Cebula Hélène, Po Chrystelle, Mura Carole, Lhermitte Benoit, Cazzato Roberto Luigi, Rame Marion, Le Fèvre Clara, Todeschi Julien, Mallereau Charles-Henry, Gangi Afshin, Noël Georges, de Mathelin Michel, Proust François, Burckel Hélène
Department of Neurosurgery, Hautepierre University Hospital, 1, Avenue Molière, 67200 Strasbourg, France.
Université de Strasbourg, CNRS, ICube UMR 7357, 67000 Strasbourg, France.
Cancers (Basel). 2025 May 17;17(10):1692. doi: 10.3390/cancers17101692.
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.
Tumor growth, survival and response were evaluated using MRI and histological analysis.
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.
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.
背景/目的：冷冻疗法是将冷冻探头插入肿瘤，通过在数分钟内暴露于极低温度来诱导细胞破坏。这种局部治疗方式可能会提高现有疗法（如放射疗法）的疗效，尤其是对于胶质母细胞瘤。我们的研究旨在为免疫功能正常的C57BL/6小鼠皮下脑肿瘤（GL-261）联合冷冻疗法和放射疗法的疗效提供概念验证。
使用磁共振成像（MRI）和组织学分析评估肿瘤生长、存活情况及反应。
单纯局部冷冻疗法未显示出治疗效果。然而，冷冻疗法与放射疗法联合使用显著增强了治疗效果。与对照组、冷冻疗法组和放射疗法组相比，联合治疗组观察到了具有统计学意义的生存获益。值得注意的是，接受联合治疗的小鼠中有40%表现出完全缓解，MRI或组织学分析均未检测到肿瘤细胞。此外，基于MRI的监测显示，表观扩散系数（ADC）图能够在治疗后14天预测完全缓解，这与基于卡尺测量的结果不同。
这些发现表明，冷冻疗法可能会提高放射疗法的疗效，10例中有4例实现了肿瘤完全消退。ADC分布可作为治疗反应的预测标志物。然而，鉴于该模型的局限性，需要在原位模型中进行进一步研究以验证这些发现并评估其临床相关性。
