Objectives MCST CICI MCST CICI. Population & Background 4/1/2016

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1 Metacognitive Strategy Training for Breast Cancer Survivors with Chemobrain: Translating Research into Clinical Practice Meghan Doherty, MSOT, OTR/L, OTD/S Timothy Wolf, OTD, OTR/L, MSCI, FAOTA Objectives Describe the outcomes of a metacognitive strategy training pilot intervention on client occupational performance Explain components of a metacognitive strategy training program for use with women with CRCI. List outcome measures to assess participation and cognition in breast cancer survivors in the clinic. MCST CICI MCST CICI THE EFFECT OF METACOGNITIVE STRATEGY TRAINING (MCST) ON CHEMOTHERAPY-INDUCED COGNITIVE IMPAIRMENT (CICI) Timothy J. Wolf, OTD, MSCI, OTR/L, Principal Investigator Jay F. Piccirillo, MD, FACS, CPI, Sub-Investigator, Professor Otolaryngology - Head and Neck Surgery Bradley Schlaggar MD, PhD, Sub-Investigator, Associate Professor Radiology, Anatomy & Neurobiology & Pediatrics Joshua S. Shimony MD, PhD, Sub-Investigator, Assistant Professor Radiology Cynthia X. Ma, MD, PhD, Sub-Investigator, Associate Professor-Medicine, Division of Oncology, Section of Medical Oncology Carolyn Baum, PhD, OTR/L, FAOTA, Sub-Investigator, Elias Michael Executive Director, Program in Occupational Therapy, Professor of Occupational Therapy, Neurology, and Social Work Joyce E. Nicklaus, RN, BSN, CCRC, Clinical Research Nurse Coordinator, Otolaryngology Meghan Doherty, MSOT, OTR/L, Research Coordinator, Occupational Therapy Caroline Bumb, MS, CCRP, Division of Oncology, Medicine Rebecca Coalson, BS, Department of Neurology funded by the McDonnell Center for Systems Neuroscience, Washington University Institute of Clinical and Translational Sciences grant UL1 TR from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH), Mallinckrodt Institute of Radiology at the Washington University School of Medicine Population & Background Epidemiology Breast cancer is the most common malignancy (28%) in females in the United States The use of chemotherapy has led to dramatic improvements in survival in breast cancer patients and is now considered standard of care Population & Background Chemotherapy and Cognitive Deficits Recent findings of decreased productivity, impaired community involvement, and poor role-functioning resulting from cognitive dysfunctions after chemotherapy Studies in BRCA survivors have shown deficits in the domains of attention, learning, working memory, motor speed, visuo-spatial skills, executive function (planning, problem solving, multitasking), and information processing after chemo These are referred to as chemotherapy-induced cognitive impairments (CICI) or chemobrain The rate of CICI in the literature ranges from 16% to 50% 1

2 Background CICI Assessment Left Right Wide range in published rates of CICI is largely due to methodological issues related to assessment of cognitive function Tools Timing Follow-up period Functional neuroimaging being used in research Resting-state functional MRI (rs-fcmri) Our research group found differences in the frontal-parietal cognitive control regions in those who self-report CICI vs. those who do not Moment-to-moment control of cognitive function Cognitive flexibility Dorsal Background Intervention Background Intervention Traditionally rehab for BRCA survivors postchemotherapy has focused on exercise programs management of edema psychosocial adjustment arm range of motion ADLs However, cognitive dysfunction is having the greatest negative impact on return to complex everyday life activities such as work/productivity and community living Past studies addressing CICI in BRCA and other cancers have focused on specific cognitive impairment reduction which has had little impact on everyday life performance Little work has looked at the use of metacognitive strategy training which targets the mechanisms associated with the frontal-parietal network Cognitive-Orientation to daily Occupational Performance (CO-OP) approach Study Aims Study Aims Specific Aim 1: To assess the effect of metacognitive strategy training on self-reported cognitive performance in a sample of breast cancer survivors with self-reported CICI. Hypothesis: Metacognitive strategy training will improve self-reported cognitive performance in patients with self-reported CICI. Specific Aim 2: To assess the effect of metacognitive strategy training brain networks as defined by rs-fcmri in a sample of breast cancer survivors with selfreported CICI. Hypothesis: Metacognitive strategy training will improve functional connectivity characterized by rsfcmri-in patients with self-reported CICI in the two connections in the frontal-parietal network found to be negatively impacts with CICI. 2

3 Study Design Single group, pre/post pilot study Obtained approval from WU Human Research Protection Office and Protocol Review Monitoring Committee Participants recruited from Siteman cancer center N=14 Inclusion & Exclusion Criteria Inclusion criteria : Females years old Self-reported CICI (Global Rating of Cognition dysfunction as Moderately Strongly or Extremely and a Cognitive Failures Questionnaire score >30) Completed adjuvant (or neoadjuvant) chemotherapy at least 6 months prior to participation Able to read, write, and speak English fluently Able to provide valid informed consent Have a life expectancy >6 months at time of enrollment Diagnosed with BRCA (invasive ductal or lobular Stages I, II, or III) and completed chemotherapy within the preceding 2 years On stable doses (i.e., no changes in past 90 days) of medication that impact cognitive function (i.e., anti-depressants). Inclusion & Exclusion Criteria Methods Exclusion criteria: Prior CA diagnoses of other sites with evidence of active disease within 1 yr Active dx of any acute or chronic brain-related neurological conditions that can alter normal brain anatomy or function (e.g., Parkinson s disease, dementia, cerebral infarcts) Severe depressive symptoms (Personal Health Questionnaire score of 21) History of traumatic brain injury Weigh over 350 pounds (limit of MRI machine) Received skull-based radiation treatment within the past year for any reason Implanted metal objects not compatible with MRI History of claustrophobia or inability to lie flat that will preclude undergoing MRI Any medical condition which would render the study unsafe or not in the best interest of the participant Potential participants completed a screening survey with medical background questions and two cognitive screens: Cognitive Failures Questionnaire (CFQ) & the Global Rating of Cognition (GRC) Face to Face assessment: consent, baseline assessment battery, and neuroimaging 12 sessions of CO-OP metacognitive strategy training with an occupational therapist Discharge assessment battery and MRI What is CO OP? Treatment Approach Client-centered Performance-based Problem solving Enables skill acquisition Strategy use Guided discovery Focuses on occupational performance Haskins, E. (2012). Rehabilitation for Impairments of Executive Functions. In L. Trexler (Primary Ed) Cognitive Rehabilitation Manual (pg. 12). Reston, VA: American Congress of Rehabilitation Medicine Reproduced from ACRM Publishing, 2012, by permission 3

4 Other Metacognitive Strategy approaches Why was CO OP developed? WSTC What should I be doing? (Lawson & Rice, 1989) PST problem-solving training (von Cramon, Matthes-von Cramon, & Mai, 1991) GMT Goal management training (Levine et al., 2000) STP Self-talk Procedure (Cicerone & Wood, 1987; Ciccerone and Giacino, 1992). Basic premise: engagement in activity is necessary for healthy development Developed as an alternative to motor interventions that focused on remediation of deficits Bottom-up approach remediation of deficits should result in improved performance (limited evidence) Bottom-up interventions = intensive Current motor theory shifted to focus more on task-oriented Needed an intervention that focused on performance Solution Combine contemporary task-oriented motor theory with learning theory Bottom up approaches Top Down Approaches Improved Improved Cognition Cognitive Exercises Activity Participation Memory Problem solving memory attention Metacognitive Strategy Training Direct Skill Training Improved Activity Participation Improved Cognition? Uses Health & Disability Model of ICF Goals of CO OP Focus not at disability & impairment Focus on discovering strategies to eliminate barriers & create supports that enable activity & participation Mandich & Polatajko, 2005 Skill acquisition Cognitive strategy use Generalization of learning Transfer of learning Clientchosen goals Self evaluation Global Strategy Training Guided Discovery Activity Performance 4

5 Why CO-OP is Valuable CO-OP Prerequisites It meets the demands of three key players: Therapists it is client-centered and performance based Administrators it is cost-effective, efficient, and evidence based Clients and caregivers it is effective in helping adults and children succeed Polatajko and Mandich, 2004 language skills to respond to Canadian Occupational Performance Measure (COPM) ID 3+ occupational goals Respond and attend to therapist Have potential to perform task Have motivation to learn 3 skills Awareness Polatajko, 2006 CO-OP Key Features Client Chosen Goals Mandich & Polatajko, 2005 Daily logs Activity Card Sort Canadian Occupational Performance Measure Guided process Measureable goals Can be used as an outcome measure VIDEO CO-OP Key Features Dynamic Performance Analysis Observe performance Identify breakdown, test potential strategies Correct problem, not underlying skill TASK ANALYSIS! Mandich & Polatajko,

6 CO-OP Key Features Cognitive Strategies Global Domain-specific Mandich & Polatajko, 2005 Global Strategy: Goal, Plan, Do, Check GOAL: What do I want to do? PLAN: How am I going to do it? DO: Do it! CHECK: How well did my plan work? Domain Specific Strategies Body position Attention to task Task specification/modification Supplementing task knowledge Feeling the movement Verbal mnemonic Verbal script Mental imagery Relaxation techniques CO-OP Key Features Guided Discovery Try to figure it out on your own, but I will help you if you get stuck. High: Explicit Instruction Mid: Guided Discovery Low: Discovery Learning Just Listen! I will tell you what to do! Mandich & Polatajko, 2005 Trial and Error Learning: Figure it out on your own! 6

7 Guided Discovery Guided Discovery Posing questions to the client that focus on factors that are relevant and irrelevant to help client identify relevant cues Similar to scaffolding Process questions One thing at a time Ask, don t tell (verbal) Coach, don t adjust (physical) Make it obvious Video CO-OP Key Features This is how we should be cuing Mandich & Polatajko, 2005 Enabling Principles Significant Other Involvement Make it fun Promote learning Progress through stages Small steps Support, feedback, practice, and review Motivation Behavioral strategies (e.g., reinforcement, shaping) Work toward independence Promote generalization and transfer Primary role Support in skill acquisition Help facilitate transfer/generalization Therapist shares info so that success can be celebrated & new skills supported Caregiver change their perspective on the client - See lack of success as failure of the PLAN, not personal failure 7

8 CO-OP Key Features Intervention Format Mandich & Polatajko, Sessions Phase I-Preparation Establishing the goals COPM Phase II-Acquisition Typically 10 sessions Start: introduce GPDC Work through GPDC for all 3 goals (plan, do, check) Phase III-Verification Progress reviewed COPM re-rated Mistakes are OKAY! Goal Plan Do Check Strategy Training > Direct Skill Training Generalization Learning can be inhibited when we prevent patients from discovering their own solutions Learning may be best when: Patients overcome their difficulty challenges (with guidance from therapist) Patients develop their own reasoning and problemsolving skills GOAL What do I want to do? PLAN How? When? Where? CHECK Did I do my plan? Did it work? DO The plan Goal is achieved Putting it all Together Data Analysis Clientchosen goals Self evaluation Global Strategy Training Guided Discovery Activity Performance Behavioral Data Distribution of scores described using median and range Change scores calculated Median difference and 95% CI calculated Wilcoxon signed rank test Non-parametric effect size r 8

9 Analysis Neuroimaging Data Timecourses calculated for each subject an each scan for two frontoparietal control regions Fisher z-transformed Pearson correlation coefficients calculated between two frontal-parietal region s timecourses (functional connectivity) Functional connectivity changes across the brain compared using Object Oriented Data Analysis (OODA) Iterative approach using Gibb s distribution Pearson correlations to evaluate relationship between changes in connectivity and behavioral outcomes Results Table 2: Study sample characteristics (n = 14) Variable Median (Min Max) or % Age (Years) (36 to 65) Time since completion of chemotherapy 9.5 (7 to 34) (months) Race n (%) Caucasian 12 (86%) African American 1 (7%) Asian 1 (7%) Highest level of education High School or Associate Degree 2 (14%) Bachelor s Degree 3 (21%) Master s or Doctoral Degree 9 (65%) Work Status Full time 12 (86%) Part time 1 (7%) Retired 1 (7%) Results Behavioral Table 3: Behavioral Outcomes Assessment Cognitive Failures Questionnaire Pre Score Median (Min Max) Post Score Median (Min Max) Median of difference (prepost) (95%CI) Effect Interpretation size (r) b 50 (39 68) 36 (15 49) 15 (8.9 to 25.2) a.85 Significant decrease in subjective cognitive symptoms DKEFS Trail Making 12 (1 13) 12 (7 14) 1 ( 2.1 to 0) a.50 Sig improvement in objective EF (cog flexibility) Dysexecutive Questionnaire 23 (3 39) 11 (0 33) 9 (4 to 16) a.75 Sig improvement in subjective EF Montreal Cognitive 28 (21 30) 28 (21 30) 0( 1.05 to 0.05).28 Stable general cognitive Assessment function The Canadian Occupational 4.8 ( ) 7.7 ( ) 3 ( 3.3 to 1.6) a.88 Sig improvement in self rated performance of activities Performance Measure of activities 2.8 ( ) 8.0 ( ) 4.5 ( 5.3 to 3.3) a.88 Sig improvement in self rated satisfaction with performance PHQ 9 Depression 6.5 (1 13) 4.5 (0 11.0) 1.5 ( ).53 Decrease in depressive symptoms approaching sig Results Neuroimaging 10 subjects had enough data for analysis The amount of data kept did not differ between two scans (p =.59) Using object oriented data analysis (OODA) A one-tailed, paired t-test on the connection between the two frontal parietal control regions previously described showed trend level significance (p=.054) Increase in functional connectivity strength after treatment in 6 of the 10 subjects 1 Results Neuroimaging 0.8 The change in Personal Health Questionnaire (PHQ-9) explained 35% of the difference in connection strength (p=0.057) The change in the Trailmaking subtest of the Delis- Kaplan Executive Function System (DKEFS), a measure of EF explained 26% of the change in connection strength (p=0.108) z transformed Correlation Coefficient Before Treatment After Treatment Subject 9

10 35 Study Limitations 30 CFQ Score Change No control group Small sample Heterogeneity in terms of age, time since chemo, and response to intervention 0-5 Individual Participants Conclusions & Clinical Implications Next Steps CO-OP is a feasible intervention for BRCA survivors CO-OP has a positive effect on: subjective cognitive performance objective cognitive performance Activity performance Quality of life CO-OP showed a positive change in functional connectivity in one brain network Translation into clinical program Future research projects Community based OT services for Survivors AOTA Guidelines for cancer How can a research-based protocol be adapted for clinical use? Is it feasible? How will it be assessed? How can we track outcomes to add strength to the evidence base? Who will benefit? Evaluating the individual s physical, emotional, and cognitive abilities in order to make appropriate recommendations Identifying specific cognitive deficits affecting occupational roles, and providing compensatory training to successfully complete activities. Deluliis ED, Hughes JK. Occupational Therapy's Role in Breast Cancer Rehabilitation 2012; /media/corporate/files/aboutot/professionals/whatisot/hw/facts/breastcancer.pdf,

11 Other cancers with similar problems Transitioning research into practice Survivors of all types experience challenges with returning to work, work performance, and 1 in 10 never returns to work. Cognitive dysfunction is well recognized among patients with non-central nervous system cancers 14 and cognitive symptoms related to cancer treatment are a major contributor to difficulty with return to work and other productive roles. Difficulty with prolonged mental concentration; with analyzing data; and with learning new things. While definitions of cognitive impairment vary from study to study, the literature demonstrates cognitive impairment both during chemotherapy and longitudinally after treatment. The research design of MCST-CICI was purposely set up to be clinically feasible It included clinical cognitive and participation measures that showed good effect sizes poststudy Cancers of all types can cause treatmentrelated cognitive impairment Expansion to term CRCI Cancer-related Cognitive Impairment Clinic clients may have non-cognitive therapy concerns as well Creating a clinical program Logic Model Create a logic model Develop treatment protocol and assessment battery Build relationships Marketing IRB approval Logic Model Assumptions Logic Model Assumptions Cancer survivors are individuals w/ a cancer diagnosis Many survivors have cognitive deficits resulting from cancer or cancer treatments that impact daily life participation. Cancer survivors in the St. Louis metro region have limited access to community-based outpatient therapy services to address their cognitive concerns. Rehabilitation services for survivors will help prevent or treat side-effects of cancer or its treatment and decrease healthcare costs (i.e. time lost from work, caregiving & hospital readmissions). Metacognitive Strategy Training (MCST) improves occupational performance and self-management skills in neurological populations. Occupational Therapists are uniquely capable of addressing the cognitive, physical, and psychosocial limitations of survivors that limit their independence in daily activities. Interdisciplinary community partnerships will improve health-related quality of life (HRQOL) for cancer survivors. 11

12 Logic Model Logic Model Inputs Cancer survivors WUOT Therapists experienced in MCST Cancer health care providers Payers (insurance, out of pocket pay) Students Logic Model Logic Model Activities Administer focus groups and surveys for therapists involved in cancer care Develop assessment battery including web-based data management to measure program outcomes. Build relationships with Siteman Cancer Center staff who provide referrals Instruct therapists in metacognitive strategy training approach and assessment tools Market program including print and web materials Deliver program to survivors Survey Completed by Jenna Rebhun, OTD/S Survey of Therapists N=61 therapists, 28 PTs and 33 Ots In response to questions regarding OT s expertise in helping address symptoms/side effects in adult cancer survivors, OT and PT responses significantly differed in the following areas: fatigue/energy conservation management, gait/postural issues/balance issues, and equipment needs. PT viewed OT as having less expertise than OT s viewed themselves as having. The large majority of respondents from both professions (n=60) believe OT has the expertise in helping address cognitive deficits with cancer survivors (96%) 52% of respondents believe all therapists should receive advanced specialty training before working with cancer survivors. Of 58 respondents, 69% believe oncologists do not understand the difference between OT and PT Biggest barrier to expanding OT practice: Lack of recognition and understanding of OT role in cancer survivorship (63%) 12

13 Logic Model Logic Model Outputs Increased referrals of cancer survivors to WUOT Refined assessment battery Measurable change of occupational performance Comprehensive approach to individualized rehabilitation Logic Model Logic Model Outcomes Cancer survivors report high satisfaction with program and staff on patient satisfaction surveys Survivors promote the program s value to the cancer community Increased referrals translate into profits for WUOT clinic Survivors report improved self-management skills and psychosocial health Logic Model Logic Model Impacts Improved health related quality of life of cancer survivors Decreased overall healthcare costs due to greater use of primary care and better return to work outcomes. Comprehensive, integrated health care delivery system 13

14 Develop Treatment Protocol Assessment Battery Goal: skill acquisition and skill improvement minute sessions: Session 1-2 Preparation Sessions 3-11 Treatment Session 12 Review and Re-evaluation Measure Description Method & Time Administered Cognitive Failures Questionnaire (CFQ) 24 CFQ measures lapses in motor function memory, and perception. This questionnaire contains 25 items and scores range from 0 to 100. Redcap Pre and Post Montreal Cognitive Assessment (MOCA) 25 Personal Health Questionnaire (PHQ 9) Depression 26 The Weekly Calendar Planning Activity (WCPA) 27 The Behavioural Assessment of Dysexecutive Syndrome (BADS) 28 The MOCA is a publically available cognitive screening tool validated to distinguish normal from those with mild cognitive impairments. The PHQ 9 is a quick screening tool for depression that has been used in research and clinical settings to screen for depressive symptoms. The WCPA is used as a screen for difficulties in executive functioning across a variety of populations to understand the underlying nature of performance problems. The Behavior Assessment of Dysexecutive Syndrome contains 7 tests to evaluate planning, organization, problem solving, and attention. We will use the Zoo Map Test of planning. Face to Face Session 1 Face to Face Session 1 Session 12 Face to Face Session 2 Session 12 Face to Face Session 1 Session 12 Develop Assessment battery Measure Description Method & Time Administered Assessments to be completed as Needed Upper Extremity Range of Motion, Strength, and somatosensation Face to Face Screen screening tests Whisper Test 29 Audition screening measure to detect hearing impairment for further referral. Face to Face Tinetti Performance Oriented Mobility Assessment (POMA 1) 30 The POMA I is a task oriented test that measures adult gait and balance with an ordinal scale from 0 (most impairment) to 2 (independence). Face to Face Build Relationships Marketing With regional cancer center, Siteman WU Physicians Nurses coordinators and navigators Resource center staff WU Physical Therapy Ethics board staff Support groups Development of materials Print Web Patient-centered Physician-centered Sharing of materials throughout regional cancer center satellites 14

15 IRB Approval Tracking Outcomes Required navigation of the Protocol Review and Monitoring Committee (PRMC) AND Human Research Protection Office at WU Needed to collect patient outcomes for dissemination and program improvement Utilizing REDCap online data collection tool as well as EMR and paper assessments Will streamline assessment battery Will measure client change on activity participation and subjective and objective cognitive performance Will measure client satisfaction with the program through client satisfaction surveys Conclusions Questions? Our intervention (CO-OP) is a feasible intervention for BRCA survivors in clinical trials and in an outpatient community-based clinic If you build it, they will come = WRONG Contact Information Meghan Doherty Washington University School of Medicine Program in Occupational Therapy dohertyme@wustl.edu Timothy Wolf Department of Occupational Therapy University of Missouri wolftj@health.missouri.edu 15