title: Effective Rat Lung Tumor Model for Stereotactic Body Radiation Therapy.
abstract: Stereotactic body radiation therapy (SBRT) has found an important role in the treatment of patients with non-small cell lung cancer, demonstrating improvements in dose distribution and even tumor cure rates, particularly for early-stage disease. Despite its emerging clinical efficacy, SBRT has primarily evolved due to advances in medical imaging and more accurate dose delivery, leaving a void in knowledge of the fundamental biological mechanisms underlying its activity. Thus, there is a critical need for the development of orthotropic animal models to further probe the biology associated with high-dose-per-fraction treatment typical of SBRT. We report here on an improved surgically based methodology for generating solitary intrapulmonary nodule tumors, which can be treated with simulated SBRT using the X-RAD 225Cx small animal irradiator and Small Animal RadioTherapy (SmART) Plan treatment system. Over 90% of rats developed solitary tumors in the right lung. Furthermore, the tumor response to radiation was monitored noninvasively via bioluminescence imaging (BLI), and complete ablation of tumor growth was achieved with 36 Gy (3 fractions of 12 Gy each). We report a reproducible, orthotopic, clinically relevant lung tumor model, which better mimics patient treatment regimens. This system can be utilized to further explore the underlying biological mechanisms relevant to SBRT and high-dose-per-fraction radiation exposure and to provide a useful model to explore the efficacy of radiation modifiers in the treatment of non-small cell lung cancer.
authors.affiliation: a   Department of Radiation Oncology.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: b   Department of Radiology.
authors.forename: Michelle
authors.initials: M
authors.lastname: Wodzak
authors.affiliation: d   Hamon Center for Therapeutic Oncology Research, and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Belzile
authors.affiliation: b   Department of Radiology.
authors.forename: Heling
authors.initials: H
authors.lastname: Zhou
authors.affiliation: a   Department of Radiation Oncology.
authors.forename: Brock
authors.initials: B
authors.lastname: Sishc
authors.affiliation: a   Department of Radiation Oncology.
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.affiliation: a   Department of Radiation Oncology.
authors.forename: Strahinja
authors.initials: S
authors.lastname: Stojadinovic
authors.affiliation: b   Department of Radiology.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
authors.affiliation: c   Department of Surgery and Pharmacology.
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Brekken
authors.affiliation: b   Department of Radiology.|e   Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Simmons Cancer Center, Dallas, Texas 75390-9187.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chopra
authors.affiliation: a   Department of Radiation Oncology.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Story
authors.affiliation: a   Department of Radiation Oncology.
authors.forename: Robert
authors.initials: R
authors.lastname: Timmerman
authors.affiliation: a   Department of Radiation Oncology.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Saha
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D054893:Cone-Beam Computed Tomography; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D016634:Radiosurgery; D061089:Radiotherapy, Image-Guided; D051381:Rats; D016896:Treatment Outcome