Evaluation of Deformable Image Registration and Dose Accumulation Using Histogram Matching Algorithm between kVCT and MVCT with Helical Tomotherapy

Purpose: To evaluate the accuracy of deformable image registration (DIR) between the planning kVCT (pCT) and the daily MVCT combined with the histogram matching (HM) algorithm, and evaluate the deformable dose accumulation using a suggested method for adaptive radiotherapy with Helical Tomotharapy (HT). Methods: For five prostate cancer patients (76 Gy/38 Fr) treated with HT in our institution, seven MVCT series (a total of 35 series) acquired weekly were investigated. First, to minimize the effect of different HU values between pCT and MVCT, this image-processing method adjusts HU values between pCT and MVCT images by using image cumulative histograms of HU values, generating an HM-MVCT. Then, the DIR of the pCT to the HM-MVCT was performed, generating a deformed pCT. Finally, deformable dose accumulation was performed toward the pCT image. Results: The accuracy of DIR was significantly improved by using the HM algorithm, compared with non-HM method for several structures (p ±0.05, 0.83 ±0.06, and 0.90 ± 0.04 for the CTV, rectum, and bladder, respectively, while that of the HM method was 0.81 ±0.06, 0.81 ±0.04, and 0.92 ±0.06, respectively. For the deformable dose accumulation, some difference was observed between the two methods, particularly for the small calculated regions, such as rectum V60 and V70. Conclusion: Adapting the HM method can improve the accuracy of DIR. Furthermore, dose calculation using the deformed pCT using HM methods can be an effective tool for adaptive radiotherapy.

KDM2B promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma

Epigenetic regulators have been implicated in tumorigenesis of many types of cancer;however,their roles in endothelial cell cancers such as canine hemangiosarcoma(HSA)have not been studied.In this study,we find that lysine-specific demethylase 2 b(KDM2 B)is highly expressed in HSA cell lines compared with normal canine endothelial cells.Silencing of KDM2 B in HSA cells results in increased cell death in vitro compared with the scramble control by inducing apoptosis through the inactivation of the DNA repair pathways and accumulation of DNA damage.Similarly,doxycycline-induced KDM2 B silencing in tumor xenografts results in decreased tumor sizes compared with the control.Furthermore,KDM2 B is also highly expressed in clinical cases of HSA.We hypothesize that pharmacological KDM2 B inhibition can also induce HSA cell death and can be used as an alternative treatment for HSA.We treat HSA cells with GSK-J4,a histone demethylase inhibitor,and find that GSK-J4 treatment also induces apoptosis and cell death.In addition,GSK-J4 treatment decreases tumor size.Therefore,we demonstrate that KDM2 B acts as an oncogene in HSA by enhancing the DNA damage response.Moreover,we show that histone demethylase inhibitor GSK-J4 can be used as a therapeutic alternative to doxorubicin for HSA treatment.