bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a nonbiologic nanoparticle form of paclitaxel in metastatic pancreatic cancer.
Authors: Motamed Kouros , Hwang Larn , Hsiao Chao , Trieu Vuong N. 
Published: March 2020

e15076 Background: The (nab-Pac)/Gemcitabine (Gem) combination has recently been shown to impart a significant survival advantage over Gem alone in patients with metastatic pancreatic cancer. The goal of this study was to define a non-biologic, nanoparticle paclitaxel (NBN-Pac) which has a similar toxicity profile and utilizes the same albumin-mediated transport mechanism. Herein, we report in vitro, preclinical and phase I clinical results for this NBN-Pac in metastatic pancreatic cancer. Methods: In vitro drug cytotoxicity was measured as mean IC50 values following a 72-h exposure in four pancreatic cell lines (MIA Paca-2 and Capan-1 and multi-drug resistant cell lines PANC-1 and ASPC-1). In vivo anti-tumor activities were assessed in xenografted MIA PaCa-2 and PANC-1 models in nude mice treated with three i.v. doses of NBN-Pac (20, 50 mg/kg) and Taxol (20 mg/kg) on days 0, 3, and 6 (q3dx3), and twelve i.v. doses of Gem (140 mg/kg) on every 3 days (q3dx12). A phase I clinical trial (N=18) was conducted to determine the MTD and the recommended phase II dose of the combination therapy with NBN-Pac (220-300 mg/m2, q3w) and Gem (1250 mg/m2) as primary endpoints in first line treatment of subjects with advanced pancreatic cancer. Reduction in the plasma levels of CA19-9 was measured as a PD biomarker. Results: The mean IC50 value of NBN-Pac in four pancreatic cell lines was approximately 30-fold lower than that of Gem. NBN-Pac formulation (50 mg/kg) produced superior anti-tumor activity in the two xenograft models tested over Taxol and Gem at clinically equivalent doses. Our phase I trial established the MTD of this NBN-Pac formulation as 300mg/m2. Moreover, 5 out of 16 subjects (31.3%) were CR or PR with 95% exact confidence interval of (11.0%, 58.7%). The median PFS time was 5.6 month (95% C.I = 2.9). The median OS time could not be estimated as the survival rate did not fall below 50%. Other safety variables revealed no significant abnormality that may have affected the result of the study. Conclusions: NBN-Paclitaxel formulation has superior anti-tumor activity vs. Taxol and Gem in in vitro toxicity assays, preclinical models of pancreatic cancer, as well in a phase I clinical study in patients with advanced pancreatic cancer.
Chemoembolization with super absorbent polymer microspheres (SAP-MS) loaded with doxorubicin (D) using escalating doses and adverse events (AE) in resectable hepatocellular carcinoma.
Authors: Peixoto Renata D'Alpino , Lim Howard John , Ibrahim Fady , Wasan Ellen , Ford Jo-Ann , Liu David M. 
Published: March 2020

e15084 Background: SAP-MS have demonstrated utility in the treatment of hepatocellular carcinoma (HCC) as a bland embolic and have demonstrated the ability to load and release D in vivo. Little is known about its toxicity profile. We aimed to determine if the dose and maximum plasma concentration (Cmax) of D were correlated with occurrence of AE. Methods: A phase II dose-escalation study was performed to systematically evaluate AEs relating to outpatient-based D/ SAP-MS embolization in HCC using a D dose of 0-75 mg. D plasma levels were assessed at multiple time points (0.5, 2, 24 and 675h), in addition to standard analyses of liver and hematologic function. All AEs were reported following the Common Toxicity Criteria Version 3.0. A Pearson product-moment correlation was run to determine the relationship between Cmax and AE. Results: Of 25 patients enrolled, 24 were evaluable (6 = 0mg, 6 = 25mg, 6 = 50mg, 6 = 75mg). The side-effect profile was similar to other abdominal embolization procedures, with abdominal pain (62.5%), fatigue-like symptoms (41.7%), and nausea (41.7%) being the most common AE. There were no correlation between the administered doses of D and all grade AE (r = .209, p .328) or between Cmax's of D and all grade AE (r = .321, p .127). All patients were discharged on the same day. There were no grade 4 or 5 AE and no hepatic decompensation. One patient required hospitalization 7 days post-procedure for groin puncture related complication. Conclusions: In our phase II dose-escalation study, patients experienced minimal post-embolization syndrome, which was not correlated with the amount of doxorubicin administered. The toxicities relating to SAP-MS delivery likely result from the embolic effect as opposed to dose response relating to the use of doxorubicin and can be managed on an outpatient basis. Clinical trial information: NCT01116635.
Factors affecting the administration of adjuvant therapy in patients with pancreatic adenocarcinoma.
Authors: Serrano Aybar Pablo Emilio , Kim Peter Tae Wan , Leung Kenneth , Cleary Sean P. , Gallinger Steven , Greig Paul David , Moulton Carol-anne , Wei Alice Chia-chi 
Published: March 2020

e15087 Background: Adjuvant therapy for pancreatic adenocarcinoma is now considered standard of care. The proportion of patients receiving adjuvant therapy (ADT) following pancreatic resection is a good quality indicator of cancer care. The aim of this study was to evaluate factors associated with receiving ADT in patients with pancreatic cancer. Methods: Between years 2000-2010, all patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma at a single high-volume hepatotopancreatobiliary center were evaluated. The impact of demographic, peri-operative and pathological risk factors affecting the administration of ADT were analyzed using univariate and multivariate logistic regression analysis. Results: There were 258 patients identified. Median age was 65 (37-84) years, 54% were females. There was a 15% margin positivity rate, 14% pancreatic leak rate, 14.7% major complication rate, and 1.2% 90 day/in-hospital mortality rate. Overall, 160/258 (70%) of patients received adjuvant therapy. On multivariate analysis; age, presence of major complications, node-negative disease and earlier era (2000-2004) were significantly associated with a lower probability of receiving ADT. Reasons for not receiving ADT were; patient preference: 20/67 (32%), not recommended: 14/67 (23%), disease recurrence: 12/67 (9.5%) and being medically unfit for ADT: 18/67 (11.5%). None of these reasons were different between time-periods except for fewer patients being offered ADT from 2000-2005 (15.4% vs. 2.5%, p <0.001). Conclusions: Thirty percent of patients do not receive ADT following pancreatectomy. Those with advanced age; node-negative disease and those who had major complications after pancreaticoduodenectomy were less likely to receive ADT. The impact of these factors should be taken into account when considering the administration of ADT.
Clinicopathologic features predicting HER2 overexpression in gastric cancer.
Authors: Park Ji Soo , Jung Minkyu , Kim Hye Ryun , Rha Sun Young , Chung Hyun Cheol , Kim Hyo Song 
Published: March 2020

e15098 Background: HER2-based therapy was found to improve survival outcome of patients with HER2-positive advanced gastric cancer. In gastric cancer, HER2 overexpression is commonly defined as IHC 3+ or IHC 2+/FISH amplification. Because positivity of HER2 overexpression is reported in below 20%, identifying the predictive clinical factors for the HER2 overexpression before the pathologic analysis may be helpful and cost-effective. Methods: From JAN 2005 to DEC 2010, 517 gastric cancer patients performed with HER2 IHC and/or FISH tests at Yonsei University College of Medicine were enrolled. Results: Among the 517 patients, 61 patients (11.8%) were confirmed as HER2 overexpression. Forty three out of stage IV, 258 patients (16.7%) and 18 out of 259 (6.9%) localized gastric cancer patients had HER2 overexpression (p <0.001). HER2 overexpression was more common in male (14.2% vs. 7.5% in female, p-value 0.024), moderately differentiated (26.4% vs. 11.1%, 8.9%, 4.9% and 5.9% in well differentiated, poorly differentiated, signet ring cell, and mucinous, retrospectively, p <0.001). Patients with elevated CEA (> 5.0 ng/mL vs. ≤ 5.0 ng/mL: 24.3% vs. 8.4%, p <0.001), metastasis to distant lymph node (with vs. without: 28.6% vs. 14.8%, p-value 0.042), without carcinomatosis (without vs. with: 21.2% vs. 11.6%, p-value 0.039) and pulmonary metastasis (with vs. without: 47.4% vs. 14.2%, p <0.001) also frequently had HER2-positive disease. In addition, high risk patients with 4 or more of the 7 features (metastatic disease, male, moderate differentiated adenocarcinoma, elevated CEA level, metastasis to distant lymph node, pulmonary metastasis, and without carcinomatosis) had 32.9% of HER2 positivity. (p <0.001). Conclusions: Those clinicopathologic factors may be helpful to predict the high likelihood of HER2 positive cases prior to pathologic confirmation in gastric cancer. Further molecular study for the HER2 overexpression is needed to clarify and explain this clinical phenomenon.
The inflammation based index (IBI) predicts survival advantage after transarterial chemoembolization in hepatocellular carcinoma.
Authors: Adjogatse Delali Akosua , Karamanakos George , Pinato David James , Sharma Rohini 
Published: March 2020

e15101 Background: Transarterial chemoembolization (TACE) is a standard treatment for unresectable, intermediate stage hepatocellular carcinoma (HCC). Survival after TACE, however, can be highly variable, with no suitable biomarker predicting for therapeutic outcome. The inflammation based index (IBI) has previously been shown to independently predict overall survival in all stages of HCC. This retrospective study explored the prognostic ability of the IBI as a predictor of survival after TACE. Methods: Sixty three eligible patients who had undergone TACE for intermediate stage HCC were selected. The IBI was calculated using serum albumin and CRP levels as previously described; giving a score of 0-2, equating to low, intermediate and high risk respectively. Survival was calculated from the date of TACE to date of death. Dynamic changes in the IBI before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model. Results: Patients with a normal IBI prior to TACE had a significant improvement in survival in comparison to those with an intermediate or high-risk score (p=0.02). Other predictors of survival on univariate analysis were radiological response to TACE (p<0.001), pre-TACE CLIP score (p<0.01), initial tumour diameter >5 cm (p=0.049) and AFP > 400 (p<0.001). On multivariate analysis; normalisation of IBI post TACE was associated with improved overall survival, compared to patients showing a persistently abnormal index (p<0.001; HR 5.5, 95% CI 1.9 – 16.5). Conclusions: Normalisation of IBI after TACE is shown to be an independent predictor of survival. Patients with a persistently raised IBI following TACE have a worse survival outcome. As a simple and accessible stratifying biomarker, IBI aides the identification of patients with a significant survival advantage following TACE.
Survival analysis of linitis plastica advanced gastric cancer patients receiving S-1 plus cisplatin.
Authors: Kumekawa Yosuke , Chin Keisho , Osumi Hiroki , Ogura Mariko , Ozaka Masato , Suenaga Mitsukuni , Shinozaki Eiji , Matsusaka Satoshi , Sano Takeshi , Mizunuma Nobuyuki 
Published: March 2020

e15105 Background: Linitis plastica gastric cancer (LPGC) has been known to have worse prognosis than non-LPGC. Clinical trial using molecular targeting agent has been ongoing for LPGC. However it remains unknown whether to be better to change the chemotherapy for the patients. S-1 plus cisplatin (SP) is the standard chemotherapy for previously untreated Japanese advanced gastric cancer (AGC). Methods: To clarify the clinical feature and outcome of LPGC treated with chemotherapy, we retrospectively compared the patients with unresectable or metastatic LPGC and non-LPGC who received SP as the first-line chemotherapy in Cancer Institute Hospital of JFCR between 2007 and 2011. Results: In the period there were 687 patients with AGC who received systemic chemotherapy and 223 (LPGC 63 and non- LPGC 160) patients received SP as first-line chemotherapy. LPGC patients were more frequent in female (44.0% vs. 26.9%; P=0.016). LPGC was more likely to have non-measurable disease (39.7% vs. 14.4%; P<0.001), peritoneal metastasis (73% vs. 35.6% P<0.001), and diffuse type histology (diffuse type 85.7% vs. 56.3%, intestinal type 7.9% vs. 27.5%; P<0.001). LPGC was less likely to have liver metastasis (7.9% vs. 27.5%; P<0.001), and no evaluable distant metastasis in computed tomography (81.0% vs. 93.8%; P=0.010). Other clinicopathological characteristics were follows (LPGC patients vs. non-LPGC patients): median age (57 vs. 62 years), disease status (recurrent 11.1% vs. 18.8%), ECOG PS 0 (81.0% vs. 81.9%), number of metastatic sites (1: 52.4% vs. 46.9, 2: 39.7% vs. 46.9%, ³a3: 7.9% vs. 6.2%), lymph node metastasis (63.5% vs. 70.6%), prior gastrectomy (31.7% vs. 35.6%). They were not significantly different. Median overall survival time is 383 days (95% CI 332-564) in LPGC patients and 473 days (95% CI 412-555) in non-LPGC patients (P=0.363). Median time to treatment failure is 229 days (95% CI 155 - 280) in LPGC patients and 189 days (95% CI 156 -219) in non-LPGC patients (P=0.245). Conclusions: Although clinicopathological backgrounds were not identical, it was suggested that the prognosis of the patients treated with SP was not different between advanced or metastatic LPGC and non-LPGC.
Prevalence of gene amplifications of SOX-2, c-MET, and FGFR1 in Asian patients with esophageal squamous cell carcinoma.
Authors: Huang Ta-Chen , Chen Wei-Wu , Hsu Ta-Wen , Lin Chia-Chi J. , Yeh Kun-Huei , Cheng Ann-Lii , Hsu Chih-Hung 
Published: March 2020

e15127 Background: Amplifications of SOX-2, c-MET, and FGFR1 have recently been recognized as important molecular derangements with therapeutic implication in squamous cell carcinoma of lung. We investigated the significance of these molecular derangements in esophageal squamous cell carcinoma (ESCC). Methods: Locally advanced ESCC patients who had received curative- intent loco-regional therapy and had available pre-treatment endoscopic biopsy tissues at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. DNA was extracted from formalin-fixed paraffin-embedded tissues. Amplifications of SOX-2, c-MET, and FGFR1 were evaluated by quantitative PCR (TaqMan Copy Number Assay, Applied Biosystems, CA, USA), using TERT as a reference gene. Amplification of specific gene was defined as a copy number more than 4. Results: Forty locally advanced ESCC patients, M: F= 39: 1 with a median age of 56 years (range: 37 to 80), were included. The primary tumors located at cervical, upper thoracic, middle thoracic, and lower thoracic esophagus in 2, 9, 23, and 6 patients, respectively; the tumor staging according to AJCC 2002 version was T3N0, AnyTN1, and M1a in 1, 37, and 2 patients, respectively. Amplifications of SOX-2 and c-MET were identified in 14 (35%) and 7 (17.5%) patients, respectively. No FGFR1 amplification was detected. The amplifications of SOX-2 and c-MET were not associated with any known clinical features of the patients, including gender, age (<60 vs ≧60), primary tumor location, clinical stage, and performance status (ECOG 0, 1). Conclusions: Amplifications of SOX-2 and c-MET, existing in significant portions of Asian patients with ESCC, are worthy of exploration as therapeutic targets of ESCC.
Long-term survival after multidisciplinary treatment of small-bowel neuroendocrine tumors with synchronous liver metastases: A single-institute experience.
Authors: Bertani Emilio , Fazio Nicola , Chiappa Antonio , Botteri Edoardo , Spada Francesca , Grana Chiara , Ravizza Davide , Cossu Laura , Bonomo Guido , Andreoni Bruno 
Published: March 2020

e15147 Background: Neuroendocrine tumors (NETs) that originate in the distal jejunum and ileum are commonly diagnosed in stage IV, with liver metastases in 50%-75% of cases. The aim of this study was to ascertain the impact of surgery in a consecutive series of patients with small bowel NET and synchronous liver metastases treated at a single institute. Methods: Ninety-one patients managed between 1995 and 2011 were extracted from the institutional tumor registry. All patients had diagnosis by histology of small bowel NET and synchronous liver metastases. Results: Among the 91 patients 28 (30.8%) underwent primary tumor removal and liver metastases resection or intraoperative termal ablation (Group 1), 54 (59.3%) underwent resection of only the primary tumor (Group 2), and the remaining 9 (9.9%) did not receive any surgery (Group 3). After a median follow-up of 64 months an overall survival (OS) of 93.1%, 81.8% and 76.2% at 3, 5 and 8 years was registered for the whole group. Cancer-specific survival (CSS) was 93.1%, 83.3% and 77.6% at 3, 5 and 8 years, respectively. Five-years OS differed significantly according to the surgical approach (96.0% for Group 1 vs 79.8% for Group 2 vs 48.6% for Group 3, p=0.02). During the course of the illness octreotide was administered in 78 patients (85.7%), peptide receptor radiotherapy in 61 (67.0%), systemic chemotherapy in 21 (23.1%), hepatic artery embolization in 17 (18.7%), interferon in 11 (12.1%), molecular targeted agents in 2 (2.2%). For patients who underwent any surgery (Group 1 and Group 2) the multidisciplinary approach was associated with a better OS (85.7% vs 77.2% 5-years OS, p=0.04). In the multivariate analysis only age was associated with OS, HR: 1.05 (C. I.: 1.01-1.10). The results of CSS were comparable to those of OS. Conclusions: In this metastatic setting of small bowel NETs the 5 year OS was as high as 82% with a maximum benefit achievable for patients who had primary tumor resection and liver disease amenable to surgical or thermal ablation. However, the potential impact of age in prognosis should be carefully considered when choosing the treatment to be delivered in such patients.
Phase II study of biweekly administration of CPT-11 and gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer in Japan.
Authors: Takada Ryoji , Ioka Tatsuya , Ishida Nobuko , Yamai Takuo , Fukutake Nobuyasu , Ashida Reiko , Uehara Hiroyuki , Katayama Kazuhiro 
Published: March 2020

e15150 Background: The current standard therapies for metastatic pancreatic adenocarcinoma in Japan are the single-agent Gemcitabine (Gem) or S-1 and Gem plus erlotinib. Irinotecan (CPT-11) is one of the promising drugs for Gem-refractory PC pts. Both Irinotecan and Gem have shown activity against these diseases with different mechanisms and are non-cross-resistant with each other. Japanese pts have the different metabolism with Irinotecan rather than pts in western countries. Methods: The aim of this phase II study was to evaluate the efficacy and safety of CPT-11 and Gem in Japanese pancreatic cancer pts. Patients with MPC and PS 0-2 were enrolled in this phase II trial. CPT-11, 100mg/m (2), was administered in 90 min. and Gem, 1000mg/m (2), was administered in 30 min. soon after CPT-11 on day1. Chemotherapy was repeated biweekly. Results: From May 2002 to May 2006 40 pts, with median age of 62 (40-74) years, were enrolled in this study. The overall response rate (RR) was 15% with disease control rate of 50%. The median progression-free survival (PFS) was 4.0 months (range: 1.0-15.0 months), and median overall survival (OS) was 7.5 months (range: 3.0-24.0 months). Grade 3/4 anemia, leucopenia occurred in 26.3, 5.2% of pts. The most common non-hematologic toxities were fatigue, diarrhea, nausea/vomiting and anorexia. Grade 3 diarrhea and nausea occurred in 10.5% of pts. Conclusions: The combination chemotherapy with Gem and CPT-11 showed favorable RR as expected and the treatment was manageable in Japanese pts with MPC. We plan to evaluate this combination chemotherapy for MPC pts after progression of FOLFIRINOX in near the future. Clinical trial information: UMIN000009963.
The influence of human papilloma virus (HPV) infection on the outcome of subjects with anal squamous cell carcinoma.
Authors: Batra Anu , Hennings Leah J , James Jennifer D , Siegel Eric R , Govindarajan Rangaswamy 
Published: March 2020

e15152 Background: HPV infection is a risk factor for the development of anal cancer. P16 expression correlates highly with HPV infection. The influence of HPV infection on the outcome of these subjects has not been well defined. To evaluate the influence of HPV infection on prognosis of subjects with anal squamous cell cancer, a retrospective analysis was conducted. Methods: Subjects with anal squamous cell cancer diagnosed at the University of Arkansas for Medical Sciences between 1992 and 2010, were identified from the tumor registry. The charts were reviewed to confirm the diagnosis, stage, treatment and outcome of the subjects. Paraffin tissue blocks of the subjects were stained for p16 expression using the immunoperoxidase method using mouse monoclonal antibody (Clone E6H4) and CINTek Histology VKit. Slides were scanned to digital file (Aperio CS, Aperio, Vista, CA). Neoplastic regions were analyzed using a color deconvolution algorithm (Aperio). Based on the percentage of pixels with weak, moderate, strong, and negative staining, each slide was given a score between 0-300. Score of 150 and above was designated as positive. P16 positive and negative groups were compared for differences in recurrence-free survival (RFS) and overall survival (OS) via log-rank test. Results: There were 19 deaths observed among 33 study-eligible subjects during 103.2 person-years of follow-up. The median age (quartiles) was 53 (45-61) years. Males were 55%; Caucasians were 94%. All subjects were treated with chemotherapy and radiation. 26 subjects were p16 positive and 7 were p16 negative. The median RFS was 2.99 years for the p16-positive group vs. 1.90 years for the p16-negative group (p = 0.32). The median OS was 3.14 years for p16-positives vs. 2.00 years for p16-negatives, (p = 0.52). Conclusions: 78% of the patients with anal squamous cell cancer in our study were p16-positive. The RFS and OS tended to be longer for patients with p16-positive cancer, but the lack of statistical significance might be explained by the small number of p16-negative subjects. A larger study needs to be conducted to further evaluate the difference. [Table: see text]