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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 4  |  Page : 854-855

Systemic chemotherapy and cognitive dysfunction in primary brain tumors – To incriminate or exculpate?

1 Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
2 Department of Medical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

Date of Submission28-Sep-2020
Date of Decision14-Oct-2020
Date of Acceptance14-Oct-2020
Date of Web Publication25-Dec-2020

Correspondence Address:
T M Anoop
Department of Medical Oncology, Regional Cancer Centre, Thiruvananthapuram - 695 011, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_301_20

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How to cite this article:
Divya K P, Cherian A, Anoop T M. Systemic chemotherapy and cognitive dysfunction in primary brain tumors – To incriminate or exculpate?. Cancer Res Stat Treat 2020;3:854-5

How to cite this URL:
Divya K P, Cherian A, Anoop T M. Systemic chemotherapy and cognitive dysfunction in primary brain tumors – To incriminate or exculpate?. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Jan 26];3:854-5. Available from: https://www.crstonline.com/text.asp?2020/3/4/854/304974

Quantum leaps in the management strategies in oncology have significantly improved the survival in patients with cancer, including those with primary brain tumors. Nevertheless, cancer-related cognitive impairment, especially in the setting of chemoradiation, has been a matter of consternation in these patients.

Cognitive dysfunction in patients with brain tumors may be multifactorial. It can be due to the tumor itself; its accompanied manifestations, particularly epilepsy; endocrine abnormalities; metabolic derangements; raised intracranial pressure; psychological distress; and treatment-related factors including surgery, radiotherapy, chemotherapy, and other medications. Tumor recurrence and leptomeningeal metastasis may also adversely affect cognition.

A study by Tucha et al. on 139 treatment-naïve patients with brain tumors reported cognitive disturbances in as high as 91% of the patients. About 78% of them had executive dysfunction, and 60% had impairment in memory and attention.[1] This could be due to acute neurotransmitter variations, chronic degeneration of fiber tracts, and impaired neuronal organization. The occurrence of the tumor in the dominant hemisphere; the location and size of the lesion; proximity of the lesion to the eloquent areas, and associated symptoms such as raised intracranial pressure, hydrocephalus, headache, and visual and motor deficits also contribute to cognitive dysfunction.[2],[3] In fact, worsening of cognition may be an early marker of tumor recurrence in treated patients that can appear even before other deficits or imaging features.[4] Surgical procedures such as biopsy or complete excision, extent of resection, and perioperative injuries may also contribute to the level of cognitive dysfunction.

Owing to its low therapeutic index for the nervous system (the dose required for tumor control is in close range with the toxic dose for the neighboring tissue), radiation acts as the key perpetrator for acute, early, and late-delayed encephalopathic complications mediated by tissue edema, demyelination, radionecrosis, diffuse leukoencephalopathy, and cerebral atrophy, depending on the degree of the injury. Additional havoc is caused by secondary endocrine dysfunction due to thyroid, adrenal, or growth hormone insufficiency after cranial irradiation.[5]

The effect of chemotherapy on cognition in patients with primary brain tumors is far from linear.[6] The direct toxicity of chemotherapy on the self-renewing, lineage-committed neural progenitor cells and non-dividing, mature oligodendrocytes has been proven in animal models.[7] The concomitant radiation (as most patients with brain tumors undergo radiation prior to systemic chemotherapy), the preexisting disruption of the blood–brain barrier in primary brain tumors, the intra-arterial and intrathecal mode of administration, and the neurotoxicity of the chemotherapeutic drugs all act incrementally to produce cognitive dysfunction. The effect of other co-prescribed medications such as steroids and antiepileptics on cognition may also be difficult to quantify. Coexistent mood disturbances such as anxiety/depression and psychosis affect attention, motivation, and vigilance.

Hence, chemotherapy affects brain function in myriad direct and indirect ways. Additional variables including the patients' age, educational status, economic background, cognitive reserve, baseline cognition level, genetic predisposition, comorbidities, and disturbances of other body organs have been implicated in chemotherapy-related cognitive impairment.

In their current work, Adak et al.[8] have assessed the cognitive scores of 100 patients using a self-administered functional assessment of cancer therapy cognitive function issues quality of life questionnaire. However, the consideration of the above-described variables and parameters that affect cognition in a multi-pronged fashion is cardinal to performing such a study and would enhance the outcomes.[9] Further, the comparison of the current scores against the scores of the patients with primary brain tumors who had not undergone systemic chemotherapy (who were excluded from the study) would add more value to the results. In the absence of the control group data and paucity of multivariate analysis of the above-described contributory factors, the effect of systemic therapy per se on the cognitive scores must be interpreted with caution. It may be valuable to apply a short, pragmatic, and validated cognitive assessment battery which is reliable, sensitive, and covers the main domains of memory, attention, executive function, and language.

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There are no conflicts of interest.

  References Top

Tucha O, Smely C, Preier M, Lange KW. Cognitive deficits before treatment among patients with brain tumors. Neurosurgery 2000;47:324-33.  Back to cited text no. 1
Scheibel RS, Meyers CA, Levin VA. Cognitive dysfunction following surgery for intracerebral glioma: Influence of histopathology, lesion location, and treatment. J Neurooncol 1996;30:61-9.  Back to cited text no. 2
Hahn CA, Dunn RH, Logue PE, King JH, Edwards CL, Halperin EC. Prospective study of neuropsychologic testing and quality-of-life assessment of adults with primary malignant brain tumors. Int J Radiat Oncol Biol Phys 2003;55:992-9.  Back to cited text no. 3
Meyers CA, Hess KR. Multifaceted end points in brain tumor clinical trials: Cognitive deterioration precedes MRI progression. Neuro Oncol 2003;5:89-95.  Back to cited text no. 4
Taphoorn MJ, Klein M. Cognitive deficits in adult patients with brain tumours. Lancet Neurol 2004;3:159-68.  Back to cited text no. 5
Dutta D, Jalali R. Impact of systemic therapies on cognition in patients with primary brain tumors. Cancer Res Stat Treat 2020;3:569-71.  Back to cited text no. 6
  [Full text]  
Dietrich J, Monje M, Wefel J, Meyers C. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 2008;13:1285-95.  Back to cited text no. 7
Adak S, Singh GK, Menon N, Dale O, Srinivas S, Das S, et al. Cognitive score in patients with primary brain tumors undergoing systemic therapy – A cross-sectional study. Cancer Res Stat Treat 2020;3:455-60.  Back to cited text no. 8
  [Full text]  
Dutta D, Jalali R. Impact of systemic therapies on cognition in patients with primary brain tumors. Cancer Res Stat Treat 2020;3:569-71  Back to cited text no. 9


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