Radical surgical resection with molecular margins is associated with improved survival in IDH wildtype GBM

In this research paper from the journal Neuro-Oncology, the researchers investigated the relationship between the residual tumor cells at the resection margin after surgical removal and the progression-free survival (PFS) and overall survival (OS) in patients with wildtype isocitrate dehydrogenase (IDH wildtype) glioblastoma (GBM).

The authors are from the departments of Neurosurgery, Pathology, and Radiology at Massachusetts General Hospital. The paper was published in 2023.

The research process included the following main parts:

a) A predictive model was established through retrospective data to evaluate the pre-operative patient characteristics (tumor volume, cystic components, contact with ventricles, multifocality, tumor location, etc.) to predict whether the patient could achieve a smaller residual volume (<4.9cc) after gross total resection. The model had an AUC of 0.83, a sensitivity of 62%, and a specificity of 90%.

b) Prospectively, surgical specimens were collected from 44 GBM patients, and tissues were sampled from the resection margins. Quantitative PCR was used to detect the mutant allele frequency of the TERT promoter mutation, thereby assessing the residual tumor cells at the resection margins.

c) The results showed that among the 29 patients with complete resection (residual volume <4.9cc), 7 cases did not detect TERT mutation at the resection margin (no residual tumor cells), and 5 of these cases had complete resection (residual volume <1cc). These 5 patients had a 30-month progression-free survival rate of 75%, while the other patients with residual tumor cells had a rate of 0% (p=0.02). There was also a trend towards prolonged overall survival (75% vs 40%, p=0.19).

The research conclusion is that for some GBM patients, achieving a “molecular negative margin” (no residual tumor cells) at the time of tumor resection can significantly prolong the postoperative progression-free survival, suggesting that this “super-total resection” strategy can benefit specific populations. Assessing the molecular signals at the tumor margin may optimize surgical efficacy and provide a basis for patient stratification in clinical trials.

The innovation of this study lies in the development of a rapid method to detect TERT mutations, which can assess the residual tumor cells at the resection margin during surgery, thus guiding the extent of “super-total resection.” Additionally, by comparing postoperative outcomes, it is the first time that patients with no residual tumor cells at the resection margin have been found to have better prognoses, providing a molecular basis for optimizing surgical strategies.