Digital quantitative evaluation system for glioma resection degree and prognosis based on cerebrospinal fluid ctDNA and application of digital quantitative evaluation system

Abstract

The invention discloses a digital quantitative evaluation system for glioma resection degree and prognosis based on cerebrospinal fluid ctDNA and application of the digital quantitative evaluation system. The digital quantitative evaluation system comprises a data acquisition module, a data processing module and a model comparison module, the data acquisition module is used for extracting ctDNA in cerebrospinal fluid before and after a glioma resection operation; the data processing module is used for performing NGS sequencing on the ctDNA; and the model comparison module is used for comparing the data of tumor specific somatic mutation before and after the glioma resection operation. According to the digital quantitative evaluation system, 'preoperative and postoperative ctDNA comparison 'is taken as a postoperative recurrence risk evaluation tool and a precise treatment decision support index for the first time, and sensitive detection and accurate prognosis prediction of postoperative tumor residues are realized, so that postoperative management and treatment decisions are optimized, the life quality of patients is improved, and the digital quantitative evaluation system has important clinical value.

Description

Technical Field

[0001] This invention belongs to the field of biomedical detection technology, specifically relating to a digital quantitative assessment system for the extent of glioma resection and prognosis based on cerebrospinal fluid ctDNA and its application. Background Technology

[0002] Gliomas are the most common malignant tumors of the central nervous system, with high incidence and mortality rates, especially glioblastoma (GBM), which is characterized by high invasiveness, rapid growth, and extremely poor prognosis. Currently, the standard treatment strategy for gliomas includes a combination of surgical resection with radiotherapy, chemotherapy, and targeted therapy. Surgical resection remains a crucial initial treatment step, with the primary goal of minimizing the tumor burden and creating conditions for subsequent treatments. Numerous studies have shown that achieving radiographically significant gross total resection (GTR) can significantly prolong patient survival. However, due to the invasive growth characteristics of gliomas, the tumor boundaries are difficult to clearly distinguish from normal brain parenchyma. Furthermore, the complex structure and dense functional areas of the brain mean that accidental damage to key neural structures during surgery can lead to severe neurological deficits. Therefore, achieving true GTR in clinical practice presents significant challenges, especially in cases of multiple, diffuse lesions such as GBM.

[0003] Currently, clinical assessment of tumor resection extent primarily relies on the surgeon's subjective judgment and comparisons of preoperative and postoperative imaging (such as MRI). This approach suffers from limitations such as a single assessment dimension, strong subjectivity, and inability to detect minimal residual disease, making it difficult to accurately reflect the true surgical outcome. Therefore, there is an urgent need for an objective, sensitive, quantifiable, and even digital postoperative assessment method to guide subsequent treatment decisions and prognostic assessments. In recent years, methods such as multimodal image analysis, machine learning algorithms, and multi-omics integrated analysis have been attempted to improve the accuracy of postoperative assessment; however, these methods are mostly indirect assessment approaches and cannot directly reflect the molecular-level information of tumor residue. Considering that tumor-specific gene mutations are important markers of all malignant tumors, if highly sensitive detection technologies can be used to dynamically monitor changes in these mutations in preoperative and postoperative samples, it is hoped that direct quantitative evidence of tumor resection extent can be provided.

[0004] With the development of next-generation sequencing (NGS) and liquid biopsy technologies, the detection of circulating tumor DNA (ctDNA) has been widely used in the diagnosis, prognostic assessment, and treatment monitoring of various cancers. Particularly in solid tumors such as lung cancer, breast cancer, and colorectal cancer, ctDNA analysis has become an FDA-approved precision medicine method. However, due to the presence of the blood-brain barrier (BBB), glioma tumor ctDNA is extremely difficult to enter the peripheral blood, significantly reducing the sensitivity of plasma ctDNA detection and limiting the clinical application of liquid biopsy in brain tumors. Given the direct contact between cerebrospinal fluid (CSF) and brain tissue, and its availability through methods such as lumbar puncture, multiple studies have confirmed its higher representativeness and sensitivity in nervous system tumors as a source of ctDNA detection. Therefore, CSF ctDNA is considered the optimal liquid biopsy specimen for molecular detection of central nervous system tumors. However, there is currently a lack of standardized methods or systems for quantitatively assessing the extent of glioma resection by using preoperative and postoperative changes in cerebrospinal fluid (CSF) ctDNA mutation characteristics, and no studies have systematically elucidated the direct correlation between this indicator and patient prognosis. Therefore, there is an urgent need to develop a CSF ctDNA-based system for assessing resection effectiveness and predicting prognosis to fill the gaps in current technologies for determining minimal residual disease and guiding individualized treatment. Summary of the Invention

[0005] Based on the aforementioned background, the existing technical problems are: existing methods for assessing the extent of glioma resection after surgery suffer from high subjectivity, difficulty in quantification, and inability to identify minute residual tumors. To address these problems, this invention provides a digital quantitative assessment system for the extent of glioma resection and prognosis based on cerebrospinal fluid ctDNA, and its application. This system enables sensitive detection of postoperative tumor residue and accurate prognostic prediction, thereby optimizing postoperative management and treatment decisions and improving patients' quality of life.

[0006] To achieve the above objectives, the present invention provides the following technical solution: A digital quantitative assessment system for glioma resection extent and prognosis based on cerebrospinal fluid ctDNA, the digital quantitative assessment system comprising: a data acquisition module, a data processing module, and a model comparison module; The data acquisition module is used to extract ctDNA from cerebrospinal fluid before and after glioma resection surgery; The data processing module is used to perform NGS sequencing on the ctDNA; The model comparison module is used to compare data on tumor-specific somatic mutations before and after glioma resection surgery.

[0007] Furthermore, the aforementioned digital quantitative assessment system includes, in addition to, the tumor-specific somatic mutation data, one or more of the following: the rate of decrease in tumor mutational burden (TMB) in cerebrospinal fluid, the rate of decrease in mean mutated allele frequency (MAF), and the clearance rate of tumor-driving mutated genes.

[0008] Furthermore, the tumor-driving mutant genes shown include, but are not limited to, one or more of IDH1 / 2, PTEN, TERT, TPS3, PIK3CA, ATRX, and ARID1B.

[0009] Based on a general technical concept, the present invention also provides the application of the aforementioned digital quantitative assessment system in the preparation of a test kit or procedure for detecting the extent of glioma resection and prognosis.

[0010] Further, in the above applications, when the average mutational allele frequency of ctDNA in the cerebrospinal fluid after glioma resection surgery decreases by ≥90% compared to the average mutational allele frequency of ctDNA in the cerebrospinal fluid before surgery, the glioma is highly resected, and the postoperative survival is long.

[0011] Further, in the above applications, when the tumor (driver) mutation burden of ctDNA in the cerebrospinal fluid after glioma resection surgery decreases by ≥90% compared to the tumor driver mutation burden of ctDNA in the cerebrospinal fluid before surgery, the glioma is highly resected.

[0012] Based on a general technical concept, the present invention provides an application of the aforementioned digital quantitative assessment system in the preparation of a test kit for detecting the prognosis of glioma patients after surgery.

[0013] Further, in the above applications, when the average mutational allele frequency of ctDNA in cerebrospinal fluid decreases by ≥90% after glioma resection surgery, and / or the clearance rate of tumor-driving mutational genes is ≥90%, the postoperative survival of patients is longer.

[0014] The above applications further refer to gliomas as glioblastomas.

[0015] Compared with the prior art, the advantages of the present invention are as follows: (1) This invention provides a digital quantitative assessment system for the extent of glioma resection and prognosis based on cerebrospinal fluid ctDNA, comprising: a data acquisition module for preoperative and postoperative CSF sample processing and ctDNA extraction; a data processing module for mutation identification, MAF / TMB calculation, and calculation of tumor driver mutations; and a model comparison module for automatic calculation of preoperative and postoperative variation changes. The system can be deployed on a hospital information platform or a cloud-based medical analysis system to assist physician decision-making.

[0016] Furthermore, the aforementioned digital quantitative assessment system also includes a scoring and output module: used to digitally reflect postoperative resection effectiveness and risk stratification, including but not limited to the following indicators: the degree of decrease in MAF in ctDNA; changes in TMB; whether driver mutations have been eliminated; whether there are multiple lesions; and whether radiographic GTR has been achieved. Based on set thresholds, it outputs the resection effectiveness grade, prognostic risk grade, and auxiliary decision-making suggestions. This scoring system can be converted into software implementation or decision support tools to assist physicians in postoperative management and individualized treatment decisions.

[0017] (2) This invention provides a digital quantitative assessment system for the extent of glioma resection and prognosis, used in the preparation of a kit or procedure for detecting the extent of glioma resection. Traditionally, the extent of resection (EOR) of brain tumors is mainly determined by intraoperative observation and postoperative MRI imaging. This method suffers from problems such as strong subjectivity, difficulty in quantification, and inability to reflect molecular residues. This invention provides a method for quantitatively assessing the surgical resection effect by comparing changes in the mutation frequency (MAF) and tumor mutation burden (TMB) of tumor-specific ctDNA in preoperative and postoperative CSF samples. When the mutation frequency and / or (driving) mutation burden in ctDNA decreases significantly after surgery (e.g., a decrease of ≥90%), it indicates that the tumor resection is more complete. This method provides a more sensitive and objective tool for assessing tumor residues than imaging, and is particularly suitable for postoperative residual monitoring in glioma patients.

[0018] (3) This invention provides a digital quantitative assessment system for glioma resection extent and prognosis based on cerebrospinal fluid ctDNA, which is used in the preparation of test kits or the development of analytical procedures for the postoperative prognosis of glioma patients. This invention provides the application of dynamic changes in CSF ctDNA as an independent prognostic biomarker. The degree of reduction in mutation frequency in postoperative CSF ctDNA and the clearance rate of tumor-driving mutations can independently predict the survival of glioma patients, without an absolute parallel relationship with whether gross resection (GTR) has been achieved based on imaging assessment. Specifically, a decrease in MAF and / or TMB or tumor-driving mutation clearance rate ≥90% is associated with significantly prolonged overall survival (OS). Therefore, this invention is the first to use "preoperative and postoperative ctDNA comparison" as a tool for assessing postoperative recurrence risk and a support indicator for precision treatment decisions, which has important clinical value.

[0019] In addition to the objectives, features, and advantages described above, the present invention has other objectives, features, and advantages. The invention will now be described in further detail with reference to the accompanying drawings and tables. Attached Figure Description

[0020] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0021] Figure 1 Detailed information on 32 patients with brain tumors.

[0022] Figure 2 This is a schematic diagram of the research process.

[0023] Figure 3 The mutation profile of ctDNA (pre-ctDNA) in brain tumor lesions and preoperative cerebrospinal fluid.

[0024] Figure 4 Comparison of NGS sequencing results of brain tumor lesions and preoperative cerebrospinal fluid ctDNA (pre-ctDNA).

[0025] Figure 5 This represents the mutation profiles of ctDNA (pre-ctDNA and post-ctDNA) in cerebrospinal fluid before and after surgery.

[0026] Figure 6 Comparison of NGS sequencing results of preoperative and preoperative cerebrospinal fluid ctDNA (pre-ctDNA).

[0027] Figure 7 To investigate the impact of dynamic changes in ctDNA on the prognosis of high-grade gliomas (HGGs).

[0028] Figure 8 The images show T1WI enhanced MRI images and MAF values ​​of one patient before and after glioma resection surgery.

[0029] Figure 9 The images show T1WI enhanced MRI images and MAF values ​​of one patient before and after glioma resection surgery.

[0030] Figure 10 The images show T1WI enhanced MRI images and MAF values ​​of one patient before and after glioma resection surgery.

[0031] Figure 11 The images show T1WI enhanced MRI images and MAF values ​​of one patient before and after glioma resection surgery.

[0032] Figure 12 The images show T1WI enhanced MRI images and MAF values ​​of one patient before and after glioma resection surgery.

[0033] Figure 13 The images show T1WI enhanced MRI images and MAF values ​​of one patient before and after glioma resection surgery. Detailed Implementation

[0034] The present invention will be further described below with reference to specific preferred embodiments, but this does not limit the scope of protection of the present invention.

[0035] The materials, reagents, and instruments used in the following examples are all commercially available. Unless otherwise specified, the experimental methods used in the following examples are conventional methods in the art.

[0036] We explored whether preoperative and postoperative cerebrospinal fluid ctDNA levels could sensitively and quantitatively assess the extent of tumor resection, and further evaluated its potential as a prognostic and survival predictor for patients.

[0037] Figure 1 Detailed information for 32 brain tumor patients is provided below: A: A heatmap shows key patient characteristics, including sex, age, tumor histological type, IDH mutation status, 1p / 19q co-deletion, MGMT promoter methylation status, Ki-67 proliferation index, tumor size, tumor extent, presence or absence of cystic changes, hydrocephalus, seizures, severe postoperative complications, and extent of resection. B: A pie chart shows the distribution of tumor pathological types. C: A pie chart shows the anatomical location of the tumor in the brain. D: A bar chart summarizes the number of patients with single and multiple lesions.

[0038] Figure 2The diagram illustrates the research process. It shows the flowchart of surgical resection of the lesion, matched preoperative and postoperative cerebrospinal fluid (CSF) ctDNA NGS sequencing, and correlation analysis with the extent of surgical resection and postoperative survival.

[0039] First, the reliability of ctDNA in reflecting the genomic characteristics of brain tumors was verified: ctDNA was detected in all cases, and there was a high degree of concordance between brain tumor tissue and preoperative CSF ctDNA (mean 83.50%). Furthermore, mean mutant allele frequency (MAF) and tumor mutational burden (TMB) were significantly correlated between tissue DNA and preoperative ctDNA (see [link to relevant documentation]). Figures 3-4 (As shown). Figure 3 This chart shows the mutation profile of brain tumor lesions and preoperative cerebrospinal fluid ctDNA (pre-ctDNA). The top bar chart displays the tumor mutation burden (TMB); the stacked bars in the middle represent the proportion of mutation types; the bottom heatmap shows the mutation profile of the top 20 most frequent mutations; and the right-hand bar chart shows the mutation frequency.

[0040] Figure 4 Comparison of NGS sequencing results between brain tumor lesions and preoperative cerebrospinal fluid ctDNA (pre-ctDNA). A: Bar chart comparing the mutational allele frequencies (MAF) in brain tumor tissue and preoperative cerebrospinal fluid ctDNA (Mann-Whitney U test). A: Preoperative MAF in ctDNA correlated with MAF in tumor tissue DNA (each point represents a shared mutation in both tissue and ctDNA; Spearman correlation coefficient r = 0.5635, P < 0.0001). B: Individual mean MAF correlated with preoperative ctDNA and tissue DNA (each point represents the mean MAF of one patient; all patients: r = 0.3926, P = 0.0262; high-grade gliomas (HGGs, red): r = 0.5870, P = 0.0051). D: Scatter plot showing TMB comparison between tissue DNA and preoperative ctDNA (Wilcoxon signed-rank test, P = 0.0551). E: Preoperative TMB in ctDNA correlated with TMB in tissue DNA (Spearman r = 0.5517, P = 0.0011). F: Preoperative TMB in ctDNA was positively correlated with Ki-67 expression in tumor tissue (Spearman r = 0.6471, P = 0.0027). G: Quantitative analysis showed that tumors with high Ki-67 expression (≥20%) had significantly higher TMB in preoperative ctDNA (Mann-Whitney U test). P < 0.01. H: Stacked bar chart shows mutations detected only in ctDNA (pre-ctDNA specific mutations), tissue- and ctDNA shared mutations, and tissue-specific mutations detected only in each patient. I: Scatter plot shows the mean mutational concordance between brain tumor tissue and cerebrospinal fluid ctDNA is 83.50% (each dot represents mutational concordance for each individual).

[0041] Next, the changes in ctDNA mutations before and after surgery were compared. The results showed a significant reduction in mutations in ctDNA after surgery: including a significant decrease in mean MAF and TMB. Figures 5-6 ).

[0042] Figure 5 This section presents the mutation profiles of cerebrospinal fluid ctDNA (pre-ctDNA and post-ctDNA) before and after surgery. The top bar chart shows the tumor mutation burden (TMB); the stacked bars in the middle represent the proportion of mutation types; the bottom heatmap shows the mutation profiles of the top 20 most frequent mutations; the heatmap and bars on the right show the changes in mutation frequency before and after surgery.

[0043] Figure 6 Comparison of NGS sequencing results of preoperative and preoperative cerebrospinal fluid ctDNA (pre-ctDNA). A: Comparison of mutational allele frequencies (MAF) in preoperative and postoperative ctDNA (Wilcoxon signed-rank test). P < 0.0001. BC: Individual mean MAF significantly decreased in postoperative ctDNA (C: Wilcoxon signed-rank test). P < 0.0001. D: Quantitative analysis showed that TMB in postoperative ctDNA was significantly lower than that in preoperative ctDNA (Wilcoxon signed-rank test). E: Scatter plot shows that the mutation burden decreased by an average of 78.47% postoperatively compared with preoperative ctDNA (red dots indicate patients with incomplete mutation clearance, i.e., residual mutations were still detected postoperatively). F: Quantitative analysis of the decrease rate of TMB in patients with LGGs (low-grade gliomas) and HGGs (high-grade gliomas) (red circles represent patients who did not achieve 100% mutation reduction, i.e., residual mutations were still detected postoperatively; solid red circles represent patients with multiple lesions; Mann-Whitney U test, P = 0.4716). G: Bar chart shows that among patients with residual mutations still detected postoperatively, most were HGG patients with multiple lesions (Fisher exact test, P < 0.0001). (P<0.01).

[0044] More importantly, the mean decrease in MAF and the clearance of driver mutations in postoperative ctDNA were significantly correlated with patient prognosis and survival, and these associations were statistically significant. Furthermore, compared with the extent of resection assessed by traditional imaging (such as T1 / T2 MRI), quantitative dynamic monitoring of ctDNA was more consistent with survival prediction. Figure 7 It has superior prognostic guidance value, especially showing its potential in patients with glioblastoma (GBM).

[0045] Figure 7 The impact of dynamic changes in ctDNA on the prognosis of high-grade gliomas (HGGs). A: Comparison of total tumor resection (GTR) and non-GTR based on T1WI and their survival analysis. Left: T1WI enhanced and T2WI images (arrow: tumor lesion); Right: Survival curve analysis (Log-rank test, median survival for non-GTR and GTR was 10.00 months and 18.50 months, respectively, P = 0.0831). B: Comparison of GTR and non-GTR based on T2WI and their survival analysis. Left: T2WI image (arrow: tumor lesion); Right: Survival curve analysis (Log-rank test, median survival was 11.50 months vs. 21.00 months, P = 0.0516). C: Survival analysis of patients with a 90% reduction in MAF in ctDNA after surgery compared to before surgery (Log-rank test, median survival: 10.00 months vs. 19.00 months, P = 0.0126). D: Survival analysis of patients with a 90% reduction in driver mutation MAF (Log-rank test, median survival: 8.00 months vs. 17.50 months, P = 0.0294). E: Four risk factors affecting survival in HGG patients: multiple lesions, non-GTR, high residual MAF, and high detectable driver mutation burden. Patients 14 and 29 had all four high-risk factors.

[0046] In summary, dynamic monitoring of cerebrospinal fluid ctDNA can not only sensitively and quantitatively reflect the tumor resection status, but also serve as a survival prognosis predictor, highlighting its potential to improve the postoperative management of GBM.

[0047] Example 1 A digital quantitative assessment system for glioma resection extent and prognosis based on cerebrospinal fluid ctDNA includes: (1) Data acquisition module: used to extract ctDNA from cerebrospinal fluid before and after glioma resection surgery; (2) Data processing module: used for NGS sequencing of the ctDNA; (3) Model Comparison Module: Used to compare data on tumor-specific somatic mutations before and after glioma resection surgery. Data on tumor-specific somatic mutations include the rate of decrease in tumor mutation burden in cerebrospinal fluid, the rate of decrease in average mutation allele frequency, the clearance rate of tumor driver mutation genes, and / or the extent of surgical resection (EOR).

[0048] Example 2 The application of a digital quantitative assessment system of Example 1 in the preparation of a test kit or procedure for detecting the extent of glioma resection and prognosis.

[0049] Figure 8 This image shows T1WI enhanced MRI images and MAF values ​​of a patient before and after glioma resection surgery. As shown in the figure: This patient had multiple tumor lesions and underwent non-total glioma resection (non-GTR) surgery. Top left: Pre- and post-operative T1WI enhanced MRI images (arrows indicate enhanced lesions); Bottom left: Heatmap showing gene mutations detected in pre-operative ctDNA, including PTEN, WT1, and TERT, with PTEN and TERT still detectable in post-operative ctDNA. Right: MAF values ​​in each sample (Wilcoxon signed-rank test, P = 0.2500). The figure shows that the mean MAF value decreased by 81.27% before and after surgery, and the tumor driver mutation clearance rate was 0%; the patient's survival was 6 months.

[0050] Figure 9 This image shows T1WI enhanced MRI images and MAF values ​​of a patient before and after glioma resection surgery. As shown in the figure, this patient also had multiple tumor lesions and underwent incomplete resection. Top left: Pre- and post-operative T1WI enhanced MRI images (arrows indicate enhanced lesions); Bottom left: Heatmap showing mutations detected in ctDNA before surgery, including PTEN, SERPINB3, TERT, and LRP1B, of which only LRP1B was not detected post-operatively. Right: MAF values ​​in each sample (Wilcoxon signed-rank test, P = 0.1250). Driver mutations are marked in red. The figure shows that the mean MAF value decreased by 56.58% before and after surgery, and the tumor driver mutation clearance rate was 0%; the patient's survival was 8 months.

[0051] Figure 10This image shows T1WI enhanced MRI images and MAF values ​​of a patient before and after glioma resection surgery. As shown in the figure: The patient underwent incomplete glioma resection, with residual lesions located near the anterior horn of the lateral ventricle (top left: MRI image, arrow indicating T2WI lesion location); although PMS2 mutation was detected in ctDNA preoperatively, no mutation was detected in ctDNA postoperatively (bottom left). The figure shows that the mean MAF value decreased by 100% before and after surgery, indicating a 100% clearance rate of tumor-driving mutations; the patient's survival was 29 months, significantly exceeding the average survival for incomplete glioma resection.

[0052] Figure 11 This image shows T1WI enhanced MRI images and MAF values ​​of a patient before and after glioma resection surgery. As shown in the figure, this patient had the highest MAF in ctDNA preoperatively (37.10%) and underwent complete resection based on T2WI assessment (left); no mutations were detected in ctDNA postoperatively (right, Wilcoxon signed-rank test). (P<0.0001) As can be seen from the figure, the mean MAF value of the samples decreased by 100% before and after surgery, the tumor driver mutation clearance rate was 100%, and the overall survival (OS) of the patients was 33 months.

[0053] Figure 12 This image shows T1WI enhanced MRI images and MAF values ​​of a patient before and after glioma resection surgery. As shown in the figure, the patient had the highest TMB in ctDNA preoperatively (22.73) (left). Postoperatively, the patient underwent complete resection under T2WI evaluation (top right), and no mutations were detected in the ctDNA postoperatively (bottom right, Wilcoxon signed-rank test). (P<0.0001) As can be seen from the figure, the mean MAF value of the samples decreased by 100% before and after surgery, and the tumor driver mutation clearance rate was 100%; the overall survival of the patients was 48 months, and they remained in good condition at the follow-up endpoint.

[0054] Figure 13 This image shows T1WI enhanced MRI images and MAF values ​​of a patient before and after glioma resection surgery. As shown in the figure, although the patient underwent total resection under T1WI evaluation (top), residual mutations of TERT and AURKB were still detectable in the postoperative ctDNA (bottom). The MAF values ​​in the preoperative and postoperative ctDNA were 10.52% and 1.39%, respectively. Wilcoxon signed-rank test... (P < 0.0001). As shown in the figure, the mean MAF value of the samples decreased by 86.82% before and after surgery. The overall survival of the patients was 12 months. Driver mutations are marked in red.

[0055] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make many possible variations and modifications to the technical solutions of the present invention using the methods and techniques disclosed above, or modify them into equivalent embodiments with equivalent changes, without departing from the spirit and technical essence of the present invention. Therefore, any simple modifications, equivalent substitutions, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solutions of the present invention shall still fall within the protection scope of the technical solutions of the present invention.

Claims

1. A digital quantitative assessment system for glioma resection extent and prognosis based on cerebrospinal fluid ctDNA, characterized in that, The digital quantitative assessment system includes: a data acquisition module, a data processing module, and a model comparison module; The data acquisition module is used to extract ctDNA from cerebrospinal fluid before and after glioma resection surgery; The data processing module is used to perform NGS sequencing on the ctDNA; The model comparison module is used to compare data on tumor-specific somatic mutations before and after glioma resection surgery.

2. The digital quantitative assessment system according to claim 1, characterized in that, The data on tumor-specific somatic mutations include the rate of decrease in tumor mutational burden, the rate of decrease in average mutational allele frequency, and / or the clearance rate of tumor-driving mutational genes.

3. The use of the digital quantitative assessment system according to claim 1 or 2 in the preparation of a detection procedure or kit for the extent of glioma resection.

4. The application according to claim 3, characterized in that, A high degree of glioma resection is indicated when the average mutational allele frequency of ctDNA in the cerebrospinal fluid after glioma resection is ≥90% lower than the average mutational allele frequency of ctDNA in the cerebrospinal fluid before surgery.

5. The application according to claim 3, characterized in that, A high degree of glioma resection is indicated when the tumor driver mutation burden of ctDNA in cerebrospinal fluid decreases by ≥90% after glioma resection compared to the preoperative value.

6. The use of the digital quantitative assessment system of claim 1 or 2 in the preparation of a test kit for detecting the prognosis of glioma patients after surgery or in the development of an analytical procedure.

7. The application according to claim 6, characterized in that, Patients with longer postoperative survival are those whose mean mutational allele frequency of ctDNA in cerebrospinal fluid decreases by ≥90% after glioma resection surgery, and / or whose clearance rate of tumor-driving mutational genes is ≥90%.

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