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



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.



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.



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.
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Shisuo
S
Du
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Virginia
V
Lockamy
Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Lin
L
Zhou
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Christine
C
Xue
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Justin
J
LeBlanc
Xstrahl, Inc, Suwanee, Georgia.
Shonna
S
Glenn
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Gaurav
G
Shukla
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Yan
Y
Yu
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Adam P
AP
Dicker
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Dennis B
DB
Leeper
Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
You
Y
Lu
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: bo.lu@jefferson.edu.
Bo
B
Lu
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000662:veterinary*; D051379:Mice / Q000235:genetics*; D016634:Radiosurgery / Q000295:instrumentation* / Q000662:veterinary*; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided / Q000295:instrumentation / Q000662:veterinary; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000662:veterinary; D016896:Treatment Outcome
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