Background
At present, the in vivo gene evolution of human glioma after surgery is unknown. We need to understand the real-time in vivo gene evolution information of the tumor to dynamically reflect the real behavior of the tumor, so as to drive therapeutic decisions. TISF-ctDNA can provide real-time in vivo gene information after surgery, and then reveal postoperative glioma behavior more realistically.
Methods
This retrospective, Single center, sample collection, validation study conducted at Zheng Zhou University People's hospital from July 1st, 2016, to November 1st, 2021, assessed patients with glioma who were receiving surgical treatment and adjuvant radiotherapy and chemotherapy. The study including 69 patients, with radiological relapse identified in 44 patients forming the main cohort.
RESULTS
In the primary tumor, a total of 199 mutations were detected in 58 tumor tissue samples,12 patients (21%) with 1 mutation and 45 patients (79%) with multiple mutations,TP53 (44%) followed by IDH1(39%) and PTEN(25%), mean VAF from 2.1%-79.5%,with a median 40.5%.At or after a diagnosis of recurrence, A total of 613 gene mutations were found through TISF ctDNA sequencing, including TP53 (48%), NF1 (38%), PTEN (31%), mean VAF from 0.2%-34.14%, with a median 1.54%, and we also found Pseudo-progression and hypermutation associated with TMZ resistance. In the main cohort of 44 patients (mean age, 52 years) with a median follow-up of 190 days (20-1530 days), mean VAF of TISF ctDNA during follow-up was associated with relapse (hazard ratio, 4.058; 95% CI, 1.089 to 15.12; P = 0.0012). Similar outcomes were observed for tumor tissue (hazard ratio, 2.214; 95% CI, 1.003 to 4.887; P = 0.0165). Hypermutation was found in 3 patients in the cohort, and the in vivo evolution of hypermutation was tracked in 2 of these patients.
CONCLUSIONS
TISF ctDNA describes human glioma behavior, demonstrates the real tumor gene mutation landscape in vivo during treatment, providing prognostic and response data of clinical relevance.