Internal therapy for gliomas under the guidance of molecular division.

Brain cancer accounted for the 10th incidence of malignant tumors registered by sex in China in 2015, of which glioma was the most common tumor in the skull: 33.3% to 58.6% of intracranial tumors;
therefore, how to do a good job in the prevention and treatment of glioma in the clinical is of great significance.
In recent years, with the popularization and progress of molecular parting technology, the treatment of glioma in the brain under the guidance of molecular parting has made some progress, this paper attempts to combine the diagnosis and treatment norms of gliomas in China and the latest guidelines of NCCN to take stock of the relevant progress.
1, China's 2018 brain glioma diagnosis and treatment norms on molecular classification recommendations of China's 2018 brain glioma diagnosis and treatment norms pointed out that in 2016 WHO pathology classification for the first time integrated tumor histological characteristics and molecular physiology, put forward a new classification standard, this standard is an important basis for the current classification of glioma.
In accordance with this standard, China's medical norms and NCCN guidelines recommend that after the clear for all levels of glioma, it is necessary to further clarify whether there is IDH mutation, whether there is a 1p19q co-miss, MGMT starter methylation and other content.
the purpose of the first is a clear diagnosis, the other is to judge the prognosis, but also to guide the next treatment.
2. Treatment under the guidance of pathological grading and molecular differentiosis begins with low-level gliomas: low-level gliomas (WHO II.-grade) mainly include diffuse astonblastoma, less protrusion glioblastoma and less protrusion glioblastoma, accounting for about 30% of gliomas;
The European Organization for Oncology Research and Treatment (EORTC) 22844 and 22845 studies were the two largest samples of low-grade gliomas in adults, and the results showed that there were five independent adverse prognosis factors after surgery for low-level gliomas in adults: age s 40 years old, tumor s6cm, trans-midline, astrological cell tumor, preoperative neurologic dysfunction.
was divided into low-risk groups (0-2) and high-risk groups (3-5), with the lower-risk group and the high-risk group 7.2 and 3.2 years, respectively, according to the number of high-risk factors mentioned above.
further analysis found that the presence of 1p19q co-deficiency is a beneficial prognostic factor for survival of patients, the middle OS is 12.6 years and 7.3 years (p-0.03), respectively;
treatment of low-grade glioma can be divided into radiotherapy and synchronous chemotherapy.
if radiotherapy is required, it needs to be implemented as early as possible.
in a study on the long-term effects of early and delayed radiotherapy on low-level gliomas, it was found that delayed radiotherapy can improve PFS in patients, especially in patients with combined epilepsy.
therefore, the Chinese expert consensus on glioma radiotherapy (2017) points out that low-level gliomas need to be made after surgery taking into account factors such as prognosis risk, adverse reactions to radiotherapy and benefits.
high-risk group to start postoperative assisted radiotherapy and chemotherapy as early as possible, postoperative radiotherapy as early as possible, recommended to be implemented 4 to 8 weeks after surgery.
it feasible to add chemotherapy to the basis of radiation? The answer is yes.
RTOG9802 is a Phase III clinical study that compares the effects of plus or without PCV programs on outcomes based on radiotherapy, and the initial results show that the patient's PFS status is improved, further, through a mid-12-year The study found that on the basis of radiotherapy plus PCV program, the improvement of total survival is significant, the medium survival is 13.3 years vs7.8 years, thus establishing the standard status of radiotherapy synchronous PCV program for high-risk low-level glioma.
And another study on the high-risk low-level gliomas of tamothamine synchronous chemotherapy also showed that, on the basis of radiotherapy, oral use of tamomin was also improved for patient survival, with a three-year OS rate of 73.1%, a significant difference compared to historical control values, with a p.01, 3-year PFS rate of 59.2%.
is also good, with level 3 and level 4 adverse events at 43% and 10%, respectively.
The PFS did not benefit from radiotherapy alone compared to thymolamphetamine chemotherapy, but patients who used TMZ for IDH mutations were not co-mutations, the results of which were published in The Lancet Oncology in 2016.
Therefore, for low-level gliomas, the five risk factors after surgery can obviously affect the prognosis, but also the decision-making basis of postoperative auxiliary treatment;
look at high-level gliomas: there is no doubt that high-level gliomas, the preferred maximum tumor excision.
treatment is also divided into radiotherapy, chemotherapy and molecular targeting therapy.
, how about the timing, dosage, and chemotherapy options of these treatments? 1. Timing of radiotherapy: A study published in 2000 examined the prognosis of radiation delay in patients with high-level glioma, including 63 WHO III patients and 119 WHO IV patients, and showed that for every 1 day delay in radiotherapy, the risk of death increased by 2%.
retrospective analysis of larger samples further validated these conclusions, clearly indicating that patients with gliomas had significantly shorter survival if they did not start radiotherapy within 6 weeks of surgery.
, the current NCCN guidelines and Chinese glioma diagnosis and treatment norms emphasize the start of radiotherapy within 6 weeks after surgery.
2. Radiotherapy Split Dose: A randomized clinical study included 474 patients with glioma (star cell tumor) level 3 or 4, with a 2:1 randomization of 318 patients receiving 60 Gy (30 times, 6 weeks) radiotherapy vs. 156 patients who received 45 Gy (20, 4 weeks) of radiotherapy without complementary chemotherapy showed significant survival benefits in patients who received a total dose of 45 Gy/20 treatments for high-level gliomas (mid-life September vs. December, P.007).
it feasible to increase the dose on top of 60 Gy or to push the tumor bed? The answer is no.
7 series of studies have found that increasing the total dose of radiotherapy to 70 Gy, or even 90 Gy, has no significant survival benefit for patients with high-level glioma, whereas local dedation leads to an increase in symptomatic radioactive brain necrosis, with an estimated risk of symptomatic radioactive brain necrosis of 5% and 10%, respectively.
the current split pattern of radiation doses is 60 Gy/30 times.
3. Synchronous chemotherapy program: The Stupp program (radiotherapy synchronous tymomosamine chemotherapy plus 6 cycles of complementary chemotherapy) published in the New England Journal of Medicine in 2005 established its position in GBM's standard treatment program, with studies showing that the total survival rate of 2 years in the combined TMZ chemotherapy group and the radiotherapy group was 27.2 per cent and 10.9 per cent, and updated its five-year survival follow-up data in 2009, found that the five-year total survival rate was 9.8 per cent and 1.9 per cent (p.0001), respectively, and its status remained unshakable to this day.
6 cycles of tymosamine is the standard, more than 6 cycles is okay? A 2012 extension of the assisted chemotherapy cycle (more than 6 cycles) on the basis of a standard programme had significant survival benefits, with a mid-life time of 24.6 months and 16.5 months (p-0.031), respectively, and multifa factor analysis showed that prolonging the TMZ-assisted chemotherapy cycle (more than 6 cycles) was an independent prognosm for improving progression-free survival and total survival.
4, the use of molecular targeted drugs: In recent years, bevadin monoantigenic because of its multi-target anti-tumor angiogenescity is used in a variety of solid tumors, in the brain glioma in what position? A large randomized double-blind, placebo-controlled study published in the New England Journal of Medicine in 2013, which included 637 patients with gliomas, analyzed whether the addition of bevazoma to TMZ standard chemotherapy improved patient survival, and showed that increasing bevadding monotherapy on the basis of standard TMZ chemotherapy did not improve OS (1) 5.7 months vs16.1 months, p-0.21), only indicates an extended trend of PFS (10.7/7.3 months, p.001);
therefore, for newly diagnosed GBM, the molecularly targeted drug berets are not recommended.
5, MGMT launcher methylation status in high-level glioma: MGMT is a DNA damage repair enzyme, the key factor of MGMT gene silencing is the methylation of CpG Island in the initiators region.
MGMT starter region methylation phenomenon is very common in gliomas, its proportion of occurrence in various types of gliomas is different, the proportion of less protrusion glioblastoma is 40% to 60%, in GBM MGMT launcher un methylation can be as high as 50% to 70%.
it is well known that the standard treatment option for MGMT launcher methylation is the STUPP scheme, but even in patients with no methylation of the starter, the STUPP scheme cannot be used as a result.
, why do we need to detect if MGMT is methylated? Its significance lies in judging the prognosis, in clinical, combined with the status of IDH and 1p19q can judge the patient's prognosis, there are MGMT initiation methylation and combined IDH mutation and 1p19q co-missing patient prognosis is better, and more sensitive to chemotherapy.
therefore, current NCCN guidelines recommend TMZ treatment for newly diagnosed or recurrent GBMs, regardless of the status of MGMT starter methylation.
, with the deepening of the concept of precision medicine, the diagnosis and treatment of gliomas has entered the era of precision medicine.
on the basis of distinguishing different pathological types, the introduction of integrated molecular diagnosis of new technologies, so that the diagnosis of glioma brain glioma more accurate, more refined treatment, more well-founded prognosis.
, of course, more forward-looking clinical research is needed to truly achieve individual treatment of gliomas under the guidance of molecular division! Ren Doo source: Tumor information !-- end of the content display -- !-- determine whether the login ends.