Hepatic Arterial Infusion Chemotherapy (HAIC)-Based Conversion Hepatectomy in Patients with Hepatocellular Carcinoma

Academic Background

Hepatocellular carcinoma (HCC) is one of the most common liver malignancies worldwide, particularly in China, where its incidence and mortality rates remain high. Despite advancements in treatment strategies, radical surgery remains the primary treatment for HCC patients. However, over 70% of HCC patients are not suitable for radical surgery at the time of initial diagnosis due to tumor-related factors such as vascular invasion, multiple lesions, or insufficient residual liver volume, leading to poor prognosis. In recent years, conversion therapy has been proposed as a method to reverse unresectable tumors by shrinking tumor volume or downstaging, thereby providing patients with an opportunity for surgical resection and extending survival.

Hepatic arterial infusion chemotherapy (HAIC) has shown satisfactory therapeutic efficacy in patients with unresectable HCC and is considered an important conversion treatment. However, there is still a lack of clear information regarding the optimal timing for HAIC-based conversion surgery. This study aims to explore the optimal timing for HAIC-based conversion surgery in HCC patients and evaluate its efficacy and safety.

Source of the Paper

This paper was co-authored by Min Deng, Chong Zhong, Dong Li, and others, with affiliations including Sun Yat-sen University, Guangzhou University of Chinese Medicine, and Guangdong Provincial People’s Hospital, among others. The paper was published online on August 14, 2024, in the International Journal of Surgery, with a DOI of 10.1097/js9.0000000000002043.

Research Process and Results

Study Design

This study is a multicenter retrospective cohort study that included 424 HCC patients who underwent HAIC-based conversion hepatectomy between January 2016 and December 2022 at four medical institutions. Based on tumor response to HAIC, patients were divided into a responder group (CR/PR, n=312) and a non-responder group (SD/PD, n=112). The primary endpoints were overall survival (OS) and recurrence-free survival (RFS), while secondary endpoints included tumor response rate, hepatic hilum inflow occlusion time, intraoperative blood loss, and postoperative complications.

Research Process

1. Patient Screening and Grouping: All patients received HAIC treatment, and tumor response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The responder group consisted of patients who achieved complete response (CR) or partial response (PR), while the non-responder group included those with stable disease (SD) or progressive disease (PD).
2. HAIC Treatment Protocol: HAIC was administered using a modified FOLFOX regimen (oxaliplatin, fluorouracil, and leucovorin), with each cycle lasting 3 weeks and a maximum of 6 cycles.
3. Surgical Timing and Procedures: Surgery was performed 4-8 weeks after the last HAIC treatment and was conducted by experienced liver surgeons. Intraoperative ultrasound was used to confirm tumor size, number, and location, ensuring margin-negative resection (R0 resection).
4. Follow-up and Data Analysis: Patients were followed up every 2 months postoperatively, with liver function tests, tumor marker tests, and imaging examinations. OS and RFS were analyzed using the Kaplan-Meier method, and the Cox regression model was used to assess prognostic factors.

Key Results

1. Survival Analysis: The median OS was not reached in the responder group, while the median OS in the non-responder group was 53.2 months (HR=2.581, p<0.001). The 1-year, 3-year, and 5-year OS rates in the responder group were 97.6%, 82.3%, and 74.2%, significantly higher than the 93.3%, 62.5%, and 46.5% in the non-responder group. The median RFS in the responder group was 17.7 months, significantly longer than the 9.7 months in the non-responder group (HR=1.565, p=0.001).
2. HAIC Cycles and Survival: There was no significant difference in OS and RFS between patients who achieved CR/PR after 1-2 cycles and those after 4-6 cycles of HAIC. However, patients who achieved CR/PR after 4-6 cycles of HAIC had significantly better OS and RFS compared to the non-responder group.
3. Barcelona Clinic Liver Cancer (BCLC) Staging and Survival: In BCLC stage C patients, the OS and RFS in the responder group were significantly better than those in the non-responder group (median OS not reached vs. 39.6 months, p<0.001; median RFS 12.9 months vs. 5.8 months, p=0.016).
4. Surgical Indicators: The responder group had a shorter hepatic hilum inflow occlusion time (23 minutes vs. 26 minutes, p=0.041) and less intraoperative blood loss (300ml vs. 300ml, p=0.046). There were no significant differences in operative time or postoperative complications between the two groups.
5. Prognostic Factor Analysis: Multivariate analysis showed that tumor response, differentiation, postoperative AFP levels, postoperative PIVKA-II levels, age, microvascular invasion (MVI), pre-HAIC neutrophil-to-lymphocyte ratio (NLR), and preoperative systemic inflammatory response index (SIRI) were independent risk factors affecting OS and RFS.

Conclusions and Significance

This study demonstrates that HAIC-based conversion therapy significantly prolongs OS and RFS in HCC patients who achieve CR/PR, with fewer surgical complications. Therefore, conversion surgery should be considered when patients achieve CR or PR after HAIC treatment. These findings provide important references for clinicians and patients in decision-making regarding HAIC-based conversion hepatectomy.

Research Highlights

1. Survival Advantage: The OS and RFS in the responder group were significantly better than those in the non-responder group, particularly in BCLC stage C patients.
2. Surgical Safety: The responder group had a shorter hepatic hilum inflow occlusion time and less intraoperative blood loss, indicating higher surgical safety.
3. Prognostic Factors: The study identified multiple independent risk factors affecting long-term survival in HCC patients, providing a basis for personalized treatment.
4. Clinical Guidance: The results provide important evidence for the optimal timing of HAIC-based conversion surgery, helping to optimize treatment strategies for HCC patients.

Other Valuable Information

This study also explored the combination of HAIC with other anticancer treatments, such as tyrosine kinase inhibitors and immune checkpoint inhibitors, suggesting that HAIC combination therapy may further improve the success rate of conversion surgery and patient survival. Additionally, the study emphasized the importance of postoperative AFP and PIVKA-II levels in predicting tumor recurrence, providing references for the selection of postoperative adjuvant therapy.

This study provides significant clinical evidence for conversion therapy in HCC patients, offering high scientific and practical value.