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Imaging primary lung cancers in mice to study radiation biology.

ABSTRACT: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy.The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT.The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold.Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.

SUBMITTER: Kirsch DG

PROVIDER: S-EPMC2847457 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Imaging primary lung cancers in mice to study radiation biology.

Kirsch David G DG Grimm Jan J Guimaraes Alexander R AR Wojtkiewicz Gregory R GR Perez Bradford A BA Santiago Philip M PM Anthony Nikolas K NK Forbes Thomas T Doppke Karen K Weissleder Ralph R Jacks Tyler T

International journal of radiation oncology, biology, physics 20100301 4

<h4>Purpose</h4>To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy.<h4>Methods and materials</h4>The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tum ...[more]

PMID: 20206017

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Project description:Accurate tumor tracking remains a challenge in current radiation therapy. Many strategies including image guided radiation therapy alleviate the problem to certain extents. The authors propose a new modality called emission guided radiation therapy (EGRT) to accurately and directly track the tumor based on its biological signature. This work is to demonstrate the feasibility of EGRT under two clinical scenarios using a 4D digital patient model.EGRT uses lines of response (LOR's) from positron emission events to direct beamlets of therapeutic radiation through the emission sites inside a tumor. This is accomplished by a radiation delivery system consisting of a Linac and positron emission tomography (PET) detectors on a fast rotating closed-ring gantry. During the treatment of radiotracer-administrated cancer patients, PET detectors collect LOR's from tumor uptake sites and the Linac responds in nearly real-time with beamlets of radiation along the same LOR paths. Moving tumors are therefore treated with a high targeting accuracy. Based on the EGRT concept, the authors design a treatment method with additional modulation algorithms including attenuation correction and an integrated boost scheme. Performance is evaluated using simulations of a lung tumor case with 3D motion and a prostate tumor case with setup errors. The emission process is simulated by Geant4 Application for Tomographic Emission package (GATE) and Linac dose delivery is simulated using a voxel-based Monte Carlo algorithm (VMC++).In the lung case with attenuation correction, compared to a conventional helical treatment, EGRT achieves a 41% relative increase in dose to 95% of the gross tumor volume (GTV) and a 55% increase to 50% of the GTV. All dose distributions are normalized for the same dose to the lung. In the prostate case with the integrated boost and no setup error, EGRT yields a 19% and 55% relative dose increase to 95% and 50% of the GTV, respectively, when all methods are normalized for the same dose to the rectum. In the prostate case with integrated boost where setup error is present, EGRT contributes a 21% and 52% relative dose increase to 95% and 50% of the GTV, respectively.As a new radiation therapy modality with inherent tumor tracking, EGRT has the potential to substantially improve targeting in radiation therapy in the presence of intrafractional and interfractional motion.

Project description:The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose-response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors.This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site-specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR).Linear dose-response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries.The results suggest that the effect of high-dose irradiation is consistent with a linear dose-response for most organs, but they also reveal important organ-specific and host-specific differences in susceptibility and interactions between different aspects of treatment.

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Imaging primary lung cancers in mice to study radiation biology.

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Imaging primary lung cancers in mice to study radiation biology.

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