Stereotactic Body Radiotherapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer

Publication date: Available online 21 July 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Shisuo Du, Virginia Lockamy, Lin Zhou, Christine Xue, Justin LeBlanc, Shonna Glenn, Gaurav Shukla, Yan Yu, Adam P. Dicker, Bo Lu
PurposeTo implement clinical stereotactic body radiotherapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer.Methods and MaterialsA murine model of multi-nodular Kras-driven spontaneous lung tumors was utilized for this stiudy. High resolution cone-beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules wheras off-target lung nodules in the contralateral lung were utilized as a non-irradiated control. CBCT imaging helps to localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose and dose limits to normal tissue follow the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry.ResultsThe image-guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. 60 Gy delivered in three weekly fractions markedly reduce proliferation index, Ki-67 and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules.ConclusionsIt is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide rationale for clinical trials involving SBRT, especially in the setting of being combined with immunotherapeutics.

Teaser

This work demonstrates the feasibility of using human SBRT protocols to deliver image-guided SBRT treatments in rodent models utilizing a small animal irradiator. The use of genetically engineered mice with Kras-driven spontaneous lung tumors that closely mimic human NSCLC is a unique preclinical model for SBRT. We have demonstrated that SBRT can be precisely delivered to murine lung peripheral tumors while sparing on adjacent tissues and OARs. In addition, we validated biological effects from SBRT in irradiated tissues. This novel platform provides new research opportunities that investigate the combination of SBRT with other therapeutic agents.


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