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Changes in neurocognitive functioning (NCF) scores calculated from a baseline-3 months and b 3–6 months at domain level and c patient level. VeM verbal memory; ViM visual memory; AT attention; EF executive functioning; WM working memory; IPS information processing speed; VC visuoconstruction
Source publication
Background:
Recently, it has been shown that at group level, patients with limited brain metastases treated with stereotactic radiotherapy (SRT) maintain their pre-treatment levels of neurocognitive functioning (NCF) and health-related quality of life (HRQoL). The aim of this study was to evaluate NCF and HRQoL changes over time at the individual...
Citations
... Previous research indicated stable cognitive performance up to 9 months after SRS at group-level, while almost 40% showed declined performance on the individual level. 19,20 Despite significant progress, many studies had limited follow-up durations and small sample sizes. Hence, it is crucial to confirm and continue to build upon previous findings. ...
... Nevertheless, both compliance rates and available patients for follow-up, especially in the long-term, were comparable to or higher than previous studies. 13,14,20,[47][48][49] Most importantly, these results can be used to design future studies to best capture the complexity of individual cognitive changes in patients with BMs. For example, as memory seems particularly vulnerable, multiple tests each capturing different aspects of this multifaceted cognitive function should be incorporated. ...
Background
The increasing incidence of brain metastases (BMs) and improved survival rates underscore the necessity to investigate the effects of treatments on individuals. The aim of this study was to evaluate the individual trajectories of subjective and objective cognitive performance after radiotherapy in patients with BMs.
Methods
The study population consisted of adult patients with BMs referred for radiotherapy. A semi-structured interview and comprehensive neurocognitive assessment (NCA) were used to assess both subjective and objective cognitive performance before, 3 months and ≥ 11 months after radiotherapy. Reliable change indices were used to identify individual, clinically meaningful changes.
Results
Thirty-six patients completed the 3-month follow-up, and 14 patients completed the ≥ 11-months follow-up. Depending on the domain, subjective cognitive decline was reported by 11–22% of patients. In total, 50% of patients reported subjective decline in at least one cognitive domain. Intracranial progression 3 months postradiotherapy was a risk-factor for self-reported deterioration (P = .031). Objective changes were observed across all domains, with a particular vulnerability for decline in memory at 3 months postradiotherapy. The majority of patients (81%) experienced both a deterioration as well as improvement (eg, mixed response) in objective cognitive functioning. Results were similar for the long-term follow-up (3 to ≥11 months). No risk factors for objective cognitive change 3 months postradiotherapy were identified.
Conclusions
Our study revealed that the majority of patients with BMs will show a mixed cognitive response following radiotherapy, reflecting the complex impact. This underscores the importance of patient-tailored NCAs 3 months postradiotherapy to guide optimal rehabilitation strategies.
... Similar to previous studies, memory deficits were prominent in our sample 11,12,22,23 with severe memory impairment in one out of every three patients. Moreover, in the cluster analysis the presence of memory deficits was a major determining factor. ...
Objective
Patients with brain metastases (BrMs) are a heterogeneous population, with almost 50% experiencing cognitive impairment before brain radiotherapy. Defining pre‐radiotherapy cognitive profiles will aid in understanding of the cognitive vulnerabilities and offer valuable insight and guidance for tailoring interventions.
Methods
The study population consisted of 58 adult patients with BrMs referred for radiotherapy. A semi‐structured interview and comprehensive battery including 10 neuropsychological tests were used to assess subjective and objective cognitive performance prior to radiotherapy.
Results
A majority (69%) of patients report decline in cognitive performance compared to their premorbid level (i.e. pre‐cancer). Objective testing revealed memory (52%), processing speed (33%) and emotion recognition (29%) deficits were most frequent. 21% of patients had no cognitive deficits while 55% had deficits (−1.5SD) in at least two cognitive domains. Hierarchical cluster analysis based on patient deficit profiles identified four clusters: (I) no or limited cognitive deficits selectively restricted to processing speed or executive function, (II) psychomotor speed deficits, (III) memory deficits and (IV) extensive cognitive deficits including memory. No patient or clinical‐related (e.g. age, number of BrMs, previous treatment) differences were found between clusters.
Conclusions
Patterns of cognitive performance in patients with BrMs are heterogeneous, with most experiencing at least some degree of neurocognitive dysfunction. We identified four meaningful cognitive clusters. Stability of these clusters over time and in different samples should be assessed to advance understanding of the cognitive vulnerability of this patient population.
... Already before treatment, patients with BM experience more fatigue as compared to the general population (Habets et al. 2016;Noh and Walbert 2018;van der Meer et al. 2018;Verhaak et al. 2019b). In our previous study on fatigue after Gamma Knife radiosurgery (GKRS) (Verhaak et al. 2019b), patients' general and physical fatigue increased over 6 months, while mental fatigue decreased during this period. ...
... We concluded that different aspects of fatigue showed different patterns over time in patients with BM after GKRS (Verhaak et al. 2019b). Habets et al. (2016) and van der Meer et al. (2018) also reported a significant increase of fatigue in patients with BM over 6 months after stereotactic radiosurgery (SRS). These previous studies (Habets et al. 2016;van der Meer et al. 2018;Verhaak et al. 2019b) on (multidimensional) fatigue in patients with BM after SRS evaluated patients up to 6 months after SRS. ...
... Habets et al. (2016) and van der Meer et al. (2018) also reported a significant increase of fatigue in patients with BM over 6 months after stereotactic radiosurgery (SRS). These previous studies (Habets et al. 2016;van der Meer et al. 2018;Verhaak et al. 2019b) on (multidimensional) fatigue in patients with BM after SRS evaluated patients up to 6 months after SRS. Since life expectancy of patients with BM is increasing (Johnson et al. 2015;Nayak et al. 2012), insight in fatigue beyond 6 months after treatment is becoming more important. ...
Purpose
The aims of this study were to evaluate long-term multidimensional fatigue in patients with brain metastases (BM) up to 21 months after Gamma Knife radiosurgery (GKRS) and (change in) fatigue as predictor of survival.
Methods
Patients with 1 to 10 BM, expected survival > 3 months, and Karnofsky Performance Status ≥ 70, and Dutch non-cancer controls were included. Fatigue was measured with the Multidimensional Fatigue Inventory. Levels of fatigue between patients and controls were compared using independent-samples t-tests. Linear mixed models were used to evaluate fatigue within the patient group up to 21 months after GKRS. Pre-GKRS fatigue and minimal clinically important (MCI) changes in fatigue in the first three months (defined as a 2-point difference) after GKRS were evaluated as predictors of survival time.
Results
Prior to GKRS, patients with BM (n = 92) experienced significantly higher fatigue on all subscales than controls (n = 104). Over 21 months, physical fatigue increased, and mental fatigue decreased significantly. More specifically, general, and physical fatigue increased significantly between pre-GKRS and 3 months, followed by stable scores between 3 (n = 67) and 6 (n = 53), 6 and 12 (n = 34) and 12 and 21 (n = 21) months. An MCI increase in general or physical fatigue over the first 3 months after GKRS was a significant predictor of shorter survival time.
Conclusion
Except for mental fatigue, all aspects of fatigue remained elevated or further increased up to 21 months after treatment. Furthermore, an increase in general or physical fatigue within three months after GKRS may be a prognostic indicator for poorer survival.
ClinicalTrials.gov identifier
NCT02953756, November 3, 2016.
... Especially subjective toxicities are at high risk to be underreported by clinicians, even when prospectively collected within treatment study protocols [16]. Although evaluation of patients functioning status may be stable during and after CRT, patients' individual and subjective evaluation of HRQoL may differ considerable during the same period [17]. Several studies have demonstrated that PROMs are the most sensitive method for capturing treatment related toxicity as clinicians' assessment often report fewer symptoms with lower severity than patients. ...
Background
The ProtonCare Study Group (PCSG) was formed with the purpose to develop and implement a framework for evaluation of proton beam therapy (PBT) and the related care at a novel clinic (Skandionkliniken), based on patient reported data.
Method
A logic model framework was used to describe the process of development and implementation of a structured plan for evaluation of PBT for all diagnoses based on patient reported data. After the mission for the project was determined, meetings with networks and stakeholders were facilitated by PCSG to identify assumptions, resources, challenges, activities, outputs, outcomes, and outcome indicators.
Result
This paper presents the challenges and accomplishments PCSG made so far. We describe required resources, activities, and accomplished results. The long-term outcomes that were outlined as a result of the process are two; 1) Improved knowledge about health outcomes of patients that are considered for PBT and 2) The findings will serve as a base for clinical decisions when patients are referred for PBT.
Conclusion
Using the logical model framework proved useful in planning and managing the ProtonCare project. As a result, the work of PCSG has so far resulted in long-lasting outcomes that creates a base for future evaluation of patients’ perspective in radiotherapy treatment in general and in PBT especially. Our experiences can be useful for other research groups facing similar challenges. Continuing research on patients´ perspective is a central part in ongoing and future research. Collaboration, cooperation, and coordination between research groups/networks from different disciplines are a significant part of the work aiming to determine the more precise role of PBT in future treatment options.
... Studies evaluating changes in NCF at the individual patient level concluded that, in LINAC patients with 1-4 BM, NCF was maintained compared to their pre-treatment level up to 6 months after SRS [17]. Up to 9 months, NCF was maintained or improved compared to pre-treatment levels among GK patients with 1-10 BM [17,18]. ...
... Studies evaluating changes in NCF at the individual patient level concluded that, in LINAC patients with 1-4 BM, NCF was maintained compared to their pre-treatment level up to 6 months after SRS [17]. Up to 9 months, NCF was maintained or improved compared to pre-treatment levels among GK patients with 1-10 BM [17,18]. Earlier studies used limited neuropsychological tests [19] and a relatively insensitive method to measure neurocognitive change, without taking practice effects into account [17]. ...
... Up to 9 months, NCF was maintained or improved compared to pre-treatment levels among GK patients with 1-10 BM [17,18]. Earlier studies used limited neuropsychological tests [19] and a relatively insensitive method to measure neurocognitive change, without taking practice effects into account [17]. ...
Purpose
Brain metastases (BM) themselves and treatment with stereotactic radiosurgery (SRS) can influence neurocognitive functioning. This prospective study aimed to assess neurocognitive decline in patients with BM after SRS.
Methods
A neuropsychological test battery was assessed yielding ten test outcomes. Neurocognitive decline at 3 and 6 months post SRS was compared to measurement prior to Gamma Knife (GK) or linear accelerator (LINAC) SRS. Reliable change indices with correction for practice effects were calculated to determine the percentage of neurocognitive decline (defined as decline on ≥ 2 test outcomes). Risk factors of neurocognitive decline were analyzed with binary logistic regression.
Results
Of 194 patients pre-SRS, 40 GK and 29 LINAC patients had data accessible at 6 months. Compared to baseline, 38% of GK patients declined at 3 months, and 23% declined at 6 months. GK patients declined on attention, executive functioning, verbal memory, and fine motor skill. Of LINAC patients, 10% declined at 3 months, and 24% at 6 months. LINAC patients declined on executive functioning, verbal memory, and fine motor skills. Risk factors of neurocognitive decline at 3 months were high age, low education level and type of SRS (GK or LINAC). At 6 months, high age was a risk factor. Karnofsky Performance Scale, BM volume, number of BM, tumor progression and neurocognitive impairment pre-SRS were no risk factors.
Conclusion
Neurocognitive decline occurs in a considerable proportion of patients with BM treated with GK or LINAC SRS. Overall, high age appears to be a risk factor for neurocognitive decline after SRS.
... Verhaak et al. conducted a systematic review of HRQOL outcomes for BM patients who received SRS [107]. Although some studies reported stable HRQOL scores at the group level, individual changes have been challenging to deduce given that test scores can remain constant in the event of improvement in some symptoms and declines in others [108]. Furthermore, different questionnaires were utilized across studies (e.g., EQ-5D, FACT-Br), leading to incongruent results; studies that used EQ-5D reported a decline in physical HRQOL [109][110][111], whereas studies using FACT-Br reported stable scores over time [112][113][114]. ...
Brain metastases (BMs) account for a disproportionately high percentage of cancer morbidity and mortality. Historically, studies have focused on improving survival outcomes, and recent radiation oncology clinical trials have incorporated HRQOL and cognitive assessments. We are now equipped with a battery of assessments in the radiation oncology clinic, but there is a lack of consensus regarding how to incorporate them in modern clinical practice. Herein, we present validated assessments for BM patients, current recommendations for future clinical studies, and treatment advances that have improved HRQOL and cognitive outcomes for BM patients.
... In the majority of studies (n = 10) at group level, the was no significant post-SRS change in global FACT-Br [21,23,24,[27][28][29], EQ-5D [30,31], and EORTC [19,32,33] scores. Some authors did not report changes of global HRQoL scale scores at group level or in subgroup of patients who were treated with the SRS [20,22,26,34,35]. However, both stability, improvement, and deterioration of HRQoL global and subscale scores at patient level was common [19,23,25,27,30,31,[33][34][35]. ...
... Some authors did not report changes of global HRQoL scale scores at group level or in subgroup of patients who were treated with the SRS [20,22,26,34,35]. However, both stability, improvement, and deterioration of HRQoL global and subscale scores at patient level was common [19,23,25,27,30,31,[33][34][35]. ...
... A study from Germany and Austria that included 38 patients treated with SRS for 1-3 BMs reported no significant change of the global EORTC score before vs. after SRS with significant deterioration in physical function, fatigue, nausea, appetite loss, drowsiness, hair loss, itchy skin and future uncertainty [33]. Berger [34]. A study of 50 patients with 1-4 BMs and one large resection cavity (4.2 to 33.5 cm 3 ) treated with SRS reported significant improvement of insomnia and worsening of future uncertainty during a median of 11.8 month follow-up [25]. ...
Purpose
Health related quality of life (HRQoL) is often used as an outcome measure of cancer treatment. Stereotactic radiosurgery (SRS) is a mainstay treatment of brain metastases (BMs) with constantly improving treatment envelope. The goal of this systematic review was to evaluated HRQoL trajectories after SRS, identify important predictors of HRQoL after SRS, and to evaluate clinical importance of post-SRS HRQoL trajectories of BM patients treated with SRS.
Methods
A systematic literature review according to the PRISMA guidelines analyzing HRQoL trajectories after SRS for BM published in the Pubmed/MEDLINE database before January, 2022.
Results
We identified 18 studies that evaluated HRQoL before and at least once after SRS for BMs. The majority of studies were single-institution retrospective series and included patients with different cancer types. Different instruments were used to assess HRQoL. In the majority of studies (n = 10) at group level, there was no significant change in global HRQoL after SRS. Stability, improvement, and deterioration of HRQoL global and subscale scores at individual patient level were common. Post-SRS HRQoL deterioration was predicted by worse functional status, greater number of BMs, delayed SRS, symptomatic BMs, and presence of seizures and cognitive impairment. Shorter post-SRS survival and adverse radiation effects (AREs) were associated with worse HRQoL.
Conclusions
SRS for BMs is often associated with sustained preservation of HRQoL. Individual variation of HRQoL domains after SRS is common. Shorter survival and AREs are associated with worse HRQoL. Worse functional status and greater disease burden predict unfavorable HRQoL trajectories after SRS for BMs.
... Data on the incidence of baseline cognitive impairment before SRS were explicitly reported for the pilot study by Chang et al. [29,31] (N = 15) and by Habets et al. [30,43] (N = 77) [29,30]. Pre-radiotherapy, 53-67% of patients had cognitive impairment (Z-score ≤1.5 SD) on ≥1 neuropsychological test. ...
... Patients with a baseline BMs volume of >3 cm 3 performed worse on attention than those with smaller lesion volumes [29]. Similarly, Onodera et al. [25] reported higher total lesion volume but not the number of BMs at baseline corresponded with worse cognitive performance, while Habets et al. [30,43] reported no significant association with BMs volume [25,30]. ...
... van Results regarding cognitive performance after SRS at short-term follow-up (1-4 months) were variable; approximately half of the included studies observed cognitive deterioration, most frequently for verbal L&M, fine motor coordination, and EF [29,31,32,42]. The other studies found no changes in cognition compared to baseline [25,30,43]. At both midterm (5-8 months) and longterm follow-up (9-12 months), all studies reported either stable or (slightly) improved cognitive performance compared to baseline [25, 29-32, 42, 43]. ...
Background & Objectives: Radiotherapy is standard treatment for patients with brain metastases (BMs), although it may lead to radiation-induced cognitive impairment. This review explores the impact of whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) on cognition.
Methods:
The PRISMA guidelines were used to identify articles on PubMed and EmBase reporting on objective assessment of cognition before, and at least once after radiotherapy, in adult patients with nonresected BMs.
Results:
Of the 867 records screened, twenty articles (14 unique studies) were included. WBRT lead to decline in cognitive performance, which stabilized or returned to baseline in patients with survival of at least 9-15 months. For SRS, a decline in cognitive performance was sometimes observed shortly after treatment, but the majority of patients returned to or remained at baseline until a year after treatment.
Conclusions:
These findings suggest that after WBRT, patients can experience deterioration over a longer period of time. The cognitive side effects of SRS are transient. Therefore, this review advices to choose SRS as this will result in lowest risks for cognitive adverse side effects, irrespective of predicted survival. In an already cognitively vulnerable patient population with limited survival, this information can be used in communicating risks and aid in making educated decisions.
... BM are an important cause of morbidity and mortality (Ahluwalia et al. 2014;Tabouret et al. 2012) and the prevalence is rising, mainly due to increased surveillance and improvements in systemic therapies that allow longer survival, which in turn allows for BM to develop (Nayak et al. 2012;Tsao 2015). Preserving health-related quality of life (HRQoL) is a highly important treatment goal in this patient group (Tsao 2015;van der Meer et al. 2018;Wong et al. 2008). ...
... Number of BM (up to 4) was not predictive of HRQoL over time in previous studies (Bragstad et al. 2017;Habets et al. 2016;Skeie et al. 2017). HRQoL was associated with (change in) Karnofsky Performance Status (KPS): higher KPS was predictive of higher or stable HRQoL (Bragstad et al. 2017;Habets et al. 2016;Skeie et al. 2017;van der Meer et al. 2018), and in two studies, larger baseline volume of BM was associated with worse HRQoL over time (Bragstad et al. 2017;Habets et al. 2016), while in two other studies no such association was found (Skeie et al. 2017;van der Meer et al. 2018). ...
... Number of BM (up to 4) was not predictive of HRQoL over time in previous studies (Bragstad et al. 2017;Habets et al. 2016;Skeie et al. 2017). HRQoL was associated with (change in) Karnofsky Performance Status (KPS): higher KPS was predictive of higher or stable HRQoL (Bragstad et al. 2017;Habets et al. 2016;Skeie et al. 2017;van der Meer et al. 2018), and in two studies, larger baseline volume of BM was associated with worse HRQoL over time (Bragstad et al. 2017;Habets et al. 2016), while in two other studies no such association was found (Skeie et al. 2017;van der Meer et al. 2018). ...
Purpose:
Increasingly more patients with multiple (> 4) brain metastases (BM) are being treated with stereotactic radiosurgery (SRS). Preserving patients' health-related quality of life (HRQoL) is an important treatment goal. The aim of this study was to assess (individual) changes in HRQoL in patients with 1-10 BM over time.
Methods:
A total of 92 patients were assessed before (n = 92) and at 3 (n = 66), 6 (n = 53), and 9 (n = 41) months after Gamma Knife radiosurgery (GKRS), using the Functional Assessment of Cancer Therapy-Brain (FACT-Br). The course of HRQoL was analyzed using linear mixed models. Clinical minimally important differences were used to evaluate individual changes.
Results:
At group level, patients' physical well-being worsened, whereas emotional well-being improved over 9 months. Scores on other HRQoL subscales did not change significantly. Number (1-3 versus 4-10) and volume (small, medium, and large) of BM did not influence HRQoL over time, except for the subscale additional concerns; medium intracranial tumor volume was associated with less additional concerns. On the individual level as well, physical well-being declined while emotional well-being improved in most patients over 9 months after GKRS. At patient level, however, most patients had both declines as well as improvements in the different HRQoL aspects.
Conclusion:
Our results indicate that even in patients with up to 10 BM, both at group and individual subscale level, aspects of HRQoL remained stable over nine months after GKRS, except for an improvement in emotional well-being and a decline in physical well-being. Nevertheless, HRQoL scores varied considerably at the individual patient level.
Trail registration number:
ClinicalTrials.gov Identifier: NCT02953756, November 3, 2016.
... A review on the cognitive effects after stereotactic radiosurgery (SRS) concluded that patients with brain metastases experience little to no objective cognitive decline in the early phase after SRS, followed by a trend towards improvement or stabilisation up to 12 months after SRS [5]. Furthermore, evaluation of individual cognitive changes after SRS showed that in most patients with brain metastases, cognitive functions remained stable for at least 6 or 12 months after SRS [6,7]. ...
... In accordance with the results at group level, and with van der Meer et al. [6], for most patients, both at the patient level and at the test level, cognitive functioning remained stable or improved over 9 months after GKRS, except for non-dominant hand dexterity. Performance on nondominant hand dexterity, a measure that was not included in the study of van der Meer et al. [6], varied considerably at the individual level: there were significantly more improvements as well as more declines in patients as compared with controls. ...
... In accordance with the results at group level, and with van der Meer et al. [6], for most patients, both at the patient level and at the test level, cognitive functioning remained stable or improved over 9 months after GKRS, except for non-dominant hand dexterity. Performance on nondominant hand dexterity, a measure that was not included in the study of van der Meer et al. [6], varied considerably at the individual level: there were significantly more improvements as well as more declines in patients as compared with controls. The individual variations in motor dexterity were not reflected in our group-level results. ...
Aims
Stereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS).
Materials and methods
Ninety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated.
Results
At the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients).
Conclusions
Cognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance.
