bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amrubicin monotherapy for patients with platinum-refractory gastroenteropancreatic neuroendocrine carcinoma.
Authors: Ando Takayuki , Hosokawa Ayumu , Yoshita Hiroki , Ueda Akira , Kajiura Shinya , Mihara Hiroshi , Nanjo Sohachi , Fujinami Haruka , Nishikawa Jun , Sugiyama Toshiro 
Published: February 2017

328 Background: Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, because studies on salvage chemotherapy are limited, its role remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods: Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2006 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results: Eight males and two females ((median age, 67 years (range, 52–78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. A total of 30 cycles of amrubicin was administered in 10 patients, with a median number of cycles per patients was 2.5 (range, 1-7). Median progression-free survival (PFS) and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Two patients with partial response had characteristics of NEC with a high Ki-67 index (99% and 89%, respectively) and had received cisplatin and irinotecan as first-line treatment. Grade 3–4 neutropenia and anemia were observed in four (40%) and five (50%) patients, and they were manageable in all cases by careful monitoring of myelosuppression and appropriate dose reduction of amrubicin. Conclusions: Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.
The antitumor effect of epigallocatechin-3-gallate on gastroenterological cancer.
Authors: Iwahashi Shuichi , Shimada Mitsuo , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Arakawa Yusuke , Saito Yu , Yamada Shinichiro , Yismaw Gizachew 
Published: February 2017

335 Background: Green tea is one of the most popular beverages it contains many catechins such as epigallocatechin-3-gallate (EGCG) inhibits cancer growth. The aim of this study was to elucidate the anti-tumor effect and the effect for spheres of EGCG. Methods: Human hepatoma-derived cell line (HepG2) and human colorectal carcinoma cell line (HCT-116) were used. The anticancer effects of EGCG was studied by MTT assay. We made cancer sphere from HepG2 cells, and we added EGCG to cancer sphere. And we compared the gene expressions of RT-PCR between normal HepG2 and cancer sphere groups. Results: EGCG had the anti-tumor effect in dose-dependent. Furthermore, EGCG cancelled this spheroid formation, EGCG down-regulated the Nanog and CD133, related stemnesss genes. And then, EGCG down-regulated the ABCG1and Nek2, related ABC transporter genes, expression in sphere. Conclusions: EGCG had the anti-tumor effects on gastroenterological cancer, and EGCG had the effect to sphere, same as cancer stem cell thorough the down-regulation of ABC transporter related genes. Therefore, EGCG might be used as the safe and novel antitumor agents.
Gastrointestinal metastases from melanoma: Does surgical resection improve survival when performed in combination with immunotherapy?
Authors: Deutsch Gary B. , Kirchoff Daniel D. , Bailey Mariel , Vitug Sarah , Flaherty Devin C. , Foshag Leland Jay , Bilchik Anton , Faries Mark B. 
Published: February 2017

340 Background: Prior studies have shown the benefits of metastasectomy and more recently, immunotherapy, in Stage IV melanoma. We report the largest series of gastrointestinal (GI) melanoma metastases, in order to clarify the role of surgical resection in the setting of systemic treatment options. Methods: A review of our institutional melanoma database identified all patients with hollow viscus GI metastases diagnosed between 1971 and 2013. Patient age and sex; primary tumor location, thickness and ulceration; GI-metastasis free interval; and types of treatment were analyzed. The primary endpoint was melanoma-specific survival (MSS), measured from the diagnosis of GI metastases. Survival analyses compared combination therapy to immunotherapy (i.e. vaccine, interleukin-2, interferon, ipilimumab) or surgery alone. Operative patients were further stratified by surgical intent (curative or palliative). Results: The 393 study patients had a median GI-metastasis free interval of 49.5 (0 – 416.0) months from the initial diagnosis; their mean age at GI metastases was of 53.5 ± 14.1 years. Median MSS was 20.0 months with surgery plus immunotherapy (n=160), 13.0 months with surgery alone (n=111), 8.0 months with immunotherapy alone (n=64), and 5.0 months with neither treatment (n=58) (p<0.001). By multivariable analysis, age at GI metastasis diagnosis (HR=1.014; p=.014), truncal melanoma site (HR=1.659; p=.017), immunotherapy (HR=0.675; p=.030), and metastasectomy (HR=0.544; p<.001) were significant predictors of MSS. Surgical intent was known in 98 patients: curative surgery had a median MSS of 30.0 months (n=49) and palliative surgery had a median MSS of 12.0 months (n=49) (p=.015). Conclusions: Treatment of GI melanoma metastases should use a combination of metastasectomy and immunotherapy, instead of either modality alone. Select patients are likely to obtain an enhanced benefit from GI metastasectomy, specifically curative surgery, in the setting of newer immunotherapy options.
Surgical outcomes of patients with pancreatic cancer treated with stereotactic body radiation therapy.
Authors: He Jin , Moningi Shalini , Blair Alex B , Zaki Ahmed , Laheru Daniel A. , Cameron John L. , Pawlik Timothy M. , Weiss Matthew J. , Wolfgang Christopher Lee , Herman Joseph M. 
Published: February 2017

341 Background: The surgical outcome of patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BRPC/LAPC) treated with stereotactic body radiation therapy (SBRT) is unclear. Methods: A comparative study was performed to determine if surgical outcomes were different among patients receiving neoadjuvant SBRT vs chemoradiation therapy (CRT) vs chemotherapy only. Results: Between 2011 and 2014, 29 patients with BR/LA-PDAC underwent neoadjuvant chemotherapy and SBRT (6.6 Gy x 5 fractions) followed by pancreatectomy. Eighteen of 29 patients (62%) had LAPC. Their outcomes were compared with 82 patients who received neoadjuvant CRT and 26 patients who received neoadjuvant chemotherapy only (Table). When compared to neoadjuvant CRT and chemo only, the neoadjuvant SBRT group had a higher R0 resection rate (90% vs 84% vs 62%, p=0.02) and vascular resection rate (41% vs 13% vs 31%, p=0.005), respectively. Although the vascular resection and complication rates (Clavien grade 3 or above) were higher in the neoadjuvant SBRT group, no in-hospital mortality was encountered. In the SBRT group, the complete pathological response rate (21%) was higher than that of the other groups (4% and 0% respectively, p<0.001). Survival will be updated later as the current median postoperative follow-up is 6 months in the SBRT group. Conclusions: Neoadjuvant chemotherapy and SBRT is associated with improved surgical outcomes and pathologic complete response rates in selected patients with BRPC/LAPC. Longer follow-up is needed to determine its impact on survival. [Table: see text]
Liver resection and outcome of hepatocellular carcinoma (HCC) in a transplant center.
Authors: Barzi Afsaneh , Cao Shu , Genyk Yuri , Kahn Jeffrey , Wallman Melissa A , El-Khoueiry Anthony B. 
Published: February 2017

350 Background: HCC has rising incidence and mortality in the US. Liver transplantation and surgery are the definitive treatment options. The median time to liver transplant in California is longer than many other regions. Given the expertise of our surgeons in liver resection we investigated the outcome of HCC at our institution. Methods: We extracted Norris Cancer registry data for patients (pt) with diagnosis of HCC from 2000 to 2010 who received their initial treatment at our facility. Overall survival (OS) is the primary end point of this study. We classified pt into transplant candidates (TC) vs. non-transplant candidates (NTC) based on the combination of T stage and vascular involvement. Results: We identified a total of 497 pts with HCC (Table). 98 pts had incomplete staging and 20 had metastatic disease and excluded from the analysis. We classified 221 pts as TC and 158 pts as NTC. The median OS for the TC was 2.9 years (yr) (95% CI 2.1-3.9) and in the NTC was 1.4 yr (95% CI 1.1 – 1.6). Amongst TC, 44 received transplant, 33 had surgical resection, and 144 had loco-regional treatment. Transplant recipients had an OS of 9.7 yr versus 4.3 yr (95% CI 1.9-9.1) in surgical patients, those with no definitive treatment had a OS of 1.8 yr (95%CI 1.6 -2.3). Among TC Hispanics had the best OS 4.3 yr (95% CI 1.9 – 9.7), followed by Asians 4.0 (95% CI 2.4-5.8), and Whites 2.0 (95% CI 1.4 -2.7) (p-value 0.0125). Among NTC Hispanics had the best OS 1.8 yr (95% CI 1.3 – 2.6), Asians 1.5 (95% CI 1.0 -2.1), and Whites 1.0 (95% CI 0.7 -1.4) (p-value 0.079). Conclusions: Liver transplantation continues to offer the best survival outcomes; however, in a region with long wait times, surgical resection offers a reasonable alternative with favorable survival outcomes. The trend of superior survival amongst Hispanics is noteworthy and subject of further investigation at our center. [Table: see text]
Characterization of HER2 testing and treatment patterns among patients with gastric cancer in the United States using the Oncology Services Comprehensive Electronic Records (OSCER) database.
Authors: Lowe Kimberly A , Reich Adam , Bobiak Sarah , Chau Dina , Quigley Jane M , Kelsh Michael A. 
Published: February 2017

36 Background: There is a paucity of data related to HER2 testing and treatment patterns among gastric cancer patients in a real-world setting. Our primary objectives were to (1) identify the proportion of gastric cancer patients who received HER2 testing, the proportion of patients with HER2+ve tumors, and the proportion of HER2+ve patients who received trastuzumab; (2) describe treatment patterns among gastric cancer patients, including the proportion of patients who received surgery and/or radiation with chemotherapy; (3) identify the proportion of patients who received singlet, doublet, or triplet chemotherapy treatments and specific first- and second-line regimens. Methods: The study participants were randomly selected to undergo a detailed chart review from a source population of patients included in the OSCER database who were diagnosed with gastric cancer from 2009 to 2013. OSCER is a data warehouse of electronic medical records from 565 community and hospital-affiliated oncology clinics in the U.S. from 2004 forward. All patients were required to have metastatic gastric cancer at the time of the chart review and have been treated with chemotherapy to be included. Descriptive statistics were used to characterize HER2 testing and treatment patterns. Results: The study patients (n=238) were mostly male (62%), Caucasian (58%), >65 years of age (57%), with the following stage distribution at diagnosis (Stage II: 7%; Stage III: 11%; Stage IV: 63%; unknown: 19%). HER2 testing was documented in n=121/238 (51%), of which n=30/121(25%) were HER2+ve. Among HER2+ve patients, n=20/30 (67%) received trastuzumab. Of the total sample (n=238), 79% were treated with only chemotherapy, 4% received chemotherapy and surgery, 15% received chemotherapy and radiation, and 2% received all three treatments. First-line treatment was as follows: singlet (17%); doublet (33%), triplet (38%), other (12%). Conclusions: Only half of patients were tested for HER2 status; however, the use of trastuzumab among HER2+ve patients was high. Chemotherapy alone was the primary treatment in this population.
Radiotherapy in locally advanced pancreatic cancer: SEER experience.
Authors: Mahipal Amit , Sajjad Monique Z. , Denson Aaron , Shridhar Ravi , Springett Gregory M. , Batra Sachin 
Published: February 2017

364 Background: Pancreatic cancer is the fourth most common cause of cancer deaths in the US. Despite the fact that the radiotherapy in addition to chemotherapy is frequently employed, the role of radiation therapy in the treatment of locally advanced pancreatic cancer (LAPC) remains controversial. The majority of the data evaluating the efficacy of this approach is derived from small randomized trials. Methods: The Surveillance, Epidemiology and End Results (SEER) registry dataset from 2004-2011 was queried to identify patients with locally advanced pancreatic adenocarcinoma. Pts with survival <2 months, unknown radiation status and those who received post-operative radiation were excluded. Multivariate analysis of prognostic factors related to survival was performed using a Cox proportional hazard regression model. Results: We identified 4,460 patients that met the inclusion criteria; 59% of pts received radiation and 41% did not. The two groups were similar with respect to gender, race and tumor differentiation. Pts in the radiation group were younger (ages<65: 49% vs. 38%), had smaller tumor size (largest dimension <4.5 cm: 80% vs. 75%), lesser lymph node involvement (33% vs. 36%) and lower rate of surgical resection (4% vs. 9%). Radiation treatment, age, tumor grade and surgical resection were significantly associated with survival on univariate analysis. Patients who received radiation therapy had better survival (median OS: 11 vs. 7 months; HR: 0.77; 95% CI 0.69-0.78). On the multivariate analysis, radiation was independently associated with improved survival (Table). Conclusions: In this population-based registry, radiation therapy was associated with improved survival in patients with LAPC in both univariate and multivariate analysis. Larger randomized trials are needed to confirm these findings. The optimal schedule and type of radiation therapy remains unknown. [Table: see text]
Evaluation of liver toxicity using Child-Pugh, MELD, and MELD-Na following stereotactic body radiation therapy (SBRT) of hepatocellular carcinomas.
Authors: Lu Louis , ElAlfy Eman , Wahl Daniel , Stenmark Matthew H. , Lawrence Theodore Steven , Feng Mary Uan-Sian 
Published: February 2017

365 Background: Radiation-induced liver disease (RILD) has been tracked when assessing the safety of fractionated liver radiotherapy. However, due to the rarity and severity of events, a more sensitive measure of liver damage is necessary. This study characterizes the time course of changes in generalizable measures of liver function as potential toxicity metrics. Methods: In this IRB-approved retrospective study, the records of 63 patients with 87 HCC tumors treated with SBRT at the University of Michigan between 2006 and 2012 were reviewed. Changes in Child-Pugh (CP), MELD, and MELD-Na were analyzed using the Student t test and chi-squared test. Results: 83% of the patients had cirrhosis, 62% hepatitis (hep) C, 7% hep B, 25% alcoholic, and 13% other. 83% had prior liver-directed therapy. 24% had >1 tumor concurrently treated with SBRT. Median tumor size was 2.3 cm (0.7-10), gross tumor volume was 9.2 cc (0.6-469), and mean liver dose-GTV was 4.4 Gy (0-17.6 Gy). Prior to SBRT, 73% were CP A, 25% CP B, and 2% CP C. Median baseline CP, MELD, and MELD-Na were 5, 9, and 10. Mean CP increases after 3, 6, 9, and 12 months were 0.84, 1.79, 1.72, and 1.33; increases in MELD 1.47, 2.88, 5.38, and 3.91; increases in MELD-Na 1.45, 2.03, 4.24, and 2.48. All changes were significantly increased from baseline. On univariate analysis, >1 tumor and cirrhosis predicted for a 1+ point increase in CP and >1 tumor and higher mean liver dose-GTV for a 2+ point increase in CP. Older age, >1 tumor, smaller GTV, and smaller max tumor dimension predicted for a 10+ point increase in MELD and >1 tumor, hep C cirrhosis, and higher baseline MELD-Na for MELD-Na. Patients treated concurrently to >1 tumor had greater increases in CP (3.60 vs. 0.81), MELD (9.33 vs. 1.97), and MELD-Na (8.47 vs. 2.19), p < 0.0001 for all, compared to those with 1 tumor. No differences were seen with gender, portal vein thrombosis, number of prior treatments and baseline Child-Pugh classifications. Conclusions: We describe a time course and predictive factors for change in CP, MELD, and MELD-Na scores after SBRT for HCCs. These should be investigated further for potential use in toxicity modeling after incorporating dosimetric parameters.
The incidence and clinicopathologic features of metachronous gastric tumors after endoscopic submucosal dissection.
Authors: Park Sung Won , Lee Yun Ho , Kim Dae Young , Bae Song I , Yoon Won Jae , Ryu Soo Hyung , Kim You Sun , Moon Jeong Seop 
Published: February 2017

37 Background: Endoscopic submucosal dissection (ESD) has become a standard method of treatment for gastric tumors. The synchronous and metachronous development of two or more primary adenocarcinomas occurs in 10 to 20% of all cases of stomach cancer. Therefore, metachronous recurrence should be a consideration after ESD has been performed. The aim of this study was to review our experiences in the management of patients with synchronous and metachronous lesions, and to evaluate their incidence and clinicopathologic features. Methods: We reviewed 194 patients who underwent ESD for gastric tumors between January 2007 and December 2011. Synchronous lesions were defined as secondary gastric tumors detected within 6 months after the initial ESD. Metachronous tumors were defined as those detected more than 6 months after the initial ESD. We investigated the incidence and clinicopathologic features of synchronous and metachronous tumors after ESD. Results: In total, 20 patients (10.3%) had synchronous lesions and 19 patients (9.8%) had metachronous lesions. The annual incidence of metachronous tumors after ESD was 2.93%. The median period until discovery after initial ESD was 40.1 months. Female patients developed synchronous and metachronous tumors more frequently than male patients (p = 0.037). Patients with H. pyloriinfections developed tumors more frequently than those without (p = 0.04). There were no significant differences with respect to the type and differentiation of tumors. Conclusions: Synchronous and metachronous lesions of gastric tumors were considerably prevalent after ESD. Considering the results of this study, careful endoscopic investigation should be performed after ESD for female patients and those with H. pylori infections. However, further large-scale and longer prospective studies are needed.
Utilizing Ki67 score to predict optimal liver-directed treatment in patients with metastatic neuroendocrine tumors.
Authors: Singla Smit , Attwood Kristopher , Levea Charles , Tomaszewski Garin , Kuvshinoff Boris W. , Iyer Renuka V. 
Published: February 2017

370 Background: Patients with metastatic neuroendocrine tumors (NETs) benefit from treatment with yttrium-90 radioembolization (Y-90) or transarterial chemoembolization (TACE), however the criteria for patient selection are not well defined. We sought to determine if the proliferative index (Ki67 score) could be utilized to select patients for one therapy over the other. Methods: A single institution analysis of all patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 scoring, and the data was analyzed using multivariate association for survival outcomes. Results: Amongst 72 patients (M: 39, F: 33; median age, 57 years) included in the study, the most common site of tumor origin was small bowel (n=35, 49%), and the most common histology subtype was carcinoid (n=58, 85%). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) in the TACE group. In Y-90 group, there was a higher concomitant use of sandostatin (94% vs 75%, p=0.023), longer time between diagnosis and treatment (median, 32 vs 11 months, p=<0.001), and less number of total treatments completed (89% vs 46%, p<0.001). There was no significant difference in overall survival (OS) between the groups (median, 69 vs 82 months, respectively; p=0.477); however when adjusted for Ki67 score of 3, patients with Ki67 score >3% were found to have better OS when treated with Y-90 as compared to TACE (HR, 0.083; CI, 0.008-0.854). On the other hand, in patients with Ki67 <3%, OS was better when treated with TACE (HR, 13.5; CI, 1.2-148.8). Further, patients in Y-90 group had higher incidence of carcinoid syndrome (39% vs 21%, p=0.195) and bilobar liver disease (95% vs 89%, p=0.371), whereas hepatic tumor burden >25% was greater in the TACE group (26% vs 20%, p=0.614), but these differences were not significant. Conclusions: In patients with metastatic NETs, Ki-67 score >3% may be predictive of treatment benefit with Y-90 and <3% with TACE. A longer time from diagnosis and an increased number of prior therapies may indicate a need for aggressive therapy; however a prospective validation is warranted.
Investigating autophagy and glutamine metabolism as therapeutic targets for pancreatic cancer.
Authors: Jardon Mario , Kalloger Steve , Iggulden Christina , Erro Go Nancy , Sathiyaseelan Paalini , Yapp Donald , Renouf Daniel John , Schaeffer David , Gorski Sharon 
Published: February 2017

381 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, for which new therapeutic approaches are urgently needed. We are developing novel combination therapy approaches based on the inhibition of glutamine metabolism and autophagy, to improve current treatments for PDAC. Since both processes are key mediators of multiple cancer hallmarks, and have inter-related but non-redundant roles, this combination may result in a more efficient disruption of cancer cell resistance to treatments. Methods: We interrogated the Pancreas Centre BC tissue micro-array, containing the epithelial component of 252 PDAC samples, for expression of three key glutamine-metabolizing proteins and two autophagy-related proteins: glutamine synthetase (GLUL), asparagine synthetase (ASNS), glutaminase C (GLS-GAC), microtubule-associated protein 1 light chain 3 beta (MAP1-LC3B or LC3B) and autophagy-related protein 4B (ATG4B). While previous efforts by other groups have focused on GLS-GAC, the role of GLUL in cancer has remained less well understood. We thus investigated the functional relevance of GLUL using a panel of PDAC cell lines. We are also investigating interactions between glutamine metabolism and autophagy, including the exploration of strategies to target GLUL and the evaluation of a new class of ATG4B inhibitors for the treatment of pancreatic cancers. Results: We found that GLUL, ASNS, GLS-GAC, LC3B and ATG4B were expressed in 31%, 58%, 99%, 51% and 73%, respectively, of PDAC samples. Furthermore, higher LC3B expression correlated with poor outcome. Our functional studies revealed that various PDAC cells express GLUL, which can be upregulated upon glutamine deprivation. In all cell lines tested, GLUL knockdown sensitized them to gemcitabine, as assessed by a long-term recovery assay. We also found that the candidate ATG4B inhibitors, shown to inhibit this target in cell-free assays, effectively inhibit PDAC cell proliferation at micromolar concentrations. Conclusions: Our study reveals that glutamine metabolism and autophagy are clinically relevant in PDAC and may have potential as therapeutic targets. Supported by Pancreas Centre BC, BC Cancer Foundation and VGH Foundation.