Validating clinical practice using SARRP; simulating clinical radiotherapy in a model mimicking spontaneous occurring NSCLC
Review of Shisuo Du, Virginia Lockamy, Lin Zhou, Christin Xue, Justin LeBlanc, Shonna Glenn, Gaurav Shukla, Yan Yu, Adam P. Dicker, Bo Lu. Stereotactic Body Radiotherapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer. IJROPB. 2016
Over 60% of cancer patients worldwide will receive radiotherapy as a part of their overall treatment plan. Recently, stereotactic body radiation therapy (SBRT) has been recognized as a favorable treatment option for those cancer types that remain inoperable. SBRT administers very high doses of radiation in a small number of fractions, and has been shown to achieve 3-year control rates of roughly 90% in stage 1 NSCLC’s. A recent study out of Thomas Jefferson University investigates the effect of SBRT on lung nodules in a murine model. In this study, Du et al. mimicked clinical delivery by utilizing image guided micro irradiation through the use of SARRP, with a clinically relevant treatment (SBRT) plan. Additionally, they utilized a genetically engineered mouse model that yielded spontaneously occurring lung tumors, the closest representation to naturally occurring lung tumors in humans. The investigators were able to identify lung nodules using the SARRPs on-board, high resolution, cone beam CT capabilities. This allowed them to target peripheral lung nodules using Muriplan software while avoiding off-target nodules in the contralateral lung as a control. By using Muriplan, the investigators were able to mimic dose planning representative of the RTOG 0813, 0236, and 0618 clinical trials. Here, they specified organs at risk, treated only single tumors within the middle or lower lobe of peripheral lung, and delivered a total of 60Gy in 3 fractions over two weeks. As a result of mimicking clinical practice; Du et al. were able to show that targeted tumor volumes decreased significantly, confirming the SBRT treatment plan effectively targeted lesions of interest. To confirm these observations, post treatment histology was performed on irradiated and non-irradiated lung nodules which showed a significant decrease in Ki-67 (cell proliferation) staining in the irradiated nodules. In addition, an increase in apoptotic index was observed when comparing non-irradiated and irradiated lung nodules. These data support the effectiveness of SBRT in this model.
This study is unique as it satisfied requirements set forth in clinical practice in a pre-clinical setting. It utilizes a spontaneously occurring lung tumor model (representative of naturally occurring tumors in humans) and incorporates clinically relevant treatment planning and dose delivery. Furthermore, this study was able to replicate clinical practice, an important aspect in preclinical research for clinical validation. In addition, the authors comment on the importance of using this model and moving forward by combining SARRP based treatments with immunotherapies. Most of the immunotherapeutic data being generated is done in syngeneic flank tumor models. As this study shows, it is important to move forward with our research in the most translational way, in both a treatment (SARRP) and animal modeling (spontaneous orthotopic tumors).
Link to article: http://www.redjournal.org/article/S0360-3016(16)32877-2/abstract