Comparison of conventional and hippocampus-sparing radiotherapy in nasopharyngeal carcinoma: In silico study and systematic review

Background and purpose: Radiation-induced damage to the hippocampi can cause cognitive decline. International recommendations for nasopharyngeal cancer (NPC) radiotherapy (RT) lack specific guidelines for protecting the hippocampi. Our study evaluates if hippocampi-sparing (HS) RT in NPC ensures target coverage and meets recommended dose limits for other at-risk organs. Materials and methods: In a systematic literature review, we compared hippocampal D40% in conventional and HS RT plans. In an in silico dosimetric study, conventional and HS-VMAT plans were created for each patient, following international recommendations for OAR delineation, dose prioritization and acceptance criteria. We assessed the impact on neurocognitive function using a previously published normal tissue complication probability (NTCP) model. Results: In four previous studies (n = 79), researchers reduced D40% hippocampal radiation doses in HS plans compared to conventional RT on average from 24.9 Gy to 12.6 Gy. Among 12 NPC patients included in this in silico study, statistically significant differences between HS and conventional VMAT plans were observed in hippocampal EQD2 Dmax (23.8 vs. 46.4 Gy), Dmin (3.8 vs. 4.6 Gy), Dmean (8.1 vs. 15.1 Gy), and D40% (8.3 vs. 15.8 Gy). PTV coverage and OAR doses were similar, with less homogeneous PTV coverage in HS plans (p = 0.038). This translated to a lower probability of memory decline in HS plans (interquartile range 15.8-29.6 %) compared to conventional plans (33.8-81.1 %) based on the NTCP model (p = 0.002). Conclusion: Sparing the hippocampus in NPC RT is safe and feasible. Given the life expectancy of many NPC patients, their cognitive well-being must be paramount in radiotherapy planning.