Stereotactic Radiation Therapy (SBRT) is a treatment that uses imaging equipment to capture images of tumors and surrounding normal tissues, and with the cooperation of a treatment planning system, uses stereotactic principles and techniques to precisely locate tumors in the human body, concentrates narrow beams of radiation at the target site, and gives a large dose of radiation to cause focal destruction of tumors while minimizing damage to normal tissues. Stereotactic radiotherapy equipment is diverse and can be as simple as a common linear gas pedal, a set of limiting cylinders made of high-density materials of different diameters (10-35 mm), a computer-controlled treatment planning system and a set of stereotactic frames, which can produce a knife-like effect when used, hence the name X-knife. If the radiation source is focused by multiple radioactive cobalt-60s, it is called a gamma knife. In addition, there are more complex radiotherapy devices, such as radio wave knife, spiral tomotherapy system, rotational pull-arc conformal radiotherapy technique (RapidArc-SBRT), and image-guided radiotherapy device with CT. The construction and principle of the radio wave knife is automated robotic tracking with 180° non-coplanar rotation. The most important feature of treating intrahepatic tumors with the radio wave knife is the ability to track the tumor in real time. Spiral tomotherapy is radiation therapy using the inverse principle of spiral CT imaging, which in principle enables various required dose distributions to be achieved in the human body. Its biggest advantage is that it can irradiate multiple target areas at the same time, achieving a much higher conformal dose distribution and a large therapeutic range, which is more suitable for radiation therapy of middle and advanced liver cancer. Advantages of stereotactic radiation therapy for primary liver cancer Firstly, in terms of radiotherapy effect, liver cancer is a dose-dependent tumor. The liver is a parallel organ, part of the liver is damaged by high dose of radiation, and the uninjured normal liver can compensate for the proliferation. Secondly, liver tumors are far from vital organs or tissues (such as intestines), and radiation therapy will not endanger other tissues leading to complications. Thirdly, liver tumor will move with breathing, and stereotactic radiation therapy equipment can have breathing tracking function to reduce the damage to normal liver. Fourthly, stereotactic radiation therapy can be used for high dose and low fractionation radiotherapy, and the radiotherapy time can be shortened to less than 1 week, which is convenient for patients. Safety of stereotactic radiotherapy for hepatocellular carcinoma Currently, conventional fractionation is used for tumor radiotherapy, i.e. 1.8~2.0 Gy/time, 5 times a week, and 5~7 weeks of radiotherapy, which aims to reduce the toxicity of radiation to normal tissue. Stereotactic radiotherapy can shorten the duration of radiotherapy by increasing the dose of each radiotherapy session. Radiotherapy at a dose greater than the conventional fractionated dose per session is called hypofractionated radiotherapy. For small (<5 cm in diameter) intrahepatic tumors, hypofractionated (1 to 3 times) radiotherapy can be performed to shorten the radiotherapy time and facilitate patients in the field. Most of the current reports on stereotactic radiation therapy for liver cancer are limited to safety studies. The Memorial Sloan-Kettering Cancer Center in the United States reported stereotactic radiotherapy for patients with liver metastases from intestinal cancer with a single dose starting at 18 Gy and increasing in increments of every 4 Gy up to a maximum of 30 Gy, with no complications of grade 3 or higher. In Japan, 16 patients with hepatocellular carcinoma were reported to receive stereotactic hypofractionated radiotherapy, and the authors concluded that it was safe and feasible to treat hepatocellular carcinoma with radioactive wave knife hypofractionation. Yuan Zhiyong of Tianjin Cancer Hospital in China treated 17 patients with hepatocellular carcinoma with stereotactic radiation at a total dose of 39 to 52 Gy/3 to 8 times with mild adverse effects. A study at the University of Colorado in the United States showed that 20 Gy×3 times of radiation treatment for patients with metastatic liver cancer was safe for the liver at this radiation splitting dose without radiographic hepatitis if the patient had normal liver function before radiotherapy, normal liver volume was greater than 700 cm3, and the normal liver tissue received no more than 5 Gy each time. As mentioned above, the selection of radiotherapy patients requires strict indications. Stereotactic Radiation Therapy (SBRT) is to use imaging equipment to capture images of the tumor and surrounding normal tissues. For hepatocellular carcinoma that cannot be surgically resected but is confined to the liver, interventional embolization chemotherapy or intratumoral radiofrequency ablation is firstly considered because of its evidence-based medical evidence of grade A. In contrast, for patients for whom interventional or radiofrequency treatment is not appropriate and for whom these treatments have poor outcomes, radiotherapy or stereotactic radiotherapy is the best alternative treatment. Effectiveness of stereotactic radiation therapy for liver cancer The Korea Cancer Center Hospital reported that 32 patients with primary liver cancer were treated with radioactive knife for intrahepatic lesions with radiation doses of 30-39 Gy/3 times. Seven cases achieved complete remission and 16 cases partial remission, with 1-, 2-, and 3-year survival rates of 68%, 61%, and 42%, respectively, and a median survival of 32 months. Treatment failure was due to recurrence in the radiation field. There is a dose-dependent relationship between survival and radiotherapy, that is, the higher the dose of radiotherapy, the longer the survival time. Tianjin Cancer Hospital in China reported that the median survival was 14.3 months in 17 cases of primary liver cancer patients with intrahepatic lesions treated with radiofrequency knife. The difference between the results of the Korean and Tianjin Cancer Hospital studies was mainly due to the difference in patient selection. Spiral tomographic radiotherapy is the best radiotherapy device for patients with intermediate to advanced multifocal primary liver cancer. Yonsei University in Korea reported that in patients with concurrent intra- and extra-hepatic lesions (lung, adrenal, and soft tissue metastases and an average of 3.5 lesions per patient) treated with tomotherapy, the median survival of patients was 12.3 months, and the local control rate of lesions subjected to radiotherapy was 79% within 1 year with no grade IV toxic side effects. Problems and prospects of stereotactic radiotherapy for hepatocellular carcinoma Stereotactic radiotherapy requires high-level evidence-based medical evidence For hepatocellular carcinoma that cannot be surgically resected but is confined to the liver, interventional embolization chemotherapy, or intratumoral radiofrequency ablation is first considered because its evidence-based medical evidence is level A. Currently, the highest evidence-based medical evidence for radiotherapy for hepatocellular carcinoma is only grade C (i.e., retrospective control). For intermediate to advanced hepatocellular carcinoma confined to the liver that is inoperable, stereotactic radiation therapy still requires a multicenter, prospective, randomized group clinical study to produce level A evidence-based medical evidence before it can be promoted. For the treatment of extrahepatic metastases from hepatocellular carcinoma, there is a lack of high-level evidence-based medical evidence for various treatment approaches. This is due to the lack of effective treatment for extrahepatic metastases and the fact that extrahepatic metastases often have multiple sites of metastasis or a variety of intrahepatic lesions, making it difficult to establish a good inclusion criteria. In addition, radiotherapy alone for confined intrahepatic hepatocellular carcinoma is generally selected for patients who cannot undergo surgery or intervention due to medical disease, or whose tumors are too large for radiofrequency ablation (e.g., poor iodine oil deposition, presence of arteriovenous leaks, complete portal vein obstruction without formation of collateral circulation, etc.), and patients with poor interventional results. And the situation of these patients is not comparable with patients who can be operated or can be intervened. The optimal radiation dose for stereotactic radiotherapy of hepatocellular carcinoma needs to be explored. Some investigators have suggested that the linear quadratic (L-Q) mode BED = nd[1 + d/(α/β)], which we currently use, is not suitable for hypo-segmentation radiotherapy, that is, the higher the dose per segmentation, the less suitable the L-Q mode is. For the specific dose of hypofractionated radiotherapy, it is worthwhile to figure out the relationship between the incidence of normal tissue complications and radiotherapy dose-volume for the purpose of predicting radiological liver injury. Hypofractionated radiotherapy reported in Europe and the United States is mainly for metastatic liver tumors, and those reported in Asia are mainly for primary liver cancer. Primary liver cancer is often associated with hepatitis and cirrhosis; therefore, the experience of hypofractionated radiotherapy in Europe and the United States cannot be applied to Asian patients. Exploring the relationship between different hypofractionated radiotherapy doses and radiological liver injury in primary liver cancer in Asian population is also the goal of future research. Stereotactic radiation therapy is not yet a substitute for other local treatments For patients with peripheral non-small cell lung cancer that cannot be surgically resected, stereotactic radiation therapy is comparable to surgery. Therefore, some investigators believe that stereotactic radiation therapy can also replace surgical resection of hepatocellular carcinoma. The current results of stereotactic radiotherapy for liver cancer show that the main reason for failure of radiotherapy is tumor recurrence and metastasis in the radiation field, which is similar to the reason for failure after surgical resection. Therefore, radiotherapy combined with interventional therapy to prevent tumor recurrence and metastasis in the liver is a good research topic. Since stereotactic radiotherapy can also only target small lesions (≤5 cm in diameter), these intrahepatic tumors can often be treated by traditional treatments such as surgical resection, radiofrequency ablation, and intervention. These traditional treatments are well established, while stereotactic radiotherapy for hepatocellular carcinoma is only available in phase I and II clinical studies. Therefore, at present, stereotactic radiotherapy cannot replace the traditional treatment of liver cancer. Strictly speaking, stereotactic radiotherapy can only be used as a supplement to these treatments, especially for patients with liver cancer that cannot be surgically resected for various reasons. For example, for patients whose tumors have a maximum diameter of ≥3 cm and are located around large blood vessels, on the surface of the liver, immediately adjacent to the gallbladder and other areas that are not suitable for radiofrequency ablation, stereotactic radiation therapy shows its advantages. For patients whose tumors have metastasized outside the liver, stereotactic radiation therapy can show even more advantages, which is difficult to be achieved by other treatments, but more clinical data are needed to support it.