# Synergistic Effects of Cryotherapy and Radiotherapy in Glioblastoma Treatment: Evidence from a Murine Model

## TL;DR

This study shows that combining cryotherapy with radiotherapy can significantly improve treatment outcomes for glioblastoma in a mouse model.

## Contribution

The first study to demonstrate a synergistic effect of cryotherapy and radiotherapy in a glioblastoma model using MRI and histology.

## Key findings

- Combining cryotherapy and radiotherapy significantly improved survival and led to complete tumor regression in 40% of mice.
- ADC distribution from MRI was a better predictor of treatment response than caliper-based measurements.
- Partial cryotherapy alone showed no therapeutic benefit in the study.

## Abstract

Glioblastoma is a highly aggressive brain tumor with a poor prognosis. Radiotherapy is a standard treatment, but its effectiveness is often limited. Cerebral cryotherapy, a technique involving controlled cooling of the tumor, has been shown to be safe in patients. This longitudinal study, using MRI (T2-weighted imaging and Apparent Diffusion Coefficient (ADC)) and histology, is the first to evaluate the combined effects of cryotherapy and radiotherapy in a glioblastoma mouse model. The results demonstrated a synergistic interaction between the two treatments, suggesting that their combination could improve therapeutic outcomes. Furthermore, ADC distribution was found to be a predictive marker of treatment response in this study. These findings could contribute to the development of more effective therapeutic strategies for glioblastoma, potentially advancing clinical practice and improving patient survival.

Background/Objectives: Cryotherapy involves the insertion of cryoprobes into tumors to induce cell destruction through exposure to extremely low temperatures over several minutes. This localized treatment modality may enhance the efficacy of established therapies, such as radiotherapy, particularly for glioblastomas. Our study aimed to provide proof-of-concept for the efficacy of combining cryotherapy and radiotherapy in the treatment of subcutaneous murine brain tumors (GL-261) in immunocompetent C57BL/6 mice. Methods: Tumor growth, survival and response were evaluated using MRI and histological analysis. Results: Partial cryotherapy alone showed no therapeutic efficacy. However, combining cryotherapy with radiotherapy significantly potentiated treatment outcomes. A statistically significant survival benefit was observed in the combined therapy group compared to control, cryotherapy and radiotherapy groups. Notably, 40% of mice receiving the combined treatment exhibited complete responses, with no detectable tumor cells on MRI or histological analysis. Furthermore, MRI-based monitoring revealed that the Apparent Diffusion Coefficient (ADC) map could predict complete response 14 days post-treatment, unlike caliper-based measurements. Conclusions: These findings suggest that cryotherapy may enhance radiotherapy efficacy, resulting in complete tumor regression in 4 out of 10 cases. ADC distribution may serve as a predictive marker for therapeutic response. However, given the limitations of the model, further studies in orthotopic models are needed to validate these findings and assess their clinical relevance.