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

Journal Article · Tue Nov 01 04:00:00 EDT 2016 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2016.07.008· OSTI ID:22645672

Du, Shisuo; Lockamy, Virginia ^[1]; Zhou, Lin ^[2]; Xue, Christine; LeBlanc, Justin ^[1]; Glenn, Shonna ^[3]; Shukla, Gaurav; Yu, Yan; Dicker, Adam P.; Leeper, Dennis B. ^[1]; Lu, You ^[2]; Lu, Bo ^[1]

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1. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)
2. Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan (China)
3. Xstrahl, Inc, Suwanee, Georgia (United States)

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.

• OSTI ID: 22645672
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 96; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BIOMEDICAL RADIOGRAPHY
CELL PROLIFERATION
CLINICAL TRIALS
COMPUTERIZED TOMOGRAPHY
DOSE LIMITS
GY RANGE 10-100
IMAGES
IRRADIATION
LUNGS
MICE
NEOPLASMS
RADIOTHERAPY