Histopathological evaluation of the effects of Flattening Filter (FF) and Flattening Filter Free (FFF) X-ray: In vivo malignant melanoma cancer models

Abstract

The objective of this study was to investigate the radiobiological effects of Flattening Filter (FF) and Flattening Filter Free (FFF) beams on Malignant Melanoma cancer (MMe Ca) modeled NOD-Prkdc IL2rg tm1 (NSG) mice in vivo, with a specific focus on necrotic and immunofluorescent changes.Thirty-five adult NSG mice models were randomly divided into four groups; MMe Ca, FF with a low dose rate of 400 MU/min (FF-400) and FFF with a high dose rate of 1400 MU/min (FFF-1400), and Control. The NSG mice in FF-400 and FFF-1400 groups (MMe Ca plus RT groups) were irradiated with a single dose of 20 Gy at 400 MU/min and 1400 MU/min. Radiotherapy was administered to NSG mice 20 days after tumor transplantation. The mice were then sacrificed 2 days after radiotherapy for assessment of the necrotic area, cell proliferation and apoptosis.The Ki-67 proliferation index showed a significant increase (p < 0.05) in the MMe Ca group (G1) compared to the FF-400 and FFF-1400 radiotherapy groups (G2 and G3) and the control group (G4), whereas a significant decrease was observed in the radiotherapy groups due to single-dose 20Gy irradiation (p < 0.05). The apoptotic index increased with irradiation in the FF-400 and FFF-1400 radiotherapy groups (p < 0.05). The necrotic area values of FF-400 and FFF-1400 at different dose rates (G2 and G3) increased statistically significantly (p < 0.05) compared to the MMe Ca group (G1). In addition, the Ki-67 cell proliferation, apoptotic index, and necrotic area parameters exhibited statistically significant differences between the FF-400 and FFF-1400 beams (p < 0.05). The FFF-high dose rate beams were found to be more effective on MMe Ca compared to the FF conventional beams (p < 0.05).It was concluded that FF and FFF beams caused significant radiobiological changes in cell proliferation (Ki-67), apoptosis (TUNEL) and necrosis histopathological parameters and the FFF beam was more effective on MMe Ca.