Response Evaluation Criteria In Cancer Of The Liver Research Articles

Response Evaluation Criteria in Cancer of the liver version 6 (Response Evaluation Criteria in Cancer of the Liver 2021 revised version).

Response Evaluation Criteria in Solid Tumors (RECIST) is inappropriate to assess the direct effects of treatment on hepatocellular carcinoma (HCC) by locoregional therapies, such as radiofrequency ablation or transarterial chemoembolization. Therefore, establishment of response evaluation criteria solely devoted to HCC is needed in clinical practice, as well as in clinical trials of HCC treatment, such as systemic therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2021 by the Liver Cancer Study Group of Japan based on the 2019 version of RECICL, which was commonly used in Japan. The major revised points of the RECICL 2021 is inclusion of RECIST version 1.1 and modified RECIST as response evaluation criteria in systemic therapy for HCC. We hope this new treatment response criteria, RECICL, proposed by the Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of daily clinical practice and clinical trials as well, not only in Japan, but also internationally.

Response Evaluation Criteria in Cancer of the Liver version5 (RECICL 2019 revised version).

Response Evaluation Criteria in Solid Tumors (RECIST) is inappropriate to assess the direct effects of treatment on hepatocellular carcinoma (HCC) by locoregional therapies, such as radiofrequency ablation and transarterial chemoembolization. Therefore, establishment of response evaluation criteria solely devoted to HCC is needed in clinical practice, as well as in clinical trials of HCC treatment, such as systemic therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2019 by the Liver Cancer Study Group of Japan based on the 2015 version of RECICL, which was commonly used in Japan. The major revised points of the RECICL 2019 are as follows: (i) CEA and CA19-9 have been newly added as tumor markers that should be recorded for use as criteria in the response evaluation for intrahepatic cholangiocarcinoma; (ii) the criteria now state that the details of molecular targeted therapy should be specified; and (iii) specific methods for overall evaluation are now described. Also, as an assessment of overall TE4 requires that TE4 is achieved in all nodules (even non-target lesions), the same calculation methods described above are used. We hope this new treatment response criteria, RECICL, proposed by the Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of daily clinical practice and clinical trials as well, not only in Japan, but also internationally.

Preoperative MRI features and clinical laboratory indicators for predicting the early therapeutic response of hepatocellular carcinoma to transcatheter arterial chemoembolization combined with High-intensity focused ultrasound treatment.

To evaluate the value of preoperative MRI features and laboratory indicators in predicting the early response of hepatocellular carcinoma (HCC) to transcatheter arterial chemoembolization (TACE) combined with high-intensity focused ultrasound (HIFU) treatment and to establish a preoperative prediction model. A total of 188 patients with 223 tumors who underwent TACE/HIFU treatment from January 2011 to June 2017 were included. Tumors were divided into three groups (< 2 cm, 2 - 5 cm,> 5 cm) and classified as non-complete response (NCR) and complete response (CR) cohorts according to the Response Evaluation Criteria in Cancer of the Liver (RECICL) 2015 revised version. Univariate analysis and multivariate logistic regression analysis were used to determine independent predictors, and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic power of each predictor. The prediction model was derived on the β coefficient of the multivariate regression analysis of the predictors. Irregular margins in the 2 - 5 cm group were closely related to early NCR. Irregular margins, arterial peritumoral enhancement and abnormal alpha-fetoprotein (AFP) were independent predictors of early NCR in the > 5 cm group. The prediction model of this group suggests that irregular margins combined with arterial peritumoral enhancement and abnormal AFP combined with irregular margins and arterial peritumoral enhancement predict an increased risk of early NCR. Irregular margins of 2 - 5 cm tumors and irregular margins, arterial peritumoral enhancement, and abnormal AFP of tumors > 5 cm can be applied to predict the early response of HCC to TACE/HIFU treatment. TACE combined with HIFU treatment may be able to significantly improve survival in patients with advanced HCC. Conventional MRI features and laboratory indicators are readily available without complex post-processing. It is feasible to predict the response of HCC after TACE/HIFU treatment based on preoperative conventional MRI features and laboratory indicators, the combination of multiple features predicts high-risk of non-complete response.

Value of texture analysis based on enhanced MRI for predicting an early therapeutic response to transcatheter arterial chemoembolisation combined with high-intensity focused ultrasound treatment in hepatocellular carcinoma

To evaluate the potential value of texture analysis (TA) based on contrast-enhanced magnetic resonance imaging (MRI) for predicting an early response of patients with hepatocellular carcinoma (HCC) who were treated with transcatheter arterial chemoembolisation (TACE) combined with high-intensity focused ultrasound (HIFU). Patients with HCC (n=89) who underwent contrast-enhanced MRI at 1.5 T 1 week before and 1 week, 1 month, and 3 months after TACE/HIFU were included in this retrospective study. Early responses were evaluated by two radiologists according to the Response Evaluation Criteria in Cancer of the Liver (RECICL). An independent Student's t-test and the Mann-Whitney U-test were used to compare the TA parameters between the complete response (CR) group and the non-complete response (NCR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the predictive value of the NCR lesions. Among the 89 patients, 58 showed CR and 31 showed NCR. Before TACE/HIFU, the CR group showed higher uniformity and energy but lower entropy than the NCR group (p<0.05). After TACE/HIFU, the CR group showed higher uniformity and energy but lower entropy and skewness than the NCR group (p<0.05). The logistic regression and ROC curve analyses showed that the entropy before TACE/HIFU and the skewness and entropy 1 week after TACE/HIFU were predictors of an early response. TA parameters based on contrast-enhanced MRI images 1 week before and after TACE/HIFU may act as imaging biomarkers to predict an early response of patients with HCC.

Inter-operator variability and source of errors in tumour response assessment for hepatocellular carcinoma treated with sorafenib.

To assess the inter-operator concordance and the potential sources of discordance in defining response to sorafenib in hepatocellular carcinoma (HCC). All patients who received sorafenib between September 2008 and February 2015 were scrutinised for this retrospective study. Images were evaluated separately by three radiologists with different expertise in liver imaging (operator 1, >10 years; operator 2, 5 years; operator 3, no specific training in liver imaging), according to: response evaluation radiological criteria in solid tumours (RECIST) 1.1, modified RECIST (mRECIST) and response evaluation criteria in cancer of the liver (RECICL). The overall response concordance between the more expert operators was good, irrespective of the criteria (RECIST 1.1, ĸ = 0.840; mRECIST, ĸ = 0.871; RECICL, ĸ = 0.819). Concordance between the less expert operator and the other colleagues was lower. The most evident discordance was in target lesion response assessment, with expert operators disagreeing mostly on lesion selection and less expert operators on lesion measurement. As a clinical correlate, overall survival was more tightly related with "progressive disease" as assessed by the expert compared to the same assessment performed by operator 3. Decision on whether a patient is a responder or progressor under sorafenib may vary among different operators, especially in case of a non-specifically trained radiologist. Regardless of the adopted criteria, patients should be evaluated by experienced radiologists to minimise variability in this critical instance. • Inter-operator variability in the assessment of response to sorafenib is poorly known. • The concordance between operators with expertise in liver imaging was good. • Target lesions selection was the main source of discordance between expert operators. • Concordance with non-specifically trained operator was lower, independently from the response criteria. • The non-specifically trained operator was mainly discordant in measurements of target lesions.

Transarterial embolization of hypervascular tumors using trisacryl gelatin microspheres (Embosphere): a prospective multicenter clinical trial in Japan.

To evaluate the feasibility and safety of transarterial embolization (TAE) using trisacryl gelatin microspheres (TGMs) for hypervascular tumors. This was a prospective multicenter clinical trial involving five institutions. TAE using TGMs was performed for hypervascular tumors in various locations. The primary endpoint was the technical success. The secondary endpoints included catheter accessibility, preservation of the feeding arteries, local tumor response based on the Response Evaluation Criteria in Cancer of the Liver (RECICL) and adverse events related to TAE based on the Common Terminology Criteria for Adverse Events, version 4.0. Twenty-three patients with liver tumors (n=9), uterine fibroids (n=3) and other tumors (n=11) were enrolled. The technical success rate was 95.7% (22 of 23 patients). Catheter accessibility and preservation of the feeding arteries were obtained in all 55 target vessels (100%). Local tumor response rates were 46.7 and 55.8% at 4 and 12weeks, respectively. Eighteen (78.3%) patients developed 53 symptomatic events including grade ≧3 events: hypertension 21.7%, pain 8.7%, vomiting 4.3% and anorexia 4.3%, all related to postembolization syndromes. TAE using TGMs was technically feasible and safe for devascularization of hypervascular tumors.

Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Single-Center Experience

Objective: To investigate whether balloon-occluded transcatheter arterial chemoembolization (b-TACE) can produce a more dense accumulation of iodized oil in various stages of hepatocellular carcinoma (HCC), from single to uncountable, to overcome inferior local control. Materials and Methods: We studied 27 patients with HCC, including single to uncountable multiple lesions, who underwent b-TACE between August 2013 and April 2015. Dynamic CT was performed at baseline and 1-3 months after b-TACE. The treatment effect (TE) after b-TACE was evaluated using the Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan. Results: In the countable HCC group, contrast-enhanced CT demonstrated RECICL TE4 in 43.8% (14/32), TE3 in 12.5% (4/32), TE2 in 37.5% (12/32), and TE1 in 6.3% (2/32) of patients. For the TACE-naïve cohort, the objective response rate was 52.9%. The objective response rate was 60% for the previously TACE-treated cohort. In the uncountable multiple HCC group, the objective response rate was 0% (0/10), with progressive disease in 90% (9/10) of patients. Conclusion: Our observations suggested that b-TACE did not reduce the efficacy of retreatment for HCC with an insufficient outcome from conventional TACE, but it could not improve the efficacy of treatment for uncountable multiple HCCs.

Real-Life Clinical Practice with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Center Experience Second Analysis

Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan. Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs. Results: OS was 14.3 months. According to the RECICL, the objective response and disease control rates were 18.6% (43 of 241) and 61.1% (137 of 241), respectively. AEs were seen in 77.3% (187 of 241), with Grade 3 or higher in 23.6% (57 of 241). The most frequent AE was hand-foot skin reaction in 109 patients (45.0%), and 28 patients (11.8%) showed Grade 3 or higher. Significant factors contributing to the OS were treatment duration (p = 0.0204), up-to-7 criteria (p = 0.0400), increase of Child-Pugh score (p = 0.0008) and tumor response determined by the RECICL (p = 0.0007). Conclusion: Based on the analysis, using many cases at a single center, we concluded that continuation of treatment with sorafenib for ≥90 days without decrease of liver function was critical if tumor response was determined as stable disease or higher.

Response Evaluation Criteria in Cancer of the Liver (RECICL) (2015 Revised version).

The Response Evaluation Criteria in Solid Tumors (RECIST) is inappropriate to assess the direct effects of treatment on hepatocellular carcinoma (HCC) by locoregional therapies such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted to HCC is needed urgently in clinical practice as well as in clinical trials of HCC treatment, such as molecular-targeted therapies, which cause necrosis of the tumor. The Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2015 by the Liver Cancer Study Group of Japan based on the 2009 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2015 is to define the target lesions of two lesions per organ or three lesions per liver, up to a maximum of five lesions. The second revised point is that setting the timing at which the overall treatment response has been changed. The third point is that the definition of treatment effect 1 has been changed to more than 50% tumor enlargement, excluding the area of necrosis after treatment. Overall evaluation of treatment response has been amended to make it possible to evaluate the overall response including extrahepatic lesions by systemic therapy, which is similar to RECIST or modified RECIST. We hope this new treatment response criteria, RECICL, proposed by the Liver Cancer Study Group of Japan will benefit HCC treatment response evaluation in the setting of daily clinical practice and clinical trials, not only in Japan, but also internationally.

Comparison of systems for assessment of post-therapeutic response to sorafenib for hepatocellular carcinoma

BackgroundTo test the hypothesis that use of the response evaluation criteria in cancer of the liver (RECICL), an improved evaluation system designed to address the limitations of the response evaluation criteria in solid tumors 1.1 (RECIST1.1) and modified RECIST (mRECIST), provides for more accurate evaluation of response of patients with hepatocellular carcinoma (HCC) to treatment with sorafenib, a molecularly targeted agent, as assessed by overall survival (OS).MethodsThe therapeutic response of 156 patients with advanced HCC who had been treated with sorafenib therapy for more than 1 month was evaluated using the RECIST1.1, mRECIST, and RECICL. After categorization as showing progressive disease (PD), stable disease (SD), or objective response, the association between OS and categorization was examined using the Kaplan–Meier method to develop survival curves. The 141 cases categorized as PD or SD by the RECIST1.1, but objective response by the mRECIST and RECICL, were further analyzed for determination of the association between OS and categorization.ResultsOnly categorization using the RECICL was found to be significantly correlated with OS (p = 0.0033). Among the patients categorized as SD or PD by the RECIST1.1, reclassification by the RECICL but not the mRECIST was found to be significantly associated with OS and allowed for precise prediction of prognosis (p = 0.0066).ConclusionsOnly the use of the RECICL allowed for identification of a subgroup of HCC patients treated with sorafenib with improved prognosis. The RECICL should, therefore, be considered a superior system for assessment of therapeutic response.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-014-0936-0) contains supplementary material, which is available to authorized users.

DC Bead Transarterial Chemoembolization Is Effective in Hepatocellular Carcinoma Refractory to Conventional Transarteral Chemoembolization: A Pilot Study

Background/AimsTo determine if hepatocellular carcinoma refractory to conventional transarterial chemoembolization (TACE) responds to TACE with DC beads.MethodsBetween July 2008 to June 2010, 435 patients underwent TACE. Of these, 10 patients who had tumors refractory to conventional TACE and who thus were treated with TACE with DC beads were enrolled in this study. The treatment response after TACE with DC beads was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and the Response Evaluation Criteria in Cancer of the Liver (RECICL).ResultsTen tumors were treated in 10 patients. Using the mRECIST and the RECICL, a complete response was observed in four (40%) of the tumors, and six tumors (60%) showed a partial response. Eight (80%) out of 10 HCCs showed delayed enhancement patterns upon angiography, and better responses were observed in these cases following DC bead treatment. The adverse effects of treatment with DC beads became tolerable.ConclusionsTACE with DC beads was effective for HCCs refractory to conventional TACE, and this treatment elicited a better response, especially when the tumors were small and showed a delayed enhancement pattern upon angiography.

Early Response to Anti-Tumoral Treatment in Hepatocellular Carcinoma - Can Quantitative Contrast-Enhanced Ultrasound Predict Outcome?

In order to detect an early response to anti-angiogenic therapy, this study aims at analyzing specific effects of a sorafenib-based regime on intra-tumoral D-CEUS flow parameters of patients with HCC. Videos of the arterial phase were captured before initiation of a therapy with sorafenib and 1 and 3 months after (n = 9). Patients receiving a non-anti-angiogenic therapy (TACE, n = 10) served as a comparison group. Cross-sectional imaging was performed at the same time points and patients were followed up for 1 year. In the responder group (RE), the absolute (percentage) TTP was 11.28 s ± 2.03 s (1.00) before treatment, 13.60 s ± 1.52 s (1.53 ± 0.08) after one month (p = 0.0405), and 16.17 s ± 2.35 s (1.46 ± 0.07) after three months of treatment (p = 0.0071). The TTP increased significantly in the RE group as early as 1 month after initiation of sorafenib compared to the non-responder group. There were no significant differences in the non-responder group or between the NR and the TACE group at any time point. D-CEUS values from all sorafenib-treated patients showed good accordance with RECICL (response evaluation criteria in cancer of the liver) criteria (R2 = 0.7154, p = 0.0001). Quantitative CEUS reveals variations of dynamic parameters of blood flow during anti-tumoral therapy in liver cancer patients. Further investigations and clinical trails have to confirm that the TTP is a promising parameter in the prediction of early response to sorafenib-based therapy.

Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version)

The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2009 is to provide TE4a (Complete response with enough ablative margin) and TE4b (complete response without enough ablative margin) for local ablation therapy. Second revised point is that setting the timing at which the overall treatment effects are assessed. Third point is that emergence of new lesion in the liver is regarded as progressive disease, different from 2004 version. Finally, 3 tumor markers including alpha-fetoprotein (AFP) and AFP-L3 and des-gamma-carboxy protein (DCP) were also added for the overall treatment response. We hope this new treatment response criteria, RECICL, proposed by Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of the daily clinical practice and clinical trials as well not only in Japan, but also internationally.

肝癌治療効果判定基準（2009年改訂版）

肝癌治療効果判定基準（2009年改訂版）