Chemoembolization (TACE)

Efficacy and alternatives

• Ablation alone is ideal (and potentially curative) for lesions <3 cm. TACE + ablation helpful for intermediate to large HCC (3-5 cm, superior to TACE alone, should be done within 30d)

• Bland embolization vs TACE: multiple trials have suggested no major difference in outcomes, e.g., Brown et al in 2016, but more pain and hospitalization after bland embo. Suggests the embolic effect is more important than the chemo. However, there are studies suggesting cisplatin, particularly anhydrous cisplatin cTACE, may be superior to doxorubicin cTACE. There is also ongoing work using TACE for targeted delivery of other drugs such as immunotherapy for uveal melanoma mets.

• Systematic review of cTACE: OS 53%, TTP 3.1-13.5m, OS 1, 3, 5y 70, 40, 32%

• DEB-TACE vs cTACE: DEB-TACE has shown higher intralesional chemo concentration, less systemic chemo levels, and less adverse events with similar TTP and OS (PRECISION V trial with subsequent RCTs confirming)

  • cTACE lipiodized oil preferentially targets larger tumor neovasculature, accumulates portal venules and sinusoids, facilitates endocytosis of chemo. Longer track record.

  • DEB-TACE embolizes terminal arterioles resulting in necrosis and prolonged drug elution into the tumor.

  • cTACE has less post-embolization syndrome but more systemic side effects of the chemotherapy used

• B-TACE vs TACE: Balloon-occluded TACE (B-TACE) has been shown in some studies to improve delivery to the target tumor(s) and improve outcomes. Pressure enabled drug delivery (PEDD) with the TriNav catheter likely achieves similar benefits.

• TACE + systemic therapy

  • E.g. EMERALD-1 trial (durvalumab +/- bevacizumab +/- TACE in advanced HCC), LEAP-012 (RCT of lenvatinib + pembrolizumab + TACE vs TACE in unresectable HCC), TALENTACE (atezo/bev + TACE vs TACE), EMERALD-3 (STRIDE vs STRIDE + lenvatinib vs TACE), Cam + Rivo (cam+rivo vs TACE)

  • Generally, trials have shown increased PFS but no difference in OS with the cost of greater adverse events and toxicity. Some believe we may be asking the wrong question, and we need to differentiate which patients and tumors may benefit from this approach rather than applying to all, e.g., a decent percentage of LDT patients achieve complete response, so concurrent therapy is not going to help these patients. What are the tumor markers that respond better to TACE?

  • Some argue that BCLC-B patients beyond the “up to 7 criteria” may benefit from a systemic first strategy, e.g., study of this population initially treated with lenvatinib had better median OS than TACE (38 vs 21 mo), so perhaps best to start systemic followed by selective TACE

  • Combination therapy for mets is like better with second and third round therapy if the first line therapy is very effective. This is likely while trials combining LDT with first-line chemotherapy for CRC mets have tended not to show benefit over first-line therapy alone, whereas trails combining LDT with second-line therapy for CRC mets have demonstrated benefit, e.g., DEBIRI TACE.

• TACE vs TARE:

  • Some studies have suggested better outcomes with TARE for local tumor control, particularly for those amenable to radiation segmentectomy. TARE is also likely better for tumor in vein because it’s note embolic. However, there are tumor markers that make tumors more or less susceptible to ischemia and more or less radioresistant, so some tumors can respond better to TACE than TARE.

  • TACE generally has higher rates of post-embolization syndrome due to being embolic.

• Can use the Assessment for Retreatment with TACE (ART) score to help predict benefit for repeat TACE, >2.5 suggests poor prognosis while 0.5-1.5 suggests potential benefit

• TACE can also be used outside the liver, e.g., promising data in the lungs both via transvenous  pulmonary chemoembolization via the pulmonary artery and/or transarterial via the bronchial arteries which more often are the dominant supply, mean OS for palliation 19.7 mo and paired with ablation 30.1 mo.