Table 3.

Cognitive impairment induced by medical oncology treatments other than chemotherapy in patients

Study	Study design Country	Patients, control group Age	Cognitive assessment	Cognitive measures	Other measures	Statistical analysis	Main outcomes
Hormone therapy—breast cancer
Schilder et al. [43]	Randomized Longitudinal The Netherlands	Breast cancer, tamoxifen users (n=80, 69 years old ±7.6), exemestane users (n=99, 68 years old ±6.8) versus HC (n=120)	Before and after 1 year of HT (CT naïve)	CFQ and interview questions about cognitive complaints	Cognitive tests (only to assess the relation with cognitive complaints), HSCL, fatigue subscale (EORTC-QLQ-C30), FACT-B-ES	ANOVA, ANCOVA and logistic regressions (anxiety, depression covariates)	In tamoxifen users: increased attention/concentration complaints (not in exemestane users)
Danhauer et al. [44]	Randomized Longitudinal USA	Breast cancer (n=1479, 67 years old ±4.3), tamoxifen and raloxifen groups (randomized)	Baseline, 2 and 3 years follow-up	3MSE, PMA vocabulary, verbal fluencies, BVRT, CVLT, digit span, card rotations, finger tapping	PANAS, GDS	Linear mixed models for repeated measures	No significant interactions between treatment and any of the cognitive test results
Ganz et al. [27]	Longitudinal USA	Breast cancer with HT (n=122, 52 years old ±7.9, tamoxifen or aromatase inhibitor) versus without (n=51)	Before HT and 6 months later	WTAR, CVLT, WMS, BVMT, ROCF, block design, digit symbol, TMT, Stroop, letter-number sequencing, grooved pegboard	PAOFI, BDI, SF-36	Bivariate analyses and multivariable linear regression models	Cognitive complaints (language and communication) increase in HT patients but no significant changes in cognitive scores
Bender et al. [45]	Longitudinal USA	Breast cancer with CT and anastrozole (n=114, 59 years old ± 5.5) versus anastrozole alone (n=173) versus HC (n=110)	Before, 6, 12, and 18 months after the start of HT	CANTAB, digit vigilance, rivermead story, ROCF, RAVLT, verbal fluency, Stroop, grooved pegboard, digit symbol substitution, NART	BDI, POMS	Linear mixed effects modelling (age and estimated verbal intelligence controlled)	Patients with anastrozole (±CT): poorer executive function from before treatment initiation to 18 months than HC and decreased on visual working memory and concentration at 6 months Patients with anastrazole alone: second deterioration in working memory and concentration at 12 and 18 months
Le Rhun et al. [46]	Randomized Longitudinal France	Breast cancer (n=74, 61 years old [49–69]), with tamoxifen (n=37) versus AI (n=37)	Before, 6 and 12 months after the start of HT	MMSE, RAVLT, BVRT, digit and spatial span, TMT, Stroop, verbal fluency, Wisconsin card sorting test	CDS, IADL, EORTC QLQ-C30, HADS	Mixed design analysis models of variance (adjusted for baseline performance)	No significant difference between groups on cognitive scores for all the follow-up
Phillips et al. [47]	Randomized Longitudinal International	Breast cancer with ovarian function suppression + tamoxifen or exemestane (n=54, 44 years old) versus tamoxifen alone (n=20, 46 years old)	Before HT and 1 year later	CogState (seven tasks)	CFQ, GHQ, Brief fatigue inventory	Wilcoxon rank-sum tests to compare the change between the t groups (CT treatment and baseline characteristics controlled)	No significant difference in the changes of objective cognitive scores between all groups
Van Dyk et al. [48]	Longitudinal USA	Breast cancer with HT (n=126, 52 years old ±7.9) versus without (n=63, 52 years old ± 9.2)	Before, 6 and 12 months and 3–6 years after the start of HT	CVLT, BVMT, Digit span, coding, letter-number sequencing, PASAT, ROCF, block design, TMT, Verbal fluency, Grooved pegboard, Stroop	BDI, State Anxiety Inventory, WTAR	Linear mixed effect models for repeated measures, analysis of covariance and binary logistic regression	No detrimental effect of HT on cognition
Androgen deprivation therapy—prostate cancer
Wiechno et al. [49]	Cross-sectional Poland	Prostate cancer with ADT (n=88, 67 years old [50–80]) and without (n=61)	After RT and LH-RH analogue	MMSE	HADS, questions on QoL	Mann–Whitney and Kruskal–Wallis non-parametric tests	No significant difference between groups for MMSE
Gonzalez et al. [50]	LongitudinalUSA	Prostate cancer with ADT (n=58, 67 years old ±8.9 versus without (n=84) and HC (n=88)	Before, 6 and 12 months after the start of ADT	HVLT, WMS logical memory, digit and spatial spans, BVMT, colour trails, COWA, NART	TIADL	Mixed models and logistic regressions	Patients with ADT: more cognitive impairment at 6 and 12 months No differences between groups in changes in mean-level performance
Morote et al. [51]	Longitudinal Spain	Prostate cancer (n=308, 71 years old ±8.1)	Before and 6 months after the start of LHRH analogues	Digit span, visual memory, judgment of line orientation and mental rotation tests, matrix reasoning test	None	Changes outside the baseline 95% confidence intervals were considered significant	20% of patients had significant decline on ≥1 test
Thiery-Vuillemin [52]	Longitudinal International	Prostate cancer with AAP (n=46, 73 years old [53–90]) versus ENZ (n=59, 76 years old [60–92])	1, 2, and 3 months	FACT-Cog	EORTC QLQ-C30, BFI-SF, BPI-SF	Multivariate repeated measures logistic models and clinically meaningful change	More cognitive complaints in patients with ENZ than AAP and higher risk to develop depression
Antiangiogenic
Joly et al. [7]	Longitudinal France	Renal cancer (n=75, 65 years old [28–81])	Before, 3 and 6 months after the start of AATs	Grober–Buschke test, ROCF, arithmetic, digit-span, letter-number sequencing, TMT, verbal fluencies	MFI, FACT-G and FKSI, BDI, STAI	Fisher’s exact test, Wilcoxon test, and Spearman correlation coefficient	Cognitive decline in one-third of patients post-AATs independently of fatigue

AAP, Abiraterone Acetate plus Prednisone; AATs, antiangiogenic therapies; AI, Aromatase inhibitors; ADT, Androgen Deprivation Therapy; BDI, Beck Depression Inventory; BFI-SF, Brief Fatigue Inventory-Short Form; BPI-SF, Brief Pain Inventory-Short Form; BVMT, Brief Visuospatial Memory Test; BVRT, Benton Visual Retention Test; CANTAB, Cambridge Neuropsychological Test Automated Battery; CDS, cognitive difficulties scale; CFQ, Cognitive Failures Questionnaire; CT, chemotherapy; CVLT, California Verbal Learning Test; ENZ, Enzalutamide; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; FACT- (B-ES; G; FKSI), Functional Assessment of Cancer Therapy (Breast-Endocrine Subscale; General; Kidney Symptom Index); GDS, Geriatric Depression Scale; GHQ, General Health Questionnaire; HADS, Hospital Anxiety and Depression Scale; HC, healthy controls; HSCL, Hopkins Symptoms Checklist; HT, hormone therapy; QoL, quality of life; LHRH, luteinizing hormone-releasing hormone; MFI, Multidimensional Fatigue Inventory; MMSE, Mini Mental State Examination; NART, National Adult Reading; PANAS, positive and negative affect schedule; PASAT, Paced Auditory Serial Addition Task; PMA, primary mental abilities vocabulary test; PAOFI, Patient’s Assessment of Own Functioning Inventory; POMS, Profile of Mood States; ROCF, Rey Osterreith Complex Figure; RT, radiotherapy; STAI, Spielberger State-Trait Anxiety Inventory; TIADL, Instrumental Activities of Daily Living Test; TMT, Trail Making Test; WMS, Wechsler Memory Scale; WTAR, Wechsler Test of Adult Reading.