Dataset Information

Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy.

ABSTRACT: Background:Tumoral macrovascular invasion (MVI) of hepatic and/or portal vein branches is a common phenomenon in hepatocellular carcinoma (HCC) and is associated with poorer prognosis when compared to HCC without MVI. Summary:Current international guidelines for the management of HCC recommend sorafenib as the only treatment option in case of MVI. Despite guideline recommendations, several alternative options have been tested to manage HCC with MVI: surgery, transarterial chemoembolization, external or internal radiation, hepatic arterial infusion chemotherapy, percutaneous treatment, cryotherapy, or the combination of two or more of these strategies, with or without sorafenib. Here we will provide a comprehensive state-of-the-art review for the management of this challenging clinical entity based on the most recent available data. Key Messages:There is a growing body of evidence suggesting that alternative strategies to standard-of-care sorafenib might improve survival in patients with advanced HCC with MVI but the level of evidence remains weak. Randomized phase III trials are ongoing and will hopefully provide information leading towards a more personalized treatment algorithm.

SUBMITTER: Costentin CE

PROVIDER: S-EPMC5704715 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy.

Costentin Charlotte E CE Ferrone Cristina R CR Arellano Ronald S RS Ganguli Suvranu S Hong Theodore S TS Zhu Andrew X AX

Liver cancer 20171019 4

<h4>Background</h4>Tumoral macrovascular invasion (MVI) of hepatic and/or portal vein branches is a common phenomenon in hepatocellular carcinoma (HCC) and is associated with poorer prognosis when compared to HCC without MVI.<h4>Summary</h4>Current international guidelines for the management of HCC recommend sorafenib as the only treatment option in case of MVI. Despite guideline recommendations, several alternative options have been tested to manage HCC with MVI: surgery, transarterial chemoemb ...[more]

PMID: 29234639

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Project description:BackgroundModels predicting future macrovascular invasion in hepatocellular carcinoma are constructed to assist timely interventions.MethodsA total of 366 HCC cases were retrospectively collected from five Chinese hospitals between April 2007 and November 2016: the training dataset comprised 281 patients from four hospitals; the external validation dataset comprised 85 patients from another hospital. Multi-task deep learning network-based models were constructed to predict future macrovascular invasion. The discrimination, calibration, and decision curves were compared to identify the best model. We compared the time to macrovascular invasion and overall survival using the best model and related image heterogeneity scores (H-score). Then, we determined the need for a segmentation subnet or the replacement deep learning algorithm by logistic regression in screening clinical/radiological factors. Finally, an applet was constructed for future application.FindingsThe best model combined clinical/radiological factors and radiomic features. It achieved best discrimination (areas under the curve: 0·877 in the training dataset and 0·836 in the validation dataset), calibration, and decision curve. Its performance was not affected by the treatments and disease stages. The subgroups had statistical significance for time to macrovascular invasion (training: hazard ratio [HR] = 0·073, 95% confidence interval [CI]: 0·032-0·167, p < 0·001 and validation: HR = 0·090, 95%CI: 0·022-0·366, p < 0·001) and overall survival (training: HR = 0·344, 95%CI: 0·246-0·547, p < 0·001 and validation: HR = 0·489, 95%CI: 0·279 - 0·859, p = 0·003). Similar results were achieved when the patients were subdivided by the H-score. The subnet for segmentation and end-to-end deep learning algorithms improved the performance of the model.InterpretationOur multi-task deep learning network-based model successfully predicted future macrovascular invasion. In high-risk populations, besides the current first-line treatments, more therapies may be explored for macrovascular invasion.

Project description:Background and aimsNivolumab was the first immune checkpoint inhibitor approved for hepatocellular carcinoma (HCC). External beam radiation therapy (EBRT) is locally effective and may enhance the effectiveness of immunotherapy. This study investigated the efficacy and safety of concurrent nivolumab and EBRT in HCC with macrovascular invasion.MethodsIn this phase II multicenter trial, patients with HCC and macrovascular invasion were concurrently treated with intravenous nivolumab (3 mg/kg every 2 weeks) and EBRT, followed by maintenance nivolumab until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) and safety, and secondary endpoints were overall survival, time-to-progression, objective response rate, and disease control rate.ResultsBetween January 2020 and June 2021, 50 patients (male 84%, median age 62.5) were enrolled; 47 (94.0%) and 13 (26.0%) with portal (Vp1/2, n = 21; Vp3, n = 23; Vp4, n = 3) and hepatic vein invasion, respectively. Patients received EBRT (median dose: 50 [IQR 43-50] Gy) after the first nivolumab dose. The median number of nivolumab doses was 8.5. Median PFS was 5.6 (90% CI 3.6-9.9) months. Median overall survival and time-to-progression were 15.2 (90% CI 10.8-19.6) and 5.6 (90% CI 3.6-9.9) months, respectively. The objective response rate and disease control rate were 36.0% and 74.0%, respectively. The median duration of response was 9.9 months. Of 35 patients with follow-up data, 23 received subsequent systemic treatment, including atezolizumab-bevacizumab, sorafenib, lenvatinib, and regorafenib. Treatment-related any grade adverse events (AEs) and grade 3/4 AEs occurred in 40 (80.0%) and 6 (12.0%) patients, respectively. Common treatment-related AEs included pruritus (38.0%) and rash (16.0%), with no treatment-related deaths.ConclusionConcurrent nivolumab therapy and EBRT showed encouraging PFS with acceptable safety in patients with advanced HCC and macrovascular invasion.Impact and implicationsImmune checkpoint inhibitors, the standard care for advanced hepatocellular carcinoma (HCC), show relatively poor therapeutic effects in patients with advanced HCC and macrovascular invasion. In this investigator-initiated phase II study, we, for the first time, show that concurrent external beam radiation therapy with nivolumab, an immune checkpoint inhibitor, led to encouraging progression-free survival in patients with HCC and macrovascular invasion. The concurrent treatment was tolerable without significant safety concerns. Further randomized studies investigating the combination of immunotherapy and external beam radiation therapy are required.Clinicaltrialsgov identifierNCT04611165.

Dataset Information

Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy.

Publications

Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy.

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