Prediction of Complications in Hepatic Tumors

Official title

Prediction of Complications in Patients Undergoing Surgical Treatment of Hepatic Tumors

Overview

Liver failure is one of the most severe complications in patients undergoing liver surgery for hepatic malignancies. However, it can be predicted through preoperative assessment of liver function. Technetium-99m galactosyl human serum albumin (\[99mTc\] Tc-GSA), combined with single-photon emission computed tomography fused with computed tomography (\[99mTc\] Tc-GSA SPECT/CT), is widely used in Asia due to its superiority in predicting postoperative liver failure. Unfortunately, its clinical use in Western countries remains limited due to concerns about disease transmission. In 2022, the Department of Clinical Physiology and Nuclear Medicine at Rigshospitalet optimized the in-house production of \[99mTc\] Tc-GSA under European regulations, and in April 2025, received approval from the Danish Medicines Agency for its clinical use. This study aims to evaluate, for the first time, the diagnostic accuracy of \[99mTc\] Tc-GSA SPECT/CT in quantifying liver function in European patients with hepatic tumors. Hypothesis: \[99mTc\] Tc-GSA SPECT/CT is capable of and superior to indocyanine green clearance test (ICG), Child-Pug score, Model for End-Stage Liver Disease (MELD) score, and ultrasound elastography in quantifying liver function and predicting surgical outcomes in a Danish cohort of patients with liver tumors. Perceived quality of life may be associated with postoperative complications. However, postoperative complications and survival can be more accurately predicted when quality of life is assessed in combination with preoperative liver function and clinical conditions. Objectives Primary objectives: 1. To evaluate the correlation between \[99mTc\] Tc-GSA SPECT/CT and established liver function assessments, including ICG clearance, Child-Pugh score, MELD score, and ultrasound elastography. 2. To compare the discriminative ability of \[99mTc\] Tc-GSA SPECT/CT with existing liver function tests in predicting postoperative complications. Secondary objectives: 3. To assess the correlation of \[99mTc\] Tc-GSA SPECT/CT, ICG clearance, Child-Pugh score, MELD score, and ultrasound elastography with postoperative outcomes. 4. To develop and internally validate a multivariable predictive model combining the best predictive liver function test with preoperative clinical characteristics to predict postoperative complications.

Interventions

• Diagnostic test [99mTc] Tc-GSA SPECT/CT
  To evaluate preoperative liver function using \[99mTc\] Tc-GSA SPECT/CT, participants will receive an intravenous injection of 185 MBq/3 mg \[99mTc\] Tc-GSA through a peripheral vein. SPECT imaging will be performed 20 minutes after tracer injection.

Primary outcome measures

• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and ICG clearance [Time frame: Once before receiving the planned treatment for a hepatic tumor.]
• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and Child-Pugh score [Time frame: Once before receiving the planned treatment for a hepatic tumor.]
• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and the Model for End-Stage Liver Disease (MELD) score [Time frame: Once before receiving the planned treatment for a hepatic tumor.]
• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and liver stiffness measured by ultrasound elastography [Time frame: Once before receiving the planned treatment for a hepatic tumor.]
• Discriminative ability of [99mTc] Tc-GSA SPECT/CT compared with standard liver function tests to predict major postoperative complications [Time frame: Once after the completion of 90-day follow-up.]

Secondary outcome measures (5)

• Association of [99mTc] Tc-GSA, ICG, Child-Pugh, MELD, and ultrasound elastography with 90-day mortality [Time frame: Once during the final analysis after completion of 90-day follow-up.]
• Association of [99mTc] Tc-GSA, ICG, Child-Pugh, MELD, and ultrasound elastography with post-hepatectomy liver failure [Time frame: Once during the final analysis after completion of 90-day follow-up.]
• Association of [99mTc] Tc-GSA, ICG, Child-Pugh, MELD, and ultrasound elastography with length of stay. [Time frame: Once during the final analysis after completion of 90-day follow-up.]
• Association of [99mTc] Tc-GSA, ICG, Child-Pugh, MELD, and ultrasound elastography with readmission. [Time frame: Once during the final analysis after completion of 90-day follow-up.]
• Model development and internal validation of a multivariable predictive model combining the most accurate liver function test with preoperative clinical factors (frailty, sarcopenia, grip strength, age, sex, etc.) to predict complications. [Time frame: Once during the final analysis after completion of 90-day follow-up.]

Eligibility criteria

Inclusion criteria

Adults over 18 years who have the capacity to act, with a confirmed or suspected diagnosis of one or more hepatic tumors and a planned local treatment proposed by a multidisciplinary team of specialists, specifically those:

• Patients undergoing major liver resection (FLR < 40%).
• Patients undergoing minor resections or open/laparoscopic ablations with a risk of impaired liver function, defined by at least one of the following:

• Histological diagnosis of liver cirrhosis or fibrosis (Meta-analysis of Histological Data in Viral Hepatitis scoring system \[METAVIR\] score 1 to 4).
• Radiological signs of cirrhosis.
• Preoperative chemotherapy.
• Known liver disease associated with cirrhosis: metabolic dysfunction-associated steatohepatitis, chronic infection with hepatitis B or C, primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis.

Exclusion criteria

• History of hypersensitivity to Technetium-99m or albumin
• Diagnosis of pulmonary hypertension,
• Pregnant or breastfeeding individuals. For fertile women, non-pregnancy must be confirmed by a negative pregnancy test. No contraception methods are required after the study due to the short radioactive half-life of the IMP.
• Patients under 18 years old or unable to make autonomous care decisions.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Denmark · 1 center

• Rigshospitalet — Copenhagen

Identifiers

NCT: NCT07358975 · GSA-HEPSURU-RH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗