bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical treatment of hepatocellular carcinoma with advanced portal vein tumor thrombus combined with pre-operative radiotherapy.
Authors: Wakayama Kenji , Kamiyama Toshiya , Orimo Tatsuya , Nagatsu Akihisa , Shimada Shingo , Yokoo Hideki , Kamachi Hirofumi , Taketomi Akinobu 
Published: January 2019

385 Background: Hepatocellular carcinoma (HCC) with advanced portal vein tumor thrombus (PVTT) in the main portal trunk (MPT) or the first branch of portal vein has poor prognosis. We attempted a multidisciplinary treatment to irradiate the PVTT prior to surgical resection. In this study, we evaluate the therapeutic effect of preoperative radiotherapy (Pre-RT) for HCC with advanced PVTT. Methods: The postoperative prognosis was retrospectively examined in 75 patients with advanced PVTT out of 1,045 patients who underwent hepatectomy for HCC between 1990 and 2015 in our institute. The treatment outcome was compared between the patients who underwent Pre-RT (30Gy/10fr) for PVTT before operation (RT group, n = 34) and patients not underwent Pre-RT (non-RT group, n = 41). Results: Among 75 patients with advanced PVTT, there was no difference in age, sex, extent of PVTT (MPT or first branch of PV), HBV, HCV, T-Bil, PT(%), ICG R15%, Child-Pugh classification, AFP, DCP, intra-operative blood loss, tumor size, tumor number, coexisting hepatic vein or bile duct tumor thrombus, presence of the residual tumor between RT and non-RT group other than adjuvant chemotherapy administration (p = 0.0009). The 5-year overall survival rate of all 75 cases was 18.5%. There was a significant overall survival extension in RT group with 29.4% compared to 16.2% in non-RT group (p = 0.039, log-rank test). Surgery without residual lesions was performed in 64 patients, of which the 5-year recurrence-free survival rate was 10.9%. The 5-year recurrence-free survival rate of RT group (n = 30) (16.1%) was significantly better than non-RT group (n = 34) (5.5%) (p = 0.027, log-rank test). Univariate analysis using Cox proportional hazard model demonstrated that the Pre-RT was the only significant prognostic factor (HR 0.595, 95% CI 0.356 - 0.981, p = 0.042) for overall survival, and the Pre-RT and tumor size over 10cm for recurrence-free survival among these patient’s factors. Conclusions: Multidisciplinary treatment combined preoperative radiotherapy to PVTT and subsequent surgical resection improve the prognosis for the patients of HCC with advanced PVTT extend to MPT or first branch of PV.
An easy-to-use nomogram to predict overall survival (OS) at 6 months after initiation of FOLFIRINOX first-line chemotherapy in patients (pts) with metastatic pancreatic cancer (mPC).
Authors: Fornaro Lorenzo , Leone Francesco , Vienot Angelique , Casadei Gardini Andrea , Vivaldi Caterina , Lombardi Pasquale , Meurisse Aurelia , Passardi Alessandro , Vasile Enrico , De Luca Emmanuele , Edeline Julien , Musettini Gianna , Satolli Maria Antonietta , Neuzillet Cindy , Spadi Rosella , Vernerey Dewi , Falcone Alfredo , Clerico Mario , Lievre Astrid , Montagnani Francesco 
Published: January 2019

394 Background: FOLFIRINOX achieved a significant step forward in the treatment of mPC. However, patient prognosis remains dismal, and better discrimination of outcomes could be useful to guide clinical decision-making and patient stratification. We aimed at developing and validating a prognostic model and nomogram able to predict the risk of early death (within 6 months post-treatment initiation) in mPC pts treated with first-line FOLFIRINOX. Methods: Data from 137 mPC treated with the GONO FOLFOXIRI schedule at a single institution were used as developing set. Univariate associations with death in the first 6 months after treatment initiation were investigated. Based on the multivariate model, a nomogram was developed assigning points equal to its weighted relevance to each significant variable. The nomogram was externally validated on an independent, parallel cohort of 206 mPC pts treated with FOLFIRINOX at different Italian and French centers. Predictive ability was assessed with the concordance index (C-index) and visual inspection of the calibration plot. Results: 4 out of the 27 considered variables were retained in the multivariable model: ECOG performance status (PS), neutrophils-to-lymphocytes ratio (NLR), liver metastases, and basal serum CA19.9. The nomogram demonstrated adequate discriminative ability in the validation set with a C-index of 0.754. When grouped in different prognostic categories (according to none, 1, 2, or > 2 risk factors), pts included in our study showed significantly different outcomes with median OS ranging from 6.2 ( > 2 risk factors) to 19.5 months (no risk factors, P < 0.05). Conclusions: PS, NLR, liver metastasis, and CA19.9 were the major determinants of 6-month OS. Our nomogram may help clinicians in discussing with pts the benefits and risks of therapy, and in designing future clinical trials. A visual format of the nomogram will be presented. [Table: see text]
Percutaneous radiofrequency versus microwave ablation for the treatment of colorectal liver metastases.
Authors: Bonne Lawrence , De Paepe Katja , Fotiadis Nicos , Starling Naureen , Chau Ian , Gerlinger Marco , Rao Sheela , Watkins David J. , McCall James , Koh Dow-Mu , Brown Gina , Cunningham David 
Published: January 2019

401 Background: Microwave (MWA) and radiofrequency (RFA) ablation are commonly used for the treatment of unresectable liver metastases from colorectal cancer (CRC). MWA has a few theoretical advantages over RFA (active heating, less affected by heat sink effect, larger ablation zones, faster) however limited data exists on this field. Our aim was to analyse the safety and efficacy of MWA and RFA in the treatment of CRC liver metastases. Methods: All patients with unresectable CRC liver metastasis who were treated with RFA or MWA in a single center between March 2006 and December 2016 were included. Medical records and imaging studies were reviewed retrospectively for demographic data, to assess for local tumour recurrence and overall survival and to evaluate ablation-related adverse events. Results: 456 ablations were performed in 193 patients (123 men) with a median age of 66 (range 32-91). The majority of patients had a history of surgery of the primary tumour (n=170, 88,1%) and systemic chemotherapy (n=183, 94,8%). 68 patients had a history of liver surgery (35,2%). RFA was used in 343 procedures (75,2%) and MWA in 113 (24,8%). Median number of procedures per patient was 2 (range 1-10). Median lesion size was 17mm (range 3-80mm). Mean follow-up per lesion was 2.0 years in the RFA group and 1.3 years in the MWA group. Local tumour recurrence rate was 45% for RFA and 28% for MWA, with a hazard ratio of 0.6 in favour of MWA (95% CI 0.4-0.9). Two and five year overall survival rates from diagnosis of liver metastasis were 88% and 35% for RFA and 89% and 66% for MWA, respectively. Complications were reported in 43 of 456 procedures (9,4%); In 8,2% of RFAs (n=28) and 13,3% of MWAs (n=15). Complications classified as CTCAE grade 3 or higher were: haemothorax requiring surgery (n=1 for RFA), biloma (n=2 for RFA & MWA), biliary stricture (n=2 for RFA and n=1 MWA), liver failure (n=2 for RFA), liver abscess (n=1 RFA), pneumonia (n=2 for RFA) and pulmonary embolism (n=1 RFA). Segmental portal vein occlusion was only seen with MWA (n=2; 1,8%). One patient died due to multi-organ failure post RFA. Conclusions: MWA could achieve better local tumour control compared with RFA in the treatment of CRC liver metastasis, with slightly higher complication rate.
Association of adjuvant chemotherapy with overall survival in resected pancreatic adenocarcinoma previously treated with neoadjuvant therapy.
Authors: Swords Douglas S. , Garrido-Laguna Ignacio , Mulvihill Sean J. , Stoddard Gregory J. , Firpo Matthew A. , Scaife Courtney L. 
Published: January 2019

404 Background: Guidelines for adjuvant chemotherapy in patients with resected pancreatic adenocarcinoma (PDAC) who received neoadjuvant chemotherapy are equivocal. A lymph node ratio (LNR) ≥ 0.15 may predict lack of benefit, but conflicting results are reported. Methods: The National Cancer Database was searched to identify patients who were resected after neoadjuvant chemotherapy in 2006-2013. Exclusions: metastases at surgery, 90-day postoperative mortality, adjuvant radiation, and outlier interval from diagnosis to surgery (<2.5 or >10 months). The association between adjuvant chemotherapy and overall survival (OS) from diagnosis was examined using multivariable Cox regression and inverse propensity of treatment weighted (IPTW) Cox regression. An IPTW based estimator of the average treatment effect (ATE) was used to quantify the population average survival benefit of treatment. Outcomes were examined in all patients and in those with LNR < 0.15 and ≥ 0.15. Results: 681/2488 patients (27%) received adjuvant chemotherapy. In multivariable Cox regression, adjuvant chemotherapy was associated with improved OS in the overall cohort and in patients with LNR < 0.15. A trend towards improved OS was also observed for those with LNR ≥ 0.15. After accounting for indication bias using IPTW, a significant survival benefit for was observed only for patients with LNR < 0.15. The ATE among LNR < 0.15 patients was 3.3 (95% CI 1.0, 5.7) months, indicating that the average survival of the population would be 3.3 months longer if all received treatment. Conclusions: Adjuvant chemotherapy in resected PDAC patients who received neoadjuvant therapy appears to be beneficial in patients with negative lymph nodes or minimal nodal burden. High LNR after neoadjuvant therapy may be an indicator of adverse tumor biology that is less likely to derive a therapeutic benefit. [Table: see text]
Clinical outcomes of gemcitabine plus nab-paclitaxel (GnP) in initially diagnosed locally advanced pancreatic cancer.
Authors: Hashimoto Yusuke , Takahashi Hideaki , Ohno Izumi , Imaoka Hiroshi , Sasaki Mitsuhito , Umemoto Kumiko , Watanabe Kazuo , Kimura Gen , Mitsunaga Shuichi , Ikeda Masafumi 
Published: January 2019

407 Background: Gemcitabine plus nab-Paclitaxel has shown improved survival in patients with metastatic pancreatic cancer in MPACT. Many studies have been investigating the survival benefit of GnP in LACP patients. The aim of this study is to clinical outcome of GnP in initially diagnosed LAPC in our single tertiary institution. Methods: LACP patients who received GnP as initial chemotherapy were identified between December 2014. and December 2016 from our database retrospectively. Demographic characteristics, disease status, response, conversion to resection and survival was reviewed. Resectability was determined at our hepatobiliary pancreatic tumor board, reflecting Japanese guideline of pancreatic cancer. Results: We identified 55 LACP patients initially treated with GnP (median age: 67 year old, female was 49%, ECOG PS 0/1, 62%/38%, pancreatic head 58%, baseline tumor size: median 32mm (18-62), CA19-9: median 139ng/ml (3.9-12956)). Best objective response rate was 58% and median time to partial response was 60 days (40-212). Median overall survival (mOS) was 24.7 months (95%CI :15.5-not reached). Nine patients (16%:9/55) were re-evaluated as resectable with CT and normalized CA19-9/CEA and subsequently proceeded to conversion to resection. Seven patients (13%:7/55) achieved R0 resection and sequentially performed adjuvant six- month duration of GnP. Median time to resection from initial GnP administration was 5.2 months (4.0-7.3). LAPC patients who achieved conversion to resection was associated with better overall survival than non-resected LAPC in log-rank test (mOS: all alive :12.1-25.4months vs 21.5 months 95%Cl:15.5-, HR:0.493 range: NA, P = 0.043). Shrinking tumor minimal size from the baseline was the factor to successful conversion in univariate analysis (P = 0.006). Conclusions: GnP showed promising results of response and overall survival in uLAPC patients. Conversion to resection in carefully selected uLAPC currently suggests an early surgical benefit, but longer follow-up and more cases will be required to assess the potential long-term benefit of conversion therapy.
Hand-foot skin reaction (HFSR) and overall survival (OS) in the phase 3 RESORCE trial of regorafenib for treatment of hepatocellular carcinoma (HCC) progressing on sorafenib.
Authors: Bruix Jordi , Merle Philippe , Granito Alessandro , Huang Yi-Hsiang , Bodoky Gyorgy , Yokosuka Osamu , Rosmorduc Olivier , Breder Valeriy Vladimirovich , Gerolami René , Masi Gianluca , Ross Paul J. , Qin Shukui , Song Tianqiang , Bronowicki Jean-Pierre , Ollivier-Hourmand Isabelle , Kudo Masatoshi , Xu Lei , Baumhauer Annette , Meinhardt Gerold , Han Guohong ,   on behalf of the RESORCE Investigators
Published: January 2019

412 Background: Skin toxicity is a known adverse effect of multikinase inhibitors, and was shown to be a predictor of OS in patients (pts) with HCC treated with sorafenib (Reig M, 2014). In the RESORCE trial, regorafenib improved OS versus placebo in pts with HCC progressing on sorafenib (HR 0.62, 95% CI 0.50, 0.78; Bruix J, 2017). This retrospective analysis explored whether HFSR with regorafenib was associated with OS in RESORCE. Methods: Pts in RESORCE who were randomized to regorafenib 160 mg/day during the first 3 weeks of each 4-week cycle were divided into subgroups based on whether or not they had HFSR. Estimates of OS (95% CI) were calculated using the Kaplan–Meier method. Pts who were randomized, but not treated, were included in the no HFSR group for the analysis of survival. Results: Of 379 pts randomized, 374 received at least one dose of regorafenib. Of the treated pts, 53% (n = 199) had HFSR of any grade and 13% (n = 47) had grade 3 HFSR. Among pts with HFSR at any time during the study, 77% (n = 153) had the first HFSR event (any grade) during Cycle 1. Subgroups of pts with and without HFSR at any time had some imbalances in baseline characteristics (Table). OS was improved in pts who had HFSR at any time versus those who did not (Table). Pts who had a HFSR event during Cycle 1 also had improved OS versus those who did not (median OS 13.2 vs 8.5 months; HR 0.66, 95% CI 0.51, 0.86). Conclusions: In this post-hoc exploratory analysis, HFSR with regorafenib was associated with improved OS, as was previously shown for sorafenib. The potential confounding influence of baseline factors requires further investigation. Clinical trial information: NCT01774344. [Table: see text]
Phase I study of hepatic arterial infusion (HAI) therapy with floxuridine (FUDR) combined with systemic gemcitabine and oxaliplatin in patients with locally advanced intrahepatic cholangiocarcinoma (ICC).
Authors: Grierson Patrick , Oza Aabha , Doyle Maria Majella , Fowler Kathryn , Fields Ryan , Hawkins William G. , Hammill Chet , Wang-Gillam Andrea , Amin Manik A. , Pedersen Katrina , Lim Kian-Huat , Morton Ashley , Cordova Christine , Tan Benjamin R. , Chapman William C. 
Published: January 2019

417 Background: The standard of care for unresectable ICC is palliative systemic chemotherapy with cisplatin and gemcitabine. HAI therapy with FUDR in ICC resulted in high response rates [Kemeny 2011]. The use of HAI FUDR with systemic chemotherapy may improve outcomes. We conducted a phase 1 study of HAI FUDR with systemic gemcitabine and oxaliplatin. Methods: We enrolled patients in 3 cohorts: FUDR 0.16mg/kg/day x 14 days (Cohort 1), FUDR 0.12 mg/kg/day x 14 days with gemcitabine 1000mg/m2 on days 1, 8, 15 (Cohort 2), and FUDR 0.10 mg/kg/day x 14 days with gemcitabine 800mg/m2 days 1, 15 and oxaliplatin 85mg/m2 days 1, 15 (Cohort 3). The primary endpoint was the recommended phase 2 dose (RP2D) for Cohort 3. DLTs were assessed during cycle 1. Secondary objectives were response rate and survival. Results: We enrolled 24 patients, 6 male, age range 42-81 years (median 64). No DLTs were observed in Cohort 1 (FUDR). In Cohort 2 (FUDR + Gem), the addition of gemcitabine at 1000mg/m2 days 1, 8, 15 resulted in grade 3 LFT elevation in 2 patients; for subsequent patients, the gemcitabine dose was reduced to 800mg/m2, and no further DLT were noted. No DLT were observed in Cohort 3 (FUDR + GemOx). 10 patients experienced partial responses and conversion to resectable disease occurred in all cohorts. No other significant toxicities occurred. Conclusions: FUDR via HAI with systemic gemcitabine and oxaliplatin is well-tolerated in patients with unresectable cholangiocarcinoma, with a high rate of response and disease control, allowing for resection in some patients. Our RP2D is FUDR 0.10 mg/kg/day x 14 days, with gemcitabine 800mg/m2 days 1, 15 and oxaliplatin 85mg/m2 days 1, 15. Collaboration with MSKCC is ongoing. Clinical trial information: NCT01525069. [Table: see text]
Real-world analysis of treatment patterns and persistence of octreotide LAR and other agents in patients with advanced gastrointestinal neuroendocrine tumors (GI NET): A multicenter study.
Authors: Kulke Matthew H. , Benson Al Bowen , Dasari A. , Huynh Lynn , Cai Beilei , Totev Todor , Roesner Nina , Duh Mei Sheng , Neary Maureen , Bergsland Emily K. 
Published: January 2019

424 Background: Limited data are available to document recent treatment paradigms that span NET disease course. This study aims to report long-term, real-world treatment patterns of advanced GI NET patients (pts) based on data from four tertiary cancer centers (Dana-Farber, MD Anderson, UCSF and Northwestern). Methods: Retrospective chart review was conducted in pts diagnosed with advanced, well differentiated GI NET at age ≥18 years and treated with somatostatin analogs (SSAs), targeted therapy (TT), cytotoxic chemotherapy (CC), peptide receptor radiotherapy, liver-directed therapy (LDT) or interferon from 7/2011-12/2014. Eligible pts were followed from advanced NET diagnosis date (earliest recorded diagnosis: 3/1987) to end of follow-up/death (latest recorded date: 5/2017). Analyses of treatment and dosing patterns were performed and persistence of therapy was estimated using Kaplan-Meir analysis. Results: 273 pts were included with mean age of 59 years at advanced NET diagnosis; 64% had functional NET; 57% had ileum as primary tumor site; and 63% had carcinoid syndrome (CS). Most common CS symptoms were diarrhea (87%) and flushing (73%). Majority of pts received octreotide alone (88%) or in combination (2%) with LDT, TT or CC as first-line. Of the 161 pts on second-line, 88% received octreotide alone or in combination; 5 pts (3%) received lanreotide. Most common dose at initiation for octreotide was 30mg/4 weeks (51%) and 20mg/4 weeks (32%); 68% of pts never received > 30mg/4 weeks over the entire treatment course. Median time to treatment discontinuation was 145 months (mos) for octreotide (functional NET: 145; non-functional NET: 117), 13 mos for TT and 6 mos for CC. Conclusions: This study showed that octreotide is the mainstay of treatment for advanced GI NET, as 90% of pts received octreotide alone or in combination with other treatment modalities agents as first-line therapy. 74% continued octreotide alone or in combination with other treatment modalities in the second-line. Most commonly prescribed dose was 30 mg/4 weeks. Pts remained on octreotide long term, with median treatment duration of 12 years.
Baseline anemia in patients with biliary tract cancer (BTC) and its association with survival: A retrospective cohort study.
Authors: Doherty Mark , Moignard Stephanie , Sapisochin Gonzalo , O'Kane Grainne M. , McNamara Mairead Geraldine , Horgan Anne M. , Jang Raymond Woo-Jun , Hedley David W. , Dhani Neesha C. , Knox Jennifer J. 
Published: January 2019

426 Background: The prognostic significance of anemia in BTC is unknown, but is common and may be multifactorial; data regarding its causes are limited. This study interrogated a large institutional database to examine the effect of anemia on overall survival (OS) in BTC, and explore factors associated with anemia. Methods: This Princess Margaret Cancer Centre cohort study included patients with BTC with available baseline hemoglobin (Hb) (1987-2016). Anemia was defined as Hb < 132 mg/dL for men > 60 years, < 137mg/dL for men aged 20-59, and < 122mg/dL in women. Additional relevant covariates were included in multivariable Cox regression for OS, and linear regression for association with Hb. Results: Of 1398 patients included, 711 (51%) were anemic at baseline (mean Hb 112 mg/dL). Anemic versus non-anemic patients were older (median age 66 vs 64 yrs, p = 0.006), had worse ECOG PS (12% ECOG 2-3 vs 6%, p < .001), BMI < 20 (31% vs 27%, p = 0.006) and elevated neutrophil:lymphocyte ratio (NLR), (64% vs 47%, p < .001), but cancer staging was not significantly different. Anemia was associated with shorter OS on univariate (HR 1.35, p < .001) and multivariable (HR 1.39, p < .001) regression (Table). Factors associated with lower Hb included older age, male gender, worse ECOG PS, tumor site, thrombocytopenia, elevated NLR. Conclusions: Baseline anemia was associated with shorter survival following diagnosis of BTC, independent of tumor stage or ECOG PS. Clinicians should be aware of this prognostic marker; validation in prospective datasets is warranted. [Table: see text]
Second-line chemotherapy in patients with advanced biliary tract cancer.
Authors: Takahara Naminatsu , Nakai Yousuke , Isayama Hiroyuki , Sasaki Takashi , Ishigaki Kazunaga , Saito Kei , Mizuno Suguru , Kogure Hirofumi , Tada Minoru , Koike Kazuhiko 
Published: January 2019

429 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is a palliative chemotherapy. Although the survival benefit of first-line chemotherapy (CT1) including gemcitabine and cisplatin (GC) had been established in prospective randomized trials, the safety and efficacy of second-line chemotherapy (CT2) have yet to be elucidated. Methods: Consecutive advanced BTC patients receiving CT1 followed by CT2 between 2000 and 2016 were enrolled. We investigated factors associated with receiving CT2, treatment outcomes of CT2, and the prognostic factors for overall survival (OS) with CT2 to determine which patients could be expected to benefit from CT2. Results: Among 309 advanced BTC patients receiving CT1, including those with 108 intrahepatic bile duct cancer, 96 gallbladder cancer, 88 extrahepatic bile duct cancer and 17 papilla cancer, CT2 was given in 139 patients (45%). Compared to patients without CT2, younger patients (median; 67 vs. 70 years, p < 0.01) and patients with better PS (PS 0-1; 98% vs. 94%, p = 0.06), and those who achieved higher tumor response by CT1 (response rate; 19% vs. 7%, p < 0.01) had higher chance to receive CT2. Objective response rate and disease control rate of CT2 were 4% and 50%, respectively. Median progression-free survival (PFS) and overall survival (OS) from the beginning of CT2 were 2.8 and 7.7 months, respectively. Prognostic factors impacting OS with CT2 were PS (0 vs. 1-2, hazard ratio [HR] 1.28, p=0.05), tumor response to CT1 (PR-SD vs. PD, HR 1.62, p = 0.02), and CEA (<5.0 vs. ≥5.0 IU/mL, HR 1.52, p = 0.03). Conclusions: Although the efficacy of CT2 was modest at present, it may deserve to be considered in patients who maintained systemic condition in clinical practice. Further investigations are necessary both to to develop more effective regimens and to select patient who will benefit from CT2 in order to maximize the efficacy and to avoid unnecessary toxicity and expense.