scholarly journals Objective Response by mRECIST Is an Independent Prognostic Factor for Overall Survival in Hepatocellular Carcinoma Treated with Sorafenib in the SILIUS Trial

Liver Cancer ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 505-519 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Yasutaka Chiba ◽  
Sadahisa Ogasawara ◽  
Shuntaro Obi ◽  
...  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Yasutaka Chiba ◽  
Sadahisa Ogasawara ◽  
Shuntaro Obi ◽  
...  

Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p < 0.0001), where median OS was 27.2 (95% CI, 16.0–not reached) months for responders and 8.9 (95% CI, 6.5–12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 206-206
Author(s):  
Zhan-Hong Chen ◽  
Yingfen Hong ◽  
Xiao-kun Ma ◽  
Xing Li ◽  
Dong-hao Wu ◽  
...  

206 Background: Inflammatory microenvironment plays an important role in the progression of HCC. Peripheral blood LMR, as a novel inflammatory biomarker combining an estimate of host immune homeostasis and tumor microenvironment, has been found to be a predictor for clinical outcomes in various malignancies. There have been no reports regarding the prognostic value of LMR in advanced HCC until now. We want to investigate the prognostic value of LMR in patients with advanced HBV-associated hepatocellular carcinoma. Methods: From September 2008 to June 2010, a total of 174 patients with HBV-associated advanced HCC without fever or signs of infections were analyzed. Clinicopathological parameters, including LMR, were evaluated to identify predictors of overall survival. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. The best cutoff was determined with time-dependent receiver operating characteristic curve. Results: Univariate and multivariate analyses showed that LMR was an independent prognostic factor in overall survival in patients with advanced HCC(P < 0.01 ). The best cutoff point of LMR was 4.52. All patients were dichotomized into either a low LMR group( ≤ 4.52) or a high LMR group( > 4.52). Overall survival(OS) of high LMR group was significantly longer than that of low LMR group(P < 0.01 ). High LMR group patients had significantly higher 6-month OS rate(50% vs 23%, P < 0.01) than that of low LMR group patients. Higher LMR level was significantly correlated with the presence of metastasis and larger tumor size(P < 0.05). Conclusions: LMR is an independent prognostic factor of advanced HCC patients. Higher Baseline LMR levels indicates better prognosis.


Author(s):  
Osman Öcal ◽  
Kerstin Schütte ◽  
Juozas Kupčinskas ◽  
Egidijus Morkunas ◽  
Gabija Jurkeviciute ◽  
...  

Abstract Purpose To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9–8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2–4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22–7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02–4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). Conclusion IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.


2004 ◽  
Vol 22 (13) ◽  
pp. 2671-2680 ◽  
Author(s):  
Hiroya Takeuchi ◽  
Donald L. Morton ◽  
Christine Kuo ◽  
Roderick R. Turner ◽  
David Elashoff ◽  
...  

PurposeDetection of micrometastases in sentinel lymph nodes (SLNs) is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative SLNs subsequently develop recurrent disease. We hypothesized that a quantitative realtime reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded (PE) SLNs to upstage and predict disease outcome.Patients and MethodsqRT was performed on retrospectively collected PE SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least 8 years. PE SLNs (n = 308) from these patients were sectioned and assessed by qRT for mRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family), GalNAc-T (β1→4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3).ResultsFifty-three (25%) patients had histopathology-positive SLNs by hemotoxylin and eosin and/or immunohistochemistry. Of the 162 patients with histopathology-negative SLNs, 48 (30%) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by a Cox proportional hazards model analysis (P < .0001; risk ratio, 7.48; 95% CI, 3.70 to 15.15). The presence of ≥ one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P = .0002; risk ratio, 11.42; 95% CI, 3.17 to 41.1).ConclusionMolecular upstaging of PE histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early-stage melanoma.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1272 ◽  
Author(s):  
Laura Marconato ◽  
Silvia Sabattini ◽  
Giorgia Marisi ◽  
Federica Rossi ◽  
Vito Ferdinando Leone ◽  
...  

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191–535) in dogs treated with sorafenib versus 27 days (95% CI, 0–68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0–909) in dogs receiving sorafenib, while 32 days (95% CI, 0–235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.


BMC Surgery ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Akihiro Tanemura ◽  
Shugo Mizuno ◽  
Aoi Hayasaki ◽  
Kazuyuki Gyoten ◽  
Takehiro Fujii ◽  
...  

Abstract Background Several inflammation-based scores are used to assess the surgical outcomes of hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the prognostic value of the prognostic nutritional index (PNI) in HCC patients who underwent hepatectomy with special attention to preoperative liver functional reserve. Methods Preoperative demographic and tumor-related factors were analyzed in 189 patients with HCC undergoing initial hepatectomy from August 2005 to May 2016 to identify significant prognostic factors. Results Multivariate analysis for overall survival (OS) revealed that female sex (p = 0.005), tumor size (p < 0.001) and PNI (p = 0.001) were independent prognostic factors. Compared to the High PNI group (PNI ≥ 37, n = 172), the Low PNI group (PNI < 37, n = 17) had impaired liver function and significantly poorer OS (13% vs. 67% in 5-year OS, p = 0.001) and recurrence-free survival (RFS) (8 vs. 25 months in median PFS time, p = 0.002). In the subgroup of patients with a preserved liver function of LHL15 ≥ 0.9, PNI was also independent prognostic factor, and OS (21% vs. 70% in 5-year OS, p = 0.008) and RFS (8 vs. 28 months in median PFS time, p = 0.018) were significantly poorer in the Low PNI group than the High PNI group. Conclusions PNI was an independent prognostic factor for HCC patients who underwent hepatectomy. Patients with PNI lower than 37 were at high risk for early recurrence and poor patient survival, especially in the patients with preserved liver function of LHL ≥ 0.9.


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