scholarly journals Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Osman Öcal ◽  
Regina Schinner ◽  
Kerstin Schütte ◽  
Enrico N. de Toni ◽  
Christian Loewe ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Diameter ◽  
Advanced Hepatocellular Carcinoma ◽  
Tumor Shrinkage ◽  
Sorafenib Treatment ◽  
Early Tumor Shrinkage ◽  
Early Tumor ◽  
The Relationship

Abstract Background The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. Methods Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. Results The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22–0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. Conclusion OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.

scholarly journals Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

2021 ◽  
Author(s):  
Osman Öcal ◽  
Kerstin Schütte ◽  
Juozas Kupčinskas ◽  
Egidijus Morkunas ◽  
Gabija Jurkeviciute ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Post Hoc Analysis ◽  
Y90 Radioembolization ◽  
Baseline Values ◽  
Post Hoc

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.

scholarly journals Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-Ge Zhang ◽  
Ping Yang ◽  
Tao Jiang ◽  
Jian-Ying Zhang ◽  
Xue-Juan Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
External Beam Radiation ◽  
Rank Test ◽  
Beam Radiation ◽  
Kaplan Meier ◽  
Target Volumes ◽  
The Relationship

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.

scholarly journals Early Tumor Shrinkage as a Predictive Factor for Outcomes in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Analysis

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 754 ◽  
Author(s):  
Aya Takahashi ◽  
Michihisa Moriguchi ◽  
Yuya Seko ◽  
Toshihide Shima ◽  
Yasuhide Mitsumoto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Characteristic Curve ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Tumor Shrinkage ◽  
Discrimination Ability ◽  
Early Tumor Shrinkage ◽  
Early Tumor

We investigated the association between early tumor shrinkage (ETS) and treatment outcome in patients with hepatocellular carcinoma treated with lenvatinib (LEN). A retrospective analysis was performed in 104 patients. ETS was defined as tumor shrinkage at the first evaluation in the sum of target lesions’ longest diameters from baseline according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 5.0 months. The receiver operating characteristic curve analysis in differentiating long-term responders (PFS ≥ 5.0 months) from short-term responders (PFS < 5.0 months) revealed an ETS cut-off value of 10%. ETS ≥ 10% was significantly correlated with better PFS and OS compared with ETS < 10%. Additionally, ETS ≥ 10% showed a better discrimination ability on prognosis compared with modified RECIST-based objective response at the first evaluation. Multivariate analysis confirmed ETS ≥ 10% as an independent predictor of better OS, as well as a Child–Pugh score of 5 and macrovascular invasion. In conclusion, ETS ≥ 10% was strongly associated with outcome in patients treated with LEN. This biomarker could allow earlier assessment of the treatment response and guide treatment decision-making for HCC.

Early tumor shrinkage under first-line tyrosine kinase inhibitor as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 523-523
Author(s):  
Hideaki Miyake ◽  
Ken-ichi Harada ◽  
Masato Fujisawa
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Surrogate Endpoint ◽  
Tumor Shrinkage ◽  
First Line ◽  
Early Tumor Shrinkage ◽  
Early Tumor

523 Background: The objective of this study was to assess the prognostic impact of early tumor shrinkage induced by first-line tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Methods: This study included a total of 185 consecutive Japanese patients with mRCC, consisting of 120 and 65 who were treated with sunitinib and sorafenib, respectively, for at least 3 months as first-line therapy. Prognostic outcomes in these 185 patients were retrospectively assessed focusing on the significance of tumor shrinkage at 12 weeks after the introduction of TKIs as a predictive factor of OS. Results: As the best responses to TKIs, 3, 40, 105 and 37 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and OS in the 185 patients was 7.3 and 33.6 months, respectively. At 12 weeks after the introduction of TKIs, 9 patients reached a tumor shrinkage from -100 to -50%, 42 patients from -49 to -25%, 59 patients from -24 to 0%, and the remaining 70 patients had a gain of tumor size or new metastatic lesions. The median OS stratified according to tumor shrinkage at 12 weeks after the introduction of TKIs as shown above was 59.2, 39.1, 27.8 and 19.1 months, respectively. Univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, Heng risk classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, PS and tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis and tumor shrinkage were shown to be independently associated with OS by multivariate analysis. Conclusions: These findings suggest that tumor shrinkage at 12 weeks after the introduction of TKIs was shown to have a significant impact on the OS in mRCC patients; therefore, early tumor shrinkage could be used as a reliable surrogate endpoint of OS in patients with mRCC receiving TKI as first-line agent.

scholarly journals Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment

Liver Cancer ◽  
2016 ◽  
Vol 5 (4) ◽  
pp. 257-268 ◽  
Author(s):  
Hiroyuki Nakanishi ◽  
Masayuki Kurosaki ◽  
Kaoru Tsuchiya ◽  
Yutaka Yasui ◽  
Mayu Higuchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
C Reactive Protein ◽  
Sorafenib Treatment ◽  
Reactive Protein

A population-based analysis of prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 163-163
Author(s):  
Alan D. Smith ◽  
Winson Y. Cheung
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Elevated Serum ◽  
Advanced Hepatocellular Carcinoma ◽  
Clinical Factors ◽  
Conventional Chemotherapy ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Staging Systems

163 Background: Available clinical prognostic scoring systems for advanced hepatocellular carcinoma (HCC) were developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care for advanced HCC due to its survival benefit. The utility of these prognostic models in the setting of sorafenib is unclear. Our aims were to assess for new prognostic factors in patients treated with sorafenib and compare these with known prognostic systems. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 in British Columbia, Canada and treated with sorafenib at any 1 of 5 regional cancer centers were eligible. Based on the established Okuda, CLIP, Barcelona, and French staging systems, we collected baseline demographic and disease characteristics of patients prior to receipt of sorafenib. Multivariate logistic regression models were constructed to examine for associations between these clinical factors and overall survival. Results: Of 183 patients identified, 152 were evaluable: median age was 63 years, 78% were men, average number of sorafenib treatment was 5.3 cycles, and median overall survival was 9.6 months. The prevalence of hepatitis B, hepatitis C, and alcohol-related liver disease were 32%, 15%, and 11%, respectively. Univariate analyses showed that poor performance status, presence of clinical ascites, as well as elevated serum AST, GGT, ALP, bilirubin and platelet levels were each associated with worse overall survival (all p<0.05). In multivariate analyses, however, none of these clinical factors continued to be independently predictive of outcome (all p>0.05). Conclusions: Traditional clinical prognostic factors developed in the era of conventional chemotherapy do not appear to have the same prognostic utility in this contemporary Western cohort of advanced HCC patients treated with sorafenib. This observation underscores the need to identify molecular biomarkers that provide better prognostic information.

Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15678-e15678
Author(s):  
Beom Kyung Kim ◽  
Do Young Kim ◽  
Hye Jin Choi ◽  
Seung-Hoon Beom ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Median Overall Survival ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Sorafenib Treatment

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.

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