Guide Interpretation of Professor Ma Wenbin: Innovation and Integration, the Future Can Be Expected - The Future Research Direction of Brain Glioma

In order to improve the level of diagnosis and treatment of common tumors in China, promote the construction of the guideline standard system in the field of oncology in China, and formulate tumor diagnosis and treatment guidelines that conform to the characteristics of the Chinese population and reflect the concept of integrated medicine, the China Anti-Cancer Association organized authoritative experts on tumors in various fields in China, which lasted 1 Over the past year, collectively compiled and completed China's first "Chinese Guidelines for Integrated Diagnosis and Treatment of Cancer (CACA)" (hereinafter referred to as CACA Guidelines)
.

The guideline includes 51 types of tumors, 2,100 pages and 1.

In 2022, the China Anti-Cancer Association will launch the "CACA Guidelines Intensive Reading Series Tour Lectures" activity
.

At the second stop of the " China Guidelines for Integrated Diagnosis and Treatment of Cancer (CACA) " - Frontier Forum on Integrated Diagnosis and Treatment of Glioma, Professor Ma Wenbin of Peking Union Medical College Hospital gave a special lecture on the "Innovative Integration, Future Expectation" part of the CACA Guidelines.

Guidelines for Integrated Diagnosis and Treatment of Cancer in China (CACA)

Screening for gliomas

glioma screening glioma screening

1.
The importance of brain CT screening

1.
The importance of brain CT screening

The incidence of brain tumors in the age group of 40+ has reached 42.
85/100,000 person-years, and the earlier the diagnosis, the higher the patient survival rate and the lower the case fatality rate
.

Therefore, the CACA Brain Glioma Special Committee calls for the addition of cranial CT screening for Chinese people over 40 years old in various physical examinations and life insurance screening

2.
Liquid-based marker-based screening

2.
Liquid-based marker-based screening

Screening based on liquid-based markers has been very well applied in other tumors (such as liver cancer), and it also has a very promising development prospect in glioma, especially for the elderly with high incidence.
Screening based on liquid-based markers [obtaining body fluids (cerebrospinal fluid, blood, urine) → obtaining molecular information → analysis and diagnosis] can enable patients to receive early diagnosis and early treatment
.

3.
Database Drug Screening

3.
Database Drug Screening

Using China's own CGGA database and international database, combined with pharmacological knowledge, and various research findings in vivo and in vitro, new drugs are designed to provide more powerful ammunition for defeating gliomas
.

Glioma Treatment

glioma treatment glioma treatment

The treatment methods for brain glioma are constantly changing.
At present, a comprehensive treatment method has been formed, which is mainly surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy and electric field therapy
.

1.
Temozolomide (TMZ) resistance research guides new treatments

1.
Temozolomide (TMZ) resistance research guides new treatments

The drug resistance of glioma mainly occurs in TMZ resistance.
In recent years, researches have mainly focused on the following aspects: stem cell research of glioma, tumor microenvironment (tumor-associated macrophages & perivascular cells), epigenetic modification ( Histone & RNA modification), metabolomics (mitochondria-related protein & purine) research,
etc.

It is hoped that these studies will be integrated into TMZ resistance research and lead to better drug treatment for patients

2.
One of the future directions: molecular targeted therapy

2.
One of the future directions: molecular targeted therapy

Molecular targeted therapy continues to progress with the development of tumor molecular genetics, and the research on receptor tyrosine kinase PTK family and pathways is the most concentrated
.

VEGFR-2 and multi-kinase target inhibitor regorafenib: Phase II clinical trials confirmed that compared with lomustine group, regorafenib group had better overall survival (OS) in patients with recurrent glioblastoma (rGBM) ) were significantly prolonged; subgroup analysis suggested a significant benefit in both MGMT methylated and unmethylated patients
.

MET Inhibitors Britinib/Crizotinib: The team of Professor Jiang Tao from Tiantan Hospital showed that MET inhibitors can inhibit the growth of MET fusion gene-positive tumors; laboratory and phase I clinical trials suggest that Britinib can effectively target PTPRZ1-MET fusion gene
.

MET inhibitors can inhibit the growth of MET fusion gene-positive tumors; laboratory and phase I clinical trials suggest that britinib can effectively target the PTPRZ1-MET fusion gene
.

MET inhibitors can inhibit the growth of MET fusion gene-positive tumors; laboratory and phase I clinical trials suggest that britinib can effectively target the PTPRZ1-MET fusion gene

3.
The second direction of the future: immunotherapy

3.
The second direction of the future: immunotherapy

Current immunotherapy for GBM mainly includes tumor vaccination, oncolytic virus, immune checkpoint inhibitor and CAR-T cell therapy
.

(1) Tumor vaccine

EGFRvIII vaccine (Rindopepimut): The phase III clinical trial for newly diagnosed glioblastoma (nGBM) has no survival benefit; the phase II clinical trial for rGBM has significantly prolonged progression-free survival (PFS) and OS
.

(2) Immune checkpoint inhibitors: PD-1/PD-L1

Phase III clinical trials of adjuvant PD-1 inhibitors in the treatment of nGBM and rGBM were unsuccessful; neoadjuvant PD-1 inhibitors can improve local immune responses and patient survival
.

(3) CAR-T: IL13Rα2 CAR-T

A case study in 2016 suggested that IL13Rα2 CAR-T therapy could regress to varying degrees in patients with intracranial and intramedullary tumor lesions; the clinical response lasted 7.
5 months
.

4.
The third direction of the future: new physical therapy

4.
The third direction of the future: new physical therapy

(1) Electric field therapy for glioma - TTFields

Electric field therapy exerts an anti-tumor effect by inhibiting the mitosis of tumor cells, and its treatment of glioblastoma (GBM) has high evidence-based medical evidence.
CACA guidelines recommend electric field therapy for adjuvant treatment of nGBM and recurrent high-grade gliomas
.

(2) Laser Interstitial Hyperthermia (LITT)

LITT: Creates controlled thermal damage by heating surrounding tissue
.

Intraoperative MRI real-time thermometry allows continuous monitoring of the ablation area

Scope of application: glioma, metastases, epilepsy, radiation necrosis,

Total treatment time correlated with tumor size, number of trajectories, laser type, tissue hydration, and proximity to cortical or white matter tracts

(3) MRI-guided high-intensity focused ultrasound hyperthermia

After ultrasound-induced blood-brain barrier opening, many anti-tumor agents (chemotherapy drugs, targeted drugs, immune agents, etc.

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