bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of chemosaturation in patients with primary and secondary liver tumours: A single-centre experience after 54 treatments.
Authors: Kirstein Martha , Marquardt Steffen , Jedicke Nils , Marhenke Silke , Koppert Wolgang , Manns Michael , Wacker Frank , Vogel Arndt 
Published: September 2018

e15625 Background: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT Delivery System; Delcath Systems Inc, USA) is a novel medical device, which delivers high doses of melphalan directly to the liver in patients with primary and secondary liver tumours while limiting systemic toxicity through hemofiltration of the hepatic venous blood. The aim of this study was to analyse the safety and efficacy of the second generation CS-PHP after 54 treatments at Hannover Medical School, Germany. Methods: Overall response rates (ORR) were assessed according to Response Evaluation Criteria In Solid Tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Results: A total of 29 patients were treated with CS-PHP as last-line therapy up to five sessions. 19 patients had unresectable hepatic metastases from solid tumors (ocular melanoma [OM] n = 11; colorectal carcinoma n = 2; pancreatic adenocarcinoma n = 2; periampular carcinoma n = 2; breast and endometrial cancer each n = 1) and 10 patients were diagnosed with hepatocellular or cholangiocarcinoma (HCC/CCA). ORR was 19.2%. Patients with OM had the highest ORR (33.3%). Similar to patients with OM, patients with hepatobiliary tumours had durable disease stabilisation (40%). Median OS, PFS and hPFS were 261, 117 and 135 days, respectively. Tumour volume negatively correlated with OS. Complications and toxicites included thrombopenia, cardiovascular events, ulcerous bleeding and edema. Conclusions: Second generation CS-PHP seems to be effective and tolerable. Patient selection based on tumour volume end entity is of importance. Particularly patients with OM and hepatobiliary tumours represent promising candidates for CS-PHP.
The effect of treatment delay on survival in patients with hepatocellular cancer.
Authors: Akce Mehmet , Sansgiry Shubhada , Temple Sarah Louise , Davila Jessica , Sada Yvonne 
Published: September 2018

e15645 Background: Hepatocellular cancer (HCC) is the fastest increasing cause of cancer related death in the U.S. Only one-third of patients are candidates for curative treatment, and treatment delays occur in 30% of patients. Data on the effect of treatment delays on HCC survival outcomes are limited to small single center studies. The aim of this study was to identify predictors of treatment delays and the impact of treatment delay on survival. Methods: We conducted a retrospective study using a national cohort of patients from the Department of Veterans Affairs who were diagnosed with HCC from October 1, 2004 to September 30, 2011. Demographics, clinical factors, treatment and death were ascertained from the medical records. Treatment delay was defined as greater than 60 days between HCC diagnosis and first treatment. Treatment was categorized as curative (surgery or ablation), liver-directed therapy, or chemotherapy. Cox Proportional Hazard models were used to examine the effect of treatment delay on survival stratified by stage (BCLC 0 and A, B, or C). Results: Among 742 patients with HCC, 223 (30%) had a treatment delay. The majority of patients were Barcelona Stage C (43%), and 131 patients (17.7%) had metastatic disease. On univariate analysis, patients with treatment delay were more likely to have tumor board discussion, single tumors, and PTSD (p < 0.05). Treatment delay was not associated with increased risk of death for patients with BCLC stage 0 and A (HR 0.74 [0.48-1.14]) or BCLC stage B (HR 0.83 [0.61-1.14]). For BCLC stage C, treatment delay was associated with a 50% decrease in risk of death (HR 0.50 [0.37-0.67]), adjusting for demographics, clinical factors, stage, and treatment. Patients with BCLC stage C HCC and treatment delay were more likely to have curative intent therapy (32.9% vs 16.3%) or liver directed therapy (43.4% vs 36.3%, p = 0.0006) than those with no delay. Conclusions: Treatment delays occurred in 30% of patients. Treatment delay was not associated with increased risk of death for earlier stage HCC, but treatment delay was associated with decreased risk of death for patients with BCLC stage C. This finding may be due to delays from coordination of curative and liver directed therapy that may result in improved survival.
Evidence-based treatment algorithm for BCLC C advanced hepatocellular carcinoma: A comprehensive review and meta-analysis.
Authors: Prajapati Hasmukh J. , "Kevin" Kim Hyun S. 
Published: September 2018

e15649 Background: Barcelona clinic liver cancer (BCLC) C advanced hepatocellular carcinoma (aHCC) has a poor prognosis. Different treatment methods have shown a survival benefit. The purpose of the study is to suggest the treatment algorithm based on a comprehensive review of the literature on aHCC treated with different methods. Methods: Studies were identified by searching Google Scholar using the following keywords: ‘‘advanced hepatocellular carcinoma’’ or ‘‘advanced HCC’’ or “BCLC C” in a time period from 2008 to 2017. Search identified more than 700 articles. Then, articles were searched manually for BCLC C HCC. Articles were excluded if they dealt with only liver metastases or portal vein thrombosis, or if they did not report median survival. A total of 3 randomized control studies (RCT) and 21 non-RCT studies met the inclusion criteria and were reviewed. Results:Overall median survivals (OS) according to different methods is shown in table 1. OSs of aHCC treated with TACE, Yittrium 90 transarterial radioembolization (Y90 TARE) and sorafenib were not significantly different (p>0.5). The pooled results of NRCT demonstrated that Child Pugh class A or without portal vein thrombosis (PVT) or ECOG PS 0 treated with TACE had best median survivals of 15 months(m), 17 m and 20 m respectively. Conclusions: No treatment method appears clearly better than any other. However, aHCC patients with Child Pugh class A or ECOG PS 0 or without PVT treated with TACE showed highest survival. Sorafenib/TACE or sorafenib/Y90 TARE combinations show promise as an effective and a tolerable treatment strategy for advanced HCC. Radiation therapy alone showed poor survival benefit. [Table: see text]
Comparison of prognostic models for hepatocellular carcinoma (HCC) in patients treated with the sorafenib: Results from a Canadian multi-center HCC database.
Authors: Samawi Haider , Sim Hao-Wen , Chan Kelvin K. , Alghamdi Mohammed Abdullah , Lee-Ying Richard M. , Knox Jennifer J. , Gill Parneet , Romagnino Adriana , Batuyong Eugene , Ko Yoo-Joung , Cheung Winson Y. , Tam Vincent C. ,   On Behalf of the CHORD Consortium
Published: September 2018

e15653 Background: Several staging systems and models (TNM, BCLC, Okuda, CLIP and ALBI) have been developed to estimate the prognosis of patients with HCC. Most of these were developed prior to the prevalent use of sorafenib. The purpose of this study was to compare the prognostic and discriminatory power of these models in predicting survival for HCC patients treated with sorafenib. Methods: Patients who received sorafenib for the treatment of HCC between January 1, 2008 and June 30, 2015 in the provinces of British Columbia and Alberta, as well as Princess Margaret Cancer Centre and Sunnybrook Odette Cancer Centre in Toronto, Ontario were included. Survival outcomes for each model were assessed with Kaplan-Meier (KM) curves and compared with the log-rank test. Time dependent area under the curve (t-AUC) was used to test the discriminatory power of each model (higher t-AUC = more discriminatory power). Akaike information criterion (AIC), a measure of goodness-of fit of models while penalizing overly complex models, was used to compare the models (lower AIC = better model). Results: A total of 681 patients were included in this analysis. Median age was 64 years (range 8-91). Majority were males (80%), had a Child-Pugh score A (86%), ECOG performance status 0 (30%) and 1 (60%). 37% of patients were of East Asian ethnicity. Most common etiology for liver disease was hepatitis B (33%) and C (29%). At start of sorafenib, most patients were BCLC stage C (92%) and TNM stage IV (61%). The median overall survival for the entire cohort was 9.2 months (95% CI 8-10.4). See table below for t-AUC and AIC results. Conclusions: According to ourlarge multi-center study, CLIP appears to be the most informative in predicting survival in HCC patients treated with sorafenib. Prospective studies are needed to determine its role in patient selection for clinical trials and in guiding treatment decisions. The TNM and BCLC staging systems were the least useful in predicting survival in this population. [Table: see text]
Overall survival (OS) in patients (pts) with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP): A real-world retrospective study.
Authors: Hennenfent Kristin L. , Girvan Allicia C. , Chaudhry Aafia , Abada Paolo , Sheffield Kristin , Herren Catherine K , Raju Aditya , Farrelly Eileen , Bowman Lee , Landsman-Blumberg Pamela 
Published: September 2018

e15658 Background: HCC is associated with a worse prognosis in pts with high baseline AFP levels. The relationship between elevated baseline AFP and survival benefit with systemic HCC treatments in the real world setting is poorly characterized. Methods: A retrospective analysis of clinical outcomes among newly diagnosed advanced HCC pts treated in US community-based oncology practice settings was conducted. Pts treated with sorafenib or best-supportive care (BSC) between 10/1/2007 and 12/31/2013 were identified in the International Oncology Network electronic medical record (EMR) database and were followed until date of death, date of last visit, or 06/30/2014 (end of study). Baseline demographics, clinical characteristics, and AFP (≤ or > 400 ng/mL), plus date of death were extracted from the EMR and physician progress notes. Treatment differences in OS were evaluated and stratified by AFP, AST/ALT, and bilirubin using unadjusted Cox proportional hazards regression models. Results: A total of 370 advanced HCC pts receiving sorafenib (217) or BSC (153) were identified. The mean age was 65.6 years and 77.0% were male. Cirrhosis (38.4%), hepatitis C (36.8%), and alcoholic liver disease (22.4%) were common hepatic-related comorbidities. 45.1% of pts had elevated AFP ( > 400 ng/mL) at baseline. The sorafenib cohort had significantly longer median OS time than the BSC cohort (29.6 vs 19.7 weeks, p= 0.048). OS for sorafenib vs BSC cohorts with AFP≤400 ng/mL and AFP > 400 ng/mL were 45.1 vs 25.3 weeks ( p= 0.128) and 25.3 vs 13.1 weeks ( p =0.197), respectively. Cox models revealed a consistent effect of sorafenib vs. BSC, regardless of AFP level (AFP ≤400ng/mL: HR = 0.79 (95% CI 0.55-1.13), p= 0.200; AFP > 400 ng/mL: HR = 0.80 (95% CI 0.53-1.52), p= 0.297). Conclusions: This study supports the poor prognosis for advanced HCC pts with baseline AFP levels > 400 ng/mL compared to baseline AFP ≤400 ng/mL. Limitations with retrospective, real-world studies require caution in interpretation, but this analysis suggests an OS benefit with sorafenib treatment compared to BSC. There remains an unmet need for effective therapies for advanced HCC associated with elevated AFP levels.
Mutational profiling of resected intrahepatic cholangiocarcinoma.
Authors: Pak Linda Ma , Goldman Debra , Gonen Mithat , Allen Peter J. , Balachandran Vinod P. , D'Angelica Michael Ian , DeMatteo Ronald P. , Kingham T. Peter , Simpson Amber , Hechtman Jaclyn Frances , Vakiani Efsevia , Sigel Carlie S. , Lowery Maeve Aine , Jarnagin William R. 
Published: September 2018

e15675 Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive neoplasm with increasing incidence and mortality. Resection is the only potential curative treatment and is associated with 5-year survival up to 44%. The objective of this study was to characterize the mutational landscape of patients with ICC undergoing resection and to identify potential prognostic genetic markers that may be unique to these patients. Methods: Sixty-six resected ICC tumor specimens were assessed for genetic alterations using next-generation sequencing of 410 cancer genes by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). We identified the gene alterations occurring with greatest frequency and grouped mutations by known cancer pathways and families, such as RAS-MAPK pathway, mTOR pathway, Notch signaling pathway, chromatin-remodeling gene family, and DNA repair gene family. Overall survival (OS) was calculated from time of resection until death and disease-free survival (DFS) was calculated from resection until recurrence or death. Kaplan Meier 5-year estimates and the log-rank test were used to evaluate the associations with OS and DFS, adjusted for multiple comparisons with false discovery rate (FDR) correction. Results: The median age of all patients was 65 years (range 29-87 years). Majority of tumors were T1 (24/66, 36%) or T2 (35/66, 53%), and of moderate differentiation (46/66, 70%). Lymphovascular invasion, perineural invasion, and periductal infiltration were present in 34 (52%), 20 (30%), and 8 (12%) patients, respectively. The median number of genetic alterations per tumor was 3 (range 0-26). The most common genetic alterations were PBRM1 (16/66, 24%), IDH1 (15/66, 23%), ARID1A (14/66, 21%) and TP53 (8/66, 12%). FGFR2 fusion mutations (5/66, 8%) were relatively rare. The median OS for all patients was 53.4 months (95%CI: 43.0-79.3 months) and median DFS was 17.4 months (95%CI: 10.4-32.6 months). None of the gene alterations or pathways were associated with OS (p = 0.29-0.84) or DFS (p = 0.23-0.65). Conclusions: In this cohort of resected ICC patients, genetic alterations or alterations within gene families, by themselves, did not stratify risk of disease recurrence or death.
High number of PD-1 positive tumoral lymphocytes as a potent biomarker for adopting cytokine-induced killer cells in hepatocellular carcinoma.
Authors: Chang Boyang , Wu Peihong 
Published: September 2018

e15680 Background: Adjuvant cytokine-induced killer cell (CIK) treatment has shown potential in reducing recurrence rate and prolong survival of patients with hepatocellular carcinoma (HCC). We aim to evaluate the PD-1/PD-L1 expression in tumor cells and tumor infiltrative lymphocytes in HCC patients and their correlation with survival benefit from cytokine-induced killer cell therapy. Methods: Between 2004 and 2011, 290 HCC patients received curative section were retrospectively enrolled by one-to-one propensity score matching, including 145 cases received adjuvant CIK cell transfusion after surgery (Surgery-CIK group), and 145 cases underwent surgery only (Surgery only group). Immunohistochemistry (IHC) was used to measure the PD-1 and PD-L1 expression in formalin fixed paraffin embedded tissue of all subjects; IHC of CD4, CD8 and Foxp3 were also conducted in the surgery-CIK group to explore their correlation with PD1/PD-L1 expression and survival of HCC patients. Results: The surgery-CIK group had significantly improved overall survival (OS; HR 0.55, 95% CI 0.33-0.92) and disease-free survival (DFS; HR 0.59, 95% CI 0.42-0.83) as compared to the surgery-only group. In the surgery-CIK group, univariate analysis showed both high PD-L1 expression and a high number of PD-1+ TILs were significantly associated with improved OS, while only the high number of PD-1+ TILs was associated with improved DFS. Multivariate analyses showed a high number of PD-1+ TILs was the only independent factor predicting favorable OS (HR 0.19, 95% CI 0.08-0.45) and DFS (HR 0.40, 95% CI 0.24-0.66) in the surgery-CIK group. By contrast, in the surgery-only group, no significant associations between PD-1/PD-L1 expression and survival of patients were identified. Conclusions: A high number of PD-1+ TILs can serve as a potent biomarker to adopt CIK cell therapy in HCC patients after curative resection.
Prognostic factors influencing survival in small bowel neuroendocrine tumors with liver metastasis.
Authors: Manguso Nicholas , Harit Attiya , Nissen Nicholas N. , Mirocha James , Hendifar Andrew Eugene , Amersi Farin F. 
Published: September 2018

e15688 Background: Management of liver metastasis in patients with small bowel neuroendocrine tumors (SBNET) remains unclear. Complete surgical resection improves long term survival however factors that influence overall prognosis are not clear. Methods: Database review identified 301 patients diagnosed with SBNET from 1990 to 2013. Only patients with known liver metastasis who underwent resection of the primary tumor were included. Outcomes among patients who underwent complete surgical resection, incomplete debulking of liver metastasis, and resection of the primary tumor alone were compared. The Kaplan-Meier method was used for survival estimates and Cox regression was used to identify predictors of death. Results: 111 patients met study criteria. Median age was 59 years (range 16-80); 49% were male. The terminal ileum (47/111, 42%) was the most common primary tumor location. The median number of liver lesions was 8.5 (range 1-31) and median lesions resected was 1 (range 0-31). In addition to resection of the primary tumor, 36 patients (32%) had no liver resection (NR), 41 (36.9%) had complete resection of liver disease (R0) and 34 (30%) had incomplete resection of liver metastasis (R1). 58 patients (36%) had one or more wedge resections, 12 (10.8%) underwent segmentectomy and 5 (4.5%) had a lobectomy. 33 (29.7%) patients underwent post-operative chemoembolization, 25 (22.5%) had radioembolization and 23 (20.7%) had radiofrequency ablation. The R1 group differed from the R0 group in median size of primary tumor (2.5 cm R1 vs 1.6 cm R0, p = 0.05) and median number of positive lymph nodes (5.0 R1 vs 3.0 R0, p = 0.05). The 5-year OS was 80.9%, 81.1% and 100% for NR, R1 and R0 groups respectively (p = 0.01). 10-year OS did not differ between groups (72.8% NR vs 81.1% R1vs 82.5% NR, p = 0.31). Cox regression showed post-operative administration of chemotherapy (HR = 3.68, p < 0.01) and higher tumor grade (HR = 18.4, p = 0.02) increased risk of death. Conclusions: In patients with SBNET with liver metastasis, higher tumor grade and post-operative chemotherapy increased risk of death. However, resection of the primary tumor along with liver metastasis improves the 5-year OS with complete cytoreduction providing the most benefit.
Surgery in combination with peptide receptor radionuclide therapy is effective in metastatic neuroendocrine tumors and is definable by blood gene transcript analysis.
Authors: Frilling Andreja , Kaemmerer Daniel , Kidd Mark S. , Clift Ashley K , Stebbing Justin , Baum Richard P. , Castellano Leandro , Wasan Harpreet Singh , Modlin Irvin Mark 
Published: September 2018

e15697 Background: Neuroendocrine tumours (NET) of the pancreas (PNET) or small bowel (SBNET) frequently present with metastases at initial diagnosis, undermining the efficacy of surgical treatment. Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues, 90Y-DOTATOC and 177Lu-DOTATATE, has been shown to achieve prolonged progression-free survival (PFS) in a substantial number of non-surgical patients with advanced NET. Our aim was to prospectively determine the efficacy of a combination of radical loco-regional surgery and PRRT in patients with metastasised NET. Methods: A set of inclusion criteria was defined (e.g. G1/G2 NET, initial tumour diagnosis, treatment naïve patient, stage IV NET, positivity on 68Ga DOTA- PET/CT, eligibility for surgery and PRRT). Patients underwent PRRT within 3 months following surgery. Follow-up included biochemistry and imaging. In a sub-cohort, blood-based neuroendocrine gene transcript analysis of 51 genes (NETest) was used to define the effectiveness of treatment. Outcome measures included 5-year overall survival (OS) and PFS from initial diagnosis. Results: Twenty-five patients (5 PNET, 20 SBNET) met eligibility criteria and were included. There were 13 men (52%) and mean age was 57.1 years. All patients with SB NET underwent right hemicolectomy, terminal ileal resection and mesenteric lympadenectomy. In all PNET patients only limited pancreatic resection was required. The median number of PRRT cycles was 4 (range 2-6). Post-treatment mortality was 0%. Surgical morbidity was 12% (all Clavien-Dindo grade 1). Transient grade 1 toxicity occurred post-PRRT in 40%. NETest scores were increased in 8 patients (100%) pre-operatively and decreased in all following treatment. NETest decreases correlated with diminished tumour volume (R2=0.37, p=0.02). Median follow-up was 48 months (range 12-72months). Five-year OS was 90% and 5-year PFS was 84.3%. Conclusions: Radical loco-regional surgery for primary tumours combined with PRRT provides a novel, highly efficacious approach in metastasised NET. The NETest accurately measures the effectiveness of treatment.
Broad safety impact of high-dose ascorbic acid and induction chemotherapy for high-risk pancreatic cancer.
Authors: Bruckner Howard , Hirschfeld Azriel , Gurell Daniel , Lee King 
Published: September 2018

e15711 Background: High dose ascorbic acid inhibits many tumors in vitro. It may reduce chemotherapy's adverse hematologic events and improve quality of life. Moderate dose gemcitabine, fluorouracil, leucovorin, irinotecan, oxaliplatin (GFLIP) is an effective regimen for patients with many cancers (Anticancer Research 17). High dose ascorbic acid may reverse half the preexisting and largely eliminate the predicted cumulative toxicity of GFLIP (ASCO 15). Methods: High dose ascorbic acid AA 75-100 grams IV was given 1-2 times per week with GFLIP every 2 weeks until progression with serial wkly and Q2wk blood tests and 3 month imaging. Eligibility: Unresectable, III, recurrent and metastatic, mod and high grade typical pancreatic ca; ECOG 0-2; +/- prior chemo; adults of any age with consent. Results: A prescheduled 2 yr analysis found 26 patients; 16 ≥ 65, (9 ≥ 70 years of age). 25 stage IV; Nine had failed at least one prior standard chemo (35%), 3 were PS 2, 9 had severe weight loss. Safety: Five had uncomplicated 3 (19%) and none had 4 neutropenia or neutropenic infection, one (4%) had a 3 anemia and thrombocytopenia without bleeding. Prophylactic growth factors were not used and limited to 1-2 as needed low doses used infrequently. There was no limiting diarrhea, enteritis, stomatitis, weight loss or coagulopathy due to GFLIP. GFLIP is on track to reproduce/retain prior response and survival benefit (ASCO 08). Conclusions: Ascorbic Acid-GFLIP can be exceptionally safe and well tolerated. It may avoid standard 20-40% rates of severe toxicities. It can be, otherwise unavailable, safe reduced cost, treatment for many elderly and prior resistant tumor patients. Given the broad multi-disease role of the GFLIP drugs, and available personalized medicine tests (Cancer Letters), further development is very attractive and feasible. Potential outcome can spare all, and especially high risk pancreatic ca patients, 20k severe toxicities every year toxicities as much as $100 million cost and make some ineligibility criteria unnecessary. Development of safe AA regimens may benefit quality of life and improve survival for many with a broad spectrum of cancers that otherwise go untreated. Clinical trial information: NCT01905150.