We present an expert-trained deep learning model for automated delineation of 25 organs-at-risk defined in the EPTN atlas for neuro-oncological radiotherapy. Multiple input configurations were evaluated. The dual-input channel model combining contrast-enhanced T1-weighted MRI and CT achieved the best overall results (median surface Dice Similarity Coefficient = 0.84). It demonstrated robust performance across a wide range of organs-at-risk, supporting its use as a segmentation-support tool under human supervision and for fully automated retrospective dose–response analyses. We release the model publicly to the international community, while explicitly acknowledging that clinical use remains the responsibility of each institution within its regulatory context.

AIM:To evaluate clinical and radiological outcome in surgically treated Koos 4 vestibular schwannomas. MATERIAL AND METHODS:Volumetric analysis of the tumour volumes before surgery, after surgery (before radiation), and at follow-up time-points after radiation was performed. Clinical data on facial nerve function and complications were collected. Approximately 6 months after surgery, all patients were treated with a single fraction of stereotactic radiosurgery using the gamma knife radiosurgery with a mean marginal dose of 12.9 Gy to the residual tumour volume. RESULTS:Mean tumour volume was 11.64 cm3 which was reduced to a mean volume of 4.17 cm3 after partial resection. After a mean follow-up of 100 months, residual tumour showed a decrease in volume in 20 patients, stable disease in one patient and two patients showed progressive tumour volume requiring a second operation in one patient. Facial nerve function was preserved in all patients. One patient suffered from a trigeminal neuralgia after radiation. CONCLUSION:Planned partial resection followed by radiation for patients with Koos 4 vestibular schwannoma is an effective strategy to preserve facial nerve function and achieve tumour control. Residual tumours after planned partial resection showed a mean decrease in volume of 50% at the last follow-up time point.

Purpose: This study aims to create a deep learning (DL) model capable of accurately delineating the ventricles, and by extension, the periventricular space (PVS), following the 2021 EPTN Neuro-Oncology Atlas guidelines on T1-weighted contrast-enhanced MRI scans (T1CE). The performance of this DL model was quantitatively and qualitatively compared with an off-the-shelf model. Materials and Methods: An nnU-Net was trained for ventricle segmentation using both CT and T1CE MRI images from 78 patients. Its performance was compared to that of a publicly available pretrained segmentation model, SynthSeg. The evaluation was conducted on both internal (N = 18) and external (n = 18) test sets, with each consisting of paired CT and T1CE MRI images and expert-delineated ground truths (GTs). Segmentation accuracy was assessed using the volumetric Dice Similarity Coefficient (DSC), 95th percentile Hausdorff distance (HD95), surface DSC, and added path length (APL). Additionally, a local evaluation of ventricle segmentations quantified differences between manual and automatic segmentations across both test sets. All segmentations were scored by radiotherapy technicians for clinical acceptability using a 4-point Likert scale. Results: The nnU-Net significantly outperformed the SynthSeg model on the internal test dataset in terms of median [range] DSC, 0.93 [0.86–0.95] vs. 0.85 [0.67–0.91], HD95, 0.9 [0.7–2.5] mm vs. 2.2 [1.7–4.8] mm, surface DSC, 0.97 [0.90–0.98] vs. 0.84 [0.70–0.89], and APL, 876 [407–1298] mm vs. 2809 [2311–3622] mm, all with p < 0.001. No significant differences in these metrics were found in the external test set. However clinical ratings favored nnU-Net segmentations on the internal and external test sets. In addition, the nnU-Net had higher clinical ratings than the GT delineation on the internal and external test set. Conclusions: The nnU-Net model outperformed the SynthSeg model on the internal dataset in both segmentation metrics and clinician ratings. While segmentation metrics showed no significant differences between the models on the external set, clinician ratings favored nnU-Net, suggesting enhanced clinical acceptability. This suggests that nnU-Net could contribute to more time-efficient and streamlined radiotherapy planning workflows.

Glioblastoma remains a highly malignant, inevitably recurring brain tumor with dismal prognosis. Tumor progression is influenced by cellular interactions between the tumor and its microenvironment, yet quantitative data on these interactions, particularly under standard of care therapy, remains sparse. We utilized spatial, single-cell, multiome profiling to map therapy-induced changes in the architecture of >700 paired glioblastoma samples derived from 101 patients at diagnosis and recurrence. This approach categorized patients into groups reflecting specific evolutionary responses to therapy, with implications for prognosis and treatment. Favourable outcomes were linked to shifts towards enriched perivascular, oligodendrocyte-progenitor-like niches with deep tissue infiltration of activated immune cells, whereas poor outcomes correlated with shifts towards an immunosuppressive mesenchymal environment with poor immune infiltration. Finally, while mutations in EGFR/PTEN, or MGMT-promoter methylation influenced tumor evolution, we also identified a defined subset of patients that were more responsive to lomustine after early recurrence. Our findings offer a framework to stratify patient treatment based on tumor and microenvironmental evolution. Maxime Vanmechelen, Pouya Nazari, Jan Beckervordersandforth, Daphne Leunissen, Basiel Cole, Brecht Decraene, Yanti De Visser, Gautam Shankar, Maikel Verduin, Daniele Pantano, Carmen Bravo Gonzalez-Blas, Chiara Caprioli, Sien Bevers, Tom Moors, Jayesh Telang, Ivey Sebasstian, Julie Messiaen, Yannick Van Herck, Emma Geens, Danielle Eekers, Annelies Claeys, Marleen Derweduwe, Axel Zur Hausen, Francesca Bosisio, Frank Weyns, Thomas Daenekindt, Peter Van Eyken, Mieke Govers, Ferdinand Mennens, Koos Hovinga, Steven De Vleeschouwer, Paul Clement, Martijn Broen, Marc Vooijs, Raf Sciot, Asier Antoranz, Jon Pey, Ernst-Jan Speel, Ann Hoeben, Frederik De Smet. Characterization of therapeutic effects in glioblastoma through integrated spatial single-cell multiome profiling of longitudinal samples: Unveiling clinically relevant subtypes of pathological changes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6362.

Importance:In the literature, there is a lack of data reporting tumor control rates after radiotherapy in actively growing vestibular schwannomas (VS). Data for this rarely studied population are needed. Objective:To estimate tumor control rates in radiologically growing VS treated with first-line radiotherapy. Design, Setting, and Participants:This international, multicenter cohort study used prospectively collected data from patients with growing unilateral VS treated first-line with radiotherapy between January 2000 and December 2023 from 8 tertiary referral skull base units. The data were analyzed in June 2025. Exposures:Radiotherapy as an initial treatment for VS. Main Outcomes and Measures:The primary outcome was treatment failure, ie VS growth postradiotherapy, which was predefined as an increase in maximum intracranial tumor diameter (ICTD) of 3 mm or greater within the first 2 years after radiotherapy or 2 mm or greater thereafter. Secondary outcomes were treatment failure based on different definitions of VS growth: (1) an increase in ICTD of 2 mm or greater, (2) an increase in ICTD of 3 mm or greater, and (3) conversion to surgery. Results:A total of 1883 patients (975 female individuals [51.8%]; median age at diagnosis, 63 years [IQR, 53-71 years]) were included in the study. Using the primary definition of treatment failure (an increase in ICTD of ≥3 mm within the first 2 years postradiotherapy or ≥2 mm thereafter), the Kaplan-Meier estimate yielded a 10-year tumor control rate of 76.1% (95% CI, 72.7%-79.2%). For secondary outcome definitions, 10-year tumor control rates were 60.1% (95% CI, 57.5%-64.3%) for an ICTD increase of 2 mm or greater, 78.3% (95% CI, 75.0%-81.2%) for an increase of 3 mm or greater, and 92.6% (95% CI, 90.4%-94.3%) for conversion to surgery. Neither pretreatment tumor size nor tumor location (intracanalicular vs extracanalicular) were significantly associated with treatment failure. Conclusions and Relevance:The results of this cohort study provide tumor control outcomes for radiologically growing VS treated with radiotherapy using several clinically relevant definitions of growth. By focusing exclusively on this rarely isolated subgroup, the findings offer targeted data to potentially inform treatment expectations and future research.

Background and purpose: Radiotherapy for brain, head & neck (HN), and skull base (SB) tumors may deliver significant radiation dose to the hypothalamic-pituitary axis (HPA), leading to impaired functioning of this region and hence, to endocrine disorders. The purpose of this systematic review and meta-analysis is to investigate literature on HP dysfunction after radiation for non-pituitary brain, HN, or SB tumors at adult age, aiming to give insight in the prevalence of HP dysfunction related to radiation dose. Materials and methods: Literature search of the PubMed database was performed for HP dysfunction after radiotherapy in adult patients. A risk of bias assessment was performed to rate the quality of the included papers. Besides clinical and treatment variables, reported insufficiencies for adrenocorticotrophic hormone, thyroid stimulating hormone, growth hormone, prolactin and follicle stimulating hormone and luteinizing hormone and for insufficiency of any axis were extracted. The prevalence for hormonal insufficiency per axis and for multiple axes was calculated using a random effects meta-regression with a random effect at the study level. Results: The literature selection process resulted in a total of 22 original papers, suitable for full assessment (n = 1,462 patients). Literature showed a wide variation in HP dysfunction, along with wide dose ranges given to the hypothalamus and pituitary, with varying follow-up times. The calculated prevalence for any pituitary insufficiency was on average 0.61 (95 % CI 0.44-0.75). For growth hormone the mean prevalence was 0.40 (95 % CI 0.22-0.61), for prolactin 0.22 (95 % CI 0.17-0.28), for gonadotropin 0.20 (95 % CI 0.14-0.28), for adrenocorticotropic hormone 0.16 (95 % CI 0.08-0.30) and for thyroid stimulating hormone 0.16 (95 % CI 0.11-0.23). The prevalence for any insufficiency of 1 axis was 0.19 (95 % CI 0.11-0.30), of 2 axes 0.22 (95 % CI 0.12-0.38), of 3 axes 0.05 (95 % CI 0.03-0.09) and of panhypopituitarism 0.17 (95 % CI 0.08-0.32). Patients irradiated for nasopharyngeal carcinoma (NPC) seemed to be at highest risk for developing any endocrine insufficiency with a mean prevalence of 0.68 (95 % CI 0.45-0.85). A significant correlation between any endocrine insufficiency and follow-up time was observed (p = 0.015). A correlation between dose to the pituitary and occurrence of insufficiency on the hormonal axes could not be observed. Conclusion: Endocrine insufficiency is reported in over half of the patients irradiated for brain, HN and SB malignancies. The hypothalamus is likely to be more vulnerable to radiation dose compared to the pituitary gland. More research is needed to establish dose thresholds for the hypothalamus and the pituitary to minimize the risk for pituitary insufficiency. Based on this knowledge, radiotherapy and follow-up of these patient groups should be standardized to establish a normal tissue complication probability (NTCP) model for the HPA.

Upregulation of the Kynurenine Pathway (KP) in Glioblastoma (GBM) plays an important role in driving its treatment-resistant immunosuppressive microenvironment. Factors driving this exaggerated pathway remain poorly understood. Our aim was to explore the correlation between key KP markers; IDO1, IDO2, TDO2, its primary effector target aryl hydrocarbon receptor (AhR) and a comprehensive set of clinical- and tumour characteristics. Tissue samples from 108 newly diagnosed GBM patients were analyzed for the expression of TDO2, IDO1, IDO2, and AhR using immunohistochemistry and QuPath software. Exploratory analyses were conducted to evaluate correlations between KP marker expression and clinical, radiological, and molecular data. IDO1 expression was primarily correlated with inflammatory blood markers, while TDO2 was correlated with patient age, gender, smoking habit and medication use. In contrast, AhR and IDO2 demonstrated hardly any correlations with clinical or tumour characteristics. Notably, IDO2 exhibited a strong association with AhR expression and tumour cell density, with no observed correlation between AhR and either IDO1 or TDO2. We validated the inflammatory influences on IDO1 expression and found that TDO2 was mostly correlated with medication and patient characteristics. We could not confirm IDO1 and TDO2 as most prominent drivers of AhR activity in the KP. However, we found a strong correlation between IDO2-AhR which may be responsible for the sustained and enhanced immunosuppression within the tumour microenvironment. This could explain recent failures of IDO1 and TDO2 antagonists and might redirect future studies to intervene in the kynurenine-AhR-IDO2 axis.

Background and purpose In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity. This work aims to harmonize quantities used for clinical consideration of variable RBE for proton therapy. Materials and methods A survey was distributed to proton centres to determine agreement on RBE-related concerns and clinical implementations. A subsequent clinical expert meeting facilitated by the European Particle Therapy Network was held to achieve consensus and to make clinical recommendations how to prescribe and report beyond using dose and constant RBE. Results The survey was answered by 17 out of 23 centres contacted (74%). For proton RBE, most concerns existed regarding toxicity in serial organs, while the assumption of an RBE of 1.1 was considered valid for targets. Most physicists intended to consider a physical quantity beyond dose in clinical decision making. Conclusions A constant RBE of 1.1 was the consensus for prescribing dose. However, current practice of recording and reporting dose in proton therapy must be complemented: the recommended quantity beyond dose was the dose-averaged LET in water from primary and secondary protons, normalized to unit density. This will facilitate analyses of treatment data on effectiveness beyond dose and between centres. No consensus on a single variable RBE model was found. More clinical training on proton RBE is needed.

In the vulnerable population of patients with glioblastoma (GBM), there is a strong need for efficient treatment, while maintaining health-related quality of life (HRQoL). Since 2005, the standard of care involves radiotherapy of 2Gy in 30 fractions, with temozolomide (PMID: 15758009). A prior single arm phase II study (n=40) suggests that extreme hypofractionation (6Gyx6) may offer comparable survival with reduced treatment time and costs (PMID: 25107913). A phase III randomized clinical trial was performed to evaluate non-inferiority of a hypofractionated treatment schedule (6Gy times 6, in 2 weeks) versus standard of care (2Gy times 30), in newly diagnosed GBM patients with Karnofsky performance status ≥70. All patients received concurrent treatment and adjuvant temozolomide for six months. The primary endpoint was Overall Survival (OS); secondary outcomes included progression-free survival (PFS), toxicity and HRQoL. Enrollment was halted early, due to poor accrual (n=129 of planned 474). Patients were randomized in the experimental arm (n=65) or standard arm (n=64). At a median follow-up duration of 24 months, median OS was shorter in the experimental arm (13.0 months, 95% confidence interval [CI] 10.2-15.8) versus the standard arm (median OS not reached yet, p=0.002). Cox regression identified treatment arm (Hazard Ratio [HR] 2.19, p=0.001) and age (HR 1.04, p = 0.008) as independent predictors of poor survival. Median PFS was also reduced in the experimental arm (9 versus 10 months, p=0.048). Clinical toxicity analysis showed a significantly higher rate of reported radionecrosis in the experimental arm (58.5% vs 23.1%, p<0.001). Longitudinal HRQoL data is reported separately. In the treatment of newly diagnosed glioblastoma with temozolomide-based chemoradiation, non-inferiority of hypofractionation using 6Gy times 6, compared to the conventional 2Gy times 30 regimen, could not be demonstrated. The hypofractionation schedule is associated with inferior PFS and OS, along with increased reports of radionecrosis.

Background Living with epilepsy, especially drug-resistant epilepsy (DRE), imposes several challenges for people diagnosed with the condition. These challenges include the physical and mental implications of epilepsy on both caregivers and patients with epilepsy. For the more than 120 000 individuals living with this neurological disorder in the Netherlands, along with their families, daily activities become hazardous, limited and costly, significantly affecting their health-related quality of life (HRQoL). As data on the burden of epilepsy in the Netherlands are lacking, studies attempting to capture the impact of epilepsy on individuals, caregivers and society are needed to enhance understanding and help address the burden of epileptic seizures.Methods and analysis The study is part of the AIM@EPILEPSY project. The project aims to develop a planning suite enabling cost-saving, minimally invasive treatment for epilepsy. By surveying 330 people with epilepsy and an anticipated sample of 150–200 informal caregivers across the Netherlands, using standardised questionnaires focusing on associated societal costs and the impact on HRQoL, this bottom-up, prevalence-based prospective study aims to understand the societal burden of DRE in the Netherlands. The data will be collected at 0, 3, 6 and 12 months of follow-up. The study results will describe the economic impact of epilepsy, focusing on cost-of-illness (€) and HRQoL (utilities) in the Netherlands.Ethics and dissemination The proposed study was approved by the Maastricht University Medical Ethics Review Committee (Approval reference: FHML-REC/2024/067/Amendment/2024_16). The result of the study is planned to be published in a peer-reviewed journal and presented at international and local scientific conferences.

Background: GKRS shows a high success rate in controlling growth of vestibular schwannoma, but a small number of tumors still grow after treatment. However, only a few studies have investigated the predictive factors of this growth. Objective: Here, we aim to explore the growth determinants of vestibular schwannoma after GKRS. Methods: This paper has analyzed literature published between 2000 and 2024 from PubMed, EMBASE, and Cochrane databases. Potential determinants, including age, gender, tumor volume, radiation dose, tumor location, and imaging characteristics, have been reviewed. Conclusions: We have found that initial tumor volume, pretreatment growth rate, and imaging ADC value potentially predict growth after GKRS. These findings provide a reference for further optimizing personalized treatment in vestibular schwannoma care.

Magnetic resonance imaging (MRI) often demonstrates alterations following cranial radiotherapy (RT), which may result in clinical symptoms and diagnostic uncertainty, and thus potentially impact treatment decisions. The potential differences in MRI alterations after proton and photon RT, has raised concerns regarding the relative biological effectiveness of proton therapy. To provide an overview of MRI alterations in the brain post-RT and to explore differences between photon and proton RT, a systematic review adhering to the PRISMA guidelines was conducted, focusing on the assessment methods and definitions across studies. A systematic search of three electronic databases was performed using the concepts 'normo-fractionated radiotherapy ', 'MRI alterations' and 'brain, skull base or head and neck tumours in adult and paediatric populations'. Data extraction and quality assessment was performed on articles meeting the predefined criteria by two independent reviewers. Out of 5887 screened studies, 94 met the inclusion criteria. These studies were categorized based on confinement of the MRI alterations to temporal lobe, brainstem, or across the entire brain. Additional subclassification was performed based on MRI sequences evaluated or by the nature of the alterations, with pseudoprogression generally reserved for glioma patients. While many papers exist on MRI alterations in the brain after RT, this review highlights significant inconsistencies in the terminology and definitions, limiting the comparability of findings across studies. Our results highlight the need for and facilitate the development of a standardized framework for describing MRI alterations after RT.

BACKGROUND:Cranial irradiation is a key component of neuro-oncological treatment but can result in cognitive side effects. Preserving cognition from radiotherapy-(RT)-induced toxicity remains an ongoing debate. To spatially map radiotoxic effects in patients who underwent cranial RT, this study applied a voxel-based approach. METHODS:Cognitive assessments (Controlled Word Association (COWA), Hopkins Verbal Learning (HVLT-R), and Trail Making Tests (TMT A,B)) were conducted prospectively before, 6 months and 1 year post-RT in 111 intracranial tumor patients (18-80 years). Reliable change indices indicated cognitive changes across timepoints. CT and T1-weighted MRI scans acquired at diagnosis were co-registered, normalized to standard space, and smoothed. Voxel-wise permutation-based regression analyses examined the relationship between RT dose and cognitive decline (α < 0.05 at cluster level). RESULTS:Images of 111 patients (Mdn age = 55.39 years; 47% male; lesions were gliomas (61%), meningiomas (18%), other (21%); in frontal (33%), temporal (25%), other location (42%)) were analyzed. Reliable decline was most pronounced at 6 months, particularly on the TMT A (25.77%), TMT B (24.21%), and HVLT immediate recall (21%). At 1 year, 20% of patients continued to show a decline in TMT B. Higher RT doses to frontal gyri, temporal, occipital, and para-central regions were associated with declines in verbal fluency, memory, processing speed, and flexibility at both peak- and cluster-level. CONCLUSION:Differential voxel-wise RT dose effects at peak versus cluster level suggest local and network-based recruitment of diverse functional regions and vulnerability to cranial RT. These insights may help re-define key regions at risk from a network-based perspective, preserving cognition in future RT planning.

AIM:We previously published selection criteria for proton therapy (PT) in the Netherlands for breast cancer (BC) and thoracic lymphoma patients, based upon the Absolute Excess Risk (AER) for acute coronary events. The aim of the current paper was to define additional criteria to select BC and thoracic lymphoma patients for PT, to reduce the risk of second primary BC and lung cancer (LC). METHODS:Based on a literature review, we identified Excess Relative Risks (ERR)/Gy mean organ dose of second primary BC and LC, for selected patient groups. We combined the ERR with the absolute incidence of second primary BC and LC in the Dutch population to approximate the AER/Gy mean organ dose. This was used to define selection criteria for PT. RESULTS:The AER for second primary BC was estimated to be 2.5 %/Gy mean breast dose in female patients ≤40 years. The AER of second primary LC was calculated based on an ERR of 11 %/Gy, separately for female and male smokers ≤50 years, with an ERR of 0 % for non-smokers. Consensus was reached for the following selection criteria for PT: ≥5% absolute risk reduction of second primary BC in the contralateral breast, or a ≥2.0 % absolute risk reduction of second primary LC. Thoracic lymphoma patients were also eligible for PT if the sum of AERs of second primary BC in both breasts exceeded 7.5 %. CONCLUSIONS:Selection criteria were added to the Dutch indication protocol for proton therapy to identify BC and thoracic lymphoma patients who would benefit most from PT, based on an estimated reduced risk of second primary BC and LC.

PURPOSE:To investigate the current practice patterns in image-guided proton therapy (IGPT) for brain tumours. METHODS:A multi-institutional survey was distributed to European particle therapy centres to analyse the current practice of IGPT for neuro-oncology. The survey was subsequently used for driving a DELPHI consensus analysis aiming at defining the minimum requirements and the optimal workflow. RESULTS:Seven centres participated in the survey on proton therapy for brain tumours. All reported access to pencil beam scanning and rotating gantries; one also used passive scattering. Supine positioning with standard immobilisation tools was common, while prone and paediatric-specific methods were rare. Multimodal imaging with CT and MRI was standard; PET use was limited and SPECT absent. Rigid registration between imaging modalities was widely used, though MR imaging in treatment position was uncommon. Verification practices varied. Six centres joined the DELPHI consensus, reaching agreement on minimum requirements for immobilisation, imaging for treatment planning, image registration and pre-treatment setup. Disagreement remained on robustness criteria, imaging frequency, and dose tracking, highlighting the need for unified clinical guidelines and workflow optimisation. CONCLUSION:There is generally agreement across European proton centres, but variability remained in key components of treatment planning, verification and workflow optimisation, including the frequency and modality of control imaging, plan robustness criteria, and treatment position imaging protocols. These differences reflect both local resource availability and the absence of harmonised guidelines. The minimal requirements for image guidance in brain proton therapy achieved good consensus level and will be very useful for new centres.

Purpose Assess cognitive changes after radiotherapy (RT) in brain and head-and-neck (HN) cancer patients using patient-reported outcome measures (PROMs) and evaluate a dose–effect relationship for brain structures. Materials and methods Primary brain and HN cancer patients treated with RT between 2012–2021 were included. Patient characteristics, clinical parameters, and PROMs at baseline and 1-year follow-up were collected. Cognitive functioning (CF) from the EORTC QLQ-C30, communication deficit (CD) from the QLQ-BN20, and one cognition-related questions from the EQ6D questionnaire were used, the latter two only for brain patients. Missing data were imputed and the four-point scale scores were transformed to a 100-point scale. Change in scores from baseline to 1-year were categorized into improvement/constant or deterioration. Organs-at-risk (OARs) were contoured either clinically or retrospectively using autocontouring and dose to the OARs were calculated. Results A total of 110 brain and 356 HN cancer patients were included. Median age was 56 (brain) and 67.5 (HN) years. Baseline and 1-year CF was significantly lower for brain patients (p < 0.001). Univariate analysis for ΔCF showed that age at start RT ≤ 65 years, receiving chemotherapy, higher CF Baseline score, brain mean dose > 3 Gy, and multiple dose levels to left and right hippocampus were statistically associated with cognitive deterioration. Multivariate analysis for ΔCF identified age at RT ≤ 65 years, higher CF Baseline score, and brain mean dose > 3 Gy as significant predictors. Conclusion This study identified risk factors for subjective cognitive decline and suggests that patients’ self-perceived cognitive deterioration may be related to age, CF baseline score and brain radiation dose above 3 Gy.