bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding variations in referral patterns and treatment choices for patients with hepatocellular carcinoma.
Authors: Hyder Omar , Cosgrove David , Nathan Hari , Hirose Kenzo , Wolfgang Christopher Lee , Bridge John , Geschwind Jean-Francois , Bhagat Nikhil , Gurakar Ahmet , Herman Joseph M. , Kamel Ihab R. , Pawlik Timothy M. 
Published: February 2017

293 Background: Patterns of care of physician specialists may differ for patients with hepatocellular carcinoma(HCC). The extent and reasons underlying possible variations are poorly understood. One source of variation may be disparate referral rates to specialists leading to differences in cancer-directed treatments. Methods: We queried the Surveillance, Epidemiology, and End Results(SEER) linked Medicare database for patients with HCC diagnosed between 1998-2007 who consulted one or more physicians following diagnosis. Visit and procedure records were abstracted from Medicare billing records and factors associated with visiting a specialist and subsequent treatment were examined. Results: 6752 patients with HCC were identified;median age was 73 yrs and the majority was male(66%), White(60%) and from a West geographical region(56%). 1379(20%) patients had early-stage disease. In the six months after diagnosis, referral to a specialist varied considerably (hepatology/gastroenterology-60%; medical oncology-62%; surgery-56%; interventional radiology-33%; radiation oncology-9%). 22% patients saw one specialist, while 39% saw ≥3 specialists. Time between diagnosis and visitation with a specialist varied by sub-specialty (surgery-37 days vs. interventional radiology-55 days;P=0.04). Factors associated with referral to a specialist included younger age(OR=2.13), geographic location(Northeast OR=2.09), and presence of early-stage disease(OR=2.21)(all P<0.05). Among patients with early-stage disease, 77% saw a surgeon, while 50% had a medical oncology consultation. Receipt of therapy among patients with early-stage disease varied (no therapy-30%; surgery-39%; interventional radiology-9%; other-22%). Factors associated with receipt of therapy included younger age(OR=2.82), as well as time to consultation with cancer specialist(OR=1.05)(both P<0.05). Conclusions: Following HCC diagnosis, referral to a specialist varied considerably. Both clinical and non-clinical factors were associated with consultation. Variations in referral to a specialist and subsequent therapy need to be better understood to ensure all HCC patients receive appropriate care.
Predictive factors for outcome after biliary stenting in malignant obstructive jaundice.
Authors: Punia Pankaj , Anthoney David Alan , Khanom Koudeza , Swinson Daniel 
Published: February 2017

298 Background: Stenting of the biliary treeis a common palliative procedure to relieve obstructive jaundice in advanced malignancy. Although effective in relief of biliary obstruction and subsequent palliation of symptoms, little information is available on predictive factors for survival post-procedure to better guide selection of patients. This retrospective study sought to assess factors influencing post-procedure survival in cancer patients after biliary stenting. Methods: Case notes of all patients from a regional academic cancer centre, who underwent biliary stenting for obstructive jaundice related to malignancy during 2008 and 2009, were reviewed. We collected epidemiological, biochemical, treatment (post-stenting) and survival data on all patients. Kaplan-Meyer analysis was used to assess median survival of patients from the day of first biliary stenting (adjusted for cancer types) and Cox proportional hazard model was used for univariate and multivariate analysis. Results: 194 patients were included in the final analysis. Most cases were related to pancreatic cancer or cholangiocarcinoma (89 and 46 cases each). Median survival (MS) for all the patients was 143 days. Median survival was similar, whether obstruction was secondary to the primary tumor (141cases) or metastatic disease (53 cases). In multivariate analysis serum albumin < 3.4 g/dL ( HR 1.770; 95% confidence interval 1.312 – 2.389, P < 0.001) and age > 75 years (HR 1.490; 95% confidence interval 1.086 – 2.043, p = 0.013) at the time of procedure were two independent prognostic factors predicting for a worse survival post-stenting. The 30 day mortality post-procedure in the 194 patients was 12%. Conclusions: This study suggests that stenting of the biliary tree in cases of malignant obstruction allows durable palliation of symptoms even in cases where further active chemotherapy treatment is not possible. However, the worse outcome observed in those > 75 yrs old or with low albumin at the time of procedure, identify groups with less certain benefit from this invasive procedure and requires confirming in future studies.
Radiation therapy sequencing for resected pancreatic adenocarcinoma in the National Cancer Data Base: A multi-institutional comparative analysis.
Authors: Colbert Lauren E , Hall William A , Nickleach Dana , Liu Yuan , Switchenko Jeffrey M , Gillespie Theresa Wicklin , Lipscomb Joseph , Kooby David A. , Kauh John S. , Landry Jerome C. 
Published: February 2017

305 Background: Pancreatic adenocarcinoma (PAC) remains a devastating malignancy and the role for preoperative radiation therapy (prRT) remains uncertain. This analysis used the National Cancer Data Base (NCDB) to report outcomes for the largest known retrospective cohort of patients treated with prRT for resectable PAC to date. Methods: NCDB data were obtained for all patients who underwent resection and RT for PAC from 1998-2002. Patients with metastatic (M1) disease, combined prRT and poRT, missing OS or missing RT variables were excluded. The difference in patients’ characteristics was assessed by a Chi-square test and ANOVA. The Kaplan-Meier method was used to estimate overall survival (OS); survival differences were assessed using a log-rank test. A Cox proportional hazards model was used for unadjusted and multivariable (MV) survival analysis. Two MV logistic regression models also were used to assess for differences in margin status and lymph node (LN) status across treatment groups. Results: 5,414 analyzable patients were identified. 5.1% (277/5,414) received prRT and 94.9% (5,137/5,414) received poRT. All patients underwent resection and prRT or poRT +/- chemotherapy; 92.9% chemo. 793 patients were AJCC 5th edition stage I, 1,002 stage II, 2,990 were stage III, and 522 were stage IVa; 107 patients were M0 with unknown overall stage. There was no significant difference in OS between the two groups on unadjusted Kaplan-Meier analysis. In covariate-adjusted analysis, there was no significant difference in OS in the prRT (HR, 1.20 [95% CI .98-1.48]; p = 0.08) compared with poRT; prRT was associated with lower rates of LN positivity (OR, 0.45 [95% CI 0.31-0.65]; p < 0.001) and higher rates of negative margins (OR 1.71 [95% CI 1.17-2.52]; p = 0.006). Conclusions: In the largest published series of prRT patients to date, prRT was associated with negative margins and LN negativity at resection. There was no significant difference in OS between the groups. Limitations of this study include its retrospective nature, a small prRT cohort and lack of comorbidity data. These data may be useful in generating future prospective studies of prRT for PAC.
The efficacy and safety of the capecitabine/temozolomide (CAPTEM) regimen in the treatment of well-differentiated neuroendocrine tumors with liver metastasis after failure of previous therapy: Columbia University Medical Center experience.
Authors: Oberstein Paul Eliezer , Gulati Anthony Paul , Krantz Benjamin A , Moss Rebecca Anne , Schreibman Stephen M. , Tsushima Dawn , Mowatt Kelley B , Allendorf John , Schrope Beth , Lee James A , Sherman William H. , Chabot John A , Fine Robert 
Published: February 2017

308 Background: We have observed efficacy and tolerability of the CAPTEM regimen in pNET. We conducted a retrospective review of patients with liver metastasis from any NET, including carcinoid, who were treated with this regimen at our institution between 2002-2008. Methods: We identified patients with neuroendocrine tumors who demonstrated progressive liver metastasis while on treatment with long-acting octreotide (up to 60mg/month) and were then treated with CAPTEM as per our institutional protocol. Patients received capecitabine for 14 days at 1000mg PO bid with temozolomide at 150 or 200mg/m2 in bid dosing on days 10-14 of each 28 day cycle. All patients had contrast enhanced CT or MRI, response was assessed by a radiologist utilizing RECIST 1.0 criteria. Results: We identified 18 patients (50% female, median age- 55), 9 had pNET (2 functional, 7 non-functional), 2 had MEN1, 4 had carcinoid (1 functional), 2 with gastrinoma and 1 with glucagonoma. All patients had Ki-67 <10%, 11 patients (61%) had received previous chemotherapy (median of 2 regimens), and 50% had previous chemoembolization. Performance status at time of enrollment was 0-2 (5 patients, 28% with PS-2.)The response rate in the population was 61% (11/18) with 1 CR and 10 PR by RECIST 1.0 criteria. Stable disease was seen in 4 (22%) patients and clinical benefit (CR+PR+SD) in 83%. Response was noted in carcinoid patients (2 of 4, with 1 CR and 1 PR in this group) and in MEN1 patients (1 of 2 with PR). Median PFS was 14.0 months (range 4.2-18 months). Treatment was well tolerated; the most common grade 1/2 toxicities were lymphopenia (50%) and neutropenia (44%), 1 patient had hand-foot syndrome. Grade 3 thrombocytopenia was observed in 2 patients (11%), there was no other grade 3 or 4 toxicities. Conclusions: The CAPTEM regimen is well tolerated and is associated with a significant response in patients with liver metastasis from NET including the difficult to treat cases of carcinoid and MEN1. A prospective Phase II trial of this regimen is ongoing.
Use of total parenteral nutrition (TPN) in terminally ill gastrointestinal (GI) cancer patients (pts) compared to other malignancies (OM): A single-institution experience.
Authors: Cass-Garcia Margaret , Hodul Pamela Joy , Almhanna Khaldoun 
Published: February 2017

309 Background: TPN is increasingly used in terminally ill cancer patients. The purpose of this study is to determine the validity of TPN in terminally ill GI cancer patients compared to OM. Methods: Cancer pts with limited life expectancy were given TPN between 2007 and 2012. Patients had advanced stage cancer with inoperable non-functional GI tract or failure to thrive. The primary outcome was survival from time of initiating TPN. Results: 89 pts were started on TPN (57 with GI cancer and 32 with OM). The majority of OM were GYN cancer. The mean age was 56 in the GI group vs. 58 in the OM. 47% of all patients underwent treatment while on TPN. The median duration of TPN was 38 days (39 days in the GI group vs. 52 days in the OM group). The median time from TPN to death was 70 days (55 days in the GI group vs. 77 days in the MO group). 14 patients had restored bowel function. 3 patients are living and only one is on TPN. 26 pts required palliative gastrostomy tube. TPN complication was high with 68% of pts requiring readmission, many were admitted several times. Conclusions: Terminal cancer patients receiving TPN had a median survival of 70 days; survival was shorter in the GI cancer group. Quality of life did not improve in the majority of patients; nor did it influence ultimate outcome. These data, thus, raise the question of the validity of the use of TPN in terminally ill pts.
A phase II trial of y-90 radioembolization in patients with progressive hepatic metastases from neuroendocrine carcinoma at an NCI-designated comprehensive cancer center.
Authors: Sahai Vaibhav , Nimeiri Halla Sayed , Mulcahy Mary Frances , Salem Riad , Benson Al Bowen 
Published: February 2017

312 Background: Patients with neuroendocrine carcinoma mostly present with symptomatic metastatic disease due to mass effect or release of biologically active polypeptides or amines and have a 5-year survival rate of 22%. The objective of this study was to assess the efficacy of hepatic artery radioembolization with Yttrium (Y)-90 microspheres in patients with unresectable progressive hepatic metastasis from neuroendocrine tumors. Methods: We conducted a prospective, single institutional, one-arm phase II study at an NCI-designated comprehensive cancer center. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included objective overall response rate (ORR), 1-year overall survival (OS) rate and safety and toxicity profile. Results: A total of 22 patients were enrolled between July 2007 and September 2009 with ECOG performance status 0-1, 45% males and median age of 62.5 (28-88) years. Histology included small bowel carcinoid (n=12), pancreatic neuroendocrine (n=7) and neuroendocrine tumors of unknown primary (n=3). Patients received a median of 2 (1-2) treatments with lobar approach in 95% and segmental approach in 5%. The primary endpoint of 6-month PFS rate in patients with one, two or three hepatic lesions was 82%, 82% and 72% respectively. ORR (partial and complete response) as per RECIST v1.0 was 48% in patients with one lesion, 29% with two lesions and 29% with 3 lesions. Median PFS was 9.4 (8.0-14.8) months. One-year OS rate was 86% and at 2-year was 78%. No procedure related complications were reported and grade 3 toxicities included hyperbilirubinemia (n=1) and elevated alkaline phosphatase (n=1). Conclusions: Y-90 radioembolization is a promising treatment option for patients with unresectable progressive hepatic metastases from neuroendocrine carcinoma with acceptable toxicity. Limited prospective data is available and there is a strong unmet need for randomized clinical trials with radioembolization.
A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma (HCC).
Authors: McNamara Mairead Geraldine , Horgan Anne M , Aspinall Alex , Chen Eric Xueyu , Burak Kelly , Dhani Neesha C. , Petronis Jennifer , Sinaei Mehrdad , Kim Tae Kyoung , Rogalla Patrik , Bathe Oliver F. , Knox Jennifer J. 
Published: February 2017

314 Background: Second-line options in treatment of HCC are limited. Axitinib is a multi-targeted tyrosine kinase inhibitor (TKI) of VEGFRs 1, 2, and 3, PDGFR and c-KIT that warrants exploration in HCC. Methods: This is an open-label, single-arm, two-stage phase II trial of axitinib in advanced HCC. Eligible patients (pts) are Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib starts at 5 mg bid orally, titrated to 10 mg bid as tolerated. Treatment continues to progression (PD) or intolerable toxicity. Primary endpoint is response defined by reduction in size by RECIST 1.1 on CT scan at 16 wks, secondary endpoints to compare response by RECIST 1.1 to Choi criteria and modified RECIST, explore dynamic imaging models, feasibility, safety, PFS and overall survival. Results: We present results of 15 (of 29) pts enrolled from 01/11 - 09/12. Median age; 62y (range 18-78) with ECOG PS 0 (5 pts), 1 (10 pts) with prior therapy of Temsirolimus/Bevacizumab (2 pts), sorafenib (13 pts). A planned safety/futility interim analysis was passed. Most common axitinib-related AEs were hypertension (HTN) (60%), hand-foot skin reaction (HFSR) (60%), diarrhea (60%), fatigue (50%). Most common axitinib-related grade 3 (G3) AEs were HTN (20%) and diarrhea (20%). There were no G3 HFSR. There was 1 G4 hyperbilirubinaemia. 60% of pts had dose interruptions due to AEs; most common reasons included fatigue (20%), HTN (10%), and HFSR (10%). 20% required dose reductions, 14% of pts tolerated dose escalation above 5 mg bid. As of 09/12, 8 pts remain on study, 7 pts discontinued (4pts: PD, 3pts: AEs). Med duration of treatment; 4.0 mo (range 6 d - 15.5 mo). Out of 9 evaluable for response, there was 1 confirmed PR per RECIST 1.1; 3 other pts had tumor reduction; 10%, 22%, 23%, 2 PR by Choi criteria and none by modified RECIST. Early on-treatment perfusion changes were noted on functional imaging. Of the 9 pts with evaluable AFP response, 3 (33%) had >50% decrease from baseline. 11 pts are still alive, 4 pts are deceased secondary to PD. Conclusions: Axitinib is tolerated and has shown preliminary efficacy in this VEGF pretreated HCC pt population.This is early analysis and updated data will be presented. Clinical trial information: NCT01334112.
TH-302 plus gemcitabine (G+T) versus gemcitabine (G) in patients with previously untreated advanced pancreatic cancer (PAC).
Authors: Ryan David P. , Reddy Shantan G. , Bahary Nathan , Uronis Hope Elizabeth , Sigal Darren , Cohn Allen Lee , Schelman William R. , Stephenson Joe , Eng Clarence , Borad Mitesh J. 
Published: February 2017

325 Background: TH-302 is a hypoxia-targeted drug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G+T to standard dose G as first-line therapy of PAC. Methods: An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1,000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G+T arm. The primary efficacy endpoint was a comparison of PFS between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Overall survival (OS) was a secondary endpoint. Results: 214 pts were treated; 163 (76%) Stage IV and 51 (24%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 38% ECOG 0/62% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G+T240; 55% G+T340. Median PFS was 3.6 mo in G vs 5.6 mo in G+T240 (p=0.06) and 6.0 mo in G+T340 (p=0.01). Median OS was 6.9 mo in G vs 8.7 in G+T240 (p=0.83) vs 9.2 mo in G+T340 (p=0.80). 6-mo OS was 57% in G vs 69% in G+T240 (p=0.12) and 73% in G+340 (p=0.04); 12-mo OS was 26% in G vs 37% in G+T240 (p=0.18) and 38% in G+340 (p=0.13). RECIST best response was 10% in G vs 17% in G+T240 and 26% in G+T340. 14 and 12 pts in G crossed over to T240 and T340, respectively. Median post crossover PFS was 1.8 mo in T240 vs 2.9 mo in T340 (p=0.13). Median post crossover OS was 2.6 mo in T240 vs 13.4 mo in T340 (p=0.01). AEs leading to discontinuation were: 16% G, 17% G+T240 and 12% G+T340. Rash (47% in G+T340) and stomatitis (42% in G+T340) were greater in combination, 3 pts Grd 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G+T240 and 63% G+T340 and Grd 3/4 neutropenia were 31% G, 56% G+T240 and 60% G+T340. Conclusions: The combination of G plus TH-302 improved the PFS of G. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. A phase 3 study of TH-302 (340 mg/m2) in combination with G is planned with OS as the primary efficacy endpoint. Clinical trial information: NCT01144455.
Neuroendocrine tumors (NET) of the gastrointestinal tract: Patterns of management and experience at Winship Cancer Institute of Emory University.
Authors: Zafar Syed Farhan , Patil Dattatraya Hari , Kauh John S. , Adsay Volkan , Brutcher Edith , Maithel Shishir K. , Wang Zhibo , Chen Zhengjia , El-Rayes Bassel F. 
Published: February 2017

326 Background: NET are a group of diverse malignancies observed commonly in the gastrointestinal tract. Pancreatic neuroendocrine tumors (PanNET) have been reported to have worse outcomes as compared to neuroendocrine tumors of the gastrointestinal tract (GNET). Our objective was to compare the clinical characteristics, patterns of treatment and survival in PanNET and GNET. Methods: After IRB approval, we identified 379 patients (pts) from 1996-2011 in the Winship registry. A chart review was done. Patients were categorized in mutually exclusive groups of PanNET and GNET. Results: Demographic information and basic characteristics are listed in the table. Treatment modalities for PanNET included surgery (91%), chemotherapy (14%), biologics (sunitinib or everolimus)(6%) and somatostatin analogues (11%). Liver directed therapies were employed in 30 pts with PanNET. Most common modality was radiofrequency ablation (23 pts) followed by Yttrium-90 embolization (5 pts) and chemoembolization (2 pt).Treatment for GNET included surgery (78%), chemotherapy (11%) and somatostatin analogues (17%). Median survival for GNET (all stage) was 11.6 years and PanNET (all stage) was 10.5 years (p=0.063). Using multivariate analysis, only age at diagnosis (p<0.001 for age cohort of <55 yrs) and clinical stage (p=0.002, for local disease) were found to be significant factors. Conclusions: Pts with NET have good prognosis. In our series, both PanNET and GNET, had comparable survival outcomes even in advanced stage. [Table: see text]
Antitumor activity of nanoparticle albumin-bound paclitaxel in experimental gastric cancer.
Authors: Zhang Changhua , Ostapoff Katherine T , Awasthi Niranjan , Schwarz Margaret A. , Schwarz Roderich 
Published: February 2017

33 Background: Gastric cancer is the second most common cause of cancer related death worldwide and lacks highly effective adjuvant or definitive systemic treatment for advanced disease. Nab-paclitaxel is a novel microtubule-targeting cytotoxic agent and not tested in gastric cancer as of yet. Methods: Human gastric cancer cell lines AGS, NCI-N87 and SNU16 were studied for treatment effects on cell proliferation, mitotic arrests and apoptosis in vitro and vivo. Tumor growth and survival studies were performed in murine xenografts. Results: Nab-paclitaxel inhibited cell proliferation with an IC50 of 2.01 nM in SNU16, 23.3 nM in AGS and 48.69 nM in NCI-N87 cells after 72-hour treatment, which was lower than that of oxaliplatin (1.05 μM to 1.51μM) and epirubicin (0.12 μM to 0.25 μM). Nab-paclitaxel treatment caused increased expression of the mitotic-spindle associated phospho-stathmin, nuclear fragmentation or karyopyknosis, and apoptotic events as confirmed through increased expression of cleaved-PARP and caspase-3. After a two-week nab-paclitaxel, oxaliplatin or epirubicin treatment, the local tumor growth inhibition rate was 77, 17.2 and 21.4 percent, respectively (p=0.002). Effects of therapy on tumoral proliferative and apoptotic indices corresponded with tumor growth inhibition data, while expression of phospho-stathmin also increased in tissues. There was an increase in median animal survival after nab-paclitaxel treatment (86 days) compared to controls (24 days, p=0.0004) or to oxaliplatin therapy (37.5 days, p=0.0005). Conclusions: The strong antitumor activity of nab-paclitaxel in experimental gastric cancer supports such microtubule-targeting therapy for clinical application. Nab-paclitaxel benefits were observed independent from phosphorylated stathmin expression at baseline, putting into question the consideration of nab-paclitaxel use in gastric cancer based on this putative biomarker.