bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new prognostic model based on total tumor volume to predict survival rate in locally advanced hepatocellular carcinoma patients.
Authors: Chen Zhan-Hong , Lin Jin-Xiang , Lin Qu , Li Xing , Hong Ying-Fen , Wu Xiang-yuan 
Published: September 2018

e15622 Background: Many HCC patients are diagnosed as locally advanced and loco-regional therapies improved the prognosis of these patients. Survival rates of these patients vary differently. We want to research on the prognostic factors and establish a new prognostic model based on total tumor volume(TTV) to predict the survival rate in locally advanced hepatocellular carcinoma patients who receive loco-regional therapy. Methods: 214 locally advanced HCC patients who received TACE or PEJ were retrospectively studied. Univariate and multivariate analyses were used to assess the variables. A new prognostic model based on TTV was developed with independent prognostic factors. The predictive value was evaluated using receiver operator characteristic curve (ROC) analyses. Results: The median survival is 23.4 months. Univariate and multivariate analyses showed that total tumor volume (TTV), child-pugh garde, protal vein thrombosis and antivirus therapy were independent factors of overall survival. A risk model was establsihed and it is consisted of 4 factors mentioned above. 214 patients were classified into 5 stages by the new staging system. We researched on the predictive value of the new prognostic system by comparing it with CLIP, BCLC and TNM. When predicting 1-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.620, 0.735, 0.527 and 0.655, respectively; CLIP is best when predicting 1-year os. When predicting 2-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.623, 0.671, 0.516 and 0.577, respectively;The new prognostic system is as good as CLIP. When predicting 3-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.623, 0.645, 0.504 and 0.593, respectively; The new prognostic system is as good as CLIP and is better than BCLC(P < 0.05). Conclusions: Total tumor volume is independent prognotic factors of locally advanced hepatocellular carcinoma patients who received locoregional therapies.The new prognostic system based on TTV is as good as CLIP in predicting 2-year OS and 3-year OS. A new prognostic system based on TTV TTV(CM3) < 22.5(0) ≥22.5(1) Antivirus therapy No(0) Yes(1) Child pugh Grade A(0) B(1) Portal vein thrombosis No(0) Yes(1)
Better cancer-specific survival in young patients with nonmetastatic intrahepatic cholangiocarcinoma: A retrospective study of SEER database.
Authors: Wang Zheng , Qin Lunxiu 
Published: September 2018

e15637 Background: Intrahepatic cholangiocarcinoma (ICC) is a complicated and fatal malignancy. Aging plays a significant role in the occurrence and development of this liver cancer, but its prognostic role remains unclear. The purpose of this study is to compare the cancer specific survival (CSS) in young patients with elderly ones, and to further establish a nomogram, integrating age and other risk factors, to predict survival outcomes in ICC patients. Methods: Cases of intrahepatic cholangiocarcinoma diagnosed between 2004 and 2013 were extracted from SEER database. Patients were excluded if they had incomplete TNM staging, with distant metastasis (M1) or no evaluation on lymph node. The enrolled cases were divided into young (under 50 years of age) and elderly groups (50 years and over). 1-year and 3-year cancer CSS data were obtained. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. A predictive nomogram for prognosis was generated by software R, and the performance of the nomogram was assessed by C-index and validation curves. Results: There were 2385 patients meeting inclusion criteria with median follow up of 17.0 months. Compared with elderly group, young patients showed significantly higher pathological grading (P = 0.006), lower rate of lymph node invasion (P = 0.002), and early TNM stage (P = 0.005). The 1-year and 3-year CSS rates were 57.3% and 19.2% in young group, and 38.2% and 10.8% in elderly group. Both univariate analysis (P = 0.019) and multivariate analysis (P = 0.040) indicated significant difference of CSS between the two groups. The multi-factor, integrative nomogram was established to predict prognosis, whose predictive power was higher than the conventional tumor staging (AJCC 7thedition staging). And the calibration curves for the probability of 1- and 3-year CSS indicated that the nomogram-based prediction was in optimal agreement with actual observed survival. Conclusions: Compared with elderly patients, young patients with non-metastatic ICC appear to have more favorable clinicopathological characteristics and better prognosis.
Role of primary tumor resection in the prognosis of patients with resectable metastatic hepatocellular carcinoma.
Authors: Mao Kai , Wang Ruomei , Xu Qiaodong , Xiao Zhiyu , Zhang Jianlong , Liu Yingyue , Liu Jieqiong 
Published: September 2018

e15642 Background: Patients with metastatic hepatocellular carcinoma (HCC) are diagnosed more frequently because of introduction of increasingly sensitive imaging modalities. The majority of these patients die of progressive intrahepatic tumor but not due to extrahepatic metastasis. There has been little information about the role of primary tumor resection (PTR) for metastatic HCC patients with resectable primary tumor. Methods: Metastatic HCC patients recommended PTR were identified in SEER registry between 2004 and 2013. The effect of PTR on overall and cancer-specific survival (OS and CSS) using log-rank test and Cox proportional hazard regression model, as well as propensity score matching was assessed. Additionally, validation was performed in another cohort from Sun Yat-sen Memorial hospital (n = 131). Results: Overall, 529 metastatic HCC patients with resectable primary tumor were included. Of those 230 patients underwent PTR but 299 did not. The percentage of PTR among resectable metastatic HCCs increased from 38.6% in 2004 to 70.3% in 2013. PTR was associated with improved OS (hazard ratio (HR) 0.310, 95% CI 0.241-0.400, P< 0.001) and CSS (HR 0.326, 95% CI 0.250-0.425, P< 0.001) in the propensity score- matched patients. This improvement in outcomes remained significant after sensitivity analyses using multiple imputation. Furthermore, consistent with observations in SEER, PTR was correlated with improved OS (HR 0.496, 95% CI 0.294-0.838, P= 0.009) and CSS (HR 0.538, 95% CI 0.307-0.945, P= 0.031) in the validation cohort from Sun Yat-sen Memorial hospital. Conclusions: This study, the first population-based analysis using propensity score matching and multiple imputation, demonstrated that PTR has a favorable impact on prognosis in patients with metastatic HCC. Further prospective randomized trials is needed to conclusively determine whether metastatic HCC patients with resectable primary tumor should be offered aggressive locoregional surgery.
Phase II trial of sorafenib combined with on-demand transarterial chemoembolization for advanced stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage C): STAB study.
Authors: Sato Yozo , Nishiofuku Hideyuki , Yasumoto Taku , Nakatsuka Atsuhiro , Matsuo Kunihiro , Kodama Yoshihisa , Abo Daisuke , Okubo Hironao , Takaki Haruyuki , Inaba Yoshitaka , Yamakado Koichiro , Hirota Shozo 
Published: September 2018

e15648 Background: Sorafenib has been acknowledged as a standard treatment for advanced stage hepatocellular carcinoma (HCC). This study was conducted to evaluate the safety and efficacy of combination therapy of sorafenib and on-demand transarterial chemoembolization (TACE) for advanced stage HCC. Methods: Inclusion criteria were advanced stage HCC (Barcelona Clinic Liver Cancer stage C), a systemic chemotherapy native status, an Eastern Cooperative Oncology Group performance status 0–1, and a Child-Pugh grade-A. Sorafenib therapy (800 mg daily) was started 4–28 days after TACE. On-demand TACE was allowed. The primary endpoint was the completion rate of protocol treatment, which was defined as sorafenib administration at least for 2 months from initial TACE. Secondary endpoints were objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events. Results: From July 2013 to September 2015, a total of 32 patients were registered from 9 institutions, but one patient was excluded because his tumor turned out to be combined hepatocellular carcinoma and cholangiocarcinoma. The protocol treatment was completed in 28 of 31 enrolled patients (90.3%, 28/31). The median treatment duration was 7.0 months (range 0.5–30) with the median number of TACE was 1 (range 1–4) and the median sorafenib dosage of 400 mg daily (range 154-800). The ORR and DCR were 77% and 90%, respectively. Median OS and PFS were 17.3 months [95% confidence interval (CI), 11.9–22.6] and 5.4 months (95% CI, 4.6–6.2), respectively. The most common grade-3 or -4 adverse events were increased aspartate aminotransferase (55%, 17/31), increased alanine aminotransferase (45% 14/31), and hypertension (23%, 7/31). Conclusions: Combination therapy of sorafenib and on-demand TACE was well tolerated and safe. Furthermore, this combination treatment may provide a survival benefit to patients with advanced stage HCC. Clinical trial information: UMIN000014213.
Portal vein infiltration in patients with hepatocellular carcinoma: The relevance of correct classification.
Authors: Weinmann Arndt , Steinle Verena , Koch Sandra , Pinto dos Santos Daniel , Marquardt Jens Uwe , Sprinzl Martin , Lang Hauke , Düber Christoph , Galle Peter R. , Woerns Marcus A. , Kloeckner Roman 
Published: September 2018

e15651 Background: Portal vein invasion (PVI) is has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). Patients with PVI are classified as stage C in the BCLC score and systemic therapy is recommended. Patients with minor PVI are frequently misclassified due to radiological challenges in determining malignant PVI or non-adherence to guidelines. The concept of resection or TACE in limited PVI is sometimes followed with the assumption of a negligible influence on survival. Aim of this study is the reevaluation of PVI and the analysis of the impact of a misclassification. Methods: 763 patients with HCC of a total of 1413 were extracted from the clinical registry of our tertiary center as an ongoing effort to reevaluate the extent of PVI in all patients treated between 1/1/2000 and 12/31/2015. PVI was diagnosed by re-evaluating all available CT or MRI scans by an experienced liver imaging radiologist. PVI was documented using the Liver Cancer Study Group of Japan classification ranging from Vp0-Vp4: Vp0 = no PVI; Vp1 = segmental; Vp2 = right anterior or posterior PV; Vp3 = right or left PV; Vp4 = main trunk. The influence on survival was calculated for each BCLC stage. Results: 259 patients (pat) were classified with PVI. Median age at diagnosis was 65.3 years, 213 patients (82.2%) were male. Etiology of liver disease was alcohol (43.6%), viral hepatitis (29.8%), NASH (5.8%), and others (10.4%). No liver disease was present in 18 pat (6.9%). No liver cirrhosis (LCI) was present in 32 pat (12.4%). LCI was classified as Child Pugh stage A/B/C in 65 (25.1%)/109 (42.1%) and 52 (20.1%) of patients. BCLC classification prior to reevaluation in pat with new PVI was A/B/C/D in 9/13/164/71 of cases. Comparing the overall survival (OS) of pat initially classified as BCLC A with or without PVI was 21.3 months vs. 106.4 months (p = 0.001), in BCLC B the OS was 11.0 months vs. 37.7 months (p = 0.001). Conclusions: Even minor PVI leads to dismal prognosis. Meticulous evaluation of cross sectional imaging is crucial for the clinical management of patients with HCC. Once PVI has been diagnosed, such patients have to be classified as advanced stage. The guidelines should be followed closely, irrespective of the extent of PVI.
Survival in patients with hepatocellular carcinoma (HCC): A report of 1444 patients treated within a multidisciplinary program.
Authors: Maluccio Mary A. , Zang Yong , Pi Wenhu , Tann Mark , Kubal Chandrashekhar , Lacerda Marco A , O'Neil Bert H. , Agarwal David M , Kong Feng-Ming (Spring) 
Published: September 2018

e15652 Background: The evolution of treatment for HCC has seen novel therapies emerge as front line treatment alternatives. The aim of this study was to report survival in HCC patients treated within the context of a robust multidisciplinary program and to identify patient and tumor specific factors that direct patient centered treatment decisions and optimize outcome. Methods: This is retrospective analysis of medical records identified through the cancer registry at our institution from 2000 to 2016. Variables analyzed for survival significance included patient factors (age, gender, race, tobacco history, alcohol history, and marital status) and tumor factors (tumor size, histology grade, AFP level, SEER stage, clinical and pathologic stage). Survival was estimated from the time of diagnosis to the last contact. Results: A total of 1444 consecutive patients with confirmed HCC were eligible for this analysis. Median follow-up was 45 months. Median survival was 18 months (95% CI: 11-25 months). The overall 1-, 3-, and 5-year survival rates were 63, 40, and 35%, respectively. Significant prognostic parameters were SEER stage (HR = 2.3, p = 2x10-16 local as the reference), pathologic stage (HR = 1.2, p = 3×10-9), tobacco history (HR = 1.2, p = 0.03), , and clinical stage (HR = 1.1, p = 4x10-5). Of a total of 380 patients resected, median and 3-year survival were 75 months and 63% (95% CI: 58-69%). The only significant prognostic parameter associated with survival in resection patients was SEER stage (HR = 1.7, p = 0.002). The 5 year survival for all patients versus those resected were 44% (95% CI: 40-48) /59% (95% CI: 53-65), 21% (95% CI: 17-27) /36% (95% CI: 24-54), and 11% (95% CI: 5-20) /25% (95% CI: 6-100) for localized, regional, and distant disease, respectively. Conclusions: Survival has improved for patients with HCC due to an increased number of available options and better methods to identify tumor and patients specific variables that individualize care. The significance of SEER stage suggests that early detection remains critical for survival.
Molecular landscape of fibrolamellar carcinoma (FLC): Beyond the DNAJB1-PRKACA chimera.
Authors: El Dika Imane Hassan , Capanu Marinela , Berger Michael F. , Arcila Maria E. , Benayed Ryma , Harding James J. , Rusek Matthew , Valentino Emily , O'Reilly Eileen Mary , Saltz Leonard , Abou-Alfa Ghassan K. 
Published: September 2018

e15668 Background: FLC is a rare cancer arising in non-cirrhotic liver of young adults. A functional chimeric transcript resulting from the in-frame fusion of DNAJB1 with PRKACA genes on chromosome 19 is thought to be universal and unique in FLC. This chimera has possible role in pathogenesis, yet with no determined prognostic or therapeutic value. Methods: Archival FFPE samples from FLC patients who prospectively consented to an IRB-approved protocol from 2014 onward were analyzed using the MSK-IMPACT platform, a hybridization capture based next generation sequencing assay for targeted deep sequencing of all exons and selected introns of > 400 key cancer genes. Tumor and matched normal libraries were sequenced on an Illumina HiSeq 2500. Sequencing output was processed using a custom analysis pipeline. Archer targeted RNAseq was performed in select cases. Demographic, treatment, and outcome data was prospectively collected. Fisher’s exact tests were performed to look for associations between clinical characteristics and genetic alterations. Results: 18 patients were identified. Median age at diagnosis was 18 years and 61% were women. 17 (94%) underwent upfront surgery, and median number of therapies was 5. The DNAJB1-PRKACA fusion transcript was detected in 100% of cases. 7 samples were negative via MSK-IMPACT, (2 false-negatives, and 5 due to an older panel not including the fusion transcript) and were confirmed positive on Archer targeted RNAseq. The second most common genetic mutation was TERT, detected in 4 patients, whereas CIC, NOTCH1, ERBB3, EPHAS, MCL1, PNRC1, NCOR, INPP4B, ARID1A, CHECK1, NKX3-1, TET1, RAD52, DIS3, SF3B1, MDM2, MED12, MPL, KRAS, PAK7, BCOR, HGF, ROS1, MYCL1, CTNNB1, and YAP1 were detected in 1 patient each. 3-year overall survival (OS) was 98%, median OS was not reached. Conclusions: This limited cohort of patients with FLC exhibited universally the DNABJ1-PRKACA chimera, and demonstrated a favorable outcome compared to a 3-year OS approaching 70% previously reported by the Fibrolamellar Consortium. The fusion transcript did not imply a prognostic value considering its expression among all patients with FLC. Other drivers or the lack of may be responsible for the improved outcome in this small cohort
Prospective evaluation of the factors predicting the prognosis of advanced hepatocellular carcinoma (HCC) patients treated with sorafenib.
Authors: Adachi Takuya , Nouso Kazuhiro , Miyahara Koji , Dohi Chihiro , Wada Nozomu , Takeuchi Yasuto , Kuwaki Kenji , Onishi Hideki , Ikeda Fusao , Nakamura Shinichiro , Shiraha Hidenori , Takaguchi Koichi , Uematsu Shuji , Iwadou Shouta , Takuma Yoshitaka , Hagihara Hiroaki , Takabatake Hiroyuki , Takaki Akinobu , Okada Hiroyuki ,   Okayama Liver Cancer Group
Published: September 2018

e15674 Background: Several factors including pro-angiogenic cytokines have been reported as predictive markers for the treatment effect of sorafenib in patients with HCC; however, many of them were determined based on the results of retrospective studies. Methods: In this prospective cohort study (UMIN000009771), we recruited advanced HCC patients who were treated with sorafenib, and periodically measured serum levels of eight pro-angiogenic cytokines, which were risk factors for the prognosis reported by us and others. The effect of the cytokine expressions before and at 2 (4) weeks after starting sorafenib and at PD, on progression free survival (PFS), overall survival (OS), and post progression survival (PPS) were evaluated. The effect of early appearance of adverse events within 30 days, which were reported as other risk factors, was also evaluated. Results: Eighty patients were enrolled. Median PFS and OS were 3.1 and 11.7 months, respectively. There was no statistically significant variable that could predict PFS, which included patients’ characteristics, cytokines before the therapy, and early onset of adverse events. However, PFS of the patients who showed the decrease of platelet-derived growth factor after 2 weeks (HR2.78, 95%CI 1.35-6.21, P=0.005) or vascular endothelial growth factor after 4 weeks (HR3.31, 95%CI 1.59-6.83, P=0.001) compared to the values before sorafenib treatment was short. OS was short in patients with poor performance status, large tumor size (>30mm), large tumor number (>5), high des-gamma-carboxyprothrombin (DCP, >100mAU/mL), high hepatocyte growth factor, and high angiopoietin-2 (Ang-2) before therapy, in addition to no hand foot syndrome within 30 days. Multivariate analysis with these factors revealed that high Ang-2 (HR2.25, 95%CI 1.08-4.86, p=0.029) and high DCP (HR3.55, 95%CI 1.25-12.7, p=0.014) were the independent risk factors for OS. High Ang-2 at PD could also be a marker of short PPS. Conclusions: The prediction of PFS, OS and PPS is possible by measuring serum pro-angiogenic cytokines at appropriate timing. Ang-2 is a key cytokine for predicting the prognosis of HCC patients treated with sorafenib.
Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.
Authors: Kim Beom Kyung , Kim Do Young , Choi Hye Jin , Beom Seung-Hoon , Lee Hye Won , Kim Seung Up , Park Jun Yong , Ahn Sang Hoon , Seong Jinsil , Han Kwang-Hyub 
Published: September 2018

e15678 Background: Patients with advanced hepatocellular carcinoma (HCC) have a particularly poor prognosis of the median overall survival of less than 12 months. Even though sorafenib has been approved for treating advanced stage HCC, the unsatisfactory objective response rate still remain unresolved. In the current study, we aimed to evaluate the efficacy and safety of localized concurrent chemoradiotherapy (CCRT) followed by sequential sorafenib treatment for advanced hepatocellular carcinoma. Methods: This study is an ongoing, phase II trial. Patients with advanced HCC not amenable for curative treatments were eligible. In the course of radiotherapy for 5 weeks, hepatic arterial infusion of 5-fluorouracil (500mg/day) via implanted port was applied during the first 5 days and the last 5 days of radiotherapy. Four weeks after localized CCRT, sorafenib (400mg bid) was maintained. The primary endpoint was overall survival. Results: A total of 47 patients were enrolled. After the completion of localized CCRT, the objective response rate was 31.9%. During the overall treatment course, the objective response rate was 46.8% respectively. Overall, 7 patients (14.9%) underwent curative resection or transplantation after down-staging. The median overall survival was 18.4 months and the progression-free survival was 6.8 months. Adverse events were predictable and manageable with conservative care. Conclusions: Localized CCRT followed by sequential sorafenib treatment in patients with advanced HCC showed significant activity and good tolerability. Furthermore, such a treatment modality, when compared to the use of sorafenib alone, might provide the additional therapeutic benefit through initial tumor reduction, allowing curative treatment after down-staging in 14.9% of patients, Further randomized trial should be required to make the more robust evidence. Clinical trial information: NCT02425605.
A novel and validated inflammation-integrated prognostic model for hepatocellular carcinoma (HCC).
Authors: Chan Anthony W.H. , Chong Charing C.N. , Lai Paul B.S. , Yeo Winnie , To Ka Fai , Chan Stephen Lam 
Published: September 2018

e15679 Background: Various serum inflammatory factors are implicated in pathogenesis and prognostication of HCC but none of them is incorporated into a HCC prognostic model. We aim to build an inflammation-integrated prognostic model without any radiological feature. Methods: A prospective-retrospective cohort of patients with HCC was accrued from 2001 to 2013, and was randomly spitted into training and validation cohorts. Cox proportional hazards model was used for univariable and multivariable survival analyses. The risk score was constructed by factors and their coefficients identified by multivariable Cox model. Results: The entire cohort was composed of 1315 patients (BCLC 0/A/B/C/D 73/533/237/425/47; Surgery/Locoablation/TACE/Systemic agent/BSC 538/128/318/122/209). In the training cohort (n=657), a novel model, PANALA score, was generated by using6 independent prognostic factors: 1.488*(Performance status >0) – 0.057*Albumin + 0.098*Neutrophil – 50.4*Alkaline phosphatase-1 – 0.269*Lymphocyte + 0.11*ln(Alpha fetoprotein). PANALA outperformed other staging systems (Table) and allowed the prediction of survival of an individual patient. In the validation cohort (n=658), the prognostic performance of PANALA was still the most superior one. The goodness of fit of PANALA score in prediction of survival was evaluated by dividing patients into 4 equal quartiles by PANALA. In the quartile 1, overall survival between actual observation and prediction was highly comparable (6m survival: 100% vs. 95%, 3y survival: 80% vs. 79%, 5y survival: 72% vs. 74%; P=0.71). Discrepancies between observed and predicted survival were also insignificant in other quartiles. Moreover, PANALA was able to stratify each BCLC stage into 3 prognostically different subgroups. Conclusions: PANALA is a novel and validated model with high prognostic performance. [Table: see text]