bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of aggressive surgical debulking in older adults with gastrointestinal neuroendocrine tumors.
Authors: Jutric Zeljka , Lewis Aaron G , Raoof Mustafa , Ituarte Philip HG , Singh Gagandeep , Li Daneng 
Published: March 2017

377 Background: Carcinoid and neuroendocrine tumors are often diagnosed in older adults. However, limited evidence currently exist regarding the role of aggressive surgical debulking of primary gastrointestinal-neuroendocrine tumors (low to medium grade-pancreas, small bowel, colorectal) (GI-NETs) in older adultsage > 70 years. Methods: Patients age 70 years or older with a diagnosis of GI-NETs were identified using the California Cancer Registry between the years 2000 to2012. Linkage to patient discharge records provided information including resection of primary site (RPS), resection of liver metastases (LR), and liver directed therapy (LDT). Treatment group effects on overall survival (OS) were compared by Cox proportional hazard models. Results: A total of 2,039 patients were identified. Among the 1,661 patients without metastases, 74% (n = 1,234) received RPS and demonstrated improved survival (HR 0.50, p < 0.001) compared to those without RPS. Of the 378 number of patients with liver metastases, LDT alone (n = 23) was not significantly associated with survival (HR 0.65, p = 0.082). Reduced risk was similar for RPS alone (n = 149; HR 0.44, p < 0.001) when paired with LDT (n = 17, HR 0.45, p = 0.007). RPS with LR, either with or without LDT, indicated the greatest impact in survival risk (n = 25; HR 0.14, p < 0.001). Conclusions: Surgical management of the primary tumor and liver metastases in older adults age > 70 years with GI-NETs demonstrated a significant survival benefit.Aggressive surgical debulking should be considered among older adultsage > 70 years. Future studies among older adults with GI-NETs are warranted to better identify patients most likely to benefit from aggressive surgical management.
The efficacy and safety of sunitinib in patients with advanced well-differentiated pancreatic neuroendocrine tumors.
Authors: Raymond Eric , Kulke Matthew H. , Qin Shukui , Schenker Michael , Cubillo Antonio , Lou Wenhui , Tomasek Jiri , Thiis-Evensen Espen , Xu Jianming , Racz Dr. Karoly , Croitoru Adina E , Khasraw Mustafa , Sedlackova Eva , Borbath Ivan , Ruff Paul , Oberstein Paul Eliezer , Ito Tetsuhide , Fernandez Kathrine C. , Rosbrook Brad , Fazio Nicola 
Published: March 2017

380 Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings. Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing. Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥ 20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%). Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib. Clinical trial information: NCT01525550.
A phase I study of mFOLFOX6 and ADI-PEG-20 in patients (pts) with advanced hepatocellular carcinoma (HCC) and other gastrointestinal (GI) malignancies.
Authors: Harding James J. , Lowery Maeve Aine , Uhlitskykh Khrystyna , Wan Peter Justin , Hamilton Casey R , Barba Adalberto , Liu Kay Chia-Wei , Johnston Amanda , Bomalaski John S. , O'Reilly Eileen Mary , Saltz Leonard , Abou-Alfa Ghassan K. 
Published: March 2017

384 Background: ADI-PEG-20 (pegylated arginine deiminase), an arginine degrading enzyme, and FOLFOX each exhibit clinical activity in a HCC pt subset. Preclinical data indicate that arginine depletion interferes with folate and pyrimidine metabolism as well as DNA damage repair pathways, suggesting a role for pairing AGI-PEG-20 with cytotoxic chemotherapy. Methods: This is a single center phase 1 trial of mFOLFOX-6 and ADI-PEG-20 in treatment-refractory advanced GI tumors to assess safety and tolerability, and to identify the recommended phase 2 dose (R2PD). mFOLFOX6 was administered intravenously biweekly at standard fixed doses and ADI-PEG-20 intramuscularly weekly at 18 or 36 mg/m2. Toxicity was assessed by CTCAE v4.03 and efficacy by RECIST v1.1. A HCC RP2D expansion was completed to explore efficacy. Serum arginine, citrulline, and anti-ADI-PEG-20 antibodies were monitored every other week. Results: 17 pts were treated—7 pts with GI tumors in dose escalation and 10 HCC pts in RP2D dose expansion. Histologies included HCC (13), pancreatic (3) and fibrolamellar carcinoma (1). All HCC pts had Child-Pugh A liver function and had progressed on sorafenib. Treatment-related grade ≥ 3 laboratory adverse events (AEs) occurred in 47% of pts, including neutropenia (4), thrombocytopenia (3), anemia (2), lymphocytopenia (2) and hyponatremia (1). Treatment-related grade ≥ 3 clinical AEs occurred in 2 pts, notably grade 3 fatigue and a grade 3 cardiac event not otherwise specified. No dose limiting toxicities, treatment-related deaths, or cases of hepatic failure were observed. Efficacy data for the 13 HCC pts revealed 3 (23%) PR, 6 (46%) SD, 3 PD and 1 NE. Arginine levels were depleted with therapy (mean ± SEM: baseline 85.3 ± 13.0 uM, 8 wks 4 ± 3.0 uM, 16 wk 1.1 ± 0.8uM). Anti-ADI-PEG-20 antibodies were not detected at 8 weeks (mean ± SEM: baseline 0.7 ± 0.5, 8 wks 1.5 ± 1). Conclusions: Concurrent mFOLFOX6 plus ADI-PEG-20 intramuscularly at 36 mg/m2 weekly shows an acceptable safety profile with rapid and durable reduction in serum arginine. Further evaluation of this combination is warranted in advanced HCC pts. Clinical trial information: NCT02102022.
Treatment patterns of gastrointestinal neuroendocrine tumors (NET).
Authors: Broder Michael S. , Chang Eunice , Cai Beilei , Neary Maureen , Papoyan Elya , Benson Al Bowen 
Published: March 2017

387 Background: NET comprise a broad set of rare tumors. Almost 2/3 arise in the gastrointestinal (GI) tract. NCCN guidelines for unresectable GI NET recommend somatostatin analogues (SSA) first, however, guidelines do not recommend a particular sequence for remaining therapies. Our objective is to describe real world treatment patterns of GI NET. Methods: This retrospective study combined 2 claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included SSA, cytotoxic chemotherapy (CC), targeted therapy (TT), interferon (IF) and combinations. Patients ≥ 18 years, with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who received pharmacologic treatment from 7/1/09-6/30/14 were identified. A 6 month clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment. Results: We identified 2,258 newly treated GI NET patients. 59.6% started first line therapy with SSA monotherapy, 33.3% CC, 3.6% TT, and 0.5% IF. The remainder received combination therapies. Mean follow up was 576 days. Mean duration of first line therapy was 361 days for all newly treated patients (449 SSA, 215 CC, 267 TT). 58.9% of patients had no subsequent pharmarcological treatment after discontinuation of first line therapy.The most common second line was combination therapy with SSA (i.e., CC or TT added). In patients who did not begin with SSA, most received SSA as second line. In graphical pattern analysis, there was no clear pattern visible after first line therapy. Conclusions: More than 1/2 of pharmacologically treated patients began treatment with SSA and 1/3 with CC, with duration of use > 1 year and just over 6 months, respectively. We found treatment patterns after first line were unclear, and more than 1/2 of patients had no subsequent pharmacological treatments after discontinuing first line therapy. It is unclear whether there is underutilization of the pharmacological therapy or this is due to stable disease status after alternative non-pharmacological treatment. Future studies directed at understanding treatment patterns using patient medical records are warranted. As new treatments emerge, reassessment of treatment patterns may be needed.
NM 23-H1 gene expression of a migration suppressor in gastric lymphoma.
Authors: Kim Il 
Published: March 2017

39 Background: We previously describedthat the NDPK-A(nucleoside diphosphate kinase A) contributes variably to the migration of cancer cell. To investigate the role of the NDPK-A in gastric lymphoma, we evaluated the expression of NDPK-A in two different cancer cell lines of the same gastric lymphoma patient. Methods: The primary cell line of gastric lymphoma, RF-1, was cultured from the primary gastric lymphoma site, and the other cell line RF-48 was metastasized to the peritoneum of the same patient after 6 months. We have generated stable gastric lymphoma transfectants, pIRES-NDPKA-GFP-neo, that constitutively over-express transfected and vector form of NDPK-A, in addition to a reporter, green fluorescent protein(GFP). The transfected gastric lymphoma cell migration assay was performed 24-well modified chemotaxis chambers with FluroBloc membrane. Results: In regard to the migration rate of the gastric lymphoma cell lines, RF-1 vector was 75.8±7.5%, RF-1 transfected was 54.4±12.3%, RF-48 vector was 84.7±15.4%, RF-48 transfected type was 62.3±9.2%, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type. NDPK-A was presented more in RF-1 than RF-48, and presented more in the transfected type than the vector type, and concerning the migration rate, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type. Conclusions: Concerning NM 23-H1 gene encodes the NDPK-A in gastric lymphomas, more abundant was NDPK-A, poorer was migration, and thus it played a role of the suppressor of migration. Our analysis of pooled data found that NDPK-A acts as a migration suppressor in gastric lymphoma.
Treatment patterns among patients with metastatic GEP-NET treated at a tertiary referral center.
Authors: Jalbert Jessica J , Casciano Roman , Tao Biwen , Dutton Trevor , Brais Lauren K. , Pulgar Sonia J. , Berthon Anthony , Gabriel Sylvie , Dinet Jerome , Kulke Matthew H. 
Published: March 2017

397 Background: Treatment options for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NET) have been increasing. We describe treatment patterns among patients with advanced GEP-NET evaluated at a tertiary referral center. Methods: We conducted a cohort study of patients with well-differentiated GEP-NET recruited between June 2003-May 2015 from Dana-Farber Cancer Institute’s (DFCI) gastrointestinal clinic, using data from an institutional research database and the electronic healthcare records of DFCI and partner hospitals. Patients were required to have been evaluated ≥ 2 at DFCI and to be diagnosed with metastatic GEP-NET. Medications were categorized as cytotoxic agents (CA), angiogenesis inhibitors (AI), mTOR inhibitors (mTORI), interferons (IFN), somatostatin analogues (SSA), or investigational therapies (IT). Combination therapy (combo) was defined as treatment overlap by ≥ 30 days. Results: Among 682 patients (mean age [SD]: 58.5 [11.9], 50.1% male, 96.5% white, 44.9% midgut NET, 28.7% pancreatic NET, 38.9% carcinoid symptoms, and 62.6% with < 1 year since metastatic GEP-NET diagnosis), 89.0% initiated ≥ 1 GEP-NET medication. First line treatment distribution was: 59.5% SSA, 17.5% SSA combo, 14.8% CA, 3.0% IT, 2.8% non-SSA combo, 1.2% AI, 0.7% IFN, and 0.5% mTORI. Among patients on first line SSA monotherapy, 68.4% remained on treatment until death or end of follow-up. Of the 296 patients advancing to second line treatments, 90.5% took SSAs (13.5% monotherapy and 77.0% combo), of which 95.9% were continuing their first line SSA treatment. 86.7% of third line therapy patients (157/181) were on SSAs (6.6% monotherapy and 80.1% combo), all of which had initiated SSAs as first or second line treatment. Most common SSA combo therapy was with CA, followed by with AI. Conclusions: SSA monotherapy and SSA combination therapy with CA were the most common treatments for metastatic GEP-NET between 2003 and 2015. Sustained SSA use was frequent, reflecting the continuous nature of SSA use throughout the disease course.
The effect of sorafenib (S) starting dose and dose intensity on survival in patients with advanced hepatocellular carcinoma (HCC).
Authors: Alghamdi Mohammed Abdullah , Lee-Ying Richard , Swiha Mina , Chan Kelvin K. , Cheung Winson Y. , Ho Maria , Tam Vincent C. 
Published: March 2017

400 Background: The SHARP trial showed that S improves survival in advanced HCC. In clinical practice full dose (FD) of S at 400mg bid can be difficult to tolerate and so a reduced dose (RD) is often required. The purpose of this study was to determine whether starting dose or dose intensity of S affects survival in patients with HCC. Methods: All patients treated with S for HCC in Alberta, Canada from January 2008 to July 2016 were included in this study. Patient demographics, clinical, tumor characteristics, S starting dose and dose intensity were collected and analyzed. Patients were dichotomized into starting FD or RD of S. A mean dose intensity of > 75% and < / = 75% were considered normal and reduced, respectively. Survival outcomes were assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox-proportional hazard model was constructed with starting dose, dose intensity and relevant clinical and pathologic factors to assess their impact on survival. Results: A total of 156 patients were included. Median age was 63, 78% were men, 34% were East Asian, 77% were Childs-Pugh A, and the most common causes of liver disease were hepatitis B (30%) and C (30%). Most patients had EGOG performance status of 0 and 1 prior to starting S (29% and 62%, respectively). S was started at FD in 58% of patients and 50% had a dose intensity > 75%. The median survival for both starting FD and RD was 10.3 months, and not significantly different (p = 0.14).The median survival for a dose intensity > 75% vs < / = 75% was 10.7 vs 9.5 months, respectively (p = 0.76). In multivariable models that adjusted for demographic, stage, performance status and liver function, starting dose (HR 0.8 95%CI 0.5-1.2) and dose intensity (HR0.9 95% CI 0.6-1.4) were not associated with survival. Conclusions: Starting S with a RD may be a reasonable strategy for HCC, since it does not appear to impact survival. Also, dose intensity did not impact survival, suggesting that additional dose modifications may not compromise effectiveness. Though limited by small numbers, we are planning to confirm these findings in a larger, pan-Canadian dataset.
Effectiveness and safety of sorafenib for unresectable and advanced intrahepatic cholangiocarcinoma: A pilot study.
Authors: Luo Xiangji , Jia Weidong , Huang Zhiyong , Li Xiangcheng , Xing Baocai , Jiang Xiaoqing , Li Jun , Yang Tian , Gao Chunfang , Lau Wan Yee , Shen Feng 
Published: March 2017

405 Background: Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of the multikinase inhibitor, sorafenib, combined with best supportive care (BSC) in these patients. Methods: Forty-four patients with unresectable and advanced ICC were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12; secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs). Results: The DCR at week 12 was 15.9%. The median TTP was 5.6 months, and the median PFS and OS were 3.2 and 5.7 months (95% confidence interval [CI]: 2.4-4.1 months; 3.7-8.5 months), respectively. The median DOT was 1.8 months (95% CI: 1.9-3.9 months). Grades 1 and 2 AEs occurred in 75% of patients, and one grade 4 AE (hand and foot skin reaction) was observed in one patient. Conclusions: This is the first and only prospective pilot study to examine the use of sorafenib specifically for ICC. Sorafenib with BSC had an acceptable DCR and safety profile in patients with unresectable and advanced ICC. [Table: see text]
Characteristics of intrahepatic cholangiocarcinoma according to tumor location.
Authors: Shimada Mitsuo , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Iwahashi Shuichi , Saito Yu , Yoshikawa Masato , Teraoku Hiroki , Higashijima Jun 
Published: March 2017

406 Background: Recently, the perihilar cholangiocarcinoma was defined as a tumor existing perihilar region between the right side of the umbilical portion of the left portal vein and the left side of the origin of the right posterior portal vein, in the General Rules for Clinical and Pathological Studies on Cancer of the Biliary Tract (The 6th edition). The study was aimed to investigate characteristics of intrahepatic cholangiocarcinoma (IHCC) according to tumor location. Methods: Study 1: Sixty-two IHCC patients who underwent hepatic resection were divided into the following 3 groups; peripheral type (n=41), perihilar type (n=10) and unclassified type (peripheral type with perihilar invasion: n=11). Clinicopathological data including CA19-9 and immnohistochemical staining of Ki67 and hypoxia inducible factor-1 (HIF-1) were compared. Study 2: The effect of 2 cycles of adjuvant gemcitabine combined with 5-FU and cisplatin (GFP) (Morine and Shimada. Hepatogastroenterology 2009) was retrospectively investigated, in advanced IHCC with one of 3 prognostic factors of LN metastasis, intrahepatic metastasis and R2 resection. Results: Study 1: There was no difference in background variables except for more frequent hilar biliary invasion in perihilar and unclassified types, and the largest tumor size in unclassified-type. The 5-year survival rate in the peripheral, perihilar and unclassified-types were 44%, 20% and 0%, respectively. In addition, CA19-9 level, Ki67 labelling index and positive rate of HIF-1 expression in the unclassified type were higher than those in other 2 types. Multivariate analysis revealed the unclassified type as an independent prognostic factor. Study 2: In 29 patients (47%) having one of the 3 prognostic factors, 9 patients including 4 unclassified-type IHCCs received the adjuvant GFP. The prognosis in GFP group tended to be better than that in non-GFP group (3-year survival rate: 38% vs. 6%, p = 0.07). Two patients with unclassified-type IHCC in non-GFP group died within 1 year after surgery. Conclusions: The unclassified-type IHCC indicated the most aggressive tumor biology, and the adjuvant GFP may be a useful strategy for such a highly malignant tumor with poor prognostic factors.
Impact of duodenal invasion on outcomes in patients with pancreatic cancer treated with stereotactic body radiotherapy.
Authors: Murimwa Gilbert , Mellon Eric Albert , Frakes Jessica M. , Jin Will , Hodul Pamela Joy , Pimiento Jose Mario , Kim Richard D. , Soares Heloisa P. , Malafa Mokenge Peter , Hoffe Sarah E. 
Published: March 2017

408 Background: Clinical trials for pancreatic adenocarcinoma patients treated with a uniform SBRT tumor dose prescription exclude tumors invading the duodenum due to potential for increased GI mucosal complications. We analyzed our non-trial patients to determine the impact of SBRT in the setting of known duodenal invasion. Methods: An IRB-approved institutional database was queried identifying all 220 localized borderline resectable or locally advanced pancreatic cancer patients treated with SBRT from 2009 to 2015. Eligibility included patients with head tumors, a minimum of 6 months of follow up, and duodenal invasion on pretreatment endoscopic ultrasound (EUS). Dose painted SBRT delivered 25-30 Gy to tumor abutting the duodenum and up to 50 Gy to focal tumor/vessel abutment. Analysis evaluated whether patients with duodenal invasion had increased incidence of grade ≥ 3 (G3+) toxicity, GI ulceration or bleeding, or worsened overall survival (OS). Fisher’s Exact Test (2-tailed) compared patient characteristics and binary outcomes. Survival estimates by Kaplan-Meier were compared using log-rank test. Results: The study population included 126 patients (median F/U 14.1 months). Of 23 patients with duodenal invasion, 14 (61%) underwent resection, 3 (13%) developed G3+ toxicity and 1 (4%) had acute pre-op G3 GI bleeding that was controlled endoscopically prior to surgery. Of 103 without duodenal invasion, 48 (47%) underwent resection, 9 (9%) suffered G3+ toxicity and 7 (7%) had any GI bleed or ulceration. None of the 7 patients with GI bleeding or ulceration underwent pancreatectomy, and 3 had bleeding from tumor progression into the duodenum. There was no association between duodenal invasion and the incidence of G3+ toxicity (p = 0.76) or GI ulceration/bleeding (p = 1.0). There was no worsened OS (p = 0.17) or G3+ toxicity (p = 0.22) for patients with duodenal invasion on EUS. Patients with a GI bleeding or ulceration event had decreased OS (p = .014). Conclusions: Duodenal invasion on EUS prior to SBRT did not worsen GI bleeding risk or survival. Our data suggests that excluding pancreatic adenocarcinoma patients with duodenal invasion from SBRT when using a dose-painted approach is unnecessary.