Clinical trial NCT04813965: Breast Cancer Patients' Cognitive Symptoms After Information About Chemotherapy-Related Cognitive Symptoms
Official title: Downsides of Being Well-Informed: Tracking and Preventing Chemotherapy-Related Cognitive Problems in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Cognitive Symptoms
Cognitive Decline
Keywords: Breast cancer
Chemotherapy
Cognitive symptoms
Self-affirmation
Health communication
Nocebo
Stereotype threat
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: The Netherlands Cancer Institute
name: St. Antonius Hospital
name: Meander Medical Center
name: Ziekenhuisgroep Twente
name: Isala
name: Deventer Ziekenhuis
name: Rijnstate Hospital
name: Franciscus Gasthuis
name: St Jansdal Hospital
name: UMC Utrecht
First posted: 2021-03-24
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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:

1. 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?
2. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Between-group differences in mean change in the perceived frequency of cognitive symptoms from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in the perceived severity of cognitive symptoms from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in verbal memory performance from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in information processing speed and executive functioning from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
Secondary outcomes:
measure: Between-group differences in mean change in the levels of anxiety from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in the levels of depression from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in the perceived severity of other cancer-related symptoms from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: 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).
timeFrame: Measured at twelve months follow-up (T2)
Other outcomes:
measure: Between-group differences in mean change in the levels of the expected severity of cognitive symptoms from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in the levels of the expected severity of other cancer-related symptoms from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in the levels of motivation from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in mean change in the levels of worrying about cognitive test performance from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Low cancer-specific distress versus high cancer-specific distress subgroup analysis.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Low stigma consciousness versus high stigma consciousness subgroup analysis.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Low domain identification versus high domain identification subgroup analysis.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Low group identification versus high group identification subgroup analysis.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Low information monitoring versus high information monitoring subgroup analysis.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in changes in information source from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in changes in information content from baseline to T1, and from baseline to T2.
timeFrame: Prior to chemotherapy-initiation (baseline; T0), six months (T1), and twelve months (T2) later
measure: Between-group differences in stereotype self-relevance measured at twelve months follow-up (T2).
timeFrame: Measured at twelve months follow-up (T2)
measure: Between-group differences in the extent to which participants attributed their own and others' cognitive symptoms to chemotherapy measured at twelve months follow-up (T2).
timeFrame: Measured at twelve months follow-up (T2)
Locations:
Study officials:
affiliation: Radboud University Medical Center
name: Enny Das, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Netherlands Cancer Institute
name: Sanne B Schagen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Netherlands Cancer Institute
name: Gabe S Sonke, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jacobs W, Schagen SB, Brouwer SM, Kieffer JM, Baas IO, Los M, Sonke GS, Das E. The Effects of Being Informed About Chemotherapy-Related Cognitive Symptoms With And Without Self-Affirmation on Perceived Cognitive Symptoms of Breast Cancer Patients: A Randomized Prospective, Longitudinal Study. Clin Breast Cancer. 2022 Jul;22(5):439-454. doi: 10.1016/j.clbc.2022.03.001. Epub 2022 Mar 26.