Changing cancer mindsets: A randomized controlled feasibility and efficacy trial

A cancer diagnosis and subsequent treatment can disrupt the full spectrum of physical, social, emotional, and functional quality of life. But existing psychological treatments are focused primarily on specific psychological symptoms as opposed to improving the overall patient experience. We studied the feasibility and efficacy of a novel digital intervention targeting patient mindsets—core assumptions about the nature and meaning of illness—designed to improve overall health‐related quality of life (HRQoL) in newly diagnosed cancer patients undergoing treatment with curative intent.


| INTRODUCTION
Mindsets are assumptions we make that help us to understand our experiences. 1 The impact of mindsets about intelligence, stress, diet, and exercise on performance, health, and wellbeing outcomes of nonclinical populations is well-documented. [2][3][4] For patients with cancer, mindsets about the meaning of cancer and the role of the body may be similarly impactful. 5,6 By shaping a patient's cognitive, emotional, and physiological responses to both the illness and the subsequent treatment, these mindsets may influence multiple aspects of overall quality of life. 2 For example, adopting the mindset that cancer is "manageable" or even an "opportunity to grow" may engender a sense of hope, meaning and proactive engagement with treatment, while adopting the mindset that cancer is a "catastrophe" may lead to despair and disengagement, making an already difficult time even more challenging.
Precisely targeting and changing specific mindsets that are central to guiding our meaning-making processes can yield large and long-lasting benefits. 7 A 1-h digital intervention aimed at inspiring growth mindsets-the belief that intelligence can grow and be developed-led to improvements in academic achievement for lowerachieving adolescents transitioning to high-school. 8 Mindset interventions can also impact health outcomes and physiology.
Adopting a more adaptive mindset about stress (e.g., that stress is enhancing rather than debilitating) is associated with a more moderate cortisol response, higher DHEA-S levels, and better health and wellbeing as long as 2 years later. 2 Similar effects have also been demonstrated in clinical populations. An intervention aimed at altering patients' mindsets about side effects during oral immunotherapy led to a reduction in the number life-threating symptoms reported and an increase in peanut specific immunoglobulin G antibodies over the course of the study. 9 Interventions that target mindsets work because they "focus on the meanings and inferences people make about themselves and the situation they are in and use precise, theory-and research-based techniques to alter these meanings". 7 In doing so they evoke changes in emotion, attention, motivation, and physiology in ways that can lead to positive self-fulfilling outcomes. 10 For cancer patients, even subtle changes in mindsets (e.g., from viewing cancer as a catastrophe to viewing it as manageable) could be transformative.
While current evidence-based psychological interventions are usually offered to patients with a specific psychiatric diagnosis, like anxiety or depression, 11 brief mindset-focused interventions can be offered to all cancer patients in order to inspire positive psychological health and can lead to enhanced quality of life, better coping, and better functioning.
We used theoretically grounded methods and extensive piloting with patients and oncologists to identify the mindsets most central to patients undergoing cancer. We then developed a brief digital mindset-focused intervention aimed at helping newly diagnosed cancer patients adopt more adaptive mindsets about the nature of cancer (e.g., 'cancer is manageable') and about the role of the body (e.g., 'my body is capable'). In this clinical trial, we test the efficacy of this intervention in improving health related quality of life (HRQoL) in a cohort of patients who were recently diagnosed with nonmetastatic cancers. io/5et9g) prior to accessing the data.

| Recruitment, eligibility, & enrollment
We aimed to recruit N = 350 participants, which yielded 80% power to detect a small-to-moderate effect size of d = 0.33 This corresponds to a mean difference across conditions of 5 points on the Functional Assessment of Cancer Therapy -General (FACT-G) total score, assuming a pooled standard deviation of 15. The literature suggests a change between 5-8 points on the FACT-G represents the minimum clinically meaningful change in quality of life. 12,13 Therefore, a sample of N = 350 would provide sufficient power to detect at least the smallest clinically meaningful difference. This effect size range is also in line with existing supportive care interventions reporting FACT-G Total Score as their primary outcome. 14,15 Given the constraints of the COVID-19 pandemic, which prevented traditional in-person recruitment, we shifted to a decentralized clinical trial model that allowed us to recruit and enroll interested patients from across the country. Advertisements, similar to those commonly used for in-person studies, were adapted for an online format, and were posted on social media between November 2020 and January 2021. This style of advertising and recruitment, which is common for decentralized clinical trials, often generates a wide funnel of potential participants that quickly narrows to those who are actually interested and eligible. Clicking on an advertisement led to an online screening and eligibility survey. Adults (≥18 years) with an initial (i.e., non-recurrent) diagnosis of a non-metastatic (stage I-III) or hematological malignancy in the past 150 days who were undergoing or about to begin a course of treatment were eligible to participate in the study. Patients who failed to meet these inclusion criteria or self-indicated certain psychiatric comorbidities (e.g., severe depression, severe anxiety, bipolar disorder, posttraumatic stress disorder, or schizophrenia) that were not well controlled with treatment were excluded.
Eligible participants were provided with an overview of the study and were told they would be randomly assigned to one of two groups, that both groups were equally important to the study, and that both groups would be compensated equally. The CMI condition was described as the "Modules & Questionnaire Group", which involved watching short videos, completing written activities, and filling out questionnaires. The TAU Control condition was described as a "Health & Wellbeing Measurement Group", which involved completing questionnaires every few weeks over the course of the study. Participants received a $25 gift card for completing each survey plus a bonus $100 gift card for completing the entire study.
Informed consent was obtained for all participants prior to enrollment using RedCap's eConsent Framework. Participants were randomized 1:1 via a stratified block randomization design (block size of 10) across strata of cancer type, cancer stage, and biological sex to either the CMI or TAU condition. Randomization patterns were set before the initiation of the study using RedCap's randomization module.  Targets mindsets about cancer (e.g., that 'cancer is a catastrophe'). Film: Cancer survivors describe their own mindsets, their impact, and how they changed from diagnosis through treatment and into survivorship. Experts in oncology and psychology provide a scientific framework for these examples and suggest more useful ways of thinking about a cancer diagnosis and treatment (e.g., that 'cancer is manageable'). Reflection questions guide patients to consider their own mindsets, their impact, and how their experience would be different if they had more (or less) useful mindsets.

Module 2: My Body Is Capable (8-min film | 4 reflection questions | administered week 1)
Targets mindsets about the body and guides patients reconsider their implicit narratives about the body's role in the context of cancer. The film introduces patients to common but unhelpful mindsets patients may have about their own bodies (e.g., that their body is incapable or even an adversary) and offers alternative ways of thinking about the capability of the body. Reflection questions prompt patients to consider ways in which their bodies have been capable in the past and encourage health promoting behaviors (e.g., exercise) to help reinforce adaptive mindsets about the body. Targets the mindset that 'cancer can be an opportunity' and inspires new meaning through active reflection. Cancer survivors describe how the experience of cancer can be a catalyst for a greater appreciation for life, personal growth, stronger relationships, new possibilities, or a refined sense of purpose. 4 reflection questions prompt patients to consider the opportunities they have already experienced and choose those they want to seek out next.
Module 5: Managing Challenges (12-min film | 11 reflection questions | administered week 3) Targets how to maintain adaptive mindsets about cancer (e.g., that cancer is manageable or even an opportunity) and the body (e.g., that the body is capable and responsive) in the midst of challenges and setbacks. Cancer survivors describe some of the setbacks and challenges they faced during their cancer treatment and how they managed these challenges and maintained useful mindsets during difficult times. Reflection questions guided through strategies to help them maintain adaptive mindsets and manage current/future cancer related challenges.
Module 6: A New Normal (12-min film | 5 reflection questions | administered week 9) Targets mindsets about cancer and mindsets about the body in the context of the transition to cancer survivorship. Cancer survivors describe their experiences with finishing treatment, their mindsets about the transition to a new normal after cancer, and how they managed challenges with this adjustment. Experts provide strategies for maintaining useful mindsets after treatment ends. Reflection questions encourage patients to reflect on their cancer journey so far, consider the opportunities they want to seize after treatment ends, and develop a strategy for cultivating and maintaining useful mindsets in the future.
Module 7: Share Your Journey (review of previous responses | 1 writing activity | administered week 9) Uses a 'saying-is-believing' style prompt to help patients connect to, personalize, and take ownership of the ideas learned throughout the previous 6 modules. Patients are guided through a series of excerpts from their responses to reflection questions in previous modules. They are asked to reflect upon how their responses may be different now and how their mindsets have changed over the last few months and are asked to write a letter to a recently diagnosed cancer patient to share their own wisdom from their experience including the role of their own mindsets.
authors Zion, Dweck and Crum). 5 The cancer version of the IMI consists of 3 subscales: cancer as a catastrophe, cancer as manageable, and cancer as an opportunity. Each item is rated on a 6-point Likert scale ranging from strongly disagree (1) to strongly agree (6). The scale has strong internal consistency (α = 0.85-0.90). 5 Body mindsets were measured using The Body Mindset Scale (BMS), a 10-item measure of mindsets about an individual's body in the context of a chronic illness.
The BMS consists of 3 subscales: the body as an adversary, the body as capable, and the body as responsive. Each item is rated on a 6-point Likert scale ranging from strongly disagree (1) to strongly agree (6).

| Primary outcome
Our primary outcome measure was HRQoL as measured by the total score of the FACT-G. The FACT-G consists of 27 questions answered on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much).
Higher scores (calculated by summing the items) on the FACT-G indicate better wellbeing. Questions fall into four subscales measuring physical (7 questions), social/family (7 questions), emotional (6 questions), and functional (7-questions) wellbeing. 16 The total score is a sum of these four subscales.

| Secondary outcomes
Coping was measured using the short version of the Cancer Behavior

| Statistical analyses
All analyses were conducted in R 19 using an intention to treat (ITT) procedure that included all randomized participants. Missingness was addressed by using mixed effects models with repeated measures (MMRM) that account for missing data using a maximum likelihood estimation procedure. In analyses that did not employ MMRM, multiple imputation with predictive mean matching (50 iterations) was used.
The effects of the intervention on mindsets, primary outcomes, and secondary outcomes were analyzed using MMRMs that included fixed effects for time (in weeks) and condition and a random intercept for slope. We further quantify the magnitude of these effects by reporting effect sizes (measured by Cohen's d), which were calculated using mean change between baseline (week 0) and post-intervention (week 10) and pooled standard deviations. See

| Retention
We observed minimal loss to follow-up and no participants requested to be withdrawn from the study. Only 10% of enrolled patients were lost to follow-up over the course of the 10-week study. Loss to follow-up did not differ across conditions (CMI: N = 16; TAU: N = 14).

Comparably, trials of psychosocial interventions in cancer patients
and survivors report attrition rates of between 15% and 20%, 20

| Feasibility
Changing recently diagnosed cancer patients' mindsets was feasible using a brief 2.5-h digital intervention administered over 10 weeks.   Figure S1 and   Table S6 in the Supplemental Materials for additional details.
We also conducted mediation analyses that explored the causal relationship between changes in mindsets and subsequent changes in HRQoL. We found that adaptive changes in both illness and body mindsets mediated the relationship between condition (CMI vs TAU) and post-intervention HRQoL. See Figure S2 in the Supplemental Materials for more information.

| Clinical implications
We interpret the magnitude of the observed effect as proof of concept and attribute the effects to our success in changing a new can be challenging to maintain the use of adaptive coping behaviors and effectively manage the distress of symptoms and side effects.
Helping patients adopt more useful mindsets appears to be one way to improve these critical outcomes. Patients with more adaptive mindsets may be coping more effectively with their illness, feeling less distress from their symptoms, and experiencing a higher quality of life across multiple domains. This is important because these outcomes, especially quality of life, can reduce clinical outcomes and even affect survival rates. 25 However, implementing effective programs that evoke these sorts of improvements can be logistically challenging and financially impractical. This intervention presents a uniquely favorable cost to benefit ratio. It can be delivered efficiently (<2.5 h) alongside ongoing treatment, and its digital format allows for quick, low-cost, and widely accessible implementation and dissemination.

| Future directions
In the future, comparative efficacy studies in which the CMI is compared with existing in-person or digital interventions (e.g., CBT, MBSR, etc.) may be useful for understanding the relative efficacy of this style of intervention compared with other evidence-based therapeutics that are aimed specifically at symptom reduction. Future research is also needed to refine the intervention itself and define the proper dosing and schedule, as well as the possible value of combining CMI with other established techniques that have been shown to be effective in treating cancer related distress and anxiety.
As efficacy and effectiveness of this intervention continue to be documented, implementation research should also consider various strategies for this digital intervention to be incorporated into routine healthcare, such as whether it can be billed or and reimbursed by insurance. Future implementation efforts should also consider ways to synergize patient focused interventions with trainings focused on providing care teams with a framework and skillset to uncover patient mindsets and support constructive mindset change in their practice. Finally, given the accumulating evidence that changes in mindsets may also improve stress and immune responses 9 and even enhance treatment outcomes, 26 future research should examine the degree to which mindset interventions may improve physiological outcomes.

| CONCLUSIONS
Improving the HRQoL of recently diagnosed cancer patients has become increasingly recognized as a core component of comprehensive patient centered care in oncology. This study provides an encouraging demonstration that a brief, but targeted digital intervention can improve multiple domains of HRQoL. As such, it helps set the stage for a variety of important questions to follow, including understanding the range and benefit of digital interventions as well as how best to incorporate these interventions into routine clinical care.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.