May 24th, 2024
This study illustrates the methodological potential of combining Yttrium-90 Trans-Arterial Radioembolization (Y-90 TARE) with an anti-PD-1 monoclonal antibody as an effective neoadjuvant strategy leading to hepatectomy in hepatocellular carcinoma (HCC) patients with a high initial recurrence risk. It emphasizes the safety, feasibility, and step-by-step procedural guidance of this approach.
We are committed to exploring treatment that indicate a post-operation recovery in HCC. While launching radioembolization combined with PD-1 inhibitors caused considerable potential for addressing this critical issue. Our study aims to investigate the application and the efficacy of this combined treatment to treat AAG as a neoadjuvant therapy in HCC. This protocol regulate the junior of one HCC patient, with a high risk of recurrence from initial diagnosis through sequential therapy, while launching radioembolization and PD-1 inhibitors resection. It documents the tumor response at the various offering reference for individual case treatments and the extensive clinical research on this combined therapeutic approach. In the future, our laboratory will delve into potential molecule mechanisms and the prediction biomarkers of efficacy for Y-90 radioembolization combined with the PD-1 inhibitors in the HCC treatment. Concurrently, we will initial relative phase one and the two clinical trials.
[Presenter] To begin, instruct the patient to lie supine for the procedure. Using the Seldinger technique, insert a micropuncture needle into the right common femoral artery. Place a sheath connected to a saline flush system and advance the catheter to the celiac trunk. Conduct angiography at the origin of the celiac trunk to check if the hepatic tumor is exclusively supplied by a solitary branch of the right hepatic artery. Utilizing the coaxial microcatheter technique, perform super selective catheterization on the right inferior branch of the right hepatic artery followed by angiography. Inject 2 millicurie of Technetium-99m Macro Aggregated Albumin or Tc-99m MAA through the microcatheter into the supplying arteries. Perform cone-beam computed tomography or CBCT to delineate the targeted tumor region of intrahepatic perfusion distribution. Manually outline the region on sagittal, coronal, and axial views during the arterial phase. Calculate the volume of the targeted tumor region using the SEG4 properties option. Configure the scan mode parameters on the scanner and perform SPECT/CT imaging on the patient within one to two hours after the infusion. To calculate the Lung Shunt Fraction, manually draw the region of interest or ROI marking the distinct areas within the liver and lungs where the Tc-99m MAA distribution is discernible on the planar images. Calculate the lung and liver counts for each ROI using a standard nuclear medicine workstation. Then calculate lung shunting fraction or LSF with the equation. Use 3D segmentation application of SPECT/CT imaging to obtain the CT slices of tumor and normal liver areas. Manually draw discreet ROIs of the same size to encompass tumor and normal liver areas based on the CT slices. Calculate the average count per unit cell of the tumor over the average count per unit cell of the normal liver in each ROI using a workstation followed by the non-tumor ratio or TNR using the equation. Using the calculations and the partition model equation in the dose and activity visualizer, obtain the prescribed activity in Gigabecquerel and the dosage in Gray. Perform an angiogram directly on the blood-supplying arteries identified earlier. Advance the catheter to the supplying arteries after super selective catheterization and inject the Yttrium-90 or Y-90 microspheres into the supplying arteries. For Y-90 TARE, obtain dedicated, whole-body PET/CT scans from the chest to just above the pelvis. Assess the TNR from a volume ROI drawn on the PET/CT images and then compare it with the TNR obtained from the SPECT/CT images of the Tc-99m MAA distribution to confirm the distribution of Y-90. Observe lesion stability for at least two months following Y-90 treatment. Inject an appropriate program, Cell Death-1 or PD-1 inhibitor if high-risk factors for recurrence are found. After two months of evaluation post PD-1 inhibitor therapy, ensure no high-risk factors for recurrence are present. Administer Indocyanine green to the patient three days before the surgery. Disinfect the upper abdominal region extending superiorly to the nipple line, inferiorly to the pubic symphysis, and laterally to the mid-axillary line. Enter the peritoneal cavity. And using a laparoscope, inspect the liver and surrounding structures for any abnormalities or metastatic foci. With graspers, elevate the inferior border of the right liver to expose the tumor located in segment six. After injecting Indocyanine green intravenously, switch to fluorescence imaging mode to carefully assess the tumor's extent. Using a harmonic scalpel, dissect the connective tissues between the inferior border of the right liver, posterior peritoneum, and right kidney and progress superiorly dissecting the right triangular and coronary ligaments, thus exposing the second porta hepatis. With duckbill forceps, retract the liver to the left to expose the right lobe fully. Employ fluorescence imaging mode to clearly delineate the margin between the tumor and adjacent healthy tissue. Apply a monopolar cautery hook to mark the resection guidelines approximately one to two centimeters from the tumor margin. Tighten the tourniquets in cycles of 15-minute occlusion followed by five-minute reperfusion to temporarily interrupt the vascular inflow from the portal vein and hepatic artery. Using the harmonic scalpel, carefully transect the liver parenchyma along the guide lines. After coagulating the small bile ducts and vessels, clamp and transect larger structures. After excising the tumor specimen, send it for histopathological evaluation. Rinse the hepatic cut surface with warm normal saline, and perform bipolar coagulation to achieve hemostasis. Compared to the initial diagnosis, magnetic resonance imaging indicated that the tumor was reduced to six centimeters and the initial alpha-fetoprotein or AFP level decreased to 21,155 nanograms per milliliter one month after the Y-90 TARE treatment. Three months post-treatment, the tumor showed no significant changes. At five months following Y-90 TARE therapy, corresponding to two months after starting PD-1 inhibitor treatment, the lesion had further reduced to four centimeters and the AFP level had dramatically decreased to 1.84 nanograms per milliliter. Follow up with magnetic resonance imaging indicated no evidence of recurrence or metastasis two and seven months after the tumor excision.
This study illustrates the potential of combining Yttrium-90 Trans-Arterial Radioembolization (Y-90 TARE) with an anti-PD-1 monoclonal antibody as a neoadjuvant strategy for hepatocellular carcinoma (HCC) patients. It emphasizes the safety, feasibility, and procedural guidance of this approach.
Combining Y-90 transarterial radioembolization (TARE) with PD-1 inhibitor therapy as a neoadjuvant strategy addresses the challenge of high recurrence risk in hepatocellular carcinoma (HCC) patients. This protocol enables precise tumor targeting, quantitative response monitoring, and informed surgical decision-making, supporting risk-adjusted advancement in oncology pipelines. The approach exemplifies translational integration of interventional radiology and immunotherapy for improved portfolio outcomes in liver cancer.
This protocol integrates into the continuum from early discovery through translational research and preclinical validation, supporting lead identification and mechanistic de-risking in liver oncology.