Professor Zhu Xiaoli: Lunvatinib will be used as soon as possible in the treatment of high tumor burden and mid-stage liver cancer

Transhepatic arterial chemoembolization (TACE) interventional therapy has become the first choice for non-surgical treatment of primary hepatocellular carcinoma (HCC) in China, and it is also the most widely used liver cancer treatment option
.

The 2008-2009 analysis of the characteristics and treatment of liver cancer in China showed that among the treatments received by liver cancer patients in China, interventional treatment accounted for 61.
9%, and surgical treatment accounted for 50.
38%1
.

In the "Regulations for Diagnosis and Treatment of Primary Liver Cancer (2019 Edition)" issued by the National Health Commission in 2019, the indications for surgical resection of liver cancer have expanded from early stage Ia small liver cancer to stage IIIa without extrahepatic metastasis but accompanied by vascular invasion Liver cancer, while ablation and TACE interventional treatments cover stage Ib to IIIb liver cancer, including HCC with portal vein tumor thrombi that has a poor prognosis in current treatments
.

For the treatment of stage IIb and IIIa HCC, TACE is recommended as the main treatment
.

The clinical staging of liver cancer covered by the TACE treatment recommended in the "Specifications for the Diagnosis and Treatment of Primary Liver Cancer (2019 Edition)" However, TACE also has limitations in the treatment of advanced liver cancer
.

On the one hand, it is difficult to achieve complete tumor necrosis in a single embolization of TACE, and the biological characteristics of residual cancer cells can be changed in hypoxic environment, thereby having stronger proliferation and invasion ability; on the other hand, TACE can affect hepatitis, liver cirrhosis, etc.
The patient's liver function causes a greater burden
.

In the past two years, a new generation of anti-tumor small molecule targeted drugs represented by lenvatinib, and immunotherapy drugs represented by PD-1/PD-L1 immune checkpoint inhibitors are fundamentally changing the concept of liver cancer treatment and Clinical practice
.

The combination of the two has also brought a revolutionary leap in the efficacy of systemic treatment of HCC.

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For example, the overall survival (OS) of lenvatinib combined with PD-1 immune checkpoint inhibitors in the treatment of unresectable advanced HCC can reach more than 20 months, and the objective response rate (ORR) can also reach 46%2
.

Today, when targeted and immunotherapy drugs for liver cancer are booming and are changing the clinical practice of advanced liver cancer, the field of interventional therapy for liver cancer represented by TACE is naturally facing unprecedented “pressure”
.

On March 1st of this year, the new version of the National Medical Insurance Reimbursement Catalog that included the targeted liver cancer drug LENVIMA (lenvatinib mesylate) and multiple immunotherapeutic drugs was officially launched.
It is an indisputable reality that systemic treatment fully penetrates the entire treatment of liver cancer.
, Its combination with various local treatments also represents the mainstream trend in the treatment of advanced liver cancer
.

Professor Zhu Xiaoli, chief physician of the Department of Interventional Therapy of the First Affiliated Hospital of Soochow University, pointed out that whether it is surgery or intervention, embracing changes and taking advantage of the trend is the only way for the development of the current discipline, and it is also a huge opportunity to go to the next level.
But here In the process, how to seek change and how to move forward with "pain and joy" is obviously the "college entrance examination proposition" that both of them must face, especially for interventional therapy that has not yet formally become a discipline, steadily rushing to The forefront of this huge wave and not being submerged is related to its future "destiny"
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Expert profile Professor Zhu Xiaoli, chief physician, professor, doctoral supervisor, and director of the Interventional Department of the First Affiliated Hospital of Soochow University
.

Member of the Interventional Branch of the Chinese Medical Doctor Association, Deputy Chairman of the Interventional Special Committee of Liver Diseases of the Interventional Specialty Committee of the Chinese Radiology Branch, Member of the Technical Expert Group of Tumor Ablation Therapy of the Chinese Medical Doctor Association, Member of the Special Committee of Interventional Oncology of the Chinese Anti-Cancer Association, Minimally Invasive Tumor Member of the Standing Committee of the Interventional Special Committee, Member of the Standing Committee of the Particle Therapy Branch, Member of the Standing Committee of the CSCO Expert Committee on Tumor Ablation Therapy, Member of the Special Committee on Radiological Intervention, Vice Chairman of the Shanghai Anti-Cancer Association Minimally Invasive Tumor Therapy Committee, Jiangsu Medical Association Interventional Medicine Member of the Standing Committee of the branch, member of the Interventional Physician Branch of the Jiangsu Medical Association, leader of the non-vascular interventional group, and deputy chairman of the Interventional Tumor Diagnosis and Treatment Committee of the Jiangsu Anti-Cancer Association
.

National Nature First Instance Expert
.

The key talents of Jiangsu Science and Education Strengthening Engineering Medicine, the fourth and fifth phases of Jiangsu Province "333 High-level Talent Cultivation Project" third-level training objects, and the ninth batch of high-level talents of Jiangsu Province "six peaks of talents"
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He has published more than 70 papers as the first author and corresponding author, 22 of which are included in SCI, 11 monographs have been edited, 3 of which serve as associate editors
.

Engaged in interventional radiology for nearly 30 years, his professional focus is on interventional diagnosis and treatment of liver malignant tumors, ablation, and seed implantation; TIPS treatment of portal hypertension, portal vein thrombosis, Budd-Chiari syndrome and other interventional treatments
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Combination therapy breaks new ground for TACE Professor Zhu Xiaoli: TACE therapy is the basic treatment for advanced liver cancer, but interventional therapy alone is not enough.
The latest research results also show that systemic drug combined intervention for the treatment of advanced liver cancer has a higher The effective rate of it has shown great potential for clinical application in down-stage transformation and surgical resection
.

The results of the world's first retrospective controlled study of lenvatinib mesylate combined with TACE in the treatment of unresectable HCC carried out by Shanghai Oriental Liver and Gallbladder Hospital were published in Hepatology International this year3
.

Retrospective analysis in China: TACE combined with lenvatinib can significantly improve patient survival 3 The results of the study show that TACE combined with lenvatinib for treatment of unresectable HCC can significantly prolong overall survival compared with TACE alone (2-year OS rate: 79.
8% vs.
49.
2%, P=0.
047), progression-free survival (PFS) (1-year PFS rate: 78.
4% vs.
64.
7%; 2-year PFS rate: 45.
5% vs.
38.
0%, P<0.
001), and ORR (68.
3%) vs.
31.
7%, P<0.
001)3
.

Professor Zhu Xiaoli pointed out that a major advantage of Levima lies in its fast onset of action and is well tolerated in Asian populations
.

Studies have shown that for intermediate-stage liver cancer patients with Child-PughA whose tumor burden exceeds the Up-to-seven standard, the ORR, PFS and OS of patients who are initially treated with lenvatinib and receive TACE and other treatments in the second line are better than those of the initial Patients receiving TACE treatment4
.

"For this kind of mid-stage HCC patients, or the Chinese liver cancer stage (CNLC) stage IIB patients whose Han's'Six-and-twelve' model (that is, the sum of tumor size + number) exceeds 6 points, clinically, TACE combined with Lun is generally used as early as possible.
Treatment with vatinib allows patients to obtain the ultimate survival benefit
.

"For mid-term HCC that exceeds the Up-to-Seven standard, initial treatment with lenvatinib significantly improves ORR, PFS and OS4.
This year was formulated by the Interventional Physician Branch of the Chinese Medical Doctor Association.
The 2021 updated version of the "Clinical Practice Guidelines for Transarterial Chemoembolization (TACE) Treatment of Hepatocellular Carcinoma in China" has recommended TACE combined with targeted therapy for mid-stage HCC with high tumor burden, and lenvatinib for first-line treatment with tumor burden exceeding Up-to-seven Standard mid-stage liver cancer
.

The 2021 version of the "Clinical Practice Guidelines for Transarterial Chemoembolization (TACE) Treatment of Hepatocellular Carcinoma in China" recommends TACE combined with targeted therapy for mid-term HCC treatment.
Although TACE is indeed widely used in the clinical treatment of liver cancer, it faces hospitals at all levels, even townships.
The uneven quality of TACE treatment carried out by hospitals is overwhelming
.

Professor Zhu Xiaoli believes that we must promote the standardized and standardized clinical practice of TACE treatment, and we must clarify which HCC patients are suitable for TACE treatment and which patients are not suitable
.

For unsuitable patients, TACE treatment will not only bring no benefit, but it may also impair liver function
.

In June 2018, the "Clinical Practice Guidelines for Transarterial Chemoembolization (TACE) Treatment of Hepatocellular Carcinoma in China" formulated by the Interventional Physician Branch of the Chinese Medical Doctor Association was officially released, filling the gap that China has lacked norms and standards for this procedure for many years , It will promote the development of interventional medicine in China and the in-depth application of interventional medicine in some oncology fields
.

In April 2021, the updated guidelines not only included the latest TACE combined system treatment recommendations, but also emphasized the strict control of TACE indications, as well as the requirements for operation, especially emphasizing the choice of intubation to tumor support Intravascular embolization therapy
.

Professor Zhu Xiaoli pointed out that the current TACE technology itself has reached the extreme, and what needs to be emphasized is standardized treatment
.

To do a good job in TACE treatment, we must first grasp the indications, and judge whether it is suitable for TACE treatment based on the guideline recommendations and the actual situation of the patient; secondly, select the appropriate TACE method, using microcatheter and other instruments and the intraoperative DSA-like CT embolization navigation function.
While implementing fine TACE to kill tumors, it should protect the liver function of patients as much as possible; the third is to consider combined therapy.
Combined targeted and immunotherapy can reduce the number of TACEs, protect liver function, and improve patients' OS and quality of life
.

Professor Zhu Xiaoli believes that interventional doctors may need to understand a wider range of knowledge than other specialties
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Moreover, in addition to clinical practice, clinical research is also very important
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According to Professor Zhu Xiaoli, the clinical research project carried out by his center found that for patients with liver cancer with a large tumor load or a large number, the early use of TACE combined with targeting and immunotherapy can often improve the prognosis.
For patients, improve the portal circulation before using TACE combined with lenvatinib and immunotherapy to obtain better results
.

"For interventional doctors, this is the best time and the worst time
.

Interventional doctors must firmly master the TACE technology, strengthen the basic skills, and learn the application of targeted and immunotherapy from other departments on this basis, so that they can have a place in the future," Professor Zhu Xiaoli believes
.

References: 1.
Si Zengmei, Wang Guangzhi, Wang Jianhua, Research and progress of interventional therapy and metastasis and recurrence of liver cancer, Chinese Journal of Interventional Radiology, February 2015, Vol.
3, Issue 1, Chin J Inter Rad (Electronic Edition), Fedruary 2015,Vol.
3,No.
1· p42-46.
2.
Andrew X.
Zhu et al.
A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC).
2020 ASCO.
Abstract 45193.
Zhigang Fu, Xiaowei Li, Jiaming Zhong, et al.
Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study[J].
Hepatol Int.
2021 ;15(3):663-675.
4.
Kudo M et al.
, Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child--Pugh A Liver Function: A Proof-Of-Concept Study Cancers 2019, 11, 1084; doi: 10.
3390/cancers11081084.