1.2.2 Non-Surgical Treatment of Liver Cancer

1.2.2 Non-Surgical Treatment of Liver Cancer

1.2.2.1 Radiotherapy

For patients in generally good condition, with relatively localized tumors, no extrahepatic metastasis, no severe cirrhosis, jaundice, or ascites, and who can tolerate radiotherapy but are not eligible for surgery, radiotherapy techniques can be reasonably applied under the premise of delivering the maximum radiation dose to the tumor. Patients with compensated liver function can tolerate a total radiation dose of about 30–35 Gy for whole-liver irradiation, which is far lower than the effective dose required for curative radiotherapy of liver cancer. Therefore, many scholars believe that conventional radiotherapy cannot balance tumor control rates with normal tissue complication rates, making radical radiotherapy for liver cancer of limited significance. The rapid development of medical imaging, computer technology, and nuclear medicine has driven the advancement of liver cancer treatment methods such as three-dimensional conformal radiotherapy (3D-CRT), stereotactic body gamma knife, and radioactive particle ¹²⁵I implantation therapy.

Three-dimensional conformal radiotherapy is safe, minimally invasive, has few side effects, and demonstrates significant therapeutic efficacy. Sun Guanghui et al. used three-dimensional conformal radiotherapy to treat liver cancer in 21 patients, analyzing and evaluating its clinical effects. All cases were followed up for 3–36 months, revealing that tumor size decreased by 5%–100%, and clinical symptoms markedly improved.

The stereotactic body gamma knife treatment has a very clear boundary between the irradiated area and normal tissues, avoiding damage to surrounding healthy tissues and resulting in few side effects, making it a viable option for palliative treatment of liver cancer. Forty-seven liver cancer patients received stereotactic body gamma knife treatment, with results showing complete remission in 12.7%, partial remission in 63.2%, and an overall effective rate of 75.9%. Moreover, AFP levels decreased to varying degrees in all cases.

Interstitial implantation of ¹²⁵I radioactive particles can inhibit the growth of liver tumors while causing relatively little damage to normal liver tissue, and postoperative patients experience enhanced immune function. Nag et al. have shown that ¹²⁵I particles have a half-life of 59.43 days, which is relatively long, and feature a low dose rate. They can inhibit tumor growth by suppressing cell proliferation and directly kill tumor cells.

1.2.2.2 Chemotherapy

Commonly used chemotherapeutic drugs for liver cancer include fluorouracil, cisplatin, doxorubicin, mitomycin, and gemcitabine. However, due to the inherent high expression of multidrug resistance genes in liver cancer, systemic chemotherapy has unsatisfactory efficacy and severe adverse reactions, limiting its clinical application. Twenty advanced liver cancer patients were treated with a combined PIAF regimen—cisplatin, doxorubicin, fluorouracil, and α-interferon—for biologic chemotherapy, resulting in a disease control rate of 55%, a median survival of 6 months, and a 1-year survival rate of 27.3%. This regimen, however, has obvious toxic side effects: 55% of patients experienced bone marrow suppression, and 25% had to discontinue treatment due to intolerance. Yin et al. used a quadruple systemic chemotherapy regimen consisting of doxorubicin, cisplatin, interferon, and fluorouracil to treat 26 liver cancer patients, achieving a 1-year survival rate of 24.3% and a median survival of 6 months. Despite these limitations, chemotherapy remains an effective treatment for liver cancer, and exploring new chemotherapy regimens and improving chemotherapy indices are current research directions.

1.2.2.3 Biological Therapy and Targeted Therapy for Tumors

With the development of molecular biology, cell biology, and immunology, biological therapy, with its advantages of high specificity, good efficacy, and few adverse reactions, has become another important treatment modality following surgery, radiotherapy, and chemotherapy. Biological therapy utilizes various biological therapeutic agents to mobilize the body's natural defense mechanisms, enhancing immune function to achieve the goal of treating tumors. It mainly includes gene therapy and immunotherapy, with commonly used interferons, interleukins, and tumor necrosis factors belonging to immunotherapy. According to Schultz et al., a DNA plasmid encoding the IL-2 gene can inhibit B16F10 lung metastasis.

In recent years, the emergence of targeted therapy drugs has expanded their application in clinical research and treatment of liver cancer, becoming a new direction for systemic treatment of liver cancer. Gefitinib, cetuximab, and erlotinib have all achieved good therapeutic effects in clinical trials.

1.2.2.4 Percutaneous Ablation Therapy

Percutaneous ablation is the best treatment option for patients who cannot undergo surgery or liver transplantation. The procedure involves injecting chemical agents such as anhydrous alcohol, acetic acid, or hypertonic saline into the tumor under ultrasound guidance, or using extreme temperatures like radiofrequency, laser, or liquid nitrogen cryoablation to locally destroy the tumor. The earliest minimally invasive technique used for liver cancer ablation was percutaneous anhydrous alcohol injection (PEI), which is safe, inexpensive, and has few side effects. Wu Mengchao et al. studied 1,500 liver cancer patients treated with PEI and found that patients with tumors less than 3 cm in diameter had 1-year and 3-year survival rates of 100% and 81%, respectively, while patients with tumors between 3 and 5 cm had 1-year and 3-year survival rates of 92% and 48.9%, respectively. Guo Jia et al. researched the effectiveness of PEI treatment and found that liver cancer patients treated with PEI experienced tumor shrinkage rates ranging from 61.5% to 87.9%. For patients with tumors less than 3 cm in diameter, the 1-year, 2-year, and 3-year survival rates were 85.0%, 98.1%, and 80.0%, respectively, indicating that PEI treatment is comparable to surgical radical resection. For tumors larger than 2 cm in diameter, percutaneous radiofrequency ablation (RFA) is more effective than PEI. Other treatment methods such as microwave coagulation therapy, argon-helium cryotherapy, high-intensity focused ultrasound, and percutaneous intratumoral laser thermal therapy have all been widely used clinically depending on their respective indications.

1.2.2.5 Comprehensive and Sequential Treatment

Since the causative factors of liver cancer are diverse—environmental pollution, viral infection, genetics, etc.—there is currently no specific treatment method. Traditional surgical treatment has a high recurrence rate, while purely non-surgical treatment has the drawback of being incomplete. Therefore, adopting a combination of multiple methods or sequential treatment—shifting from a single treatment model to a combination of multiple treatment modalities—has become an inevitable trend in the treatment of liver cancer. Comprehensive treatment is not simply the addition of multiple methods, but rather the formulation of a reasonable individualized comprehensive treatment plan based on each patient's specific condition, in order to improve their quality of life and prolong survival. Cai Jianqiang et al. [3] propose that the main strategies for individualized comprehensive treatment of liver cancer include: the physician's understanding of the disease and grasp of clinical evidence, the patient's requirements and expectations regarding treatment, standardized treatment methods, and a multidisciplinary comprehensive treatment team.

1.3 Research Progress on P27 and Bcl-2 in Relation to Liver Cancer