Proposal of Primary Endpoints for TACE Combination Trials with Systemic Therapy: Lessons Learned from 5 Negative Trials and the Positive TACTICS Trial

Kudo, Masatoshi

doi:10.1159/000492535

Cited by 34 publications

(31 citation statements)

References 22 publications

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“…The failure of the negative trials could mainly be due to the deficiency of effective biomarkers (18). For HCC patients, it is known that baseline α-fetoprotein concentration and other biomarkers such as miR-26 miRNA precursor, epithelial cell adhesion molecule are suggested to be correlated with the outcomes (35,36).…”

Section: Discussionmentioning

confidence: 99%

“…Several clinical trials which attempted to address the improvement in OS of the combination treatment of TACE plus sorafenib in HCC patients have ended in failure ( 16 , 33 , 34 ). The failure of the negative trials could mainly be due to the deficiency of effective biomarkers ( 18 ). For HCC patients, it is known that baseline α-fetoprotein concentration and other biomarkers such as miR-26 miRNA precursor, epithelial cell adhesion molecule are suggested to be correlated with the outcomes ( 35 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the TACTIS trial clearly showed that TACE plus sorafenib significantly improved clinical outcomes in patients with unresectable HCC, which indicated that this combination therapy was effective and feasible in routine practice ( 14 ). However, several clinical trials failed to contribute compelling evidence for the combination of sorafenib and TACE, apart from the trial design which described the duration of sorafenib administration and TACE treatment regimen, the failure could be mainly due to the vast heterogeneity of unresectable HCCs, leading to differences in individual response ( 15 – 18 ). Therefore, a personalized prediction biomarker or model which can identify patients who may benefit from the combination therapy is crucial for treatment decision.…”

Section: Introductionmentioning

confidence: 99%

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Deep Learning Predicts Overall Survival of Patients With Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization Plus Sorafenib

et al. 2020

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Objectives: To develop and validate a deep learning-based overall survival (OS) prediction model in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus sorafenib. Methods: This retrospective multicenter study consisted of 201 patients with treatmentnaïve, unresectable HCC who were treated with TACE plus sorafenib. Data from 120 patients were used as the training set for model development. A deep learning signature was constructed using the deep image features from preoperative contrast-enhanced computed tomography images. An integrated nomogram was built using Cox regression by combining the deep learning signature and clinical features. The deep learning signature and nomograms were also externally validated in an independent validation set of 81 patients. C-index was used to evaluate the performance of OS prediction. Results: The median OS of the entire set was 19.2 months and no significant difference was found between the training and validation cohort (18.6 months vs. 19.5 months, P = 0.45). The deep learning signature achieved good prediction performance with a C-index of 0.717 in the training set and 0.714 in the validation set. The integrated nomogram showed significantly better prediction performance than the clinical nomogram in the training set (0.739 vs. 0.664, P = 0.002) and validation set (0.730 vs. 0.679, P = 0.023). Conclusion: The deep learning signature provided significant added value to clinical features in the development of an integrated nomogram which may act as a potential tool for individual prognosis prediction and identifying HCC patients who may benefit from the combination therapy of TACE plus sorafenib.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Deep Learning Predicts Overall Survival of Patients With Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization Plus Sorafenib

et al. 2020

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“…Another important option in intermediate-stage HCC is a combination strategy of TACE with molecular targeted agents. After 5 negative trials [40][41][42][43][44], the TACTICS trial clearly showed that TACE combined with sorafenib improved progression-free survival, which was specifically defined based on the concept of unTACEable progression [45,46]. Zhu [27] 12.…”

Section: Paradigm Change In Intermediate-stage Hccmentioning

confidence: 99%

A Paradigm Change in the Treatment Strategy for Hepatocellular Carcinoma

Kudo¹

2020

Liver Cancer

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“…Sorafenib is reported to improve OS and time to progression in patients with intermediate or advanced HCC that is refractory to TACE (23,24). Moreover, the Transcatheter Arterial Chemoembolization Therapy in Combination with Sorafenib (TACTICS) trial showed that the combination of TACE with sorafenib significantly improved the time to progression compared to TACE alone in patients with HCC (25,26). However, it remains unclear if further TACE or switching to MKIs is more beneficial for patients with HCC recurrence after TACE.…”

Section: Indication Of Suitable Transarterial Chemoembolization and Mmentioning

confidence: 99%

Indication of suitable transarterial chemoembolization and multikinase inhibitors for intermediate stage hepatocellular carcinoma

et al. 2020

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Prognosis of patients with intermediate stage hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) is unsatisfactory. The present study analyzed the indications for suitable TACE in patients with intermediate stage HCC. Additionally, it was investigated whether further TACE or switching to multi-kinase inhibitors (MKIs) was more beneficial for patients with HCC recurrence following initial TACE. The present retrospective study included 238 patients with intermediate stage HCC who were initially treated with TACE (median age, 74 years). A decision-tree analysis was employed to investigate the therapeutic effect profiles and overall survival (OS) rates. In the decision-tree analysis for OS, complete response (CR) by initial TACE was selected as the most important variable. In the decision-tree analysis for CR, <3 liver segments with nodule, simple nodular type and within the up-to-seven criteria were selected as the first, second and third variables associated with a high CR rate (35-64%), respectively. In patients with HCC recurrence having ≥3 liver segments with nodule, out of the up-to-seven criteria, and Child-Pugh class A, the median survival time was significantly longer in those who were treated by switching to MKIs compared with further TACE (44.9 vs. 21.9 months; P=0.003). In intermediate stage HCC, the indications for suitable TACE criteria may be '<3 liver segments with nodule', 'simple nodular type', and 'within the up-to-seven criteria'. Additionally, in patients who were ineligible for TACE criteria, the switch to MKIs may improve the prognosis compared with further TACE in cases of HCC recurrence following first TACE.

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Proposal of Primary Endpoints for TACE Combination Trials with Systemic Therapy: Lessons Learned from 5 Negative Trials and the Positive TACTICS Trial

Cited by 34 publications

References 22 publications

Deep Learning Predicts Overall Survival of Patients With Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization Plus Sorafenib

Deep Learning Predicts Overall Survival of Patients With Unresectable Hepatocellular Carcinoma Treated by Transarterial Chemoembolization Plus Sorafenib

A Paradigm Change in the Treatment Strategy for Hepatocellular Carcinoma

Indication of suitable transarterial chemoembolization and multikinase inhibitors for intermediate stage hepatocellular carcinoma

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