At the invitation of the organizing committee of the academic congress, I had the honor to attend the 1st and 2nd International Glioma Symposium held by Europe and the United States in 2005 and 2006. The meeting was co-chaired by Dr. Martin J. van den Bent, head of the Brain Tumor Group of the European Association for Research and Treatment of Cancer (EORTC), and Dr. W.K. Alfred Yung, Chief of the Division of Neuro-Oncology at MD Anderson Cancer Center in Houston, USA. The conference invited more than 30 renowned scholars from various fields of neuro-oncology, radiology oncology and neurosurgery around the world to review the experience of more than 40 years of research and treatment of glioma from different perspectives, standardize the modern treatment standards of glioma, and announce the latest progress of the world multicenter research in surgery, radiotherapy, chemotherapy and molecular markers for glioma. I also participated in the glioma case symposium held during the conference, and I deeply appreciate the gap between China and European and American countries in the individualized treatment of glioma, and many of their ideas and achievements in glioma research and treatment are worthy of our reference. Many issues that are still being researched and debated in China have already reached consensus in Europe and the United States.
By analyzing and summarizing the standards of glioma treatment and the latest research progress published in Europe and the United States, we now dedicate some of the contents to our medical colleagues and patients in China, expecting to provide reference for the standardized treatment of glioma in China, so that many patients with glioma can receive correct and standardized treatment under the existing medical conditions.
I. Treatment of low-grade glioma
1.The relationship between tissue type and prognosis
(1) Tissue types with good prognosis: (1) hairy cell astrocytoma; (2) pleomorphic yellow astrocytoma; (3) subventricular giant cell astrocytoma; (4) ganglioglioma; (5) neuroblastoma; (6) oligodendroglioma (especially in patients with 1p/19q LOH).
(2) Tissue types with poor prognosis: ① obese astrocytoma; ② astrocytoma with P53 mutation; ③ astrocytoma with 5% proliferation index.
PAK Factors affecting patient prognosis
(1) age over 40 years; (2) pathological type of astrocytoma; (3) maximum diameter of tumor over 6 cm; (4) tumor crossing the midline, (5) symptoms of neurological deficit already existed before surgery.
Those with 2 factors were considered low risk, and those with more than 2 factors were considered high risk.
3. Criteria for dynamic observation
(1) age less than 40 years; (2) no imaging enhancement of the tumor; (3) medication can control seizures
(4) no occupancy effect; (5) no neurological symptoms for a long time.
MRI imaging and neurological examination is required every 6-12 months during the observation period.
4. Indications for treatment
(1) age ≥40 years; (2) imaging examination confirms significant tumor progression; (3) in addition to epilepsy, new neurological deficit symptoms
(3) New neurological deficits in addition to epilepsy; (4) Exacerbation of existing neurological deficits; (5) Patients with intractable epilepsy who have failed systemic antiepileptic drug treatment.
5. Indications for surgery
(1) New signs and symptoms in addition to epilepsy; (2) Significant occupancy effect on neuroimaging; (3) Dynamic observation
(3) dynamic observation shows accelerated tumor growth; (4) patient age >50 years.
6. Principles of surgery
The tumor should be removed as widely as possible without damaging the function of the nervous system.
Borrowing Indications for radiotherapy (RT)
(1) Patients who are not suitable for surgery: ① Tumors with obvious infiltrative features; ② Tendency to progress and proliferate; ③ Adult patients.
(2) Postoperative patients: ① presence of adverse prognostic factors, such as elderly patients, KPS score <70, and the presence of contrast enhancement of the imaging tumor; ② patients with high-risk prognostic factors.
8. Time window for radiotherapy
The time window of radiotherapy after surgery does not affect the effect of radiotherapy.
9. Radiotherapy dose
(1) 50.4Gy for 28 fractions; (2) 54Gy for 30 fractions.
The dose of each division is <2.0Gy.
10. Indications for chemotherapy
(1) Clinically or imaging confirmed progressive LGG (progressive LGG with active cell proliferation and the possibility of interstitial transformation); (2) LGG with postoperative recurrence.
11. Chemotherapy regimen
(1) TMZ (Temozolomide) regimen; (2) PCV regimen.
II. Treatment of high-grade glioma
1.Treatment principles
Extensive surgical resection + radiotherapy + chemotherapy comprehensive treatment.
2.Radiotherapy dose
2.0Gy/time×30, completed within 6 weeks.
3.Chemotherapy regimen.
(1) TMZ regimen; (2) PCV regimen; (3) AVM regimen; (4) TMZ 12-course chemotherapy regimen: (1) dynamic MR observation showed significant tumor shrinkage; (2) patient’s general condition gradually improved; (3) patient’s neurological function improved significantly; (4) the need for corticosteroids was reduced during the treatment. Patients who can tolerate well after completing 6 courses of treatment and who meet at least one of the above four criteria can reach the maximum treatment of 12 courses after receiving 6 courses of chemotherapy.
4.Radiotherapy and chemotherapy combination treatment plan
(1) TMZ + radiotherapy
① Radiotherapy plan: radiation dose 1.8Gy/time, 5 days/week for 6 weeks.
(2) Chemotherapy plan: apply TMZ 75 mg/m2/d , 7d/week simultaneously with radiotherapy, and after the interruption of 4 weeks after the completion of radiotherapy, the patient receives 6 cycles of adjuvant TMZ treatment again, i.e. the standard treatment plan with an interval of 28 days after 5 days of continuous dosing, starting with a dose of 150 mg/m2 and the second course of 200 mg/m2.
(2) PCV + radiotherapy
① Option 1
Radiotherapy plan: 1.8Gy/dose×33, firstly, within 7 weeks.
PCV chemotherapy: CCNU 110mg/m2, Procarbazine 60mg/m2, Vincristine 1.4mg/m2, starting from the 10th week for 6 consecutive courses.
② Regimen II
PCV chemotherapy: CCNU 130mg/m2, Procarbazine 75mg/m2, Vincristine 1.4mg/m2, starting with 4 courses.
Radiotherapy plan: 1.8Gy/dose x 33, starting from week 28.
5.Treatment for elderly (65 years old and above) patients
(1) Surgery: For those who have KPS > 60 and can tolerate surgery, they should be considered to receive tumor resection first, and then adjuvant radiotherapy and chemotherapy.
(2) Radiotherapy: For elderly HGG patients who cannot tolerate surgery, radiotherapy can be applied if confirmed by clinical or tissue biopsy.
Radiotherapy regimen: ① total 40Gy, 15 divisions, 3 weeks to complete; ② total 34Gy, 10 divisions, 2 weeks to complete.
(3) Chemotherapy: Try to avoid using chemotherapy drugs with strong myelosuppressive effects, and TMZ regimen is currently the most appropriate.
6. Other treatment methods under trial
(1) the application of polymeric sheet local transport drugs; (2) Target therepy; (3) Immunotherapy; (4) Stereotactic radiotherapy; (5) the application of DNA repair inhibitors; (6) the application of radiotherapy potentiators.
7.Progress in clinical research of molecular markers
(1) Clinical significance of 1p/19q LOH: (1) it is an important molecular indicator of oligodendroglioma; (2) it can determine the prognosis of patients; (3) it can predict the sensitivity of tumor to chemotherapy; (4) it can predict the sensitivity of tumor to radiotherapy.
(2) MGMT promoter gene methylation: ① Glioblastoma multiforme with MGMT methylation
(2) MGMT promoter gene methylation: (1) Glioblastoma multiforme with MGMT methylation is better treated with radiotherapy alone and combined radiotherapy and chemotherapy than without methylation; (2) Survival of patients without MGMT methylation has not been improved; (3) PCR technique to detect MGMT methylation is complicated; (4) Multicenter clinical trials on whether to choose combined radiotherapy or radiotherapy alone for treatment of patients without MGMT methylation are underway; (5) Until the results of this clinical trial are published, the results of any individual study Until the results of this clinical trial are published, the conclusions drawn by any individual research institution cannot be used to guide clinical treatment.
(3) EGFR amplification and mutation: (1) In glioblastoma multiforme, amplification (40%), overexpression or mutation (20-30%) are frequent.
(2) EGFR status does not correlate with survival in GBM; (3) trials of EGFR tyrosinase inhibitors (Gefitinib, Erlotinib) are ongoing; (4) EGFR signals through the PI3K-AKT signaling pathway; (5) PTEN can block the PI3K pathway; (6) PTEN deficiency can increase EGFR tyrosinase inhibitor resistance.