Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2014 May 1;89(1):161-6. doi: 10.1016/j.ijrobp.2014.01.057.
To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam.
Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice.
Exposure of mice to a dose of 600 Gy of proton beam-generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10.
Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.
评估小鼠全身暴露于被动散射临床扩展布拉格峰（SOBP）质子束产生的中子后寿命和癌症风险。
将 300 只成年雌性 FVB/N 小鼠（152 只实验组和 148 只对照组）纳入实验。将小鼠置于圆柱形模体周围的环形盒中，该模体位于 165MeV 临床质子束的中 SOBP 侧面。从中 SOBP 边缘到有意识活动小鼠的平均距离为 21.5cm。每周 4 天，每天进行一次 25Gy 的分次照射，共 6 周。在小鼠的寿命期间评估其死亡年龄和死亡原因（即癌症和类型与非癌症原因）。
暴露于 600Gy 质子束产生的中子剂量会使小鼠的中位寿命缩短 4.2%（Kaplan-Meier 累积生存率，P=.053）。与对照组相比，暴露于中子的小鼠死于癌症的相对风险为所有类型癌症的 1.40（P=.0006）和实体癌的 1.22（P=.09）。对于典型的 60Gy 临床质子剂量，预计观察到的 22%实体癌风险增加将减少 10 倍。
暴露于质子剂量超过典型放射治疗剂量 10 倍的中子会导致白血病背景发病率显著增加，实体癌发病率略有增加。结果表明，来自 SOBP 质子产生的中子和典型治疗方案的场外第二实体癌风险比当前中子风险估计低 6 至 10 倍。
