Prediction Models for Radiation-Induced Neurocognitive Decline in Adult Patients with Primary or Secondary Brain Tumors: A Systematic Review

Purpose: Although an increasing body of literature suggests a relationship between brain irradiation and deterioration of neurocognitive function, it remains as the standard therapeutic and prophylactic modality in patients with brain tumors. This review was aimed to abstract and evaluate the prediction models for radiation-induced neurocognitive decline in patients with primary or secondary brain tumors.Methods: MEDLINE was searched on October 31, 2021 for publications containing relevant truncation and MeSH terms related to “radiotherapy”, “brain”, “prediction model”, and “neurocognitive impairments”. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool.Results: Of 3,580 studies reviewed, 23 prediction models were identified. Age, tumor location, education level, baseline neurocognitive score, and radiation dose to the hippocampus were the most common predictors in the models. The Hopkins verbal learning (n=7) and the trail making tests (n=4) were the most frequent outcome assessment tools. All studies used regression (n=14 linear, n=8 logistic, and n=4 Cox) as machine learning method. All models were judged to have a high risk of bias mainly due to issues in the analysis.Conclusion: Existing models have limited quality and are at high risk of bias. Following recommendations are outlined in this review to improve future models: develop a standardized instrument for neurocognitive assessment in patients with brain tumors; adherence to model development and validation guidelines; careful choice of candidate predictors according to the literature and domain expert consensus; and considering radiation dose to brain substructures as they can provide important information on specific neurocognitive impairments.

P.015 What Happens to the Worried Well? – Follow-up of Subjective Cognitive Impairment

Background: Concern around perceived neurocognitive decline is increasing, leading to increased number of referrals and anxiety for patients. We aimed to explore the likelihood of the “worried well” experiencing neurocognitive decline. Methods: 166 “worried well” patients who attended the Rural and Remote Memory Clinic between 2004 and 2019 were included. Mini Mental Status Examination, Center for Epidemiologic Studies Depression Scale, and Functional Assessment Questionnaire scores were measured and compared at initial assessment and at 1-year follow-up. MMSE scores over time were assessed with a mean follow-up of 2.95 years (SD 2.87). Results: There was no statistically significant difference in MMSE, CESD, or FAQ scores between clinic day and one-year follow-up, and no consistent pattern of MMSE score over time. Of the 166 patients with SCI on initial assessment, nine were eventually given a neurological diagnosis. Conclusions: There is no pattern of neurologic decline observed in the “worried well”. Though the likelihood of a patient with SCI developing a neurological diagnosis is reassuringly low, (9/166), it is not irrelevant. This, along with the benefits of early diagnosis and treatment for dementia, leads us to believe that patients with SCI should still be seen in follow-up at least at the one-year mark.

An assessment of factors associated with neurocognitive decline in people living with HIV

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify factors associated with neurocognitive decline. We assessed risk factors associated with neurocognitive decline in people living with HIV using a definition of decline that is statistically easy to adopt, is based on a commonly used neuropsychological cut-off and may be clinically relevant. Cox proportional hazards modeling was performed using the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study database. 581 participants were followed for up to 12 years. Neurocognitive decline was defined as the first observed drop in global T-scores of at least 2.67. Lifetime methamphetamine use had the strongest association with neurocognitive decline (adjusted Hazard Ratio; aHR = 1.48; 95% CI = 0.92–2.39) followed by no current antiretroviral medication use (aHR = 1.32; 95% CI = 0.91–1.92). Other risk factors included Hispanic ethnicity, lifetime history of major depressive disorder, lifetime cannabis use, hepatitis-C infection, and difficulty eating, dressing, bathing, or using the toilet. Results indicate that consistent use of ART may be of high significance to preserving neurocognition. Furthermore, Hispanic patients, those with a history of depression and substance use, and those having difficulty in essential activities of daily living may require vigilant follow-up.

Physiologic Frailty and Neurocognitive Decline Among Young-Adult Childhood Cancer Survivors: A Prospective Study From the St Jude Lifetime Cohort

PURPOSE Eight percent of young-adult childhood cancer survivors meet criteria for frailty, an aging phenotype associated with poor health. In the elderly general population, frailty is associated with neurocognitive decline; this association has not been examined in adult survivors of childhood cancer. METHODS Childhood cancer survivors 18-45 years old (≥ 10 years from diagnosis) were clinically evaluated for prefrailty or frailty (respectively defined as ≥ 2 or ≥ 3 of: muscle wasting, muscle weakness, low energy expenditure, slow walking speed, and exhaustion [Fried criteria]) and completed neuropsychologic assessments at enrollment (January 2008-June 2013) and 5 years later. Weighted linear regression using inverse of sampling probability estimates as weights compared differences in neurocognitive decline in prefrail and frail survivors versus nonfrail survivors, adjusting for diagnosis age, sex, race, CNS–directed therapy (cranial radiation, intrathecal chemotherapy, and neurosurgery), and baseline neurocognitive performance. RESULTS Survivors were on average 30 years old and 22 years from diagnosis; 18% were prefrail and 6% frail at enrollment. Frail survivors declined an average of 0.54 standard deviation (95% CI, −0.93 to −0.15) in short-term verbal recall, whereas nonfrail survivors did not decline (β = .22; difference of βs = −.76; 95% CI, −1.19 to −0.33). Frail survivors declined more than nonfrail survivors on visual-motor processing speed (β = −.40; 95% CI, −0.67 to −0.12), cognitive flexibility (β = −.62; 95% CI, −1.02 to −0.22), and verbal fluency (β = −.23; 95% CI, −0.41 to −0.05). Prefrail and frail survivors experienced greater declines in focused attention (prefrail β = −.35; 95% CI, −0.53 to −0.17; frail β = −.48; 95% CI, −0.83 to −0.12) compared with nonfrail survivors. CONCLUSION Over approximately 5 years, prefrail and frail young-adult survivors had greater declines in cognitive domains associated with aging and dementia compared with nonfrail survivors. Interventions that have global impact, designed to target the mechanistic underpinnings of frailty, may also mitigate or prevent neurocognitive decline.

Inflammation but not Glycemic Control is Associated with Neurocognitive Decline After Cardiac Surgery

Background: Whether perioperative glycemic control or markers of inflammation is associated with neurocognitive decline (NCD) after cardiac surgery was examined. Methods: Thirty patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) were screened for NCD preoperatively and on post-operative day four (POD4). Serum cytokine levels were measured and human transcriptome analysis was performed on blood samples. Neurocognitive data are presented as a change from baseline to POD4 in a score standardized with respect to age and gender. Results: A decline in neurocognitive function was identified in 73% (22/30) of patients on POD4. Patients with postoperative leukocytosis (WBC ≥ 10.5) had more NCD when compared to their baseline function (p=0.03). Patients with elevated IL-8 levels at 6 hours postoperatively had a significant decline in NCD at POD4 (p=0.04). Surprisingly, TNF-α, IL-1β, IL-2, or IL-6 levels were not associated with NCD (p>0.3 for all). There was no difference in neurocognitive function between patients with elevated HbA1c levels preoperatively (p=0.973) or elevated fasting blood glucose levels the morning of surgery (>126mg/dL, p=0.910), or a higher maximum blood glucose levels during CPB (>180mg/dL, p=0.252), or higher average glucose levels during CPB (>160mg/dL, p=0.639). Human transcriptome analysis demonstrated unique and differential patterns of gene expression in patients depending on the presence of DM and NCD. Conclusions: Perioperative glycemic control does not have an effect on NCD soon after cardiac surgery. Postoperative leukocytosis and elevated IL-8 levels are associated with neurocognitive decline. The profile of gene expression was altered in patients with NCD with or without diabetes.

Are there still indications for whole brain irradiation in 2021?

SummaryBrain metastases (BM) are the most frequent intracranial tumors in adults. About 10–20% of the patients with cancer will develop them. Historically, most of the patients with brain metastases were treated with whole brain radiotherapy (WBRT). The intention was to control the metastases and to eliminate distant micrometastases. Randomized control trials showed no difference in survival in patients with single and oligometastases treated with WBRT compared with stereotactic radiosurgery (SRS). To avoid treatment-related toxicities with neurocognitive decline, indications for WBRT are changing. High precision therapy with SRS or postoperative stereotactic treatments have become increasingly important. Only in exceptional cases is WBRT still the treatment of choice.