Cytokines and 90Y-Radioembolization: Relation to Liver Function and Overall Survival

Seidensticker, Max; Powerski, Maciej; Seidensticker, Ricarda; Damm, Robert; Mohnike, Konrad; Garlipp, Benjamin; Klopffleisch, Maurice; Amthauer, Holger; Ricke, Jens; Pech, Maciej

doi:10.1007/s00270-017-1622-4

Cited by 29 publications

(31 citation statements)

References 28 publications

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“…Both Fernandez-Ros et al and Seidensticker et al showed that proinflammatory cytokines were increased after Y90 treatment, the latter also suggested that high levels of IL-8 or IL-6 pre-treatment could predict decreased overall survival. 52,53 In summary, results from a number of studies suggest that locoregional therapies cause changes in tumourspecific and innate immune responses. It is very plausible that changes in the local cytokine and/ or chemokine milieu, which are difficult to measure in patients, result from locoregional therapies and affect not only effector cell responses, but also immune suppressor mechanisms such as MDSCs.…”

Section: Key Pointsmentioning

confidence: 99%

Combined locoregional-immunotherapy for liver cancer

Greten

Mauda-Havakuk

Heinrich

et al. 2019

Journal of Hepatology

161

123

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Locoregional therapies are commonly used to treat patients with hepatocellular carcinoma. It has been noted for many years that locoregional therapies may have additional systemic effects other than simple tumour elimination. Immunological ''side effects" have been described in response to locoregional therapies in animal studies and in patients. With the advent of immunotherapy for hepatocellular carcinoma, there is increasing interest in determining the best way to combine immunotherapy with locoregional therapies. Herein, we provide a compact summary of answered and unanswered questions in the field, including: What animal model is best suited to test combined immune-locoregional treatments? How does tumour cell death affect immune responses? What type of immune responses have been observed in patients treated with different types of locoregional therapies? What can be surmised from the results of the first study testing the combination of locoregional therapy with immune checkpoint blockade? Finally, we discuss the outlook for this rapidly growing area of research, focussing on the issues which must be overcome to bridge the gap between interventional radiology and cancer immunology. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.

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Section: Key Pointsmentioning

confidence: 99%

Combined locoregional-immunotherapy for liver cancer

Greten

Mauda-Havakuk

Heinrich

et al. 2019

Journal of Hepatology

161

123

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“…Due to a minimally embolic effect in comparison with PVE, radio-induced damage and cell death within the treated liver lobe are likely to be the main inducer of the hypertrophy in the contralateral RL after RE. Thus, we hypothesized that RL hypertrophy could be at least in part in relation to the levels of injuries and induction of cell death in the injected healthy liver and/or of the tumor itself possibly in relation to the production of growth factors and cytokines [ 17 – 20 ]. It is mandatory to keep in mind that the threshold doses inducing damages are different in tumor versus healthy liver.…”

Section: Introductionmentioning

confidence: 99%

Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma

Palard

Edeline

Rolland

et al. 2017

Eur J Nucl Med Mol Imaging

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PurposeThis study aimed at identifying prior therapy dosimetric parameters using 99mTc-labeled macro-aggregates of albumin (MAA) that are associated with contralateral hepatic hypertrophy occurring after unilobar radioembolization of hepatocellular carcinoma (HCC) performed with 90Y–loaded glass microspheres.MethodsThe dosimetry data of 73 HCC patients were collected prior to the treatment with 90Y–loaded microspheres for unilateral disease. The injected liver dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were calculated based on MAA quantification. Following treatment, the maximal hypertrophy (MHT) of an untreated lobe was calculated.ResultsMean MHT was 35.4 ± 40.4%. When using continuous variables, the MHT was not correlated with any tested variable, i.e., injected activity, ILD, HILD or TD except with a percentage of future remnant liver (FRL) following the 90Y–microspheres injection (r = −0.56). MHT ≥ 10% was significantly more frequent for patients with HILD ≥ 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p = 0.032). MHT ≥ 10% was also significantly more frequent for patients with a TD ≥ 205 Gy and a tumor volume (VT) ≥ 100 cm3 in patients with initial FRL < 50%. MHT ≥10% was seen in 83.9% for patients with either an HILD ≥ 88 Gy or a TD ≥ 205 Gy for tumors larger than 100cm3 (85% of the cases), versus only 54.5% (p = 0.0265) for patients with none of those parameters. MHT ≥10% was also associated with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still significantly associated with MHT ≥10%.ConclusionThis study demonstrates for the first time that HILD is significantly associated with liver hypertrophy. There is also an impact of high tumor doses in large lesions in one subgroup of patients. Larger prospective studies evaluating the MAA dosimetric parameters have to be conducted to confirm these promising results.

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“…In addition, CHE is considered to be an excellent marker in liver cirrhosis [12] and may therefore be crucial for pre-therapeutic evaluations of liver function especially in primary liver tumor patients and underlying liver cirrhosis. Up to date, only few studies take CHE levels into consideration, namely either as an inclusion criterion (baseline CHE levels within normal limits) [3] or for monitoring liver function after RE [36].…”

Section: Discussionmentioning

confidence: 99%

Impact of Baseline Cholinesterase in Patients with Primary Liver Tumors Undergoing Radioembolization: Impact on Outcome

Galiè

Paprottka

Ingrisch

et al. 2018

SN Compr. Clin. Med.

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The purpose of our study was to determine cutoff values for baseline cholinesterase (CHE) and bilirubin levels prognostic for outcome after radioembolization (RE) in patients with primary liver tumors. In this retrospective single-center study, a threshold for baseline levels of CHE and bilirubin was determined based on overall survival (OS) of patients with refractory primary liver tumors who underwent RE. Between-group differences based on the dichotomized cohort were assessed with the log-rank test. We analyzed N = 92 patients (median age 66.6 years (60.6-73.6 interquartile range), 79% male) with primary liver tumors (57 with hepatocellular carcinoma and 35 with intrahepatic cholangiocarcinoma) who were treated with RE. The median baseline level for bilirubin was 0.7 mg/dl (0.5-1.1 IQR) and for CHE 5.10 kU/l (3.64-6.56), respectively. Median OS in all patients was 429 days (307-550). Cutoff values of baseline bilirubin at 1.6 mg/dl and for CHE at 5 kU/l effectively allowed to differentiate survival groups. In patients with baseline bilirubin ≤ 1.6 mg/dl, OS was significantly higher than in those with bilirubin (> 1.6 mg/dl, P < 0.001). Patients with a baseline CHE of > 5 kU/l showed a significantly longer OS than those with CHE ≤ 5 kU/l, P < 0.001). We suggest that baseline CHE and bilirubin levels have prognostic impact on survival in patients with primary liver tumors after RE. Cutoff values of baseline liver parameters as determined in our study (bilirubin 1.6 mg/dl and CHE 5 kU/l) may help to better select patients eligible for RE. Keywords Brachytherapy. Hepatocellular carcinoma. Intrahepatic cholangiocarcinoma. Bilirubin. Cholinesterase Abbreviations ICC Intrahepatic cholangiocarcinoma CHE Cholinesterase EHD Extrahepatic disease ECOG Eastern Cooperative Oncology Group HCC Hepatocellular carcinoma Franziska Galiè and K. J. Paprottka contributed equally to this work. This article is part of the Topical Collection on Imaging Key points • Cutoff values of baseline bilirubin and cholinesterase show a prognostic impact on survival in patients with primary liver tumors after radioembolization. • Baseline levels of bilirubin of 1.6 mg/dl and cholinesterase of 5 kU/l effectively allowed to differentiate survival groups. • Cutoff values for liver function parameters may help to further guide patient selection for radioembolization.

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Cytokines and 90Y-Radioembolization: Relation to Liver Function and Overall Survival

Cited by 29 publications

References 28 publications

Combined locoregional-immunotherapy for liver cancer

Combined locoregional-immunotherapy for liver cancer

Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma

Impact of Baseline Cholinesterase in Patients with Primary Liver Tumors Undergoing Radioembolization: Impact on Outcome

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