Verslype, C. (Chris)
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- Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma(2023) Pietzner, A. (Anne); Rohwer, N. (Nadine); Leineweber, C.G. (Can G.); Verslype, C. (Chris); Sangro, B. (Bruno); Weylandt, K.H. (Karsten-H); Sengel, C. (Christian); Rabehl, M. (Miriam); Pech, M. (Maciej); Basu, B. (Bristi); Rothe, M. (Michael); Ricke, J. (Jeans); Benckert, J. (Julia); Schebb, N.H. (Nils Helge)Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.
- Prognostic role of radiomics-based body composition analysis for the 1-year survival for hepatocellular carcinoma patients(2023) Gebauer, B. (Bernhard); Hille, G. (Georg); Loewe, C. (Christian); Surov, A. (Alexey); Iezzi, R. (Roberto); Zech, C.J. (Christoph J.); Kreherm, R. (Rober); Gasbarrini, A. (Antonio); Klümpen, H. (Heinz); Verslype, C. (Chris); Saalfeld, S. (Sylvia); Öcal, O. (Osman); Bargellini, I. (Irene); Sangro, B. (Bruno); Sengel, C. (Christian); Seidensticker, M. (Max); Schuette, K. (Kerstin); Berg, T. (Thomas); Pech, M. (Maciej); Amthauer, H. (Holger); Delden, O.M. (Otto M.) van; Niemann, U. (Uli); Preim, B. (Bernhard); Vandecaveye, V. (Vincent); Ricke, J. (Jeans); Benckert, J. (Julia); Malfertheiner, P. (Peter); Hinnerichs, M. (Mattes)BackgroundParameters of body composition have prognostic potential in patients with oncologic diseases. The aim of the present study was to analyse the prognostic potential of radiomics-based parameters of the skeletal musculature and adipose tissues in patients with advanced hepatocellular carcinoma (HCC). MethodsRadiomics features were extracted from a cohort of 297 HCC patients as post hoc sub-study of the SORAMIC randomized controlled trial. Patients were treated with selective internal radiation therapy (SIRT) in combination with sorafenib or with sorafenib alone yielding two groups: (1) sorafenib monotherapy (n = 147) and (2) sorafenib and SIRT (n = 150). The main outcome was 1-year survival. Segmentation of muscle tissue and adipose tissue was used to retrieve 881 features. Correlation analysis and feature cleansing yielded 292 features for each patient group and each tissue type. We combined 9 feature selection methods with 10 feature set compositions to build 90 feature sets. We used 11 classifiers to build 990 models. We subdivided the patient groups into a train and validation cohort and a test cohort, that is, one third of the patient groups. ResultsWe used the train and validation set to identify the best feature selection and classification model and applied it to the test set for each patient group. Classification yields for patients who underwent sorafenib monotherapy an accuracy of 75.51% and area under the curve (AUC) of 0.7576 (95% confidence interval [CI]: 0.6376-0.8776). For patients who underwent treatment with SIRT and sorafenib, results are accuracy = 78.00% and AUC = 0.8032 (95% CI: 0.6930-0.9134). ConclusionsParameters of radiomics-based analysis of the skeletal musculature and adipose tissue predict 1-year survival in patients with advanced HCC. The prognostic value of radiomics-based parameters was higher in patients who were treated with SIRT and sorafenib.
- The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022(2023) Osterlund, P. (P.); O'Reilly, E.M. (E. M.); Gill, S. (S.); Tabernero, J. (J.); Berlin, J. (J.); Galle, P. (P.); Lordick, F. (F.); Van-Cutsem, E. (E.); Ruiz-Garcia, E. (E.); Cervantes, A. (Andrés); Verslype, C. (Chris); O'Connor, J.M. (J. M.); Wasan, H. (H.); Sangro, B. (Bruno); Bekaii-Saab, T. (T.); Llovet, J.M. (J. M.); Philip, P. (P.); Laurent-Puig, P. (P.); Baere, T. (T.) de; Mukherji, D. (D.); Prager, G. (G.); Haustermans, K. (K.); Ducreux, M. (M.); Macarulla, T. (T.); Eng, C. (C.); Obermannova, R. (R.); Lamarca, A. (Angela); Muro, K. (K.); Seufferlein, T. (T.); Gruenberger, T. (T.); Abou-Alfa, G.K. (Ghassan K.)This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.
- Impact of body composition in advanced hepatocellular carcinoma: a subanalysis of the SORAMIC trial(2023) Thormann, M. (Maximilian); Gebauer, B. (Bernhard); Loewe, C. (Christian); Wienke, A. (Andreas); Surov, A. (Alexey); Iezzi, R. (Roberto); Zech, C.J. (Christoph J.); Gasbarrini, A. (Antonio); Schütte, K. (Kerstin); Klümpen, H. (Heinz); Verslype, C. (Chris); Öcal, O. (Osman); Bargellini, I. (Irene); Sangro, B. (Bruno); Seidensticker, R. (Ricarda); Sengel, C. (Christian); Seidensticker, M. (Max); Omari, J. (Jazan); Berg, T. (Thomas); Pech, M. (Maciej); Amthauer, H. (Holger); Delden, O.M. (Otto M.) van; Vandecaveye, V. (Vincent); Ricke, J. (Jeans); Benckert, J. (Julia); Malfertheiner, P. (Peter); Hinnerichs, M. (Mattes)Background:Body composition parameters have been reported to be prognostic factors in patients with oncologic diseases. However, the available data on patients with HCC are conflicting. The aim of this study was to assess the impact of body composition on survival in patients with HCC treated with sorafenib or selective internal radioembolization (SIRT) and sorafenib. Methods:This is an exploratory subanalysis of the prospective, randomized controlled SORAMIC trial. Within the palliative arm of the study, patients were selected if a baseline abdominal CT was available. A broad set of skeletal muscle and adipose tissue parameters were measured at the L3 level. Low skeletal muscle mass (LSMM) and density parameters were defined using published cutoffs. The parameters were correlated with overall survival. Results:Of 424 patients in the palliative study arm, 369 patients were included in the analysis. There were 192 patients in the combined sorafenib/SIRT and 177 patients in the sorafenib group. Median overall survival was 9.9 months for the entire cohort and 10.8 and 9.2 months for the SIRT/sorafenib and sorafenib groups, respectively. There was no relevant association of either body composition parameter with overall survival in either the overall cohort or in the SIRT/sorafenib or sorafenib subgroups. Conclusions:This subanalysis of the prospective SORAMIC trial does not suggest a relevant influence of body composition parameters of survival in patients with advanced HCC. Body composition parameters therefore do not serve in patient allocation in this palliative treatment cohort.