Impact of irradiation of the neurogenic niches on survival in patients with brain metastases
Fia Cialdella,
The Netherlands
MO-0724
Abstract
Impact of irradiation of the neurogenic niches on survival in patients with brain metastases
Authors: Fia Cialdella1, Szabolcs David1, Danique E. Bruil1, Steven H.J Nagtegaal2, Arthur T. van der Boog1, Sophietje de Sonnaville3, F.Y.F. de Vos4, Joost J.C. Verhoeff1
1University Medical Center Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands; 2Erasmus Medical Center, Department of Radiation Oncology, Rotterdam, The Netherlands; 3University Medical Center Utrecht, Department of Neurosurgery, Utrecht, The Netherlands; 4University Medical Center Utrecht, Department of Medical Oncology, Utrecht, The Netherlands
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Purpose or Objective
BACKGROUND:
Neural
stem cells (NSCs)
are involved in the
brain's ability to regenerate and are located in the subventricular zone (SVZ) and
subgranular zone (SGZ) of the hippocampus (HPC), known as the primary neurogenic
niches of the brain. It is believed that irradiating these areas inhibits the
repair capacity of the brain. Indeed, it has recently been shown in glioma patients that increased radiation dose on the neurogenic
niches decreases OS. In this study, we investigate
the effects of radiation
dose in neurogenic niches on OS in a cohort of patients with brain metastases.
Material and Methods
We included 262 patients with brain metastases from various primary tumors, who
underwent radiotherapy at UMC Utrecht between November 2014 and July 2020. NSC-regions were automatically delineated on T1 MR images using CAT12. OS was
analyzed using univariable and multivariable Cox regression, corrected for covariates: age, Karnofsky
Performance Status (KPS), number of metastases and the use of chemotherapy or immunotherapy
(see table 1).
Results
All
patients received any radiotherapy in neurogenic niches (SVZ: 0.02Gy-46.75Gy
EQD2, HPC: 0.02Gy-42,04Gy EQD2). In univariable analyses, the hazard ratio (HR)
was 1.035 per Gy (P = 0.025 [95% confidence interval (CI), 1.008 – 1.062]) for the mean dose in the SVZ, and
1.014 per Gy (P = 0.258 [95% CI, 0.990 – 1.038]) for the mean HPC dose. Multivariable
analyses showed only statistically significant HRs for KPS and administration
of immunotherapy.
| Variable | Hazard ratio (HR) | 95%-Confidence interval (CI) | P-value |
| Age | 1.015
| 0.999
– 1.031
| 0.063
|
Karnofsky Performance Status (KPS)
| 0.975
| 0.965
– 0.984
| <0.001
|
Number
of mets >4 vs. 1- 3
| 0..941 | 0.602
– 1.470
| 0.788
|
Administration
of chemotherapy Yes vs. No
| 1.167 | 0.851
– 1.600
| 0.338
|
Administration
of immunotherapy Yes vs. No
| 0.555
| 0.409
– 0.753
| <0.001
|
| RT
dose on hippocampus in Gy | 1.020
| 0.989 – 1.052
| 0.220
|
RT
dose on SVZ in Gy
| 1.020 | 0.988
– 1.053
| 0.220
|
Conclusion
In
this study, we showed that irradiation of the SVZ or HPC is not correlated with
OS in patients with brain metastases after correcting for covariates. We confirmed the prognostic
value of KPS and immunotherapy in OS in patients with brain metastases. In contrast to glioma, this suggest that there is
no role for neurogenic niches avoidance in stereotactic irradiation of brain
metastases regarding OS