Exploring cognitive impairment and the efficacy of integrative neurocognitive remediation therapy in metastatic melanoma survivors treated with immunotherapy or targeted therapy: a case series

Introduction: Given the novel treatments in metastatic disease, a rising number of patients (pts) will become disease-free cancer survivors. Our previous research showed that metastatic cancer survivors treated with immunotherapy (IT) are at risk of suffering from emotional distress and/or cognitive impairment impacting their quality of life. Although it is well-known that cognitive impairment has a negative impact on emotional, social, professional and daily function, only few rehabilitation programs exist in Europe that aim to improve both neurocognitive function (NCF) and psychosocial outcome after cancer treatment. Objectives: To explore the efficacy of integrative neurocognitive remediation therapy (INCRT), offered as a 12-week clinical program (1 day/week), organized within the Clinic of Neurocognitive Remediation, Department of Psychiatry, CHU Brugmann, Brussels. The INCRT combines personalized computerized cognitive training and strategy training, with group sessions of physical rehabilitation and cognitive behavioral therapy. Methods: Patients who were successfully treated with IT or BRAF/MEK inhibitors and who were suffering from subjective cognitive complaints were eligible. Psychosocial function and NCF was evaluated through
psychometric questionnaires, paper-and-pencil and computerized neuropsychological assessment (Vienna Test System©), assessing attention, memory and executive function. The full assessment was repeated for the 2 pts that completed the INCRT. Cognitive deficits on single tests were defined as at least 1sd (standard deviation) below the mean of the healthy population in order to detect subtle differences. Results: Five metastatic melanoma survivors completed the neuropsychological and psychometric assessment between 2019 and December 2021. Patient A (F/50y) and B (F/53y) followed the INCRT; both had a history of brain metastasis of whom 1 was still on treatment. Patient C (M/57y), pt D (M/60y) and pt E (F/43y) completed the neuropsychological assessment and will enter the program in august 2022. Patients A and E were on active treatment with BRAF/MEK inhibitors; pts B, C and D were treatmentfree.
All pts demonstrated cognitive deficits on ≥ 1 neuropsychological test: selective attention (5/5), inhibition (2/5), working memory (1/5), short-term verbal memory (1/5), and long-term verbal memory (1/5). Cognitive impairment according to International Cancer and Cognition Task Force (ICCTF) criteria was only found in pt C with impairment of inhibition (sd = -1.6) and selective attention (sd = -1.8). Assessment of anxiety, depression, subjective cognition and self-esteem is available for only 4 pts. All pts had subjective complaints according to the Cognitive Failures Questionnaire, 3/4 pts had moderate
depression according to the Beck Depression Inventory, 3/4 pts had increased anxiety according to the Hospital Anxiety and Depression Scale and 2/4 pts had low self-esteem according to the Rosenberg Self-Esteem Scale. Regarding the efficacy of INCRT, pt A reported slow information processing, being easily distracted and forgetting appointments before INCRT. Objective test results showed deficits in selective attention (sd = -1.40) and verbal long-term memory (sd = -1.11). After INCRT, pt A reported improvements in concentration, recall and daily function. Objective test results showed an improvement in long-term memory, which returned to the normal range (sd = 0.96). Results on selective attention remained stable. Patient B reported difficulties to follow a conversation, in reading, organizing and prioritizing daily tasks. Objective test results showed deficits in selective attention (sd = -1.40) and working memory (sd = -1.16). Inhibition, although not strictly impaired (sd = -1), was reported as a subjective complaint. After INCRT, pt B gained better control of her inhibition, leading to improved socio-professional functioning; she reported also a better management of daily function based on newly learned strategies. Objective test results did not improve. Conclusion: Impairment of subjective and objective NCF and emotional distress may persist after successful treatment of metastatic melanoma. The 2 pts with a history of brain metastasis who followed the INRCT program, reported an improvement in subjective cognition and in emotional, social and daily function; 1 pt had improved NCF test results.