bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant interferon-based chemoradiation for locally advanced pancreas cancer: A phase II pilot study.
Authors: Jensen Eric Hans , Armstrong Leonard , Tuttle Todd M. , Vickers Selwyn M. , Sielaff Timothy D. , Greeno Edward 
Published: February 2017

266 Background: Neoadjuvant chemoradiotherapy (CRT) is a viable treatment strategy for patients with locally advanced pancreas cancer. We evaluated the Virginia Mason Protocol (5-fluorouracil, cisplatin, interferon-α and radiation) given in the neoadjuvant setting for the treatment of locally advanced pancreatic cancer. Methods: We performed a phase II pilot study treating patients with locally advanced pancreas cancer, including borderline resectable and initially non-resectable cases. Patients with evidence of metastases, previous chemotherapy, ECOG performance status >1, or inadequate hematologic, renal or hepatic function were excluded. Results: We enrolled 23 patients between 1/2005 and 10/2010. Mean age at enrollment was 58.6 years. Males made up 73.4% of the cohort. Of 23 patients, 7 (30.4%) completed all treatments. The remaining 16 (69.6%) patients did not receive all scheduled treatments due to severe side effects (n=7, 30.4%), progressive disease (n=3, 13%), alternative treatment (n=3, 13%), patient withdrawal (n=1, 4.3%), other disease (n=1, 4.3%), and death on study (n=1, 4.3%). Hospitalization was required due to toxicity for 47.8% (n=11) of patients. The most commonly reported grade 3 or 4 toxicities were leucopenia/cytopenia (n=19, 82.6%) and gastrointestinal (n=19, 82.6%). Other toxicities were much less common (fatigue, weight loss, pain, skin rash, all n<3). Tumor regression was not seen in any patient. Surgical resection was ultimately successful in 7 (30.4%) cases. Surgical margins were negative in 6 of 7 cases (85.7%). The mean lymph node count was 11. Positive lymph nodes were identified in 3 of 7 cases (42.8%). Overall survival for all patients was 11.5 months. Surgical resection provided significantly improved survival (22.6 months) compared to CRT alone (8.8 months). Disease free survival in resected patients was 17.2 months. Conclusions: Aggressive neoadjuvant CRT with immunotherapy may allow for resection of initially non-resectable, locally advanced pancreas cancer, but with significant toxicity. Overall survival was similar to other, less toxic regimens. In the absence of surgical resection, survival remains dismal.
Patterns of recurrence after resection of intrahepatic cholangiocarcinoma: Results from a multi-institutional cohort of 449 patients.
Authors: Hatzaras Ioannis , Choti Michael A. , Schulick Richard D. , Alexandrescu Sorin , Pulitano Carlo , Clary Bryan M. , Zhu Andrew X. , Popescu Irinel , Marques Hugo , Barroso Eduardo , Ferrone Cristina , Bauer Todd W. , Walters Dustin M , Gamblin T. Clark , Nguyen Kevin Tri , Hubert Catherine , Gigot Jean Francois , Mentha Gilles , Pawlik Timothy M 
Published: February 2017

267 Background: Outcomes following surgical management of intrahepatic cholangiocarcionma (ICC) have largely focused on overall survival. Data on recurrence following surgery for ICC are limited. We sought to investigate rates and patterns of recurrence in patients following curative intent surgery for ICC. Methods: 449 patients who underwent surgery for ICC between 1973 and 2010 were identified from an international multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. Results: Most patients had a solitary tumor (70%) with a median tumor size of 6.5 cm. The majority of lesions did not have vascular invasion (69%). Surgical treatment was < hemi-hepatectomy (47%), hemi-hepatectomy (26%), or extended hepatectomy (27%). On pathology, 23% patients had lymph node metastasis and 18% had a microscopically positive (R1) margin. A subset of patients received adjuvant chemotherapy (32%) or chemoradiation (39%). While 5-year overall survival was 31%, 351 (78%) patients recurred with a median RFS time of 13.2 months. First recurrence site was intra-hepatic only (54%), extra-hepatic only (24%), intra- and extra-hepatic (22%). There was no difference in RFS based on site of recurrence (intra-hepatic: 11.2 months; extra-hepatic 11.6 months; intra- and extra-hepatic: 9.6 months; P=0.16). An R1 surgical margin (HR: 1.56, p=0.02) and neural invasion (HR: 1.55, p=0.02) were associated with overall recurrence, while male gender (HR: 1.70, p=0.011), >50% liver parenchyma resection HR: 1.97, p=0.03), primary tumor size (1.05, p=.02), and poor differentiation (HR: 1.92, p=0.01, were associated with intrahepatic recurrence. Receipt of adjuvant therapy was not associated with risk of recurrence (P>0.05). Conclusions: Over 75% of patients developed recurrence following curative intent surgery for ICC. The pattern of failure was distributed relatively equally with half of patients recurring with liver only disease while half had an extrahepatic metastatic site of recurrence. Future efforts need to be directed toward identifying more effective adjuvant regimens given the high rate of recurrence.
Effect of treatment-related lymphopenia on survival in newly diagnosed patients with resected adenocarcinoma of the pancreas.
Authors: Balmanoukian Ani Sarkis , Ye Xiaobu , Herman Joseph M. , Laheru Dan , Grossman Stuart A. 
Published: February 2017

270 Background: Severe treatment-related lymphopenia is associated with shorter survival in patients with high grade gliomas. This study was performed to determine if patients with resected pancreatic adenocarcinoma treated with post-operative radiation and chemotherapy develop significant lymphopenia and if this affects overall survival. Methods: Patients selected for this retrospective analysis underwent pancreatic cancer resection between 1997 and 2008, and received post-operative radiation with gemcitabine or 5-FU based chemotherapy at Johns Hopkins Hospital. Serial lymphocyte counts were recorded and survival was analyzed as a function of lymphopenia and known prognostic factors. Results: Fifty-three adults met the eligibility criteria. Their median age was 64, median tumor size was 3 centimeters, 83% underwent a pancreaticoduodenectomy, 47% had positive margins, and 92% had positive nodes. Total lymphocyte counts were normal in 91% of patients prior to receiving radiation and concomitant chemotherapy with 5FU(59%) or gemcitabine (41%). Total lymphocyte counts fell to <500 cells/mm3 in 45% of patients two months after initiating therapy with a median reduction of 63% from the baseline (p<0.0001). The median survival of patients with lymphocyte counts <500 cells/mm3 at 2 months was 14 months versus 20 months in patients with more lymphocytes (p=0.0485). Univariate analysis revealed no significant association between pre-treatment patient characteristics and survival. Multivariate analysis revealed a significant association between survival and lymphocyte count (<500 vs ≥ 500 cells/mm3) at 2 months (HR 2.2, p = 0.014). Conclusions: Adjuvant radiation and chemotherapy induced lymphopenia is frequent, severe, and an independent predictor for survival in patients with resected pancreatic adenocarcinoma.
Endoscopic or percutaneous biliary drainage for Klatskin tumors? A large retrospective study.
Authors: Walter Thomas , Ho Chia , Horgan Anne M. , Warkentin Andrew , Gallinger Steven , Beecroft Rob , Hedley David W , Tan Kongten , Kortan Paul , Knox Jennifer J. 
Published: February 2017

277 Background: Controversy exists over the preferred technique of biliary drainage in patients with Klatskin tumors as few comparative studies exist. This study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD). Methods: 129 patients with Klatskin tumors with an initial EBD or PTBD were identified from 01/01/1991 to 31/05/2011 and their clinical histories were retrospectively reviewed. The primary end point was the time to therapeutic success (TTS: time between the first drainage and a total bilirubin<40µmol/L), estimated by Kaplan-Meier analysis. Results: The first biliary decompression procedure was EBD in 87 patients and PTBD in 42 patients. The technical (98% vs 78%, p=0.004) and therapeutic (79% vs 49%, p=0.002) successes were significantly higher in the PTBD group than EBD group, respectively; Forty four patients (51%) in the EBD group subsequently underwent a PTBD before achieving therapeutic success or starting their antitumoral treatment. The median TTS was 55 days in EBD group vs 44 days in the PTBD group (multivariate analysis: HR=0.63, 95% CI=0.41-0.99, p=0.045). In patients treated by surgery or chemotherapy +/− radiotherapy, the median time to treatment was 68 and 76 days in the PTBD group and the EBD group, respectively, p=0.76. 25% and 21% of cholangitis occurred in EBD and PTBD group, respectively (p=0.34). Conclusions: In the era where chemotherapy prolongs life even in advanced disease, shortening time to success matters. Our results suggest relying on PTB for biliary decompression would be an improved treatment strategy when treating patients with Klatskin tumor.
Second interim analysis of GIDEON (Global Investigation of Therapeutic Decisions in Unresectable HCC and of Its Treatment with Sorafenib): Sorafenib treatment and safety in U.S. patients with Child-Pugh B status.
Authors: Piperdi Bilal , McGuire Brendan , Mantry Parvez , Martin Robert C. G. , Gholam Pierre Michel , Marrero Jorge A. , Geschwind Jeff H. , Venook Alan Paul , Sanyal Arun 
Published: February 2017

282 Background: Sorafenib (SOR) is the first systemic therapy to demonstrate a survival benefit in patients (pts) with late-stage hepatocellular carcinoma (HCC). GIDEON is an ongoing, global, prospective, noninterventional study of HCC pts receiving SOR in real-life practice. We present results from the second interim analysis, describing dosing and safety of SOR in HCC pts with Child-Pugh (CP)-B status in the US. Methods: From Jan 2009 – Nov 2010, 326 pts were enrolled (n = 313, safety population) and followed ≥4 months at 92 US centers. Eligible pts had unresectable HCC and were treated with SOR. Demographics, initial dose, treatment duration (TD), dose modifications (mods), and adverse events (AE) were analyzed in pts with available CP status. Results: 119 (38%) pts were CP-A and 100 (32%) were CP-B. 94 (30%) pts were excluded (Table). Median (med) SOR dose was 580 mg/d in CP-A pts and 577 mg/d in CP-B pts. Med TD was 14.4 weeks (wks) in CP-A pts and 10.1 wks in CP-B pts. TD was <4 wks, 4-12 wks, and >12 wks in 14%, 29%, and 56% of CP-A pts, and 22%, 36%, and 39% of CP-B pts, respectively. Treatment-emergent (TE) drug-related AE (all grades) were similar between groups, but more CP-B pts discontinued SOR due to AE (Table). In CP-A and -B pts, all-grade AE were as follows: hand-foot skin reaction (HFSR) (28% vs 19%), diarrhea (28% vs 27%), and fatigue (15% vs 16%). All-grade elevations in ALT, AST, and bilirubin were 2.5%, 2.5%, and 3.4% in CP-A pts and 3%, 1%, and 4% in CP-B pts. Conclusions: These interim US data suggest that SOR safety may be similar in HCC pts with CP-A and CP-B status. Med SOR dose was similar, but med TD was shorter in CP-B pts. AEs were as expected, although HFSR may be underreported in CP-B pts. Limitations of an observational registry must be considered. [Table: see text]
A phase I study of temsirolimus in combination with gemcitabine in previously untreated metastatic pancreatic cancer.
Authors: Faris Jason Edward , Blaszkowsky Lawrence Scott , Abrams Thomas Adam , Enzinger Peter C. , Hezel Aram F. , Wolpin Brian M. , Ryan David P. , Kwak Eunice Lee 
Published: February 2017

296 Background: The PI3K/mTOR/Akt pathway has been demonstrated to be active in pancreatic cancer, and preclinical data in mouse xenograft models has suggested possible synergy between gemcitabine and temsirolimus, an inhibitor of the mTOR pathway. The objective of this Phase I study was to assess toxicity and tolerability of gemcitabine and temsirolimus combination therapy in patients with newly diagnosed metastatic pancreatic cancer. Methods: The study was conducted with a modified, 3+3 phase I design for dose escalation. Patients in cohort 1 received temsirolimus at a fixed dose of 10mg IV on days 1,8,15, and 22, while gemcitabine was administered at 800mg/m2 IV on days 1 and 15 of each 28 day cycle. Results: Between November 2007 and September 2008, 9 patients were enrolled in the trial, with a median age of 56. 6/9 patients were male, and all enrolled patients had a performance status of 1. One patient discontinued prior to starting treatment. 5 of the 8 patients receiving at least one infusion of gemcitabine and temsirolimus were removed from the study for toxicities associated with treatment. There were two episodes of Grade 4 neutropenia, and multiple Grade 3 toxicities, including cytopenias (neutropenia, leukopenia, and lymphopenia), elevated liver function tests, hyperglycemia, hypophosphatemia, diarrhea, and allergic reaction. There were no partial or complete responses observed. One patient demonstrated stable disease, receiving 6 cycles; this patient developed grade 3 neutropenia, requiring a dose delay and subsequent 20% dose reductions for temsirolimus and gemcitabine. No patients were enrolled after the first cohort, and no patients remain on study. In the 8 patients who began the study, the median time on study was 22 days, and overall survival was 126 days from study administration (range 88-416 days). Conclusions: This is the first published report of a human study involving gemcitabine and temsirolimus, which was associated with substantial toxicity in patients with advanced, previously untreated pancreatic cancer precluding further exploration of this combination.
A single-institution survey of de novo secondary malignancies in patients occurring after orthotropic liver transplantation.
Authors: Gillebert Quentin , Bouattour Mohamed , Durand Francois , Francoz Claire , Paradis Valerie , Dreyer Chantal , Belghiti Jacques , Raymond Eric , Faivre Sandrine J. 
Published: February 2017

297 Background: We aim to evaluate in our institution the incidence of de novo malignancies following orthotopic liver transplantation (OLT) and their impact the prognosis of patients (pts). Methods: Pts treated with OLT from August 1991 To March 2009 were considered in this analysis. All pts data had been prospectively recorded in the database of French “Bio-medecine Agence”. Pts were considered for this analysis only if they survived at least 3-months after. Occurrence of de novo malignancies we analyzed and additional data (including immunosuppressive profile, type of cancer, potential independent risk factors of cancers, prognosis and the influence of immunosuppression protocols or risk factors on occurrence of cancers) were collected in patients who developed secondary cancers. Results: A total of 833 patients who underwent OLT were considered for this analysis. With a median follow-up of 7.9 years, 72 pts developed 92 de novo malignancies. The overall incidence of cancers in our population was 10.4% occurring with a median time of 6.1 years following OLT. Sixteen pts developed 2 different types of cancer and 2 pts had more than 3 tumor types. Before 12/1998, immunosuppression was primarily based on cyclosporine, steroids and/or azathiopirine, and since 01/1999 was switched to tacrolimus. Incidence of cancers regarding these two periods is summarized in the table. Before 1998, only 3 pts (17.6%) with secondary cancer had prior history of alcoholism and/or smoking compared to 27 pts (50%) after 1999. Thirty one deaths were observed and the median overall survival (OS) after the time of diagnosis of secondary malignancy was 5.62 years. Conclusions: The risk of de novo cancer after OLT is similar to reported series. History of smoking and alcohol use, increase the incidence of de novo malignancies especially head and neck and lung cancers however, immunosuppression type may not interfere with this risk. [Table: see text]
Yttrium-90 microspheres (SIR) verses transarterial chemoembolization (TACE) in the treatment of inoperable metastatic neuroendocrine tumors (NETS).
Authors: Wu Yuhsin V. , Tomaszewski Garin , Groman Adrienne E. , Iyer Renuka V. , Kuvshinoff Boris W. 
Published: February 2017

300 Background: There are limited modalities in the treatment of inoperable liver NET metastases. This study compares the efficacy and safety of liver-directed yttrium-90 microspheres, SIR-spheres, to TACE. Methods: Medical records and axial imaging studies were retrospectively reviewed for all patients with NET liver metastases who underwent SIR or doxorubicin based TACE at our institution from Jan 2001 to Dec 2010. The demographics, immediate effects, and time to radiologic progression were assessed and compared between the two treatment modalities. Results: A total of 99 liver directed treatments were performed on 46 pts (n=19 Y-90, n=27 TACE). Median post-treatment follow-up was 20 months (range 4-103). Pt characteristics including age, performance status, type of primary NET, and systemic therapy were similar in both groups. Pts in the SIR group waited longer from the time of metastatic diagnosis to liver-directed therapy (SIR 35 mo vs. TACE 15 mo (p=0.0015)). SIR patients had less liver burden (65% with <25% liver burden) than TACE patients (23% with <25% liver burden). Immediate treatment response (1-3 mo) was measured radiologically using WHO criteria multiplied by EASL criteria. SIR pts achieved 26% complete response (CR), 51% partial response (PR), 15% stable disease (SD), and 8% progressive disease (PR). TACE pts achieved 13% CR, 59% PR, 8% SD, and 21% PD. SIR (44 mo) had a longer radiologic effect than TACE (12 mo) (p=0.015). SIR patients underwent less treatments (95% with < 2 treatments) than TACE patients (70% with < 2 treatments) (p=0.045). Both treatments were well tolerated with minimal side effects. With only 11/46 (25%) deaths, there was no statistically significant difference in overall survival between the two groups at a median follow up of 104 months (range 12-267). Conclusions: Liver metastasis from NETs can be successfully treated with yttrium-90 radioembolization. Earlier intervention using SIR allows fewer treatments with more durable responses. Prospective studies controlling for rate of disease progression and disease burden are needed to validate these findings.
Worldwide trends in locoregional therapy for hepatocellular carcinoma (HCC): Second interim analysis of the Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib (GIDEON) study.
Authors: Geschwind Jeff H. , Lencioni Riccardo , Marrero Jorge A. , Venook Alan Paul , Ye Sheng-Long , Nakajima Keiko , Cihon Frank , Kudo Masatoshi 
Published: February 2017

317 Background: Locoregional treatments (LRTs) are widely used for HCC, with recognized regional variations but no universal standard. GIDEON is a global, prospective, non-interventional study evaluating sorafenib use in HCC patients (pts). The study allows evaluation of global trends in LRTs. Methods: >3000 pts were enrolled in 39 countries (January 2009 to April 2011). Per protocol, the 2nd interim analysis was planned when ~1500 treated pts were followed for ≥4 months. Results: In the safety population analyzed (N=1571), 55% and 46% of pts received prior LRT and transarterial chemoembolization (TACE), respectively. Prior LRTs, including TACE, were more frequent in Asia-Pacific (AP) and Japan than in other regions. In pts who received TACE prior to the initiation of sorafenib therapy, the number of TACE treatments ≥3 was higher in AP and Japan than in other regions. Overall, 76% of pts received conventional TACE, and the most common TACE agent was doxorubicin. Median time from last TACE to initiation of sorafenib therapy was 3.1 months (Table). Worldwide, 8% of pts received TACE, concomitantly with sorafenib. The incidence of sorafenib-related adverse events/serious adverse events was generally similar in pts who did (70%/4%) or did not (64%/9%) receive concomitant TACE. Conclusions: The GIDEON study provides unique insight into the utilization of LRTs worldwide and contributes to better understanding and management of HCC pts. [Table: see text]
Biopsy for custom-made treatment: mRNA expression level of cancer-critical genes from gastric/colorectal cancer tissues obtained by endoscopic biopsy.
Authors: Tamura Kazuhiko , Watanabe Takafumi , Enomoto Masanobu , Sudou Hideo , Ogata Jiro , Satou Shigeki , Kataba Yoshiaki , Osaka Yoshiaki , Takagi Yuu , Tsuchida Akihiko , Aoki Tatsuya 
Published: February 2017

33 Background: In this study, we measured the mRNA expression level of cancer-critical genes from the gastric/colorectal cancer tissues obtained through endoscopic biopsy before treatments and compared its consistency with the sample tissues surgically resected from identical cases. Methods: The study was made on 13 gastric and 19 colorectal cancer cases with patients’ consent. We picked identical cases and measured mRNA expression levels from the tissues endoscopically taken before treatment and the surgically resected ones. For the measurement, DNP (DanenbergTumorProfile) method was used. Examination items are as follows: TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, Topo-I, EGFR, and VEGF. Results: Upon comparing the consistency between endoscopically sampled biopsy tissues and surgically taken tissues from identical cases, it was found that eight out of ten items showed strong correlations in colorectal cancer cases. The results are as follows: FPGS(r=0.91, p<0.001); GGH(r=0.87, p<0.001); EGFR(r=0.86, p<0.001); Topo I (r=0.81, p<0.001); TS(r=0.79, p<0.001); DHFR(r=0.70, p<0.01); VEGF(r=0.67, p<0.01); and TP(r=0.62, p<0.05). In case of gastric cancers, strong correlations were found in three out of ten items with the following results: EGFR (r=0.98, p<0.001); TS (r=0.91, p<0.001; and DPD (r=0.74, p<0.05). Conclusions: Today’s progresses of preoperative chemotherapy and radiotherapy and developments of endoscopic and surgical treatments allow diverse options for treatments. In such circumstances, the significance of knowing the expression of cancer-critical genes between individuals before treatment in conducting custom-made treatment is profound. There are two issues in applying the expression of cancer-critical genes found through endoscopic biopsy: one is whether enough cancer cells can be obtained through biopsy, and the other is whether the sampled cancer cells reflect the characteristics of primary focus. While there remain issues to be addressed, certain results were achieved in this study. Currently, we are working on accumulating cases to compare them and find out whether the results can be applied to custom-made treatments.