Tadataka Miyake, DDS (1), Hisashi Innami, DDS, PhD (2), Ryota Kawamata, DDS, PhD (2), and Takashi Sakurai, DDS, PhD (2)
(1) Tsurumi Dental Clinic, Yokohama, and (2) Division of Radiopraxis Science, Department of Maxillofacial Function Reconstruction, Kanagawa Dental University, Yokosuka, Japan
Purpose: This study evaluated the effects of combination therapy by in vivo experiment under conditions closely resembling actual clinical cancer treatment. The relationship between therapeutic efficacy and peritumoral microvascular structure changes was also evaluated with image-engineering analysis.
Materials and Methods: Fifty 8-week-old female BALB/cAJcl-nu/nu mice were used as humanoid tumor models. Five experimental groups were set; control, radiotherapy, thermoradiotherapy, chemoradiotherapy, and thermochemoradiotherapy. The therapeutic effect was evaluated based on tumor volume ratios before and after treatment, vascular structure parameters on magnified angiographic X-ray images, and histopathological examination.
Results: Tumor volume ratios in all treatment groups were significantly lower than in the control group. Magnified angiographic X-ray images showed that peritumoral vessels were decreased in each treatment group. Each combination therapy group showed further reductions and fragmentations compared with the radiotherapy group. In quantitative analysis of extracted vascular structure patterns, the reduction in blood vessels with radiotherapy was slight, thermoradiotherapy achieved strong reductions and reduced continuity and caused fragmentation, and chemoradiotherapy and thermochemoradiotherapy achieved more marked reductions and fragmentation. In histopathological evaluations, many viable tumor cells remained following radiotherapy. In contrast, viable tumor cells completely disappeared with each combination therapy.
Conclusion: These findings suggest that radiotherapy in combination with hyperthermia and chemotherapy achieves high antitumor efficacy, and triple-combination therapy will reduce the burden on patients. Furthermore, these experimental results suggest that the stronger the therapeutic effect of the combination therapy, the more peritumoral blood vessels will be reduced and fragmented. (Asian Pac J Dent 2016; 16: 35-46.)
Key Words: Chemotherapy, Hyperthermia, Image engineering analysis, Oncology, Radiotherapy