Clinical trial NCT06864221: Plasma Sphingolipid Metabolites and Radiotherapy Efficacy in Hepatocellular Carcinoma
Official title: Correlation Between Plasma Sphingolipid Metabolites and the Efficacy of Radiotherapy in Hepatocellular Carcinoma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma
Radiotherapy
Treatment Outcome
Biomarkers
Sphingolipids
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2025-03-07
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: From the start of treatment to 12 weeks post-treatment assessment
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From treatment initiation to the date of disease progression or death, up to 24 months.
measure: Overall Survival (OS)
timeFrame: From treatment initiation to death, up to 24 months
measure: Safety and Tolerability
timeFrame: From the start of treatment until 90 days after the last dose.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Yiyi Li, PhD
role: PRINCIPAL_INVESTIGATOR
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