The National Comprehensive Cancer Network (NCCN) has been widely influential in the international oncology community in formulating clinical recommendations based on the latest, high-quality evidence-based oncology research and expert consensus. Compared with the second edition of the guidelines in 2014 (hereinafter referred to as the “Guidelines”), the “New Guidelines” have more updates for hepatocellular carcinoma (HCC). Compared with the second edition of the 2014 guideline (hereinafter referred to as “the guideline”), the “new guideline” has more updates on hepatocellular carcinoma (HCC), mainly in the areas of screening and treatment. In this article, we will focus on the specific updates of the “new version of the guidelines” and explain them. 1. Screening for HCC Bruix et al. pointed out that the susceptible groups for HCC are mainly cirrhotic patients and hepatitis B virus carriers. The new guidelines recommend screening for HCC every 6 to 12 months, either by ultrasound (US) or serum alpha-fetoprotein (AFP), with the new guidelines emphasizing US as the preferred modality. AFP testing and US are the most commonly used screening tools for HCC. In a study conducted in China on a large sample of patients with hepatitis B virus infection or chronic hepatitis, the detection rate, false-positive rate, and positive predictive value of US for HCC were 84.0%, 2.9%, and 6.6%, respectively, while the AFP test was 69.0%, 5.0%, and 3.3%, respectively, and the US combined with AFP test was 92.0%, 7.5%, and 3.0%, respectively. 3.0%. These results demonstrate that US is a better detection method in the screening of HCC, but because the accuracy of US results is subjectively influenced by the operator, the detection rate of HCC can be increased if AFP testing is superimposed on the susceptible population at the same time. It should be noted that for patients in the early stages of HCC, serum AFP levels are usually not increased, which limits the application of AFP in HCC screening. The diagnosis of HCC in the “new version of the guidelines” is basically the same as the “guidelines”, and the criteria for confirming the diagnosis are the detection of occupying liver lesions on the basis of cirrhosis or chronic liver disease, and the presence of 2 or more liver lesions on 3-stage enhanced imaging examinations such as CT, MRI, ultrasonography (CEUS). The new guidelines emphasize that for occupying lesions that are negative on biopsy but continue to increase in size, if imaging does not confirm HCC, the possibility of cancer cannot be ruled out and monitoring, including multidisciplinary identification, is recommended. For patients diagnosed with HCC, the “new guidelines” recommend a comprehensive multidisciplinary assessment, including hepatitis-specific assessment, liver function assessment, chest CT, etc. Based on the assessment results, HCC patients are classified into four categories: (1) patients with resectable or transplantable lesions that can be operated on according to the patient’s physical condition or co-morbidities; (2) patients with non-resectable lesions; and (3) patients with non-resectable lesions. patients; (2) patients with unresectable lesions; (3) patients with limited lesions or limited lesions with minor extrahepatic metastases, but inoperable due to the patient’s physical condition or complications; and (4) patients who have developed metastases. The new guidelines recommend different treatments for different patients, including surgical treatment, local treatment, systemic treatment, clinical trials, and supportive care. 3.1 Surgical treatment The main surgical treatment modalities for HCC are partial hepatectomy and liver transplantation. Partial hepatectomy is a potentially radical treatment for parenchymal tumors of any size without vascular invasion, with a surgical complication rate and morbidity and mortality rate of ≤5%. However, because partial hepatectomy for HCC also requires resection of the normal functioning liver parenchyma outside the lesion, the patient’s functional status, the presence of comorbidities, overall liver function, the size and function of the residual liver after resection, and clinical skills related to tumor and liver anatomy should be carefully evaluated preoperatively. ”The new guidelines recommend partial hepatectomy as a curative option when the following conditions are met (1) good liver function: Child-Pugh class A, without the presence of portal hypertension; (2) parenchymal tumor without macrovascular invasion: the presence of visual or microscopic vascular invasion is a strong predictor of HCC recurrence; (3) adequate residual liver volume: at least 20% of the liver should be preserved in patients without cirrhosis, and in patients with cirrhosis meeting Child-Pugh class A liver function. guaranteeing bile duct inflow and outflow volume should have at least 30%-40% of liver remaining. For patients with postoperative residual liver volume (FLR)/total liver volume ratio lower than the recommended value and suitable for hepatectomy, preoperative portal vein embolization (PVE) should be considered. The results of a large retrospective study showed that the 5-year survival rate after partial hepatectomy for patients with hepatocellular carcinoma is >50%, and for patients with early stage hepatocellular carcinoma with good liver function, the 5-year survival rate can reach about 70%. However, the role of partial hepatectomy is controversial in patients with resectable multiple hepatocellular carcinomas and those who have developed vascular invasion. A recent retrospective analysis found that the overall 5-year survival rate for partial hepatectomy for a single tumor ≤5 cm in diameter or for three tumors ≤3 cm in diameter was 81%, and in this regard, the “new guidelines” state that partial hepatectomy can be considered for HCC patients who meet these characteristics, but preoperative evaluation must be done carefully. In 1996, Mazzaferro et al. proposed the Milan criteria for liver transplantation selection in patients with unresectable HCC and cirrhosis, and the United Network of Organ Sharing (UNOSG) was published. It was adopted by the United network for organ sharing (UNOS) and revised as the UNOS criteria for liver transplantation: a single tumor ≤ 5 cm in diameter or 2-3 tumors ≤ 3 cm in maximum diameter, without macrovascular invasion and extrahepatic metastases. Patients with HCC who meet the UNOS criteria can be considered for liver transplantation. Internationally, liver transplantation has been widely recognized as an initial treatment option for patients with early-stage hepatocellular carcinoma and moderate to severe cirrhosis (i.e., patients with Child-Pugh grade B and C liver function). Although UNOS criteria state that patients eligible for liver transplantation should not be candidates for partial hepatectomy, partial hepatectomy is also currently a common clinical treatment option for patients with early stage HCC in Child-Pugh class A. Unfortunately, there are no studies comparing the initial treatment of these patients with partial hepatectomy or liver transplantation, and the “new guidelines” suggest that the initial treatment of these patients should be combined with a comprehensive multidisciplinary assessment. The possibility of extending the UNOS criteria to patients with HCC who are candidates for liver transplantation but have larger tumor borders is currently a hot topic of debate in the liver transplantation field. Yao et al. from the University of California at San Francisco (UCSF) proposed an extended version of the UNOS criteria, namely the UCSF rule: HCC patients with a single tumor ≤ 6.5 cm in diameter or ≤ 3 tumors with the largest ≤ 4.5 cm (also meeting the cumulative tumor size < 8 cm) can be considered as candidates for liver transplantation. Candidates. A study of survival after liver transplantation in patients who exceeded UNOS criteria but met UCSF criteria found a large variation in 5-year survival rates, ranging from 38% to 93%. A retrospective analysis of the UNOS database showed that the subgroup of patients with tumors 3-5 cm in diameter had significantly lower survival rates compared to those with smaller tumors. Therefore, there is a debate whether patients with HCC beyond UNOS criteria can be treated with liver transplantation because they meet the extended criteria: proponents argue that patients with HCC beyond UNOS criteria can be cured with liver transplantation, while opponents argue that excessive tumor size or staging increases the risk of vascular invasion and tumor recurrence, and puts tremendous pressure on organ supply and demand. As to whether liver transplantation should be considered for patients exceeding UNOS criteria, the "new guidelines" state in the principles of HCC surgery that transplantation should be considered for patients meeting UNOS criteria, while the treatment options for patients slightly exceeding UNOS criteria are more controversial, with some research centers considering transplantation. In addition, liver transplantation may be considered in patients whose tumors exceed the Milan criteria but meet the criteria after step-down therapy. For patients with unresectable lesions and limited lesions or limited lesions with minor extrahepatic metastases that are inoperable due to the patient's medical condition or complications, the guidelines recommend non-surgical treatment modalities including local therapy, systemic systemic therapy, clinical trials and supportive care, of which the "new version of the guidelines", based on the second edition of 2014, recommends that local therapy, systemic systemic therapy, clinical trials and supportive care are preferred. The "new guideline" is based on the second edition of 2014, which recommends local treatment, including ablation, direct arterial therapy and external radiotherapy, with more updates on direct arterial therapy and external radiotherapy. For the first time, the "new guideline" uses "RE" as an acronym for radioembolization in direct arterial therapy. Transarterial radioembolization (TARE) is a newer method of embolization that delivers high doses of radiation to the tumor-associated capillary bed for therapeutic purposes. It is administered through a catheter with embedded yttrium-90 microspheres that emit beta radiation, which reduces the exposure of normal liver tissue to radiation due to limited radiation penetration. Radioembolization has been widely reported to be an effective treatment for intermediate or advanced HCC. Compared to transaterial chemotherapy embolization (TACE), there is no significant difference in survival time for HCC patients treated with TARE, but the time to disease progression is prolonged and radiotoxicity is reduced. "The new guidelines also emphasize that all direct arterial therapies are relatively contraindicated in patients with bilirubin >51.3 μmol/L (3 mg/dL) unless segmental injections can be performed. In addition, the radiation potential of yttrium-90 microspheres induces an increased risk of liver disease in patients with bilirubin >34.2 μmol/L (2 mg/dL), so particular attention should be paid to patient liver function when using TARE for HCC. ”The new guidelines add intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT) to the principles of external radiotherapy treatment for the first time. IMRT is an advanced modality of high-precision radiation therapy that delivers precise radiation doses of photons or X-rays into the tumor or into a specific field. IMRT allows for the safe delivery of higher and more effective doses of radiation to the tumor itself with fewer side effects than conventional radiotherapy. Its disadvantages include operational complexity, requiring longer daily processing times and additional planning, as well as safety screening efforts prior to treatment. IMRT is now widely used for prostate, head and neck, and central nervous system cancers, and has also been used in limited circumstances to treat liver cancer, as well as breast, thyroid, and lung cancers. PBT is a treatment that uses particles with positively charged atoms, such as positrons, to deliver conformal external radiation radiotherapy to the target area. Due to its unique dose deposition characteristics, PBT can deliver a predetermined radiation dose to the target area compared to photon external beam radiotherapy, i.e., it rapidly produces a high intensity dose distribution within a very narrow defined tissue area, forming a Bragg peak, after which the energy rapidly decays and escapes through the body without significant radiation dose deposition outside the target tissue. PBT is suitable for cases where the surrounding normal tissues cannot be protected from irradiation. Phase I clinical trials of PBT for liver cancer were completed in September 2014. 3.3 Systemic therapy Most patients with hepatocellular carcinoma are diagnosed with advanced disease and have lost the opportunity for radical treatment; therefore, systemic therapy is the only option for patients with very advanced HCC. Systemic therapy mainly includes sorafenib-based chemotherapy, which can be systemic systemic chemotherapy or intra-arterial chemotherapy. ”The new guidelines suggest that patients with unresectable tumors due to hepatic causes should be evaluated for transplantation, and if eligible for transplantation should be actively referred to a transplant center; those who are not eligible can be considered for local therapy, systemic therapy with sorafenib-based chemotherapy, clinical trials and supportive care. The new version of the guidelines recommends that local treatment is preferred, and suggests that there is no data to support whether chemotherapy is used. Currently, the most used chemotherapy regimen for advanced HCC at home and abroad is mainly sorafenib. For patients with unresectable lesions, patients with extensive lesions that are not suitable for liver transplantation, patients with limited lesions that are not suitable for surgery due to medical conditions or comorbidities, and patients with metastases, the “new guidelines” recommend sorafenib if liver function meets Child-Pugh class A. Sorafenib may also be used in patients with Child-Pugh class B liver function, but data on safety and dosing are not yet available. Therefore, the New Guideline recommends special caution in the use of sorafenib in patients with elevated bilirubin. For targeted therapies in patients with hepatocellular carcinoma, the New Guideline also mentions bevacizumab, a vascular endothelial growth factor receptor (VEGFR) inhibitor, which has shown some therapeutic efficacy in clinical trials in patients with advanced HCC, but there is a lack of validated experimental data to support its clinical treatment. However, there is a lack of validated experimental data to support its clinical treatment. The ASCO Annual Report: Advances in Clinical Oncology 2015 also mentions lenvatinib, a tyrosine kinase inhibitor, for targeted therapy in hepatocellular carcinoma, which can block a series of regulatory factors including VEGFR1-3, fibroblast growth factor receptors (FGFRs) 1-4, and platelet-derived growth factor receptor (PDGFR) β in tumor cells. but there is also a lack of clinical data to support this. The prognosis of HCC is poor, and most of the cases are diagnosed at advanced stages, and many advanced therapeutic measures have emerged after a long period of research. The “new guidelines” recommend that (1) sorafenib can be the first-line drug for patients with advanced HCC with Child-Pugh grade A liver function, and as a Class 2A option for Child-Pugh grade B liver function; (2) liver transplantation is the best treatment option for patients with early-stage HCC meeting UNOS criteria. (2) bridging therapy can be used for HCC patients to reduce the probability of tumor progression and removal from the transplant list; (3) local therapy can be considered for HCC patients who are not suitable for surgical treatment: ablation is suitable for appropriately located and small tumors diagnosed after multidisciplinary consultation; direct arterial therapy including TACE and TARE can be used for patients who are unresectable or inoperable and not suitable for ablation. External radiotherapy is suitable for patients with one to three tumors without or with minor metastases, and can also be an alternative to ablation and embolization when they are contraindicated; (4) all HCC patients should undergo pre-treatment evaluation, careful patient screening for treatment purposes and active multidisciplinary collaboration are necessary, and there are few high-quality randomized clinical trials for patients with hepatocellular carcinoma, and participation in prospective clinical trials is the best Regardless of the stage of the patient, participation in prospective clinical trials is the best treatment approach. In 2011, the Hepatocellular Carcinoma Professional Committee of China Anti-Cancer Association issued the Expert Consensus on Local Ablation Therapy for Primary Liver Cancer, and in the same year, the former Ministry of Health of China issued the Diagnostic and Treatment Standard for Primary Liver Cancer, and in 2012, the Chinese Medical Association issued a new version of the Hepatocellular Carcinoma Diagnostic and Treatment Roadmap, taking into account the situation in China. The NCCN clinical practice guidelines are the consensus reached by multidisciplinary experts in the United States based on clinical basis and treatment experience, and the “new version of the guidelines” has made more up-to-date information about hepatocellular carcinoma. However, there are some differences with the consensus of domestic experts on the management of liver tumors. We should refer to the NCCN guidelines and carry out clinical work in accordance with the actual situation in China.