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

Abstract

Purpose To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. Methods and Materials A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. Results The 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. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. Conclusions It 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 a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics.

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“…However, whether inflammation is the cause or effect of hypertension is not well understood (33). Of note, the effect of tumor location on RP2 was also tested here as it was previously reported in both patient (34) and animal studies (35,36). Although we considered it as a candidate predictor, tumor location parameter was not significant so as to be included in multivariate consideration, but not included in the final predictive GLM model.…”

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“…RT is a well-known cancer treatment, with complex and varied toxic biological effects, wanted to be provoked in diseased cells, while simultaneously avoiding healthy cells [32,33]. Stereotactic body radiation therapy (SBRT) is an advanced form of hypofractionated RT that consists of precise delivery of higher radiation doses on precised tumor location [3,15,34,35]. Stereotactic radiation using a linear accelerator has become a popular treatment for lung cancer.…”

“…with x i expressed in mg/(mL•day). When combined with antiangiogenesis, immunotherapy increases the therapeutic effect with 25% [1,16,17,45] and up to 50% when combined with radiotherapy [15,34,35,46]. A linear combination of their synergic effect is considered for the tumor Et all and drug Ed all interactions:…”