Plasma Sphingolipid Metabolites and Radiotherapy Efficacy in Hepatocellular Carcinoma
Correlation Between Plasma Sphingolipid Metabolites and the Efficacy of Radiotherapy in Hepatocellular Carcinoma
1 other identifier
observational
260
1 country
1
Brief Summary
Plasma contains a variety of metabolites, among which sphingolipids, including ceramide, sphingosine, and sphingosine-1-phosphate, serve as important intracellular second messengers and are involved in various cellular signaling pathways, such as apoptosis. We hypothesize that plasma sphingolipid levels may be associated with the efficacy of radiotherapy for liver cancer. This study will utilize LC-MS/MS technology for qualitative and quantitative analysis of plasma sphingolipids in liver cancer patients undergoing radiotherapy. Clinical data related to patient prognosis will also be collected to investigate the correlation between plasma sphingolipid levels and the therapeutic efficacy of liver cancer radiotherapy. The aim is to establish the clinical diagnostic significance of plasma sphingolipid levels in predicting the efficacy of liver cancer radiotherapy, providing new insights to enhance the effectiveness of radiotherapy in liver cancer treatment.
Trial Health
Trial Health Score
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participants targeted
Target at P75+ for all trials
Started Sep 2024
1 active site
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Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2024
CompletedFirst Submitted
Initial submission to the registry
March 3, 2025
CompletedFirst Posted
Study publicly available on registry
March 7, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2026
ExpectedMarch 12, 2025
March 1, 2025
1.3 years
March 3, 2025
March 9, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Disease Control Rate (DCR)
Disease Control Rate (DCR) is defined as the proportion of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). mRECIST is commonly used to evaluate tumor response, especially in the context of hepatocellular carcinoma and other solid tumors. DCR is an important measure to assess the overall effectiveness of the treatment in controlling disease progression.
From the start of treatment to 12 weeks post-treatment assessment
Secondary Outcomes (3)
Progression-Free Survival (PFS)
From treatment initiation to the date of disease progression or death, up to 24 months.
Overall Survival (OS)
From treatment initiation to death, up to 24 months
Safety and Tolerability
From the start of treatment until 90 days after the last dose.
Study Arms (2)
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.
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.
Eligibility Criteria
This study will enroll adult patients aged 18 to 80 years who have been clinically diagnosed with primary liver cancer according to the latest treatment guidelines. Eligible participants must be determined by their treating physicians to require radiotherapy and have an expected survival time of more than three months. Patients with malignancies of other origins, severe uncontrolled metabolic disorders, or comorbidities that could interfere with treatment outcomes will be excluded.
You may qualify if:
- Patients voluntarily signed the informed consent form.
- 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.
You may not qualify if:
- Patients who discontinued radiotherapy or did not complete the planned treatment.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515, China
Related Publications (11)
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.
PMID: 18832646RESULTKumar 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.
PMID: 21368890RESULTTaha 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.
PMID: 14988393RESULTAureli 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.
PMID: 22592846RESULTCheng 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.
PMID: 24091326RESULTGarcia-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.
PMID: 12750523RESULTLiao 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.
PMID: 10364237RESULTGomez-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.
PMID: 32579188RESULTBenson 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.
PMID: 26300327RESULTWen 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.
PMID: 35197399RESULTVogel 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.
PMID: 36084663RESULT
Biospecimen
Blood plasma samples will be collected before, during, and after radiotherapy. The samples will be stored in the institutional biobank at -80°C for lipidomic analysis. After the study, remaining samples will be disposed of according to hospital regulations.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yiyi Li, PhD
Nanfang Hospital, Southern Medical University
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE ONLY
- Time Perspective
- RETROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 3, 2025
First Posted
March 7, 2025
Study Start
September 1, 2024
Primary Completion
January 1, 2026
Study Completion (Estimated)
June 1, 2026
Last Updated
March 12, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will not share
Due to ethical and privacy concerns, the individual participant data (IPD) will not be shared. All data will be anonymized and stored securely to protect participants' privacy, as per institutional guidelines. Sharing IPD may pose a risk of re-identification or misuse of personal information, which could potentially violate the confidentiality agreement with the participants. Therefore, the data will remain confidential and only be used for the specific purposes outlined in the study protocol.