Streamlining Radioembolization for Intrahepatic Cholangiocarcinoma

Overview

Streamlining TARE for Small IHCC TARE delivers radioactive microspheres (20-60 µm) to tumors via abnormal vasculature, while normal liver sinusoids (\<15 µm) block their passage. However, microspheres may enter hepatic veins and reach the lungs, risking radiation pneumonitis. To prevent this, pre-procedural angiography and MAA-based nuclear imaging assess the lung shunt fraction (LSF). TARE is contraindicated if LSF \>20% and used cautiously if 10-20%. Large tumors, hepatic vein invasion, TIPS, and dysmorphic intratumoral vessels suggest high LSF. Dysmorphic vessels are rare in IHCC, an adenocarcinoma with typically low vascularity. Based on 10 years of data from Seoul National University Hospital, IHCC \<7 cm without vein invasion or dysmorphic vessels consistently shows LSF \<5%, with no cases of radiation pneumonitis. Thus, "streamlining TARE"-omitting nuclear imaging-is safely performed in this population to reduce procedural delays. SIR-Spheres (SIRTEX), provided in a mother vial, enable single-session TARE without advance dosimetry, unlike TheraSphere (Boston Scientific), which requires prior preparation. Protocol (n=40): Procedure: Angiography, cone-beam CT, and TARE on the same day. Dosimetry: Lung dose assumed 5%, capped at 10 Gy. Target absorbed dose \~250 Gy (single-compartment MIRD) or ≥300 Gy (boosted TARE, multi-compartment). Software: Simplicit90Y for planning; Y90 PET/CT for post-treatment dosimetry. Follow-up: 1 year; additional treatment as per institutional guidelines. This streamlined protocol increases efficiency while maintaining safety in selected IHCC patients.

○ The radioactive microspheres used in TARE (Transarterial Radioembolization) are very small, approximately 20-60 microns in size. Since the liver sinusoids are less than 15 microns in diameter, the microspheres cannot pass through normal liver parenchyma. However, tumors contain abnormally dilated tumor vasculature, allowing the microspheres to pass through the tumor and potentially drain into the hepatic veins. If a large amount of microspheres reaches the lungs, it can lead to radiation pneumonitis, which may result in death (3). Pre-procedural evaluation consists of angiography and nuclear medicine imaging. Angiography determines the number of vessels to be treated and the target area, while nuclear medicine imaging is used to evaluate the lung shunt fraction. Therefore, pre-procedural evaluation is performed first: angiography is conducted, macroaggregated albumin (MAA) is injected into the hepatic artery, and scintigraphy and SPECT/CT are performed to assess lung shunting. If the lung shunt fraction exceeds 20%, TARE is not feasible. If the shunt is between 10-20%, TARE feasibility depends on tumor size. Typically, TARE is performed 1-2 weeks after pre-procedural evaluation. * Findings that suggest a high lung shunt fraction include large tumors, hepatic vein invasion, TIPS (transjugular intrahepatic portosystemic shunt), and dysmorphic intratumoral vessels. Dysmorphic intratumoral vessels are very rare in metastatic colorectal cancer and intrahepatic cholangiocarcinoma (IHCC). As both are adenocarcinomas, they typically have lower tumor vascularity compared to hepatocellular carcinoma, resulting in a lower lung shunt fraction. According to Seoul National University Hospital's experience over the past 10 years, IHCC less than 7 cm in size, without hepatic vein invasion or dysmorphic intratumoral vessels, almost always showed a lung shunt fraction below 5%. Furthermore, when the tumor is under 7 cm, the treatment area is small, requiring less radiation activity, and the risk of radiation pneumonitis is nearly absent. In the past decade, there have been no cases of radiation pneumonitis in such patients. Therefore, at Seoul National University Hospital, TARE is performed without pre-procedural evaluation in patients meeting the above criteria. This approach is referred to as "streamlining TARE." * Recently in Korea, the number of TARE procedures has rapidly increased. To conduct pre-procedural evaluations, scintigraphy and SPECT/CT must be performed by the nuclear medicine department. However, the number of examinations has reached capacity, causing delays in nuclear imaging, which in turn delays TARE procedures in many university hospitals. If TARE is performed without pre-procedural evaluation in patients with small tumors, patients with larger tumors-who truly require evaluation-can undergo it earlier, thus avoiding delays in TARE. Therefore, it is necessary to implement streamlining TARE for IHCC smaller than 7 cm without dysmorphic intratumoral vessels. * There are two types of radioactive microspheres used in TARE. TheraSphere (Boston Scientific) requires ordering vials with specific radiation activity tailored to each vessel, which necessitates performing pre-procedural evaluation (angiography + nuclear imaging) in advance. On the other hand, SIR-Spheres (SIRTEX) are shipped to hospitals as a mother vial containing more than 7 GBq. The treating hospital determines the number of daughter vials and the necessary radiation activity during the procedure. Therefore, it is possible to perform angiography, determine the number of vessels and required radiation activity, and then proceed with TARE using SIR-Spheres in a single session. Radioembolization protocol On the day of the procedure, angiography is performed, followed by cone-beam CT of the hepatic artery. The treatment dose is determined using either the single-compartment MIRD or the multi-compartment MIRD method. The lung shunt fraction is assumed to be 5%, and the lung absorbed dose is kept at or below 10 Gy. TN ratio is assumed to be 3. When using single-compartment MIRD, the mean absorbed dose in the treatment area should range between 120 and 400 Gy, with a target of approximately 250 Gy whenever possible. When using multi-compartment dosimetry, the tumor absorbed dose must be at least 100 Gy and should ideally be within the range of 300 to 600 Gy. While there is no upper limit for the tumor absorbed dose, the lung dose must strictly be kept at or below 10 Gy. A tumor absorbed dose of ≥300 Gy is defined as boosted TARE, while a dose between 100-300 Gy is defined as regular TARE. The device used for radioembolization is limited to SIR-Spheres, and the dosimetry is planned using the personalized dosimetry software Simplicit90Y (Mirada). For treatment beyond the typical scope of radiation segmentectomy, the approach follows the method of Radiation Major Hepatectomy, used for large hepatocellular carcinomas. Y90 PET/CT is performed on the next day. Post-treatment dosimetry is calculated with Y-90 PET/CT by partition dosimetry. After radioembolization, patients are followed for one year according to a predefined schedule. During the clinical trial follow-up period, if residual or recurrent tumors are observed, further treatment is administered according to each institution's standard clinical guidelines.