Plasma Sphingolipid Metabolites and Radiotherapy Efficacy in Hepatocellular Carcinoma

March 9, 2025 updated by: Nanfang Hospital, Southern Medical University

Correlation Between Plasma Sphingolipid Metabolites and the Efficacy of Radiotherapy in Hepatocellular Carcinoma

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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Liver cancer is one of the most common malignant tumors worldwide, posing a significant challenge to public health. Radiotherapy plays a crucial role in controlling local recurrence and metastasis in hepatocellular carcinoma (HCC) and improving patient survival. Advanced radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT) have enhanced tumor dose precision, increasing local control rates while minimizing radiation-induced side effects. However, current methods for assessing radiotherapy efficacy, including CT, MRI, and PET-CT, require extended post-treatment observation periods, delaying clinical decision-making. Additionally, radiotherapy can lead to radiation-induced liver disease (RILD) and other adverse effects such as radiation enteritis and bone marrow suppression. Therefore, identifying early predictive biomarkers for radiotherapy response and toxicity is critical for optimizing treatment strategies.

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.

Study Type

Observational

Enrollment (Estimated)

260

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Recruiting
        • Nanfang Hospital, Southern Medical University
        • Contact:
          • Shaolin Shen, PhD
          • Phone Number: +86-020-62787238
          • Email: nfyyec@163.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR)
Time Frame: From the start of treatment to 12 weeks post-treatment assessment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: From treatment initiation to the date of disease progression or death, up to 24 months.
PFS is defined as the time from the start of treatment to disease progression or death from any cause, whichever occurs first, as assessed by mRECIST. This endpoint measures how long patients remain free from tumor progression.
From treatment initiation to the date of disease progression or death, up to 24 months.
Overall Survival (OS)
Time Frame: From treatment initiation to death, up to 24 months
OS is defined as the time from the start of treatment to death from any cause. This endpoint assesses the overall survival benefit of the treatment.
From treatment initiation to death, up to 24 months
Safety and Tolerability
Time Frame: From the start of treatment until 90 days after the last dose.
The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) will be evaluated according to CTCAE (Common Terminology Criteria for Adverse Events) version [specify version]. This endpoint assesses the safety profile of the
From the start of treatment until 90 days after the last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanfang Hospital, Southern Medical University

Investigators

  • Principal Investigator: Yiyi Li, PhD, Nanfang Hospital, Southern Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2024

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

March 3, 2025

First Submitted That Met QC Criteria

March 3, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 9, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NFEC-2024-389

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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