Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Purpose: To investigate changes in neurocognitive function and quality of life (QoL) and their association with dosimetric parameters of various brain structures as well as clinical cofactors in adult brain tumour patients following proton beam therapy (PBT).

Material and methods: Sixty-nine adult patients with primary brain tumours who received conventionally fractionated PBT were included in this study. Neurocognitive function according to the Montreal Cognitive Assessment (MoCA) test and QoL according to general EORTC-QLQ-C30 and brain tumour specific QLQ-BN20 questionnaires were scored prospectively at baseline and within 3-month-intervals up to one year after PBT. Dose-volume parameters of the retrospectively contoured structures hippocampus, thalamus, frontal and temporal lobes, amygdala, entire cerebellum, anterior cerebellum, and posterior cerebellum were extracted. Clinical parameters comprised age, sex, diagnosis and WHO grading, tumour volume, prescribed dose, concomitant chemotherapy, tumour resection and administration of corticosteroids. MoCA scores and differences to baseline values at different time points were correlated with self-reported QoL items (Spearman correlation rs), clinical and dosimetric parameters (Mann-Whitney U test, logistic regression). A change of ≥3 points of the MoCA total score compared to baseline was considered clinically relevant. Unless otherwise stated, differences at 3 months after PBT compared to baseline are given.

Results: The MoCA total score remained stable over time for the majority of patients: Less than 10% of the patients had clinically relevant changes at respective time points. The QLQ-C30 items did not change over time. On the QLQ-BN20 symptom scale, significant increases were observed for the items hair loss (p=0.002) and seizure (p<0.042, up to 9 months after PBT). However, future uncertainty decreased significantly (p<0.042). MoCA scores were significantly correlated with self-reported QoL scores. At all time-points, MoCA total score correlated with QLQ-C30 cognitive function (rs: 0.31-0.57) and MoCA language scores with QLQ-BN20 communication deficit (rs: 0.36-0.59).
Clinically relevant differences in the MoCA total score were significantly associated with high dose parameters in the anterior, posterior and entire cerebellum (V55Gy, p<0.05), but not with clinical parameters.

Conclusion: Neurocognitive function and QoL remained stable in the majority of brain tumour patients following PBT. Self-reported QoL was in accordance with the results of the objective MoCA test. Significant associations between dose-volume parameters and clinically relevant neurocognitive changes suggest that further sparing of organs at risk in treatment planning may lead to increased neurocognitive function and QoL for brain tumour patients. New planning constraints for further potential organs at risk, such as the cerebellum [1], should be discussed.

[1] Eekers DBP et al. (2017) Clin Transl Radiat Oncol 8, 22–26.