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Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy.

ABSTRACT: BACKGROUND:Immunotherapy represents a promising option for treatment of hepatocellular carcinoma (HCC) in cirrhotic patients but its efficacy is currently inconsistent and unpredictable. Locoregional therapies inducing immunogenic cell death, such as transarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT), have the potential to act synergistically with immunotherapy. For the development of new approaches combining locoregional treatments with immunotherapy, a better understanding of the respective effects of TACE and SIRT on recruitment and activation of immune cells in HCC is needed. To address this question, we compared intra-tumor immune infiltrates in resected HCC after preoperative treatment with TACE or SIRT. METHODS:Data fromr patients undergoing partial hepatectomy for HCC, without preoperative treatment (SURG, n?=?32), after preoperative TACE (TACE, n?=?16), or preoperative SIRT (n?=?12) were analyzed. Clinicopathological factors, tumor-infiltrating lymphocytes (TILs), CD4+ and CD8+ T cells, and granzyme B (GZB) expression in resected HCC, and postoperative overall and progression-free survival were compared between the three groups. RESULTS:Clinicopathological and surgical characteristics were similar in the three groups. A significant increase in TILs, CD4+ and CD8+ T cells, and GZB expression was observed in resected HCC in SIRT as compared to TACE and SURG groups. No difference in immune infiltrates was observed between TACE and SURG patients. Within the SIRT group, the dose of irradiation affected the type of immune infiltrate. A significantly higher ratio of CD3+ cells was observed in the peri-tumoral area in patients receiving ?100?Gy. Postoperative outcomes were similar in all groups. Irrespective of the preoperative treatment, the type and extent of immune infiltrates did not influence postoperative survival. CONCLUSIONS:SIRT significantly promotes recruitment/activation of intra-tumor effector-type immune cells compared to TACE or no preoperative treatment. These results suggest that SIRT is a better candidate than TACE to be combined with immunotherapy for treatment of HCC. Evaluation of the optimal doses for SIRT for producing an immunogenic effect and the type of immunotherapy to be used require further evaluation in prospective studies.

SUBMITTER: Craciun L

PROVIDER: S-EPMC7032008 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy.

Craciun Ligia L de Wind Roland R Demetter Pieter P Lucidi Valerio V Bohlok Ali A Michiels Sébastien S Bouazza Fikri F Vouche Michael M Tancredi Ilario I Verset Gontran G Garaud Soizic S Naveaux Céline C Galdon Maria Gomez MG Gallo Karen Willard KW Hendlisz Alain A Derijckere Ivan Duran ID Flamen Patrick P Larsimont Denis D Donckier Vincent V

BMC cancer 20200219 1

<h4>Background</h4>Immunotherapy represents a promising option for treatment of hepatocellular carcinoma (HCC) in cirrhotic patients but its efficacy is currently inconsistent and unpredictable. Locoregional therapies inducing immunogenic cell death, such as transarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT), have the potential to act synergistically with immunotherapy. For the development of new approaches combining locoregional treatments with immunotherapy, ...[more]

PMID: 32075608

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Project description:BackgroundCholangiocarcinoma (CC) is the second most primary liver malignancy with increasing incidence in Western countries. Currently, surgical R0 resection is regarded as the only potentially curative treatment. The results of systemic chemotherapy and best supportive care (BSC) in patients with metastatic disease are often disappointing in regard to toxicity, oncologic efficacy, and overall survival. In current practice, the use of different locoregional therapies is increasingly more accepted.MethodsA review of the literature on locoregional therapies for intrahepatic cholangiocarcinoma (ICC) was undertaken.ResultsThere are no prospective randomized controlled trials. For localized ICC, either primary or recurrent, radiofrequency ablation (RFA) is by far the most commonly used thermal ablation modality. Thereby, a systematic review and meta-analysis reports major complication in 3.8% as well as 1-, 3-, and 5-year overall survival rates of 82, 47, and 24%, respectively. In selected patients (e.g. with a tumor diameter of ≤3 cm), oncologic efficacy and survival after RFA are comparable with surgical resection. For diffuse ICC, different transarterial therapies, either chemotherapy-based (hepatic artery infusion (HAI), transarterial chemoembolization (TACE)) or radiotherapy-based (transarterial radioembolization (TARE)), show extremely promising results. With regard to controlled trials (transarterial therapy versus systemic chemotherapy, BSC or no treatment), tumor control is virtually always better for transarterial therapies and very often accompanied by a dramatic survival benefit and improvement of quality of life. Of note, the latter is the case not only for patients without extrahepatic metastatic disease but also for those with liver-dominant extrahepatic metastatic disease. There are other locoregional therapies such as microwave ablation, irreversible electroporation, and chemosaturation; however, the current data support their use only in controlled trials or as last-line therapy.ConclusionDedicated locoregional therapies are commonly used for primary and recurrent ICC as well as liver-only and liver-dominant extrahepatic metastatic disease. Currently, the best evidence and most promising results are available for RFA, HAI, TACE, and TARE. In cohort studies, the overall survival rates are similar to those obtained with surgery or systemic therapies. Prospective randomized controlled trials are warranted to compare safety and efficacy between different surgical, interventional, and systemic therapies, as well as their combinations.

Dataset Information

Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy.

Publications

Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy.

Similar Datasets

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