How to deal with liver cancer combined with portal vein cancer thrombus? Compare the differences between Chinese and foreign guidelines

*For medical professionals only

Due to the anatomical characteristics of the liver and the highly aggressive nature of hepatocellular carcinoma (HCC), HCC is prone to invasion of the portal vein to form portal vein cancer thrombus (PVTT).

According to literature reports, 22.
0%-62.
2% of HCCs combined with PVTT, and the disease progressed rapidly and the prognosis was very poor
.

The incidence and related factors of HCC combined with PVTT differ
between Eastern and Western populations.
In China, the incidence of HCC combined with PVTT is nearly 55%, the age of onset of patients is relatively young, and more than 70% are complicated by hepatitis B virus (HBV) infection
.
Coupled with factors such as regional ethnicity, drug approval, socioeconomics, and guideline update cycle, there are differences
in the recommended strategies for HCC combined with PVTT in the East and the West.

At the 25th National Clinical Oncology Conference and 2022 CSCO Annual Conference, Professor Weidong Jing of the First Affiliated Hospital of University of Science and Technology of China elaborated on the differences between the Eastern and Western treatment
of HCC combined with PVTT based on the guidelines for the diagnosis and treatment of Eastern and Western hepatocellular carcinoma.
The Medical Oncology Channel is compiled below for readers
.

1.
Surgical treatment

1.
Development milestones

In 1992, Japanese scholars found that the 3-year survival rate of HCC combined with PVTT patients was as high as 11.
6%, opening a precedent
for surgical treatment.
Previously, HCC combined with PVTT surgery was only used as an emergency measure to stop bleeding from esophageal varices, not as a means to
improve patient survival.

In 2003, the Japan Liver Cancer Research Group (LCSGJ) proposed PVTT grading; In 2007, Professor Cheng Shuqun of China's Oriental Hepatobiliary Hospital proposed Cheng's classification, which significantly affected the choice of treatment mode and prognosis
.

In 2016, a Japanese national study found that in patients with liver function Child-Pugh grade A, the median overall survival (OS) was 1.
77 years longer in the hepatic resection group than in the non-surgical group; subgroup analysis showed that the surgical efficacy of PVTT invasion of the main trunk or contralateral branch alone was not obvious
。 In the same year, a large-scale study in China showed that for Cheng's type I/II PVTT patients with liver function Child-Pugh A/B (partial), surgical treatment was the best solution at that time, and the median OS of type I and II PVTT patients was 15.
9 months and 12.
5 months
, respectively.

Since the efficacy of HCC combined with PVTT surgery is closely related to cancer thrombus classification, our center combined relevant literature analysis and Japanese classification and Cheng's classification in 2015-2016, and preliminarily proposed its surgical indications: portal vein branch cancer thrombus can be hepatectomy; Portal vein trunk cancer thrombus is a relative indication; Portal vein cancer thrombus extension to the superior mesenteric vein is contraindicated
.

2.
Differences between Eastern and Western diagnosis and treatment guidelines

In general, the greatest controversy between the East and the West in the surgical treatment of HCC combined with PVTT is whether to perform liver resection surgery for selected patients:

Guidelines from European and American countries, including the 2022 NCCN guidelines for hepatocellular carcinoma, the 2018 European Society of Hepatology (EASL) clinical practice guidelines for hepatocellular carcinoma, the 2021 ESMO clinical practice guidelines for hepatocellular carcinoma, and the 2022 Barcelona clinical staging of hepatocellular carcinoma (BCLC) guidelines all consider PVTT to be a marker of HCC and a contraindication to surgical resection.

Eastern countries such as China's 2022 edition of the National Health Commission's guidelines for the diagnosis and treatment of primary liver cancer, the 2022 edition of the CSCO guidelines for the diagnosis and treatment of primary liver cancer, and the 2021 edition of the Japanese Society of Hepatology Consensus Recommendations on the Management of Hepatocellular Carcinoma in Japan all proposed the classification and grading of HCC combined with PVTT, and Japan and South Korea (2018 Korean Liver Cancer Diagnosis and Treatment Guidelines) recommended that some selected patients with HCC combined with PVTT can be treated with liver resection.

In China, the 2022 Health Commission guidelines and the 2022 CSCO guidelines point out that patients with liver function Child-Pugh grade A, resectable primary lesions, PVTT type I/II, and ECOG score 0-1 can be surgically resected, and actively explore perioperative multidisciplinary treatment to improve the efficacy of surgical treatment, with Chinese characteristics and lead the future
.

2.
Interventional therapy

1.
New progress in heavy research

In 2019, the team of Professor Shi Ming of the Cancer Center of Sun Yat-sen University conducted a phase III study on the efficacy and safety of sorafenib + HAIC versus sorafenib monotherapy in patients with HCC with portal vein cancer thrombus, and the results showed that sorafenib + HAIC was superior to sorafenib monotherapy
.

At the 2021 ASCO Annual Meeting, Professor Zhao Ming of the Cancer Center of Sun Yat-sen University reported that HAIC was head-to-head versus sorafenib Phase III FOHAIC-1 study confirmed that HAIC was superior to sorafenib treatment
.

However, in two cisplatin-based HAIC studies in Japan, such as SCOOP-2 and SILIUS, HAIC + sorafenib was not successful
in treatment with sorafenib.

The relevant studies of TACE+151I particle strip/particle portal vein stent implantation conducted by Chinese scholars showed that for patients with unresectable HCC combined with type II PVTT, TACE+151I particle strip/particle portal vein stenting implantation significantly extended the median OS by 19.
3 months
compared with TACE alone.

At the 2022 ASCO Conference, Professor Kuang Ming of the First Affiliated Hospital of Sun Yat-sen University reported on the LAUNCH study
.
This phase III study comparing lenvatinib + TACE with lenvatinib first-line treatment of advanced HCC with PVTT showed that the median OS of lenvatinib + TACE and lenvatinib was 17.
9 months and 11.
5 months, respectively, the median progression-free survival (PFS) was 10.
6 months and 6.
4 months, respectively, and the objective response rate (ORR) was 45.
9% in the lenvatinib + TACE group, with 26 patients in the combination group undergoing surgical resection.
The excision conversion rate is 16%.

At present, for HCC combined with PVTT, a number of TACE combined immunotherapy studies are ongoing
.

2.
The focus of the difference between Eastern and Western diagnosis and treatment

None of the European guidelines (EAL/BCLC/ESMO, etc.
) recommend TACE/HAIC therapy; The US NCCN guidelines recommend arterial-guided therapy represented by TACE after strict selection of patients;

Guidelines from Eastern countries such as South Korea (KLCA) and Japan (JSH) state that TACE is suitable for patients with HCC and PVTT;

The 2022 Health Commission guidelines listed TACE treatment as the preferred method for HCC combined with PVTT; The 2022 CSCO guidelines are used as Level II recommendations (Class IIA evidence).

For HAIC, comprehensive 2022 Health Commission guidelines, 2022 CSCO guidelines and Japanese guidelines can be used for patients with HCC and PVTT, but there is no unified treatment technical standard, and the efficacy varies greatly
.

TACE+151I particle strip/particle portal vein stent implantation, TACE combined with immune system tumor treatment and other fields, with Chinese characteristics, leading the future
.

3.
Radiotherapy

1.
Important research progress

The European SARAH study was a phase III study to compare the efficacy and safety of SIRT (yttrium-90 resin microspheres) with sorafenib in the treatment of locally advanced HCC, and the Asian SIRveNIB study, a phase III study comparing the efficacy and safety of yttrium-90 resin microspheres (RE) and sorafenib in patients with locally advanced HCC, both studies showed that the efficacy of yttrium-90 microspheres was not better than that of sorafenib, but the rate of treatment-related adverse reactions was significantly reduced
。

Chinese studies have shown that preoperative three-dimensional conformal radiotherapy, including OS and PFS, can improve surgical outcomes, including OS and PFS, compared with surgery alone.
Another Chinese study showed that HCC combined with PVTT postoperative adjuvant intensity-modulated radiotherapy (IMRT) improved OS
.

2.
The focus of the difference between Eastern and Western diagnosis and treatment

Neither European (EASL\BCLC\ESMO) nor Japan (JSH) guidelines recommend radiotherapy;

US (NCCN) guidelines recommend external beam radiation therapy for HCC combined with PVTT, but do not recommend yttrium-90 resin microspheres for PVTT stem cancer thrombus;

Korean (KLCA) guidelines recommend radiotherapy for some patients with HCC and PVTT;

China's 2022 Health Commission guidelines and 2022 CSCO guidelines emphasize preoperative neoadjuvant or postoperative adjuvant radiotherapy for patients with resectable HCC combined with PVTT, palliative radiotherapy for unresectable HCC combined with PVTT, or combination therapy with radiotherapy and TACE
.
In the field of preoperative neoadjuvant and postoperative adjuvant radiotherapy, it has Chinese characteristics and leads the future
.

4.
Systematic anti-tumor treatment

1.
Important research progress

Systemic treatment of HCC has undergone a process
of development from monotherapy to combination.
The differences between the East and the West in systemic anti-tumor therapy are reflected in targeted therapy, immunotherapy, targeted immune combination and dual immune combination therapy
.

The 2022 ESMO Annual Meeting announced three major studies on late HCC: the LEAP-002 study of the cola combination, the 310 study of the double Ai combination, and the RATIONALE-301 study
.

Currently, there are six large immunotherapy-based end-of-phase III clinical studies in the first-line treatment of advanced HCC, including the successful HIMALAYA study, IMbrave 150 study, ORIENT-32 study, SHR-1210-310 study, and failed LEAP-002 and COSMIC-312 study
。 Among them, the 310 study of Shuangai combination is the first phase III clinical study in the world to achieve critical success in the treatment of unresectable HCC with PD-1/PD-L1 inhibitors combined with small molecule TKI, or become a new benchmark for first-line treatment of advanced liver cancer
.

2.
The focus of the difference between Eastern and Western diagnosis and treatment

In the anti-tumor treatment of HCC combined with PVTT system, there are differences between the recommended regimens for first-line and second-line treatment in the East and West due to accessibility factors such as drug approval, guideline formulation cycle, update efficiency, etc.

For patients with Child-Pugh grade A liver function, T+A is the standard choice for first-line therapy, and durvalumab plus ticimab is recommended only by BCLC and 2022 CSCO guidelines;

Based on clinical studies in China, the 2022 Health Commission guidelines added sindilimab combined with bevacizumab bioanalogues and donafenib regimens to first-line treatment; Add apatinib, carrelizumab, and tislelizumab to second-line therapy; In the 2022 CSCO guidelines, whether it is the choice of first-line or second-line treatment strategies, there are not only the latest international research results, but also the latest clinical research results led by China;

Compared with Europe, the United States and Japan, China has achieved parallel development and partial leadership in the research and development of systematic anti-tumor drugs in the field of HCC
.

summary

Based on the East-West HCC guidelines, the differences in the treatment of HCC combined with PVTT in the East and West are reflected in surgical treatment, interventional therapy, radiotherapy and systemic anti-tumor therapy:

Eastern countries represented by China, Japan and South Korea can perform liver resection surgery for selected patients; Liver transplantation is not recommended by Eastern and Western guidelines;

In addition to being recommended by Eastern country guidelines, TACE is also recommended by NCCN guidelines in the United States; HAIC is only recommended by Chinese and Japanese guidelines;

Radiotherapy is recommended by Chinese, Japanese, and American guidelines;

In the field of systemic anti-tumor therapy, the first-line treatment in Eastern and Western countries is generally the same, but the choice of drugs for first- and second-line treatment is different
.

In the era of precision medicine, regarding the treatment strategy of hepatocellular carcinoma with portal vein cancer thrombosis, we advocate the appropriate technology to carry out the appropriate treatment for the right patient at the right time
.
Establish an individualized multidisciplinary treatment model on the basis of evidence-based medicine, or the development direction
of liver cancer with portal vein cancer thrombosis treatment.

Due to the anatomical characteristics of the liver and the highly aggressive nature of hepatocellular carcinoma (HCC), HCC is prone to invasion of the portal vein to form portal vein cancer thrombus (PVTT).

According to literature reports, 22.
0%-62.
2% of HCCs combined with PVTT, and the disease progressed rapidly and the prognosis was very poor
.

The incidence and related factors of HCC combined with PVTT differ
between Eastern and Western populations.
In China, the incidence of HCC combined with PVTT is nearly 55%, the age of onset of patients is relatively young, and more than 70% are complicated by hepatitis B virus (HBV) infection
.
Coupled with factors such as regional ethnicity, drug approval, socioeconomics, and guideline update cycle, there are differences
in the recommended strategies for HCC combined with PVTT in the East and the West.