Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy

Abstract

Background: A combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma (HCC) with extrahepatic metastases. Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported.

Methods: Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed.

Results: Nine patients with localized disease who received first-line systemic therapy were enrolled. At baseline, all of them had oligometastatic disease, namely, Barcelona Clinic Liver Cancer stage C (or Chinese Liver Cancer stage IIIB). The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization, and the median time span from systemic therapy to surgery was 3.2 (IQR, 2.8-6.2) months. Three patients achieved a pathological complete response. Six patients underwent laparoscopic surgery, and the other 3 patients underwent open surgery. After a median follow-up of 10.2 (IQR, 8.6-20.0) months, 7 patients survived without disease recurrence, and 2 experienced tumour recurrence. All patients had any-grade AEs, and 55.6% of the patients experienced grade 3 AEs. Fatigue was the most common AE, followed by elevated aminotransferase levels and hypertension.

Conclusions: Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable. This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.

Keywords: Hepatocellular carcinoma (HCC); PD-1; conversion surgery; stereotactic therapy; systemic therapy.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/hbsn-21-188). Drs. XL, YM, HZ and XS serve as the unpaid editorial board members of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare.

2021 Hepatobiliary Surgery and Nutrition. All rights reserved.

Figures

Figure 1

Patients flowchart.

Figure 2

Overview of the stereotactic treatment regimens, and the x-axis represented the treatment time, and the y-axis represented different patients. Different symbols represented different therapy strategy.

Figure 3

Pre-treatment and preoperative CT or MR scans and H&E of resected regimen. (A) Pre-treatment MR or CT scans revealed that the patients had extrahepatic metastasis lesions. After stereotactic treatment, these metastatic lesions disappeared. (B) A representative case. Patient 9 was diagnosed with a solitary HCC and with an oligometastasis in lower abdominal cavity (BCLC stage C) and received TACE, radiotherapy, lenvatinib 8 mg/day and toripalimab 240 mg every 3 weeks. Four weeks later, the conventional operation was performed. H&E staining of the surgically resected specimen showed a pCR. HCC, hepatocellular carcinoma; BCLC, Barcelona Clinic Liver Cancer; TACE, transarterial chemoembolization; H&E, hematoxylin and eosin; pCR, pathological complete response.

Figure 4

Maximum percent change in the target lesion from baseline. Therapeutic efficacy in patients with advanced hepatocellular carcinoma. Maximum percent change in the sum of the diameters of the target lesions from baseline.