Breast Cancer Patients' Cognitive Symptoms After Information About Chemotherapy-Related Cognitive Symptoms

Study Overview
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Brief Summary
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Previous cross-sectional studies have shown that informing cancer patients about potential chemotherapy-related cognitive symptoms may negatively affect perceived cognitive symptoms and verbal memory performance. A multicenter, randomized study in newly diagnosed breast cancer patients receiving (neo) adjuvant chemotherapy was performed to evaluate this Adverse Information Effect (AIE) over time and investigated whether inviting patients to self-affirm can reduce such AIEs on perceived cognitive symptoms and cognitive test performance.

Detailed Description
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Rationale: Although information about their treatment and its side-effects is requested by cancer patients, is vital for informed decision making and can positively impact patients' health outcomes and illness perceptions, this kind of information can also adversely impact perceived cognitive symptoms and cognitive test performance. Previous studies have shown that informing cancer patients about potential chemotherapy-related cognitive symptoms may negatively affect perceived cognitive symptoms and verbal memory performance. A multicenter, randomized study in newly diagnosed breast cancer patients receiving (neo) adjuvant chemotherapy was performed to evaluate this Adverse Information Effect (AIE) over time and investigated whether inviting patients to self-affirm can reduce such AIEs on perceived cognitive symptoms and cognitive test performance. Main objectives and hypotheses: The overall aim of the study was to investigate the occurrence and duration of AIEs on the perceived frequency of cognitive symptoms, the perceived severity of cognitive symptoms and cognitive performance in breast cancer patients, and to examine ways to reduce such AIEs. First, evaluated the effect of providing breast cancer patients with additional factual written information about potential chemotherapy-related cognitive symptoms before chemotherapy-initiation on perceived cognitive symptoms and cognitive performance was evaluated, and the duration of such effects was assessed. Building on previous findings that breast cancer patients showed an increase in perceived cognitive symptoms and a decrease in verbal memory performance after receiving cognitive side-effect information, it was hypothesized that communicating about potential chemotherapy-related cognitive symptoms will result in AIEs, and it was explored to what extent these AIEs persist over time. Second, this study aimed to translate the beneficial effects of self-affirmation to the oncology domain, and examined the efficacy of a text-integrated self-affirmation intervention in reducing the impact of AIEs on perceived cognitive symptoms and cognitive performance in breast cancer patients when communicating about chemotherapy-related cognitive symptoms. It was hypothesized that a textual self-affirmation intervention would reduce AIEs in breast cancer patients, building on evidence from health promotion and stereotype threat research outside the oncology domain that individuals' self-concepts can be affirmed via text-integrated health messages and that allowing individuals the opportunity for self-affirmation can reduce stereotype threat effects. The main research questions were: Does written information about potential chemotherapy-related cognitive symptoms presented only once before treatment-initiation affect short- and longer-term perceived cognitive symptoms (the perceived frequency and severity of cognitive symptoms) and cognitive performance (verbal memory performance, information processing speed, executive functioning) in newly diagnosed breast cancer patients scheduled for (neo) adjuvant chemotherapy? Does providing newly diagnosed breast cancer patients with a text integrated self-affirmation intervention after being informed about potential chemotherapy-related cognitive symptoms reduce AIEs on short- and longer-term perceived cognitive symptoms and cognitive performance? Study procedure and outcome measures: Before (neo) adjuvant chemotherapy, 160 newly diagnosed breast cancer patients were randomly allocated to receive either standard information on side-effects (control condition), or standard information with additional information about chemotherapy-related cognitive symptoms (information condition), or standard and additional information with a subsequent self-affirmative text (information+SA condition; SA=self-affirmation). Online-questionnaires were completed before chemotherapy (baseline, T0), 6-months (T1) and 12-months (T2) later to measure the perceived frequency (MOS-cog) and severity (MDASI-cog) of cognitive symptoms. Patients also completed two online neuro-psychological tests (Trail Making Test; TMT, and 15 Words test) to measure verbal memory performance, information processing speed and executive functioning. Additionally, several potential underlying mechanisms and risk factors of AIEs were examined, such as cancer related distress and performance worries. Baseline-to-follow-up analyses were performed using a mixed-effects modeling approach to compare groups over time.

Official Title
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Downsides of Being Well-Informed: Tracking and Preventing Chemotherapy-Related Cognitive Problems in Breast Cancer Patients

Conditions
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Breast Cancer, Cognitive Symptoms, Cognitive Decline

Intervention / Treatment
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* Other: Written information about potential chemotherapy-related cognitive symptoms without self-affirmation
* Other: Written information about potential chemotherapy-related cognitive symptoms with self-affirmation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary breast cancer diagnosis stage I-III Scheduled to receive (neo) adjuvant chemotherapy 18 years or older Sufficient command of the Dutch language Internet access Exclusion Criteria: A history of neurological and psychiatric symptoms that influence cognitive functioning Previous cancer diagnosis Using drugs Drinking more than three alcoholic drinks a day

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A multicenter, randomized, controlled, prospective, online survey study was conducted. Before completing the study's online baseline survey (pre-chemotherapy; T0), participants were randomly assigned by the online survey program to receive either: standard information on side-effects (control condition), or standard information with additional written information about chemotherapy-related cognitive symptoms (information condition), or standard and additional information with a subsequent self-affirmative text (information+SA condition; SA=self-affirmation). The online experimental texts were presented to patients once, directly after randomization at baseline. At six months (T1) and twelve months (T2) follow-up, all groups received identical general introductions and online surveys, without any experimental manipulations. Outside of the trial, all patients received treatment information from their medical oncologist according to local practice as part of their usual care.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Participants in the control group received standard information on treatment side-effects. | |
| Experimental: Information without self-affirmation<br>Before completing the study's online baseline survey (pre-chemotherapy), participants in the information group received standard information with additional written information about potential chemotherapy-related cognitive symptoms. | Other: Written information about potential chemotherapy-related cognitive symptoms without self-affirmation<br> <br> * Other names: Information;|
| Experimental: Information with self-affirmation<br>Before completing the study's online baseline survey (pre-chemotherapy), participants in the information+SA group (SA=self-affirmation) received standard and additional written information about potential chemotherapy-related cognitive symptoms with a subsequent self-affirmative text. | Other: Written information about potential chemotherapy-related cognitive symptoms with self-affirmation<br> <br> * Other names: Information+SA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group differences in mean change in the perceived frequency of cognitive symptoms from baseline to T1, and from baseline to T2. | Six items of the revised Medical Outcomes Study - cognitive functioning subscale (MOS-cog; Stewart & Ware, 1992) to measure the perceived frequency of cognitive symptoms. Participants indicated the frequency of experiencing a range of day-to-day problems in six aspects of cognitive functioning during the past week (including today). Higher mean scores indicate better perceived cognitive functioning (range 0-100). | Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later | 
| Between-group differences in mean change in the perceived severity of cognitive symptoms from baseline to T1, and from baseline to T2. | Two items of the M.D. Anderson Symptom Inventory Multiple Myeloma module (MDASI-MM part 1; Cleeland et al., 2000; Jones et al., 2013) to measure the perceived severity of cognitive symptoms. Patients reported the severity of two cognitive symptoms at their worst in the last 24 hours on a 0-10 scale, with 0 being 'not present' and 10 being 'as bad as you can imagine': difficulty remembering and difficulty paying attention (concentrating). Higher mean scores indicate more severe symptoms. | Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later | 
| Between-group differences in mean change in verbal memory performance from baseline to T1, and from baseline to T2. | Online, adapted version of the Groningen Fifteen Words Test (Rey, 1964) measuring immediate recall (range 0-45), delayed recall (range 0-15) and recognition (range 0-30). Higher scores indicate better performance. | Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later | 
| Between-group differences in mean change in information processing speed and executive functioning from baseline to T1, and from baseline to T2. | Online version of the Trail Making Test (TMT; Reitan & Wolfson, 1985) part A and B (and TMT-B to TMT-A ratio B/A) to measure the speed of information processing and executive functioning. The score on each part represents the amount of time in seconds required to complete the task. Higher scores indicate worse information processing and executive functioning. | Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group differences in mean change in the levels of anxiety from baseline to T1, and from baseline to T2. | Dutch version of the Hospital Anxiety and Depression Scale (HADS; Spinhoven et al., 1997; Zigmond & Snaith, 1983) to measure levels of anxiety. Higher sum scores (range 0-21) indicate higher levels of anxiety. | Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later | 
| Between-group differences in mean change in the levels of depression from baseline to T1, and from baseline to T2. | Dutch version of the Hospital Anxiety and Depression Scale (HADS; Spinhoven et al., 1997; Zigmond & Snaith, 1983) to measure levels of depression. Higher sum scores (range 0-21) indicate higher levels of depression. | Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later | 
| Between-group differences in mean change in the perceived severity of other cancer-related symptoms from baseline to T1, and from baseline to T2. | Twelve items of the thirteen-item core M. D. Anderson Symptom Inventory (MDASI; part 1; Cleeland et al., 2000) to measure the perceived severity of other cancer-related symptoms. Participants reported the severity of twelve symptoms at their worst in the last 24 hours hours on a 0-10 scale, with 0 being 'not present' and 10 being 'as bad as you can imagine.' Difficulty remembering was excluded. Higher mean scores indicate more severe symptoms. | Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later | 
| Between-group differences in pre-existing knowledge (prior to the experiment) about the potential cognitive symptoms of cancer treatment measured at twelve months follow-up (T2). | Participants indicated on one item (range 1-5) at the end of the T2 survey whether they had knowledge about the potential cognitive side-effects of cancer treatment prior to the experiment to measure pre-existing knowledge. Higher scores indicate more pre-existing knowledge. | Measured at twelve months follow-up (T2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Chemotherapy, Cognitive symptoms, Self-affirmation, Health communication, Nocebo, Stereotype threat