Abstract
Simple SummaryParticle therapy with carbon ions is a promising novel option for the treatment of recurrent high-grade glioma (rHGG). Lack of initial and sequential biopsies limits the investigation of rHGG evolution under therapy. We hypothesized that peripheral blood transcriptome derived from liquid biopsies (lbx) as a minimal invasive method may provide a useful decision support for identification of glioma grade and provide novel means for longitudinal molecular monitoring of tumor evolution under carbon ion irradiation (CIR). We demonstrate feasibility and report patient, tumor and treatment fingerprints in whole blood transcriptomes of rHGG patients with pre-CIR and three post-CIR time points.Purpose: To assess the value of whole blood transcriptome data from liquid biopsy (lbx) in recurrent high-grade glioma (rHGG) patients for longitudinal molecular monitoring of tumor evolution under carbon ion irradiation (CIR). Methods: Whole blood transcriptome (WBT) analysis (Illumina HumanHT-12 Expression BeadChips) was performed in 14 patients with rHGG pre re-irradiation (reRT) with CIR and 3, 6 and 9 weeks post-CIR (reRT grade III:5, 36%, IV:9, 64%). Patients were irradiated with 30, 33, 36 GyRBE (n = 5, 6, 3) in 3GyRBE per fraction. Results: WTB analysis showed stable correlation with treatment characteristics and patients tumor grade, indicating a preserved tumor origin specific as well as dynamic transcriptional fingerprints of peripheral blood cells. Initial histopathologic tumor grade was indirectly associated with TMEM173 (STING), DNA-repair (ATM, POLD4) and hypoxia related genes. DNA-repair, chromatin remodeling (LIG1, SMARCD1) and immune response (FLT3LG) pathways were affected post-CIR. Longitudinal WTB fingerprints identified two distinct trajectories of rHGG evolution, characterized by differential and prognostic CRISPLD2 expression pre-CIR. Conclusions: Lbx based WTB analysis holds the potential for molecular stratification of rHGG patients and therapy monitoring. We demonstrate the feasibility of the peripheral blood transcriptome as a sentinel organ for identification of patient, tumor characteristics and CIR specific fingerprints in rHGG.
Highlights
Carbon ion particle irradiation (CIR) is a promising novel therapy option for recurrent high grade glioma [1]. recurrent high-grade glioma (rHGG) includes grade III and IV tumors, composed of a variety of distinct molecular subtypes [2,3] almost exclusively exhibiting a grim prognosis [4,5]
Data reported by Nyazi et al from a German Cancer Consortium (DKTK) multi-center retrospective study of rHGG re-irradiated with photons highlighted the importance of initial tumor grade, performance score and age at reRT as important prognostic factors [6] empathizing the heterogeneity of rHGG
Fourteen patients with rHGG were enrolled in the study between May 2011 and June 2021 (Figure 1A and Table 1)
Summary
Carbon ion particle irradiation (CIR) is a promising novel therapy option for recurrent high grade glioma (rHGG) [1]. rHGG includes grade III and IV tumors, composed of a variety of distinct molecular subtypes [2,3] almost exclusively exhibiting a grim prognosis [4,5]. Carbon ion particle irradiation (CIR) is a promising novel therapy option for recurrent high grade glioma (rHGG) [1]. The biological effects differ from conventional therapy and include the induction of a more immune-accessible environment [9], modulation of angiogenesis [9] and the eradication of tumor stem cells [8,9]. Tumor recurrences present predominantly at margins of the high-dose irradiated region following CIR, as opposed to in-field recurrences after conventional photon radiotherapy [14], supporting the observation of improved tumor cell killing by CIR. The first clinical data—comparing RRRS matched patients with photon and carbon therapy—showed promising results, especially for grade III glioma [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
