Prediction of Complications in Hepatic Tumors

Condition(s) studied

Investigational drug(s) / intervention(s)

[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.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and ICG clearance — Once before receiving the planned treatment for a hepatic tumor.
  The correlation between quantitative liver uptake parameters derived from \[99mTc\] Tc-GSA SPECT/CT and indocyanine green (ICG) clearance will be assessed using Pearson's/Spearman's rank correlation coefficient. \[99mTc\] Tc-GSA SPECT/CT units: Liver function test expresed in Uptake Index (UI) and percentage of total liver volume (FLR%). Indocyanine green (ICG) clearance units: Liver function test reported as: 1.- ICG retention ratio after 15 min (ICGR15), unit: percentage (%) 2.- Rate constant (k) of ICG indicator-dilution curve (KICG), unit: min-1 3.- Plasma dis-appearance rate of ICG (PDRICG), unit: % min-1.
• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and Child-Pugh score — Once before receiving the planned treatment for a hepatic tumor.
  The correlation between quantitative \[99mTc\] Tc-GSA SPECT/CT-derived liver function parameters and Child-Pugh score will be assessed using Pearson's/Spearman's rank correlation coefficient. \[99mTc\] Tc-GSA SPECT/CT units: Uptake Index (UI) and percentage of total liver volume (FLR%). Child-Pug score description and units: : Scoring system that estimates cirrhosis severity. It classifies patients into three categories: A - good hepatic function, B - moderately impaired hepatic function, and C - advanced hepatic dysfunction.
• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and the Model for End-Stage Liver Disease (MELD) score — Once before receiving the planned treatment for a hepatic tumor.
  he correlation between quantitative \[99mTc\] Tc-GSA SPECT/CT-derived liver function parameters and MELD score will be assessed using Pearson's/Spearman's rank correlation coefficient. \[99mTc\] Tc-GSA SPECT/CT units: Uptake Index (UI) and percentage of total liver volume (FLR%). MELD score definition and units: The Model for End-Stage Liver Disease (MELD) is a prognostic score to measure the severity of liver failure. The MELD score is based on results from five blood tests: Bilirubin, Creatinine, Internal normalized ratio (INR), Serum sodium, and Albumin. The MELD score ranges from 6 to 40, and quantifies end-stage liver disease for transplant planning. The higher the score, the more severe the disease.
• Correlation between [99mTc] Tc-GSA SPECT/CT parameters and liver stiffness measured by ultrasound elastography — Once before receiving the planned treatment for a hepatic tumor.
  The correlation between quantitative \[99mTc\] Tc-GSA SPECT/CT-derived liver function parameters and liver stiffness measured by ultrasound elastography will be assessed using Pearson's/Spearman's rank correlation coefficient. 99mTc\] Tc-GSA SPECT/CT units: Uptake Index (UI) and percentage of total liver volume (FLR%) Ultrasound elastography: kilopascals (kPa)
• Discriminative ability of [99mTc] Tc-GSA SPECT/CT compared with standard liver function tests to predict major postoperative complications — Once after the completion of 90-day follow-up.
  The discriminative ability of \[99mTc\]Tc-GSA SPECT/CT to predict major postoperative complications (Clavien-Dindo grade ≥ III) will be compared with standard liver function tests, including ICG clearance, Child-Pugh score, MELD score, and ultrasound elastography (units and definitions have been previously described). The Clavien-Dindo classification ranks the severity of surgical complications and consists of seven grades (I, II, IIIa, IIIb, IVa, IVb, and V). Complications of grade ≥ III will be considered major. Discriminative performance will be assessed using the area under the receiver operating characteristic curve (AUC) for each test. AUCs will be compared using DeLong's test.

Trial sites (1)

More Copenhagen University Hospital, Rigshospitalet trials in Denmark