Biomarkers associated with GBM electric field therapy

Manjari Pandey et al.
of the Western Cancer Center and Research Institute in Memphis, Tennessee, USA, obtained tumor tissues from 55 GBM patients treated with TTFields and 57 GBM patients without TTFields, and analyzed them through whole genome sequencing and comparative genomic differences, combined with clinicopathological features, treatment and prognosis information, to clarify the relationship
between genomic differences and patients' clinical prognosis.

The results were published online in June 2022 in Neuro-Oncology Advances
.

- Excerpted from the article chapter

【Ref: Pandey M, et al.
Neurooncol Adv.
2022 Jun 21; 4(1):vdac096.
doi: 10.
1093/noajnl/vdac096.
eCollection 2022 Jan-Dec.
】

Research background

In recent years, TTFields has become an important treatment modality
for newly diagnosed and recurrent glioblastoma (GBM).

However, beyond patient adherence, there are no reliable biomarkers to predict the clinical efficacy
of TTFields.

Manjari Pandey et al.
of the Western Cancer Center and Research Institute in Memphis, Tennessee, USA, obtained tumor tissues from 55 GBM patients treated with TTFields and 57 GBM patients without TTFields, and analyzed them through whole genome sequencing and comparative genomic differences, combined with clinicopathological features, treatment and prognosis information, to clarify the relationship
between genomic differences and patients' clinical prognosis.

The results were published online in June 2022 in Neuro-Oncology Advances
.

Research methods

The results showed that the PFS of TTFields was 15.
8 months compared with 6.
9 months in the control group (HR=0.
55; 95% CI, 0.
35-0.
86; P=0.
01); The OS of TTFields was 25.
5 months compared with 18.
8 months in the control group (HR=0.
54; 95% CI, 0.
31-0.
94; P=0.
03).


The authors performed whole genome sequencing on tumor tissues from 112 patients included in the study and found no significant differences
between TTFields and control groups in common molecular mutations such as PD-1, CDKN2A-WT, MGMT promoter methylation, epidermal growth factor receptor (EGFR) amplification, and TP53-WT.

Further subdivision of patients in the TTFields group according to the results of genome sequencing found that PIK3CA gene mutations generally predict a poor tumor response, which may be related to a weakened or absent response to
TTFields.

Among patients treated with TTFields, the PFS of PIK3CA mutant patients was 6.
7 months significantly shorter than that of PIK3CA wild-type patients (P=0.
0008).
The OS of PIK3CA mutant patients was 10.
0 months, which was also significantly shorter than that of PIK3CA wild-type patients at 26.
6 months (P=0.
0158).


At the same time, in the TTFields treatment group, NF1 mutant type was associated with TTFields treatment response compared with NF1 wild type, and the PFS was 18.
2 months: 14.
4 months (P=0.
07).
OS was NR: 24.
7 months (P=0.
0415).


Comparing EGFR mutant patients with TTFields with EGFR unmutated patients with TTFields, it was found that PFS in patients with EGFR mutation was 4.
6 months longer than that in EGFR mutation patients (P=0.
36).

Study results

Finally, the authors establish molecular student memory scores (MSS)
based on the combination of PIK3CA, NF1, and EGFR.

It is calculated as follows: PIK3CA-WT, EGFR-WT and NF1-WT are +1 points, and vice versa is 0 points; MSS is the sum of the scores of 3 biomarkers, and the final score is 0-3
.

0-2 is divided into low groupings and 3 is divided into high groups
.

The analysis of PFS and OS based on MSS showed that PFS and OS in patients treated with TTFields were significantly longer than those in patients with low MSS, with PFS of 25.
9 months: 12.
9 months (p=0.
019); OS is NR: 24.
5 months (p=0.
0252).

Conclusion of the study

The results of this study showed that for GBM patients carrying PIK3CA-WT, EGFR-WT and NF1-WT, calculating MSS up to 3 points predicted a good
treatment effect of TTFields.

Therefore, when large-scale prospective clinical trials study biomarkers related to TTFields treatment, the preliminary results of the above-mentioned clinical application of TTFields will provide a reliable theoretical basis
.