyama Shingo , Matsumoto Keiji 
Published: March 2017

461 Background: Carbon-ion radiotherapy (C-ion RT) has the potential advantages in terms of improved dose localization and enhanced biological effectiveness compared to conventional radiotherapy or proton therapy. C-ion RT is expected to contribute to the prolongation of survival in patients with pancreatic ductal adenocarcinoma (PDAC). We started C-ion RT for pancreatic cancer at SAGA HIMAT since April 2014. The aim of this study is to evaluate the clinical results of C-ion RT for locally advanced PDAC. Methods: From April 2014 to May 2016, 76 patients with pancreatic cancer were treated with definitive C-ion RT. 44 patients who were confirmed as unresectable locally advanced PDAC were included in this retrospective analysis. 32 patients were excluded because of resectable disease (n = 8), borderline disease (n = 6), without pathological confirmation (n = 20). C-ion RT was performed with 55.2 Gy (RBE) at 12 fractions in 3 weeks. The anti-tumor effect was evaluating using CT and FDG-PET according to RECIST ver. 4.0. Results: The median follow-up period was 12.8 (range 3.4-27.5) months from the initiation of C-ion RT. In all patients, planned C-ion RT was completed. Induction chemotherapy was performed in 35 (80%) and the median duration time was 3 (range 1-19) months. Forty patients (91%) underwent concurrent chemotherapy with gemcitabine or S-1. Local effect using CT criteria was CR in 2, PR in 5, and SD in 37. The evaluation adding FDG-PET criteria was CR in 25, PR in 6, and SD in 13. Five patients (11%) experienced local recurrence during follow-up period. Two patients who had SD by CT and CR by FDG-PET performed tumor resection and were revealed pathological CR. One and two-year survival rate from C-ion RT were 82% and 66%, respectively. The two-year survival rate from initial treatment was 75%. Only three patients (7%) experienced grade 3 toxicities that were leukopenia, anorexia, and gastric ulcer. There was no grade 4 or 5 toxicity. Conclusions: C-ion RT for locally advanced PDAC was effective and well tolerated. FDG-PET was useful for the evaluation of local effect after C-ion RT.
Cancer of unknown primary (CUP) with disseminated-lymphadenopathy presentation: Clinicopathological features, prognostic factors, and survival outcomes.
Authors: Raghav Kanwal Pratap Singh , Modha Jignesh , Lano Elizabeth A , Wang Huamin , Matamoros Aurelio , Overman Michael J. , Varadhachary Gauri R. 
Published: March 2017

465 Background: Aside from traditional favorable localized-nodal CUP (LNC) subsets including solitary nodal disease, women with isolated axillary adenocarcinoma and squamous cell carcinoma of cervical/inguinal lymph nodes, there is limited data on disseminated nodal CUP (DNC) presentation. Our study describes the clinicopathologic features and outcomes in nodal CUP (NCUP) highlighting the DNC subset. Methods: We performed a retrospective review of 61 NCUP patients (pts) at UTMDACC (2008 - 2015). For control group (CG), we utilized a cohort of consecutive non-NCUP pts (N = 201) from MDACC CUP database (2012 - 2013). Kaplan-Meier method was used to estimate median overall survival (mOS) and compared with log-rank tests. Results: Median age of NCUP was 61 y, similar to CG (59 y; P = 0.26). In this cohort, 19/61 (31%) and 42 (69%) were classified as LNC and DNC. DNC pts were predominantly women (65%), had good performance status (0/1: 90%), and presented with intrabdominal lymphadenopathy (79%). Sixty percent had carcinoma and majority were high grade (74%). Median immunohistochemical stains performed were 9; most common positive stains were CK7 and pan-keratin. The mOS for entire NCUP cohort was 76 months (m). The mOS for LNC was not reached and was 33.1 m for DNC (HR 0.36; P = 0.04). The mOS of DNC was better than CG (18.8 m; HR 0.62; P = 0.03). Male sex and high neutrophil-lymphocyte ratio (NLR > 5) were poor prognostic factors in DNC ( P < 0.01). Among NCUP pts, 21 reported subsequent development of extra-lymphatic disease [peritoneum/retroperitoneum (29%), liver (24%), lung (19%), muscle/soft tissue (19%), bone (10%)]. Among 36 pts, who had first-line systemic therapy, combination platinum-taxane was used substantially (44%) and was associated with better mOS compared to other regimens (HR 0.20; P < 0.01). Conclusions: Disseminated–lymphadenopathy CUP presentation is a unique clinical subset of CUP which is associated with a significantly better survival than non-NCUP. This distinct entity warrants dedicated research efforts towards understanding biology, developing a cost effective integrated clinical algorithm for management and developing novel therapies.
Efficacy of chemotherapy in patients with recurrent pancreatic cancer.
Authors: Ohba Akihiro , Ueno Hideki , Inagaki Yuji , Sakamoto Yasunari , Kondo Shunsuke , Morizane Chigusa , Okusaka Takuji 
Published: March 2017

466 Background: Gemcitabine (GEM) plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) are standard first-line chemotherapy regimens for metastatic pancreatic cancer (MPC) patients. GEM and S-1 are also used for these patients in Japan. However, the phase 3 trials included a small proportion of recurrent pancreatic cancer (RPC) patients, and patients who had received adjuvant chemotherapy were excluded. In clinical practice, RPC is treated in the same way as MPC. The aim of this study is to compare the efficacy of chemotherapy between RPC and MPC. Methods: We retrospectively analyzed the patients with RPC or MPC who received GnP, FFX, GEM, or S-1 as first-line chemotherapy between January 2014 and March 2016 in our institution. RPC was defined as pancreatic cancer with recurrence after R0 or R1 resection. Overall survival (OS), progression-free survival (PFS), response rate (RR), and disease control rate (DCR) were evaluated. Multivariate analyses of OS were performed with the use of a Cox proportional-hazard model. Results: A total of 181 patients, 40 RPC and 141 MPC, were selected in this study. RPC and MPC groups were similar with respect to age, sex, and performance status (PS). However, the RPC group had lower percentage of liver metastases (P < 0.001). The regimens were GnP/FFX/GEM/S-1: 10/3/20/7 in the RPC group and 37/34/67/3 in the MPC group, respectively. In the RPC group, 31 of 40 patients had received adjuvant chemotherapy; S-1/GEM: 24/7. The median OS was 16.6 months in the RPC group as compared with 9.7 months in the MPC group (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.37–1.10, P = 0.11). The median PFS was 4.8 months in the RPC group and 4.4 months in the MPC group (HR 0.86, 95% CI 0.57–1.30, P = 0.47). The RR was 10% versus 14% (P = 0.79), the DCR was 50% versus 52% (P = 0.86), in the two groups, respectively. Multivariate analysis showed PS (HR 2.19, 95% CI 1.38–3.49) and liver metastases (HR 2.34, 95% CI 1.47–2.34) were independent predictors of OS. On the other hand, RPC or MPC was not found to be an independent prognostic factor (HR 1.19, 95% CI 0.67–2.13). Conclusions: It is suggested that chemotherapy in RPC may have similar efficacy compared to MPC. The relatively longer OS in the RPC group seems to associate with the lower percentage of liver metastases.
Determinants of first-line treatment selection in advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Wong Hui-Li , Wang Ying , Yin Yaling , Kennecke Hagen F. , Cheung Winson Y. , Renouf Daniel John , Gill Sharlene 
Published: March 2017

468 Background: Chemotherapy options currently available for the first-line treatment of advanced PDAC include FOLFIRINOX (FX), gemcitabine with nab-paclitaxel (GP) and single agent gemcitabine (Gem). GP was introduced most recently and funded for clinical use in British Columbia (BC) in September 2014. In this retrospective analysis, we explore the impact of GP availability on first-line treatment selection and overall survival (OS) in advanced PDAC. Methods: The BC Cancer Agency provincial pharmacy database was used to identify patients (pts) who started FX, GP or Gem between January and August 2014 (pre-GP) or January and August 2015 (post-GP). Pts were eligible for inclusion if they received at least one cycle of first-line therapy for locally advanced or metastatic PDAC. Clinical data were extracted from electronic medical records. OS was defined as time from diagnosis of advanced PDAC to death and compared by treatment era, adjusting for age, ECOG, comorbidities, disease extent and baseline CA19-9. Results: 286 pts fulfilled eligibility criteria: 88 (31%) with locally advanced and 198 (69%) with metastatic disease. 131 and 155 pts were treated in the pre- and post-GP eras respectively. Prior to GP approval, 44% and 49% of pts received Gem and FX; this decreased to 21% and 33% after GP funding, with 46% of pts receiving GP in the latter period. Nine (7%) pts received GP in the pre-GP era, either through self-pay or addition of nab-paclitaxel after approval. There were no significant differences in pt characteristics across both eras. 46% of pts who received GP post approval had ECOG ≥ 2. The proportion of pts receiving second-line therapy was lower in the post-GP era (22% vs. 38%). Median OS in the post-GP era was 8.1 vs. 10.1 months in the pre-GP era; adjusted HR 1.28 (95% CI 0.96–1.71). Pts with ECOG ≥ 2 who received GP had a median OS of 6.5 months. Conclusions: After GP was funded, it became the preferred first-line regimen for advanced PDAC. Its more frequent use instead of FX did not appear to compromise overall survival even though a substantial proportion of pts were ECOG ≥ 2 and few pts received second-line therapy.
Preliminary analysis of FOLFIRI regimen with or without bevacizumab as second-line systemic therapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma.
Authors: Zhao Xiaoying , Wang Chen Chen , Zhang Wen , Zhu Xiaodong , Guo Weijian , Chen Zhi-Yu 
Published: March 2017

469 Background: Patients with gastroenterpancreatic neuroendocrine carcinomas (NECs) have a very poor prognosis. And the role of the second-line therapy remains unknown. Methods: We retrospectively analyzed 11 patients with gastroenteropancreatic NEC after failure of first-line chemotherapy in the last two years in our cancer center. Data examined included clinical and pathological characteristics at the time of diagnosis, efficacy and safety. Results: Median age was 51 (17-64) years old. Most were male (81.8%). Tumor origin included pancreas (6pts, 54.5%), colon-rectum (3pts, 27.3%), one stomach and one liver. Metastatic disease was evident at diagnosis in all patients (liver metastases: 100%, celiac lymph nodes: 72.7%, bone: 18.2%, pleural effusion and peritoneal metastasis: 18.2%). Median Ki-67 index was 80%. Etoposide-cisplatin combinations as first line chemotherapy were administered in 8 (72.7%) patients and 2 (18.2%) capecitabine based regimen and 1(9.1%) gemcitabine with nab-paclitaxel. All patients received the FOLFIRI regimen with a median number of 8 (3-36) courses. Three patients (27.3%) had partial response, 4 (36.4%) stable disease, and 4 (36.4 %%) tumor progression. But in 6 patients received the FOLFIRI plus bevacizumab, disease control rate was 66.7%, 3 (50.0%) partial response, 1(16.7%) stable disease. The median PFS in all 11 pts was 3.77 (1.77-24.07) months, in 6pts with bevacizumab was 4.77(1.83-24.07) months. The most severe toxicities was grade 3 neutropenia (27.2%), the other adverse effects were mild to moderate, including mild anemia, transient transferase elevation and proteinuria. Conclusions: FOLFIRI regimen is a potentially effective and safe chemotherapy given as second-line in patients with NEC. Additional anti-VEGF therapy with bevacizumab may improve the disease control and PFS time.
Phase II study of first-line radioembolization with yttrium-90 glass microspheres for intrahepatic cholangiocarcinoma.
Authors: Shridhar Ravi , Frakes Jessica M. , Yue Binglin , Kim Richard D. , Springett Gregory M. , Arslan Bulent , Choi Junsung , Kis Bela , Yeatman Timothy Joseph , Meredith Kenneth L , Hoffe Sarah E. 
Published: March 2017

482 Background: The standard of care for unresectable intrahepatic cholangiocarcinoma (ICC) is systemic chemotherapy. The role of liver directed therapy for ICC is controversial given the lack of level I data. We conducted a phase II study to determine the safety and effectiveness of first-line liver directed therapy with radioembolization with yttrium-90 (Y90) glass microspheres for ICC. Methods: Eligible patients were enrolled on an IRB-approved phase II study (NCT01253148). Patients were included if they had no evidence of extrahepatic metastases, Childs-Pugh A, without main portal vein thrombus, bilirubin < 2 mg/dL, ECOG performance status of 0-2, and no prior chemotherapy, liver embolization, or radiation therapy for ICC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and toxicity. Results: Twenty-five patients were enrolled between 2010 and 2013 with a median followup of 13 months (9-20 months). The median age was 76 years. Twenty patients came off study due to progression or death. The overall response rate was 56%. Median PFS was 6 months (95% CI: 4-12 months). This was likely due to tumors appearing larger after treatment due to tumor inflammation despite a decrease in CA19-9 levels. Univariate (UVA) and multivariate analysis (MVA) failed to identify any prognostic factors associated with PFS. Despite the low median PFS, median OS was 22 months (95% CI: 10 months to upper limit not reached). However, UVA and MVA failed to identify and prognostic factors for OS. Treatment was well tolerated with no reported grade 3 gastrointestinal or general disorder toxicities. Grade 3 ALT, AST, and alkaline phosphatase increase were reported in 4%, 4%, and 8%, respectively. Grade 4 hyperbilirubinemia and thrombocytopenia were reported in 4% and 4%, respectively. There were 2 patient who developed sepsis one patient who died within 30 days of treatment. Conclusions: First-line liver directed therapy with radioembolization with Y90 glass microspheres is a safe and effective treatment for ICC. Further prospective clinical trials are needed to identify the proper sequencing of liver directed therapy and systemic chemotherapy. Clinical trial information: NCT01253148.
Impact of nab-paclitaxel-based second-line chemotherapy on the outcomes of pancreatic cancer.
Authors: Dadi Neelakanta , Shahda Safi , O'Neil Bert H. , Sehdev Amikar 
Published: March 2017

483 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with no standard second line chemotherapies. We conducted a retrospective study with the primary aim to examine the effect of second line chemotherapy with nab-paclitaxel-based regimen on the overall survival (OS) and progression-free survival (PFS) of locally advanced and metastatic PDAC patients. Methods: Indiana University Simon Cancer Center (IUSCC) Cancer Registry was used to identify patients with locally advanced or metastatic PDAC between 2009 and 2015. Only patients who received second line chemotherapies were included in the study. These patients were divided in to two groups: a) nab-paclitaxel-based treatment and, b) non-nab-paclitaxel-based treatment. Demographic (age, race, gender, year of diagnosis, family history, comorbidity), clinical (histology, CA 19-9, bilirubin, tumor location, performance status, metastatic sites, chemotherapy, surgery or radiation) and outcome (OS, PFS) characteristics were obtained. OS and PFS were estimate by using Kaplan-Meier method and 95% CI. Cox proportional-hazard model was used for multivariate analysis. Results: Forty-seven (39%) and seventy-three (61%) patients received nab-paclitaxel-based and non-nab-paclitaxel-based second line chemotherapy, respectively. In the univariate analyses, nab-paclitaxel-based treatment was only associated with younger age (60.4 vs. 64 years; P = 0.02). The median PFS was 2.8 and 2.1 months (HR 0.62; 95% CI 0.38-1.02; P = 0.06), and the median OS was 7.5 and 4.7 months (HR 0.67; 95% CI 0.45-1.00; P = 0.05) in patients who received nab-paclitaxel based second line treatment versus not, respectively. Multivariate analyses adjusted for age showed a significantly improved PFS (adjusted HR 0.60, 95% CI 0.36-0.98; P = 0.04) and a suggestion of improved OS (adjusted HR 0.67; 95% CI 0.44-1.01, P = 0.05) in the nab-paclitaxel based second line treatment group versus not, respectively. Conclusions: In a single institution retrospective study, we report significant improvement in the PFS and a suggestion of improvement in the OS with nab-paclitaxel based treatment as compared with non-nab-paclitaxel based treatment in the second line setting.
Adjuvant stereotactic body radiotherapy (SBRT) for resected primary and metastatic liver cancers.
Authors: Bazzi Latifa , Feng Mary Uan-Sian , Lawrence Theodore Steven , Cuneo Kyle Clifford , Owen Dawn 
Published: March 2017

487 Background: Stereotactic body radiotherapy (SBRT) has been shown to be a safe and effective treatment for hepatobiliary cancers. However, little is known about the efficacy of adjuvant SBRT for resected liver tumors with positive margins. We examined the characteristics and outcomes of patients who received adjuvant SBRT for both primary and metastatic cancers of the liver. Methods: We retrospectively reviewed the charts of patients who had received liver SBRT from 2009-2015 at our institution. During that time frame, 11 patients were identified as having received adjuvant SBRT post resection. Patient data such as age, gender, portal vein thrombosis, cirrhosis, ECOG performance status, prior liver directed therapies, and SBRT dose were collected. Descriptive statistics were used for analysis given the small number of patients in this series. Results: Median age at the time of treatment was 63 years (range 51-79), and the majority of patients (72.7%) were male. Seven tumors (63.6%) were hepatocellular carcinomas, and 4 (36.4%) were adenocarcinomas. Of the tumors with adenocarcinoma histology, 3 were cholangiocarcinomas and one was metastatic colorectal cancer. Ten patients (90.9%) were treated for positive margins, and one was treated for inferior vena cava (IVC) invasion. Seven patients (63.6%) had no other liver-directed treatment prior to adjuvant SBRT. Two patients received systemic therapy prior to SBRT. Median EQD2 was 83.3 Gy (range 60-126), and 81.8% of patients received 5 fractions. There were no grade 3 or above late toxicities from treatment. Median follow-up was 14.1 months (range 5.4-38.1). None of the treated tumors progressed locally. Six patients (54.5%) progressed elsewhere in the liver, and one patient experienced distant metastatic progression. One patient experienced both intrahepatic progression and distant metastatic progression. Conclusions: Adjuvant SBRT appears to be a safe and feasible adjuvant treatment in patients with primary liver resection for either primary liver cancer or metastatic disease who are at high risk of recurrence.
Frequency of severe neutropenia occurring as an adverse events of gemcitabine plus cisplatin chemotherapy in patients with recurrent biliary tract cancer compared to those with unresectable biliary tract cancer.
Authors: Fujishiro Noriko , Mitsunaga Shuichi , Shinohara Akira , Takeno Misaki K , Funazaki Hideki , Kimura Gen , Watanabe Kazuo , Umemoto Kumiko , Sasaki Mitsuhito , Takahashi Hideaki , Imaoka Hiroshi , Hashimoto Yusuke , Ohno Izumi , Ikeda Masafumi 
Published: March 2017

488 Background: In patients (pts) with biliary tract cancer (BTC), relapse occurs at a high frequency even after curative resection. It remains unclear whether in pts with postoperative recurrence receiving chemotherapy, the surgery exerts any influence on the risk of development of toxicities. The aim of this study was to compare the outcomes and incidences of adverse events between recurrent BTC (rBTC) pts and unresectable BTC (uBTC) pts receiving gemcitabine plus cisplatin chemotherapy (GC). Methods: Data of pts with rBTC or uBTC receiving GC as the first-line chemotherapy were analyzed. The GC regimen consisted of gemcitabine 1000 mg/m2 plus cisplatin 25 mg/m2on days 1 and 8, administered every 3 weeks. All adverse events occurring during the first 180 days of GC were evaluated according to CTCAE, version 4.0. Results: A total of 151 pts, including 55 pts with rBTC and 96 pts with uBTC, were enrolled. In regard to the baseline characteristics, no significant differences between the rBTC and uBTC groups were found in the gender distribution [male: 69% vs. 57%], age [median: 68 vs. 68], or ECOG performance status (PS) [PS0: 67%vs. 55%]. The distribution of the primary tumor site (intrahepatic bile duct [27% vs. 33%] / extrahepatic bile duct [45% vs. 20%] / gallbladder [20% vs. 44%] / ampulla [7% vs. 3%]) was unbalanced between the two groups ( p < 0.01). The overall survival (OS) was significantly longer in the rBTC group than that in the uBTC group [median 15.8 months vs. 10.0 months, p = 0.02], however, there was no significant difference in the progression-free survival [median 6.8 months vs. 5.8 months] between the two groups. Grade 3-4 neutropenia was more frequent in the rBTC group [69%] as compared to that in the uBTC group [44%, p < 0.01], whereas Grade 3-4 cholangitis was significantly less frequent in the rBTC [5%] group than that in the uBTC group [21%, p = 0.02]. Conclusions: The incidence of Grade 3-4 neutropenia developing during GC was significantly higher in the rBTC group as compared to that in the uBTC group.