Transarterial Chemoembolization Combined with Sorafenib and Iodine-125 Seed Brachytherapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective Controlled Study

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Transarterial Chemoembolization Combined with Sorafenib and Iodine-125 Seed Brachytherapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Retrospective Controlled Study

Up to 40% of people diagnosed with hepatocellular carcinoma (HCC)—the most common type of liver cancer—also have portal vein tumor thrombus (PVTT): a cancerous clot in the portal vein, which carries nutrient-rich blood from the gut to the liver. PVTT is a devastating complication: it cuts survival rates sharply and limits treatment options. While sorafenib (an oral targeted therapy) is the first-line treatment for advanced HCC with PVTT, its effects are modest. Combining sorafenib with transarterial chemoembolization (TACE)—a procedure that delivers chemotherapy directly to liver tumors and blocks their blood supply—improves outcomes slightly, but it still struggles to control PVTT effectively.

To address this gap, researchers from the Second Affiliated Hospital of Guangzhou Medical University tested a new approach: adding iodine-125 (¹²⁵I) seed brachytherapy (internal radiation) to TACE plus sorafenib (called TACE-S-I) versus TACE-S alone. Their retrospective controlled study, published in the Chinese Medical Journal in 2022, offers hope for patients with PVTT in smaller portal vein branches.

The Study Design: Comparing Two Treatments for HCC with PVTT

The team reviewed data from 171 patients treated between 2015 and 2018. To be included, patients were 18–75 years old, had good functional status (Eastern Cooperative Oncology Group [ECOG] score 0–1), and mild-to-moderate liver damage (Child-Pugh class A/B). They excluded those with severe portal vein obstruction, PVTT spreading to other veins (like the superior mesenteric vein), prior cancer treatments (e.g., sorafenib, TACE), or life-threatening comorbidities (e.g., severe heart/kidney disease).

Patients were split into two groups:

  • TACE-S-I (74 patients): Received TACE, then sorafenib (400mg twice daily) 3–5 days later, plus ¹²⁵I seeds implanted into the PVTT via CT guidance 3–14 days after TACE.
  • TACE-S (97 patients): Received TACE plus sorafenib but declined ¹²⁵I brachytherapy.

Follow-ups occurred every 4–6 weeks, with repeat TACE or seed implantation if tumors progressed. Sorafenib doses were adjusted or stopped if side effects became severe.

Key Results: Better Tumor Control and Longer Survival with TACE-S-I

The results highlighted a clear benefit for TACE-S-I:

  1. PVTT Response: 58.1% of TACE-S-I patients had a partial or complete response (shrinking or disappearing clot), compared to just 11.3% of TACE-S patients.
  2. Intra-Hepatic Tumor Response: 59.5% of TACE-S-I patients saw their liver tumors shrink or stabilize, versus 30.9% on TACE-S.
  3. Time to Progression (TTP): TACE-S-I patients went 12 months without tumor growth, more than double the 5 months for TACE-S.
  4. Overall Survival (OS): Median survival jumped from 12 months (TACE-S) to 23.5 months (TACE-S-I). Three-year survival rates were 24% vs. 14%.

Who Benefited Most?

Subgroup analysis revealed the biggest gains for patients with type B or C PVTT—clots in first- or lower-order portal vein branches (smaller veins feeding the liver). Their median OS was 20.5 months, compared to just 7.5 months for those with type A PVTT (clots in the main portal vein). Type A patients saw no difference between treatments, likely because implanting seeds into the main portal vein is harder to do safely and effectively.

Safety: No Extra Risk of Severe Side Effects

A major concern with adding a third treatment (¹²⁵I seeds) was increased toxicity. But TACE-S-I did not raise the risk of severe adverse events (AEs). Most side effects were sorafenib-related (e.g., fatigue, hand-foot syndrome), and rates of grade 3+ AEs (serious enough to require hospitalization) were similar: 33.8% for TACE-S-I vs. 28.9% for TACE-S.

Limitations to Consider

The study has important caveats:

  • Retrospective Design: Treatment choices depended on patient preference, which could introduce bias (e.g., healthier patients might choose TACE-S-I).
  • Unblinded Assessment: ¹²⁵I seeds are visible on scans, so doctors couldn’t be “blinded” to which treatment patients received—this might have affected how they rated tumor response.

Randomized controlled trials (the gold standard for medical research) are needed to confirm these findings.

What This Means for Patients

For HCC patients with PVTT in first- or lower-order portal vein branches, TACE-S-I is a promising option. It improves tumor control, delays progression, and extends life without adding significant risks. Patients with type A PVTT (main portal vein) may need alternative treatments, like irradiation stents, which are easier to place in the main vein.

This study was conducted by Jingjun Huang, Mingyue Cai, and colleagues from the Department of Minimally Invasive Interventional Radiology and Department of Radiology at the Second Affiliated Hospital of Guangzhou Medical University. The full study is available at doi.org/10.1097/CM9.0000000000001537.

References:

  1. Zhu K, et al. Radiology 2014;272:284–293.
  2. Lu J, et al. J Vasc Interv Radiol 2017;28:786–794.
  3. Pan T, et al. Clin Radiol 2014;69:e553–e561.
  4. Zhang FJ, et al. Chin Med J 2008;121:2410–2414.
  5. Zhang L, et al. Cardiovasc Intervent Radiol 2020;43:196–203.

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