|Year : 2020 | Volume
| Issue : 3 | Page : 455-460
Cognitive score in patients with primary brain tumors undergoing systemic therapy – a cross-sectional study
Supriya Adak, Gunjesh Kumar Singh, Nandini Menon, Ochin Dale, Sujay Srinivas, Sudeep Das, Somnath Roy, Dilip Harindran Vallathol, Vijay Maruti Patil
Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
|Date of Submission||14-May-2020|
|Date of Decision||25-May-2020|
|Date of Acceptance||21-Jul-2020|
|Date of Web Publication||19-Sep-2020|
Vijay Maruti Patil
Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: The systemic treatment of brain tumors is complex. Apart from the disease burden and adverse effects of systemic therapy, cognitive decline of patients undergoing treatment is an added liability. However, there is limited literature on the cognitive assessment of the patients receiving systemic therapy.
Objectives: We performed this cross-sectional analysis to assess the perceived cognition status and quality of life (QOL) of patients with brain tumors receiving systemic therapy and the factors affecting them.
Materials and Methods: Adult patients receiving systemic therapy in the outpatient department of the neuro-medical oncology unit at the Tata Memorial Hospital (Mumbai, India) were enrolled in this study. The patients were administered the functional assessment of cancer therapy cognitive function issues (FACT-Cog) QOL questionnaire. A multiple linear regression analysis was performed to determine the best combination of age, gender, education, and the affected lobe for predicting the different cognitive QOL scores.
Results: The study cohort comprised a total of 100 patients with a median age of 39 (range, 18–64) years. Of these, 68 were men and 32 were women. The mean scores with standard deviations (SDs) calculated for the perceived cognitive impairment, the impact of perceived cognitive impairment on QOL, the comments from others, and the perceived cognitive abilities, were 61.96 (SD; 15.43), 11.8 (SD; 5.16), 13.82 (SD; 3.92), and 21.79 (SD; 5.16), respectively. There was no significant association between the various FACT-Cog subscales and the selected factors, namely older age (>60 years), gender, education, and the affected lobe (frontal, temporal, parietal, and others).
Conclusions: This is the first Indian study to report the perceived cognitive scores and QOL assessment for patients with brain tumors that can be useful for generating hypotheses and calculating the sample size for future studies. As none of the evaluated factors could reliably impact the cognitive score, an assessment of the cognitive QOL should be done for each patient.
Keywords: Brain tumor, chemotherapy, cognitive decline, quality of life
|How to cite this article:|
Adak S, Singh GK, Menon N, Dale O, Srinivas S, Das S, Roy S, Vallathol DH, Patil VM. Cognitive score in patients with primary brain tumors undergoing systemic therapy – a cross-sectional study. Cancer Res Stat Treat 2020;3:455-60
|How to cite this URL:|
Adak S, Singh GK, Menon N, Dale O, Srinivas S, Das S, Roy S, Vallathol DH, Patil VM. Cognitive score in patients with primary brain tumors undergoing systemic therapy – a cross-sectional study. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 30];3:455-60. Available from: https://www.crstonline.com/text.asp?2020/3/3/455/295538
The Authors Dr. Supriya Adak & Dr. Gunjesh Kumar Singh contributed equally to this work
| Introduction|| |
Chemotherapy is an integral part of the clinical management of malignant brain tumors and is known to increase overall survival. However, the effect of chemotherapy on the cognitive functions of these patients is unknown. In addition to the clinical adverse effects, evidence in the literature suggests an association between chemotherapeutic agents and cognitive impairment. Studies have shown that in patients with breast cancer, cognitive function was better in those who did not receive chemotherapy than in those who received it. For instance, Cheung et al., in their study, divided breast cancer patients into two groups based on whether or not they received chemotherapy. The investigators used the functional assessment of cancer therapy cognitive function issues (FACT-Cog) quality of life (QOL) questionnaire in both the groups. They reported better cognition in those who did not receive chemotherapy as compared to the patients in the chemotherapy group. Late cognition impairment has also been observed in patients with gliomas who had received chemotherapy with procarbazine, lomustine, and vincristine after radiation therapy. This association of chemotherapy with cognition is called chemotherapy-induced cognitive impairment (CICI), commonly known as chemo-brain or chemo-fog. CICI is known to contribute to a decrease in learning abilities, memory, attention, information processing abilities, and execution in long-surviving patients with cancer.
However, the magnitude of cognitive deterioration depends on both, the tumor characteristics such as size, location, growth rate, and histopathology as well as on patient characteristics, such as age, cognitive reserve, and the presence of comorbidities. As patients with brain tumors receive multimodality treatment, including surgery and radiation therapy, it adds to their burden of cognitive decline.,, Therefore in patients with primary brain tumors, distinguishing cognitive deficits due to chemotherapy is difficult.
All these factors contribute to the deterioration of the patients' QOL. This cross-sectional study was aimed at understanding the effects of chemotherapy on the cognitive functioning of patients with primary brain tumors. We evaluated the perceived cognition status and QOL of patients with primary brain tumors.
| Materials and Methods|| |
General study details
This was a single-center, cross-sectional study conducted in the Department of Medical Oncology at the Tata Memorial Hospital, a tertiary care oncology-only teaching hospital in Mumbai, India. The study did not require ethical clearance from the institutional ethics committee due to its non-interventional nature. All consecutive patients with brain tumors who fulfilled the eligibility criteria of the study as detailed below were enrolled in the study after obtaining verbal informed consent. The study was conducted according to the various ethical guidelines including the Declaration of Helsinki, the International Committee on Harmonization Good Clinical Practice guidelines and the Indian Council of Medical Research.
Patients with primary brain tumors with or without recurrence, who visited the Neuro Medical Oncology unit from October 2019 to January 2020, were invited to participate in this study. Patients with an Eastern Cooperative Oncology Group performance score (ECOG PS) of 0–2 were considered for enrollment in the study; the ECOG PS measures the functional ability of a person on a scale from 0 to 5, where a score of 0 means a fully active person capable of carrying out all the pre-disease activities without any restriction and 5 means death. Only those patients undergoing systemic therapy were included in the study.
The primary endpoint of the study was to estimate the mean cognitive score of patients with brain tumors receiving systemic therapy. The secondary endpoint was to assess the factors affecting the cognitive score.
The perceived cognition status and QOL were assessed in real-time during a private interview session where the participants completed the self-reported FACT-Cog QOL questionnaire. Patients who were unable to fill out the questionnaire received help from a doctor, a nurse, or a social worker.
None of the patients were followed up or called after the single interview session.
Tool for cognitive assessment and its validation
CICI and health-related QOL of the participants were captured using the FACT-Cog version 3. This tool is designed to address any cognitive disharmony in terms of memory, concentration, attentiveness, and speech. Wagner etal. developed and validated the FACT-Cog questionnaire in English., The details of the questionnaire and the guidance on its administration are available online at FACIT.org. The questionnaire has a set of 37 questions grouped into four subscales-the patients' perceived cognitive impairment (20 questions), perceived cognitive abilities (4 questions), notice ability or comments from others (9 questions), and the impact of cognitive changes on QOL (4 questions). The first 20 questions focus on the perceived cognitive impairment experienced by the patients, such as trouble in forming thoughts, slow thinking, inability to concentrate, and difficulties in verbal expression. The next set of questions is focused on comments that patients have received from others regarding their ability to retain information, speech, and mental acuity. The third set of questions targets the perceived cognitive abilities of patients, which include the ability to shift between activities that require thinking and keeping track of work. The last four questions emphasize the aftermath of cognitive decline encountered by the patients on their QOL. Each item is rated on a 5-point Likert scale, ranging from 0 (”Never” or “Not at all”) to 4 (”Several times a day” or “Very much”). The FACT-Cog score can range from 0 to 148 points, with a higher score indicative of better perceived cognitive functioning.
A sample size calculation was not performed for this study. The information regarding the baseline characteristics, diagnosis, tumor site, and chemotherapy details were extracted from the electronic medical records of the patients, and the answers to the questionnaire were entered in an Excel sheet and cross-evaluated by two random individuals. Statistical Package for the Social Sciences (SPSS) version 20 (IBM Corp., Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY, USA: IBM Corp.) was used for the analysis. A descriptive analysis was performed, and scores were reported as means with standard deviations (SD). A multiple linear regression analysis was performed to assess the association between factors such as age, gender, education, and the lobe affected with the different cognitive QOL scores. The F-test for linear regression was used to assess whether any of the independent variables in the multiple linear regression model were significant. Value of P < 0.05 was considered significant.
| Results|| |
A total of 100 patients were enrolled in the study ([Figure 1]), of which 68 were men and 32 were women. The median age of the cohort was 39 (range, 18–64) years. About 42% of the patients were university graduates, whereas 35% had acquired secondary school education. The most common histology was Grade III glioma (54%), followed by high-risk Grade II glioma (18%) and Grade IV glioma (17%). About 12% of the patients were receiving treatment for recurrent disease. The most common site for the occurrence of the tumor was the frontal lobe (47%) followed by the parietal (27%) and temporal lobes (23%), and the most commonly used chemotherapeutic agent in the concurrent, adjuvant, and salvage settings was temozolomide. The baseline characteristics of the patients are mentioned in [Table 1].
Functional assessment of cancer therapy cognitive function issues scores
The mean scores calculated for the perceived cognitive impairment (CogPCI), the impact of perceived cognitive impairment on QOL (CogQOL), the comments from others (CogOth), and the perceived cognitive abilities (CogPCA), were 61.96 (SD, 15.43), 11.8 (SD, 5.16), 13.82 (SD, 3.92), and 21.79 (SD, 5.16), respectively.
Factors affecting the cognitive scores
The multiple regression analysis performed to identify the factors contributing to cognitive impairment showed an absence of inter-variable correlation. The combination of variables was not significantly associated with CogPCI, F (7, 92) = 0.728, (P = 0.649); CogQOL, F (7, 92) = 0.324, (P = 0941); CogOth, F (7, 92) = 0.921, (P = 0.494); and CogPCA, F (7, 92) = 0.774, (P = 0.611). No significant association was observed between the various subscales of FACT-Cog and the factors such as older age (>60 years), gender, education, and the affected lobe (frontal, temporal, parietal, and others) [Table 2], [Table 3], [Table 4], [Table 5].
|Table 3: Factors affecting the impact of cognitive impairment on quality of life|
Click here to view
| Discussion|| |
We evaluated the cognition status of patients with brain tumors receiving systemic therapy and found that the mean scores for CogPCI, CogQOL, CogOth, and CogPCA were 61.96, 11.8, 13.82, and 21.79, respectively. We also assessed the effect of factors such as age, gender, education, and the affected brain lobe on these cognitive scores and observed no statistically significant association between them.
In patients with brain tumors, the disease per se along with its treatment can lead to cognitive impairment. The incidence of cognitive impairment varies from 29% in low-grade glioma (non-irradiated) to approximately 90% in different brain tumors. In our study, we used the FACT-Cog version 3 to evaluate the cognition status of patients with brain tumors receiving systemic therapy. The FACT-Cog version 3, a self-reported questionnaire, has already been validated by Wagner et al. As the data are continuous, there is no cut-off for severity; however, a higher score is suggestive of a better QOL., Zeng et al., in their study, have also used the FACT-Cog questionnaire in gynecological cancer survivors. They compared the cognition status of the patients with that of healthy individuals and found significant cognitive impairment in the former. Moreover, the difference between the cognition scores was significant for patients receiving chemotherapy and those who underwent surgery. The mean CogPCI, CogQOL, CogOth, and CogPCA scores in patients who received chemotherapy were 56.04, 11.28, 14.29, and 15.66, respectively. Employment status, depression, and chemotherapy were significantly associated with cognitive impairment. Similarly, Vardy etal. evaluated the cognitive decline in patients with breast cancer. The mean CogPCI, CogQOL, CogOth, and CogPCA scores in patients without any cognitive symptoms and who received chemotherapy, were 57.25, 14.6, 13.9, and 21.6, respectively. These findings led them to conclude that patients receiving chemotherapy who had cognitive symptoms had poorer QOL. In our study, the mean scores obtained were higher than those in Zeng etal.'s and Vardy etal.'s studies., However, these scores are continuous data, and therefore, it is not possible to grade them according to their severity. Nevertheless, a comparatively higher score indicates better cognitive functioning and QOL in our patients.
The current literature suggests that the involvement of the temporal lobe and resection of the primary tumor lead to cognitive decline.,, Bruno etal. in their study on patients with breast cancer used functional magnetic resonance imaging to evaluate their cognition status and resting-state networks in the brain and found defects in the temporal, frontal, and striatal regions when compared to the healthy cohort. However, in our study, we did not find any significant association between the affected lobes of the brain and cognitive impairment.
This area of research has remained largely unexplored in the Indian setting. Sequeira and Krishnamurthy observed that cognition was significantly poorer in patients with breast cancer than in the normal population. Rajanandh etal. used the mini-mental state examination (MMSE) to assess the cognitive function of patients receiving chemotherapy and reported a normal MMSE score for 45.7% of the total study population. Paying attention to outcomes like cognition, in addition to the diagnosis and treatment of the disease, can lead to pleasant and positive changes in the QOL of patients with cancer, both on the personal and professional fronts, especially for the younger patients.
Our study is the first of its kind to present an analysis of the cognitive status of patients with brain tumors receiving systemic therapy and offers novel insights into CICI. As none of the factors impacted the cognitive score in the patients, we suggest building a separate task force dedicated to conducting regular interviews for the evaluation of the patients' cognitive QOL. In addition, we also propose increasing the awareness about cognitive impairment among the healthcare workers and the patients and their caregivers.
The study is not without its limitations; firstly, due to the lack of longitudinal data, we assessed the cognitive score and QOL at a single time point. Therefore, the post-treatment change in cognitive decline and QOL could not be commented upon. Second, due to the unavailability of the volumetric data and dose-volume histograms of the previous treatment in a substantial number of patients, we were not able to comment on the impact of re-irradiation dose and radiation dose to the hippocampus. Third, we did not assess the impact of various chemotherapeutic agents on cognition impairment.
| Conclusion|| |
To the best of our knowledge, ours is the first Indian study to provide an assessment of the perceived cognitive scores and QOL in patients with brain tumors, which will be useful in generating hypotheses and calculating the sample size for future studies. None of the evaluated factors reliably impacted the cognitive score, and hence, cognitive QOL should be assessed for each patient.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]