Second-line treatment options for hepatocellular carcinoma: current state and challenges for the future.

INTRODUCTION: Since the approval of sorafenib for systemic treatment of advanced hepatocellular carcinoma (HCC), many tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have shown efficacy and tolerability as first-line treatments. On the other hand, these first-line therapies are associated with low objective response and drug resistance. Many drugs have been successfully tested for second-line treatment of advanced HCC. While the rapid proliferation of second-line treatments for advanced HCC brings hope to patients, it also complicates clinical decision-making. AREAS COVERED: This review aims to facilitate decisions by summarizing the latest guidelines for second-line treatment of HCC in various countries or regions. We then review existing second-line treatment options and discuss challenges that should be addressed in the future. A literature search was conducted in April 2022 of PubMed/Medline, Cochrane library, and abstracts of international cancer meetings. EXPERT OPINION: There is no standard second-line treatment, especially for the case of sequential treatment after atezolizumab plus bevacizumab (atezo+bev) and further studies focused on sequential treatment are warranted in this setting. The design of clinical trials, different etiologies, and complications or quality of life (QoL) are interesting issues in the second-line setting.

Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study.

The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.

Randomized Clinical Trial Comparing Efficacy of Simo Decoction and Acupuncture or Chewing Gum Alone on Postoperative Ileus in Patients With Hepatocellular Carcinoma After Hepatectomy.

To compare the efficacy of simo decoction (SMD) combined with acupuncture at the tsusanli acupoint or chewing gum alone for treating postoperative ileus in patients with hepatocellular carcinoma (HCC) after hepatectomy.In postoperative ileus, a frequent complication following hepatectomy, bowel function recovery is delayed, which increases length of hospital stay. Studies suggest that chewing gum may reduce postoperative ileus; SMD and acupuncture at the tsusanli acupoint have long been used in China to promote bowel movement.Patients with primary HCC undergoing hepatectomy between January 2015 and August 2015 were randomized to receive SMD and acupuncture (n = 55) or chewing gum (n = 53) or no intervention (n = 54) starting on postoperative day 1 and continuing for 6 consecutive days or until flatus. Primary endpoints were occurrence of postoperative ileus and length of hospital stay; secondary endpoints were surgical complications.Groups treated with SMD and acupuncture or with chewing gum experienced significantly shorter time to first peristalsis, flatus, and defecation than the no-intervention group (all P < 0.05). Hospital stay was significantly shorter in the combined SMD and acupuncture group (mean 14.0 d, SD 4.9) than in the no-intervention group (mean 16.5 d, SD 6.8; P = 0.014), while length of stay was similar between the chewing gum group (mean 14.7, SD 6.2) and the no-intervention group (P = 0.147). Incidence of grades I and II complications was slightly lower in both intervention groups than in the no-intervention group.The combination of SMD and acupuncture may reduce incidence of postoperative ileus and shorten hospital stay in HCC patients after hepatectomy. Chewing gum may also reduce incidence of ileus but does not appear to affect hospital stay. (Clinicaltrials.gov registration number: NCT02438436.).

Postoperative therapy options for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is associated with poor prognosis and often recurs even after curative hepatic resection (HR) or radiofrequency ablation (RFA). In fact, recurrence is the most frequent cause of postoperative death in patients with HCC; it can arise through intrahepatic metastasis by the primary tumor or through the emergence of de novo tumors. Even though studies have examined numerous adjuvant therapies and chemotherapies for their ability to prevent recurrence, no consensus recommendations exist about their clinical application. To gain a comprehensive picture of clinical options, we identified 39 randomized controlled trials, involving 4113 participants, which explore the efficacy of adjuvant or chemotherapies to prevent HCC recurrence after potentially curative HR or RFA. The available evidence suggests a significant improvement in recurrence-free survival and overall survival when transarterial chemoembolization is used for patients who are at high risk for recurrence, lamivudine for patients with hepatitis B virus (HBV)-related HCC (>500 copies of HBV DNA/ml), and interferon-α for patients with hepatitis C virus (HCV)-infected HCC. In contrast, available evidence does not definitively establish clinical benefits of interferon-ß for patients with HCV-related HCC, interferon-α for patients with HBV-related HCC, or any of the following therapies for patients with HCC: iodine-125 brachytherapy, autologous tumor vaccination, adoptive immunotherapy, or therapy involving acyclic retinoid, vitamin K2 analog, iodine-131-labeled lipiodol, sorafenib, heparanase inhibitor PI-88, or capecitabine. Though the findings of our review should be interpreted with caution because of clinical heterogeneity and small sample size in the included trials, they highlight gaps in the evidence base, and therefore, may guide future research.