INTRODUCTION
In this article, we revisit the work of Wang et al[1] published in the World Journal of Gastrointestinal Oncology. Through extensive literature review and network meta-analysis, the study provides robust evidence for the application of hepatic arterial infusion chemotherapy (HAIC) and its combined strategies in the treatment of advanced hepatocellular carcinoma (HCC). The research employs advanced network meta-analysis methods, synthesizing results from multiple studies to offer a more comprehensive assessment of efficacy and safety, which is particularly crucial in the absence of sufficient randomized controlled trials. Additionally, the paper explores the combined effects of HAIC with various other treatment strategies, a novelty in previous research.
HCC is a major cancer globally, especially prevalent in Asia and Africa, with high incidence and mortality rates. Treatment options for advanced HCC patients are limited, and prognosis is poor[2]. Over the past few years, HAIC has emerged as a regional chemotherapy approach, demonstrating distinctive benefits and innovative potential. The essence of HAIC lies in exploiting the differential blood supply to tumors vs healthy hepatocytes, enabling the direct delivery of high concentrations of chemotherapeutic agents to the cancerous tissues. This targeted approach enhances local drug concentration while minimizing systemic adverse effects[3]. The innovation of this treatment method lies in its strong specificity and minimal side effects, providing new treatment options for advanced HCC patients. The development of HAIC technology, especially with the help of interventional radiology, makes the precise delivery of chemotherapy drugs possible[4]. Through percutaneous puncture technology, catheter implantation in the hepatic artery can be achieved under local anesthesia, enhancing the safety and operability of HAIC[5]. Moreover, the innovation of HAIC in clinical application is also reflected in its combined application with other treatment methods, such as targeted therapy and immunotherapy, providing more comprehensive and personalized treatment plans for advanced HCC patients. This article will provide an in-depth examination of the current application, challenges, and optimization strategies of HAIC in the treatment of advanced HCC. It will assess the potential of HAIC to enhance patient quality of life through clinical studies, explore technological advancements that address implementation hurdles, and anticipate its role in the future of personalized medicine and multidisciplinary therapeutic approaches.
PRINCIPLES AND TECHNIQUES OF HAIC
HAIC is an innovative regional chemotherapy technique specifically targeting liver malignancies, especially HCC. Its core principle is to utilize the difference in blood supply between liver tumors and normal liver tissue, delivering high concentrations of chemotherapy drugs directly to tumor tissues while minimizing damage to normal hepatocytes and systemic side effects[6]. Tumor cells in HCC mainly rely on the hepatic artery for blood supply, while normal hepatocytes primarily receive blood through the portal vein[7]. This characteristic makes HAIC an effective treatment method. To effectively implement HAIC, an initial step involves a meticulous anatomical evaluation of the patient’s hepatic artery. This assessment is crucial for identifying arterial variations and determining the optimal site for catheter placement. Utilizing interventional radiology techniques, physicians can precisely position the catheter within the hepatic artery under the guidance of imaging. This allows for the direct infusion of chemotherapy drugs into the artery that nourishes the tumor, ensuring a targeted delivery system that enhances treatment efficacy[8]. The advantage of this method is the significant increase in local drug concentration in the tumor, enhancing the killing effect on tumor cells while reducing toxic side effects on other organs of the body[9].
The implementation of HAIC technology involves several key steps. First is percutaneous puncture and catheter placement. Common puncture routes include the subclavian artery and femoral artery, with the femoral artery approach widely used due to its simplicity and high safety[10]. Under local anesthesia, arterial puncture is performed using the Seldinger technique, followed by advancing the catheter into the hepatic artery and performing angiography to further assess vascular anatomy[4]. The precise placement of the catheter is crucial for the effectiveness of HAIC, usually placed in locations such as the gastroduodenal artery, right hepatic artery, or common hepatic artery[11]. To reduce the stimulation and potential side effects of chemotherapy drugs on adjacent organs, selective embolization is often required, such as using micro-spring coils to embolize the gastroduodenal artery and its branches. Catheter fixation is also an important part of the technical implementation[12]. To prevent catheter displacement or detachment, various fixation techniques are used, such as micro-spring coils and special W-spiral self-fixing catheters. The application of these technologies greatly improves the stability and safety of HAIC treatment. In addition, catheter fixation also helps to reduce patient pain and discomfort.
Another key aspect of HAIC treatment is the selection of drugs and the formulation of treatment plans. Based on the biological characteristics of the tumor and the specific conditions of the patient, appropriate chemotherapy drugs are chosen, and personalized treatment plans are formulated. During the treatment process, it is necessary to regularly monitor the patient’s response and potential side effects to adjust the treatment plan in a timely manner. With the continuous advancement of interventional radiology technology, HAIC technology is also constantly being optimized and developed. The application of new materials and equipment, such as drug-eluting microspheres, further improves the efficacy and safety of HAIC[13]. In addition, the combined application of HAIC with other treatment methods, such as targeted therapy and immunotherapy, is also being explored, hoping to bring more effective treatment options for advanced HCC patients.
CURRENT STATUS AND IMPACT IN ADVANCED HCC TREATMENT
The treatment options for patients with advanced HCC are relatively limited, especially when the tumor has spread or liver function reserve is poor. HAIC, as a regional treatment method, has shown significant clinical effects in the treatment of advanced HCC. HAIC improves treatment effects while reducing systemic toxic side effects by directly delivering high-concentration chemotherapy drugs to the tumor site. In some studies, HAIC has shown the ability to significantly extend the survival period of advanced HCC patients and improve the quality of life[14]. The application of HAIC in advanced HCC is mainly reflected in the following aspects. First, for advanced HCC patients who cannot undergo surgical resection or are not suitable for liver transplantation, HAIC can serve as an effective local control method[15]. Second, HAIC can be combined with other treatment methods such as targeted therapy and immunotherapy to form a comprehensive treatment plan to improve treatment effects[16]. In addition, HAIC has also been used in some studies as neoadjuvant therapy, aiming to reduce tumor volume and create conditions for surgical resection. In clinical practice, the effectiveness of HAIC is shaped by a multitude of factors. These include the patient’s tumor burden, the status of liver function, and the degree of tumor angiogenesis. Each of these elements plays a significant role in determining the success of HAIC treatment[17]. Therefore, individualized assessment and formulation of treatment plans are crucial for improving the effectiveness of HAIC treatment. Studies have shown that HAIC is more effective for patients with certain liver function reserves and relatively low tumor burden, and close monitoring and timely adjustments during the HAIC treatment process also have a significant impact on efficacy[18].
CHALLENGES AND FUTURE DIRECTIONS
HAIC, as a regional chemotherapy method, has shown significant potential in the treatment of advanced HCC. However, despite its obvious advantages, HAIC still faces many challenges in clinical application. First, the indications for HAIC treatment need to be further clarified. Not all advanced HCC patients are suitable for HAIC treatment, and more in-depth research is needed to determine the patient group most suitable for HAIC treatment. Second, the safety and side effect management of HAIC treatment are also key issues. Although HAIC reduces systemic toxic side effects, the toxicity of local chemotherapy drugs, catheter-related complications, etc., still need close attention and proper handling[19].
The challenges of HAIC technology mainly include improving accuracy and safety. Due to the high variability of liver vascular anatomy, correctly placing the catheter to the target hepatic artery branch is somewhat difficult, and catheter displacement or misplacement into non-target vessels may lead to treatment failure or increased adverse reactions. In addition, optimizing the local concentration of chemotherapy drugs, release rate, and contact time with tumors are also key factors in improving efficacy. The management of complications associated with HAIC treatment is also a challenge, including catheter-related complications such as catheter detachment, thrombosis, infection, and chemotherapy-induced local or systemic adverse reactions[1]. These complications not only affect treatment effects but may also have a negative impact on patients’ quality of life and prognosis.
Future research directions include exploring the optimal combination of HAIC with other treatment methods, such as the combined application with targeted drugs and immunotherapy, developing new chemotherapy drugs or drug carriers to improve the efficacy and reduce side effects of HAIC, using biomarkers and molecular imaging technology for individualized prediction of HAIC treatment response to achieve precision treatment, and conducting large-scale, multi-center clinical trials to verify the efficacy and safety of HAIC in the treatment of advanced HCC. With a deeper understanding of the molecular mechanisms of HCC, future HAIC treatments may be more personalized and precise. For example, based on information such as tumor gene mutations and signal transduction activation status, the most suitable chemotherapy drugs and treatment plans can be selected.
In response to the challenges of HAIC technology, future optimization directions can start from the following aspects. First, use advanced imaging technology, such as computed tomography, magnetic resonance imaging, or angiography, for precise vascular anatomy assessment to guide accurate catheter placement. In addition, develop new catheter materials and designs to improve catheter stability and biocompatibility, reducing the risk of displacement and infection. Innovation in drug delivery systems is also key to optimizing HAIC. Investigations into drug-controlled release systems, including drug-eluting microspheres and nanoparticles, are paving the way for sustained and stable local drug delivery within tumor sites. Such advancements have the potential to enhance treatment efficacy while simultaneously diminishing the incidence of systemic toxic side effects[20]. At the same time, explore intelligent responsive drug delivery systems, such as pH-sensitive or temperature-sensitive materials, to regulate drug release based on changes in the tumor microenvironment.
CONCLUSION
Looking to the future, the development of HAIC technology will continue to focus on improving the precision, safety, and quality of life for patients. With the advancement of imaging technology and innovation in biomaterials science, HAIC will achieve more precise targeted drug delivery and fewer side effects. The deepening of personalized medicine will enable HAIC treatment plans to be optimized according to the specific conditions and genetic characteristics of patients. In addition, combining with new therapies such as systemic therapy and immunotherapy, HAIC will be part of a comprehensive treatment strategy, providing more effective treatment options for advanced HCC patients. In conclusion, although HAIC has shown potential in the treatment of advanced HCC, continuous technological innovation and clinical research are key to realizing its widespread clinical application. By continuously optimizing HAIC technology, we hope to provide more effective and safe treatment methods for HCC patients in the future, improving patient prognosis.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B
Novelty: Grade B
Creativity or Innovation: Grade A
Scientific Significance: Grade A
P-Reviewer: Gikunyu CW S-Editor: Wei YF L-Editor: A P-Editor: Zhang XD
