Glioma has received considerable attention because of its potential of inducing high rates of morbidity,disability,and mortality.FLASH radiotherapy(FLASH-RT)has emerged as a popular topic in current research because o...Glioma has received considerable attention because of its potential of inducing high rates of morbidity,disability,and mortality.FLASH radiotherapy(FLASH-RT)has emerged as a popular topic in current research because of its ability to protect normal tissues.The present review summarized the current development of FLASH-RT in both the central nervous system and glioblastomas,explored the potential mechanisms underlying FLASH-RT-mediated protective effects on the central nervous system,and revealed the advantages of this new technique for glioma therapy.This study highlights the benefits and challenges of the present research and provides a reference for future research.展开更多
Our study investigated the role of oxygen in mediating the FLASH efect.This efect,which was frst reported in vitro in the 1950s and in vivo in the 1970s,recently gained prominence with a number of publications showing...Our study investigated the role of oxygen in mediating the FLASH efect.This efect,which was frst reported in vitro in the 1950s and in vivo in the 1970s,recently gained prominence with a number of publications showing diferential sparing between normal tissues and tumors.Oxygen depletion(and subsequent induction of transient hypoxia)is the oldest and most prominent hypothesis to explain this efect.To better understand how the oxygen depletion hypothesis and oxygen enhancement ratio(OER)are relevant for interpreting FLASH benefts,an analytical model was proposed to estimate the sparing factor.The model incorporated factors such as OER,oxygen partial pressure(pO_(2)),loco-regional oxygen difusion/metabolism,total dose and dose rate.The sparing factor,was used to quantify the sparing of normal tissue(initially physoxic).The radiosensitivity parameters of two cell types(V79 Chinese hamster cells and T1 human kidney cells)were selected.Furthermore,the transient behavior of OER during fnite time intervals was modeled,for both without and with the presence of oxygen transport using a difusion model.For tissues with an oxygen consumption rate of 20mmHg/s and a distance of 60μm away from blood vessels,the sparing factor demonstrates an increase from 1.03/1.06(V79/T1)at 2.5Gy/s up to 1.28/1.72(V79/T1)at 100Gy/s(total dose:10Gy).For normal tissues of initial pO_(2) between 1.5 and 8mmHg,the beneft from pushing the dose rate above 100Gy/s is found to be marginal.Preliminary animal experiments have been conducted for validation.Overall,our study predicts that the dose rate associated with maximum normal tissue protection is between 50Gy/s and 100Gy/s.Other than the postulation of the hypoxic stem cell niches in normal tissues,we believe that a framework based upon the oxygen depletion hypothesis and OER is not able to efciently interpret diferential responses between normal and tumor tissue under FLASH irradiation.展开更多
基金Shanxi Provincial Youth Research Fund(No.20210302124283),China.
文摘Glioma has received considerable attention because of its potential of inducing high rates of morbidity,disability,and mortality.FLASH radiotherapy(FLASH-RT)has emerged as a popular topic in current research because of its ability to protect normal tissues.The present review summarized the current development of FLASH-RT in both the central nervous system and glioblastomas,explored the potential mechanisms underlying FLASH-RT-mediated protective effects on the central nervous system,and revealed the advantages of this new technique for glioma therapy.This study highlights the benefits and challenges of the present research and provides a reference for future research.
基金National Natural Science Foundation of China (62175183)。
文摘Our study investigated the role of oxygen in mediating the FLASH efect.This efect,which was frst reported in vitro in the 1950s and in vivo in the 1970s,recently gained prominence with a number of publications showing diferential sparing between normal tissues and tumors.Oxygen depletion(and subsequent induction of transient hypoxia)is the oldest and most prominent hypothesis to explain this efect.To better understand how the oxygen depletion hypothesis and oxygen enhancement ratio(OER)are relevant for interpreting FLASH benefts,an analytical model was proposed to estimate the sparing factor.The model incorporated factors such as OER,oxygen partial pressure(pO_(2)),loco-regional oxygen difusion/metabolism,total dose and dose rate.The sparing factor,was used to quantify the sparing of normal tissue(initially physoxic).The radiosensitivity parameters of two cell types(V79 Chinese hamster cells and T1 human kidney cells)were selected.Furthermore,the transient behavior of OER during fnite time intervals was modeled,for both without and with the presence of oxygen transport using a difusion model.For tissues with an oxygen consumption rate of 20mmHg/s and a distance of 60μm away from blood vessels,the sparing factor demonstrates an increase from 1.03/1.06(V79/T1)at 2.5Gy/s up to 1.28/1.72(V79/T1)at 100Gy/s(total dose:10Gy).For normal tissues of initial pO_(2) between 1.5 and 8mmHg,the beneft from pushing the dose rate above 100Gy/s is found to be marginal.Preliminary animal experiments have been conducted for validation.Overall,our study predicts that the dose rate associated with maximum normal tissue protection is between 50Gy/s and 100Gy/s.Other than the postulation of the hypoxic stem cell niches in normal tissues,we believe that a framework based upon the oxygen depletion hypothesis and OER is not able to efciently interpret diferential responses between normal and tumor tissue under FLASH irradiation.
