Interventional Management of Hepatocellular Carcinoma: Articles From the Official Show Daily for Synergy 2015

Interventional locoregional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided percutaneous ablation is recommended in patients with early-stage HCC when surgical options are precluded and can replace resection in selected patients with very early tumors. Transarterial chemoembolization (TACE) is the standard of care for patients with noninvasive multinodular tumors at the intermediate stage. Yttrium-90 (Y-90) radioembolization represents a promising treatment option for patients unfit or refractory to TACE, and it is currently being investigated in the setting of phase III trials.

Liver cancer is currently the second leading cause of cancer-related death worldwide. Unlike most solid tumors, future incidence and mortality rates for HCC were projected to largely increase in several regions around the world over the next decade. Given the complexity of the disease, multidisciplinary assessment of tumor stage, liver function, and physical status is required for proper therapeutic planning.

Patients with early-stage HCC – defined as either a single tumor smaller than 5 cm or as many as three nodules smaller than 3 cm each, no evidence of vascular invasion or extrahepatic spread, performance status test of 0, and liver cirrhosis in Child-Pugh class A or B – should be considered for any of the available curative therapies, including surgical resection, liver transplantation, and image-guided ablation. In general, image-guided ablation is recommended when surgical options are precluded. The question remains however as to whether ablation can compete with surgical resection as a first-line treatment for HCC.¹ The randomized trials comparing ablation and surgery reported to date have failed to provide an unequivocal answer to this question. Importantly, however, nonrandomized studies have consistently reported similar outcomes for patients who underwent hepatic resection or ablation for very early stage tumors (a single HCC ≤2 cm in diameter), suggesting that ablation has potential as the first-line therapy in this setting.  

Several methods for focal tumor destruction have been developed and clinically tested. While radiofrequency ablation (RFA) has been the most popular technique, several novel technologies – including thermal and non-thermal methods – have recently attracted attention, because they appear to be able to overcome some specific limitations of RFA.² Microwave ablation (MWA), in particular, is emerging as a valuable alternative to RFA, and seems to have potential to improve the rate of complete ablation achieved with RFA in tumors that are larger than 2-3 cm or multiple. Irreversible electroporation (IRE) shows promise for the treatment of small tumors located in the vicinity of bile ducts and blood vessels.³ Advances in ablation systems and devices are highly warranted. However, progress in imaging guidance and monitoring is also key to success. To be able to compete with surgical resection, image-guided ablation needs to be able to offer more accurate prediction of the outcome of the procedure in each individual patient. Variability in outcomes needs to be minimized via careful treatment planning. Also, the outcome of the ablation procedure needs to be carefully documented by providing sound evidence that an “A0” treatment has been achieved.

Despite the implementation of surveillance programs of at-risk populations, the majority of patients with HCC are diagnosed late, when radical treatments cannot be applied. Transarterial chemoembolization (TACE) is the most widely used treatment for HCC patients unsuitable for curative therapies. Transarterial chemoembolization has been recommended as the standard of care for the treatment of unresectable, large, or multinodular noninvasive tumors isolated to the liver, in patients with compensated cirrhosis.⁴ The data collected in the GIDEON study, the largest global observational study completed in the field of HCC clinical management so far, suggest that nearly half of all HCC patients receive TACE at some point in the course of the disease.⁵ Conventional TACE regimens are based on the administration of an anticancer-in-oil emulsion followed by embolic agents. The key component of this procedure is lipiodol, which is used both as a vehicle to carry and localize the chemotherapeutic agent inside the tumor and as an embolic agent for tiny tumor vessels. The introduction of embolic, drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic exposure. However, the clinical trials completed so far failed to show statistically significant differences in objective response or overall survival between DEB-TACE and conventional TACE.⁴ Recent advances in drug eluting bead technology include the development of smaller and inherently radio-opaque microspheres. In experimental settings, such tiny beads were shown to allow for more concentrated drug delivery within the tumor and greater tumoral devascularization. Further investigation is warranted to understand the clinical benefit associated with these novel embolization strategies.

While patients who present or develop extrahepatic spread are typically considered for systemic therapy with sorafenib, the management of those with locally advanced disease is more controversial, especially given the data reported by multiple centers for radioembolization with Y-90.⁶ Yttrium-90 is challenging the current paradigm of HCC treatment. Multiple centers around the world have provided compelling data that suggest a clinical role in patients with portal vein thrombosis as well as in downstaging to transplantation or conversion of surgically inoperable patients (due to small liver remnant) to potential cure with resection.

Unfortunately, the clinical trials completed so far have failed to provide evidence of unequivocal benefit associated with the concurrent use of locoregional and systemic therapies. The next few years will yield important information as results from the ongoing phase III trials further define the role of novel treatment options in HCC clinical management.

Editor’s note: This article first appeared in the Synergy Daily conference newspaper, available to attendees of the Synergy Miami interventional oncology meeting, published November 5, 2015. This article did not undergo peer review. Dr. Lencioni reports no disclosures related to the content herein.

Suggested citation: Lencioni R. Interventional management of hepatocellular carcinoma: articles from the official show daily for Synergy 2015. Intervent Onc 360. 2015;3(11):E118-E120.

References

1. Mazzaferro V, Lencioni R, Majno P. Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and transplantation. Semin Liver Dis. 2014;34(4):415-426.
2. Breen DJ, Lencioni R. Image-guided ablation of primary liver and renal tumours. Nat Rev Clin Oncol. 2015;12(3):175-186.
3. Lencioni R, Crocetti L, Narayanan G. Irreversible electroporation for the treatment of hepatocellular carcinoma. Tech Vasc Interv Radiol. 2015;18(3):135-139.
4. Lencioni R. Chemoembolization for hepatocellular carcinoma. Semin Oncol. 2012;39(4):503-509.
5. Lencioni R, Kudo M, Ye SL, et al. GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib): second interim analysis. Int J Clin Pract. 2014;68(5):609-617.
6. Salem R, Mazzaferro V, Sangro B. Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives. Hepatology. 2013;58(6):2188-2197.