Plasma Sphingolipid Metabolites and Radiotherapy Efficacy in Hepatocellular Carcinoma
NCT ID: NCT06864221
Last Updated: 2025-03-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
260 participants
OBSERVATIONAL
2024-09-01
2026-06-01
Brief Summary
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Detailed Description
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Sphingolipids, including ceramide (CER), sphingosine (SPH), and sphingosine-1-phosphate (S1P), are essential cellular signaling molecules involved in apoptosis, proliferation, and inflammation. Studies have shown that radiotherapy influences sphingolipid metabolism by altering enzyme activity, thereby affecting the balance of CER, SPH, and S1P-key regulators of tumor cell apoptosis. With advancements in lipidomics, the role of sphingolipid metabolism in radiation sensitivity has become an area of growing interest. Sphingolipid levels have been correlated with radiotherapy sensitivity in various cancers, making them potential prognostic biomarkers and therapeutic targets.
This study is designed as a single-center, prospective observational study with a two-year follow-up period, enrolling 260 primary liver cancer patients receiving radiotherapy. Plasma samples will be collected before, during, and after radiotherapy for qualitative and quantitative analysis of sphingolipid metabolites using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). Clinical imaging and laboratory data related to treatment response and adverse events will also be collected. Patients will be classified according to the mRECIST 1.1 criteria into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) groups for further correlation analysis.
The primary objective is to investigate the relationship between plasma sphingolipid levels and radiotherapy efficacy by analyzing overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), disease-free survival (DFS), and time to progression (TTP). The secondary objective is to explore the association between sphingolipid levels and radiation-induced toxicity, including RILD, radiation enteritis, and bone marrow suppression, to assess their potential as predictive biomarkers for treatment-related complications.
Patients will be followed at 1, 2, 6, 12, 18, 24, 36, and 48 months post-radiotherapy. The study does not involve any interventional treatment beyond standard clinical care, and patient management decisions will remain at the discretion of treating physicians. This research aims to provide new insights into the clinical significance of sphingolipid metabolism in predicting radiotherapy outcomes and toxicity in liver cancer, potentially improving personalized radiotherapy strategies.
Conditions
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Study Design
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CASE_ONLY
RETROSPECTIVE
Study Groups
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Radiotherapy Responder Group
Participants who show a positive response to radiotherapy, as defined by mRECIST 1.1 criteria. This includes patients with Complete Response (CR) or Partial Response (PR) after radiotherapy. A decline in Alpha-Fetoprotein (AFP) levels may also be observed in some responders, serving as a potential biomarker for treatment efficacy.
No interventions assigned to this group
Radiotherapy Non-Responder Group
Participants who do not show a significant response to radiotherapy, as defined by mRECIST 1.1 criteria. This includes patients classified as Stable Disease (SD) or Progressive Disease (PD) after radiotherapy. AFP levels may remain stable or increase in these patients, indicating a lack of significant tumor response to treatment.
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* Aged between 18 and 80 years.
* Clinically diagnosed with primary liver cancer according to the latest treatment guidelines.
* Determined by the treating physician to require radiotherapy.
* Expected survival time of more than 3 months.
Exclusion Criteria
* Presence of malignancies from other origins.
* Severe metabolic diseases such as uncontrolled diabetes, significant obesity, or fatty liver disease.
* Uncontrolled comorbidities, such as severe cardiovascular or pulmonary diseases, that may affect treatment or study outcomes.
18 Years
80 Years
ALL
No
Sponsors
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Nanfang Hospital, Southern Medical University
OTHER
Responsible Party
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Principal Investigators
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Yiyi Li, PhD
Role: PRINCIPAL_INVESTIGATOR
Nanfang Hospital, Southern Medical University
Locations
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Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China
Countries
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Central Contacts
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Facility Contacts
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References
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Deng X, Yin X, Allan R, Lu DD, Maurer CW, Haimovitz-Friedman A, Fuks Z, Shaham S, Kolesnick R. Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science. 2008 Oct 3;322(5898):110-5. doi: 10.1126/science.1158111.
Kumar A, Oskouian B, Fyrst H, Zhang M, Paris F, Saba JD. S1P lyase regulates DNA damage responses through a novel sphingolipid feedback mechanism. Cell Death Dis. 2011 Feb 10;2(2):e119. doi: 10.1038/cddis.2011.3.
Taha TA, Osta W, Kozhaya L, Bielawski J, Johnson KR, Gillanders WE, Dbaibo GS, Hannun YA, Obeid LM. Down-regulation of sphingosine kinase-1 by DNA damage: dependence on proteases and p53. J Biol Chem. 2004 May 7;279(19):20546-54. doi: 10.1074/jbc.M401259200. Epub 2004 Feb 26.
Aureli M, Bassi R, Prinetti A, Chiricozzi E, Pappalardi B, Chigorno V, Di Muzio N, Loberto N, Sonnino S. Ionizing radiations increase the activity of the cell surface glycohydrolases and the plasma membrane ceramide content. Glycoconj J. 2012 Dec;29(8-9):585-97. doi: 10.1007/s10719-012-9385-2. Epub 2012 May 17.
Cheng JC, Bai A, Beckham TH, Marrison ST, Yount CL, Young K, Lu P, Bartlett AM, Wu BX, Keane BJ, Armeson KE, Marshall DT, Keane TE, Smith MT, Jones EE, Drake RR Jr, Bielawska A, Norris JS, Liu X. Radiation-induced acid ceramidase confers prostate cancer resistance and tumor relapse. J Clin Invest. 2013 Oct;123(10):4344-58. doi: 10.1172/JCI64791. Epub 2013 Sep 16.
Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A, Fuks Z, Kolesnick R. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science. 2003 May 16;300(5622):1155-9. doi: 10.1126/science.1082504.
Liao WC, Haimovitz-Friedman A, Persaud RS, McLoughlin M, Ehleiter D, Zhang N, Gatei M, Lavin M, Kolesnick R, Fuks Z. Ataxia telangiectasia-mutated gene product inhibits DNA damage-induced apoptosis via ceramide synthase. J Biol Chem. 1999 Jun 18;274(25):17908-17. doi: 10.1074/jbc.274.25.17908.
Gomez-Larrauri A, Presa N, Dominguez-Herrera A, Ouro A, Trueba M, Gomez-Munoz A. Role of bioactive sphingolipids in physiology and pathology. Essays Biochem. 2020 Sep 23;64(3):579-589. doi: 10.1042/EBC20190091.
Benson R, Madan R, Kilambi R, Chander S. Radiation induced liver disease: A clinical update. J Egypt Natl Canc Inst. 2016 Mar;28(1):7-11. doi: 10.1016/j.jnci.2015.08.001. Epub 2015 Aug 20.
Wen N, Cai Y, Li F, Ye H, Tang W, Song P, Cheng N. The clinical management of hepatocellular carcinoma worldwide: A concise review and comparison of current guidelines: 2022 update. Biosci Trends. 2022 Mar 11;16(1):20-30. doi: 10.5582/bst.2022.01061. Epub 2022 Feb 24.
Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022 Oct 15;400(10360):1345-1362. doi: 10.1016/S0140-6736(22)01200-4. Epub 2022 Sep 6.
Other Identifiers
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NFEC-2024-389
Identifier Type: -
Identifier Source: org_study_id
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