Little is known about the evolution of genetic and epigenetic changes that occur in the progression of glioma. We inferred the evolution trajectories of matched pairs of primary tumors and progression tumor in situ fluid (TISF) based on deep whole-genome-sequencing data (ctDNA). A monocentric, Gene grouping controlled trial design was used to select patients. and to compare gene evolution of different subtypes of glioma under therapy. To predict the molecular reaction of bevacizumab treatment, clarify the mechanism of drug resistance of bevacizumab treatment.
Patient: Adult glioma, pathological diagnosis combined with molecular diagnosis (i.e. IDH- mutant glioma, IDH- mutant glioma with 1p/19q- co-deletion, glioblastoma). The patients were divided into three groups: group A (IDH mutant glioma), group B (IDH mutant with 1p/19q co-deletion oligodendroglioma ) and group C (IDH wild glioblastoma). From the first day after surgery, the ctDNA was extracted with TISF before concurrent chemoradiotherapy as the baseline, and the ctDNA was detected again after concurrent chemoradiotherapy. For the third time, ctDNA was detected in temozolomide intensive chemotherapy. ctDNA was detected for the fourth time when the image showed tumor progression. After the progress, temozolomide combined with bevacizumab was used for chemotherapy. ctDNA was detected 6 weeks after the application of bevacizumab, and ctDNA was re-measured every 6 weeks during the treatment of bevacizumab. At the same time, imaging examination was performed to determine the tumor progress. Check and record adverse events and drug use in detail, and evaluate the compliance of subjects; After TISF tissue extraction, the retained blood samples were sent to simcere Company and Beijing Genetron Health Technology Co. Ltd for ctDNA quantification and detection. To study the differences of gene evolution of different subtypes of glioma under pressure therapy, to clarify the differences of molecular responses of different subtypes of glioma to bevacizumab, and to evaluate the therapeutic effect and safety.
Study Type
OBSERVATIONAL
Enrollment
100
Patients with glioma were routinely treated with temozolomide chemotherapy from the 4th week after operation, for 5 days continuously, once every 4 weeks, with a single dose as follows: Single dose = BSA (body surface area) \* 150mg/m2/day BSA(Body Surface Area)=\[weight (kg)\* height (cm)/3600\]2, According to the molecular pathological grade (WHO CNS5 grade), it is decided whether to combine radiotherapy (GBM combined with radiotherapy) and temozolomide combined with bevacizumab (600mg) in the course of tumor progression, Recording image changes
Henan Provincial People's Hospital
Zhengzhou, Henan, China
Different subtypes of glioma have different therapeutic responses to bevacizumab
We evaluated the efficacy of bevacizumab on different subtypes of glioma at recurrence according to delta-VAF and Ratio combined with imaging.The mean change in VAF (delta-VAF) was calculated per patient as the sum of the ontreatmentVAF minus the pretreatment VAF for each detected SNV or indel divided by the number of detected SNVs or indels, we found that the "molecular responce" model could generally be represented in simpler terms through a ratio of ontreatment VAF to pretreatment VAF
Time frame: 96 weeks
the molecular mechanism of bevacizumab resistance in vivo.
We compared and analyzed the genes before and after bevacizumab treatment according to the gene evolution of ctDNA.To clarify the molecular mechanism of bevacizumab resistance.
Time frame: 144 weeks
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