Feasibility and Preliminary Efficacy of an Enhanced Mindfulness Intervention for Children and Young Adults With High Grade or High-Risk Cancer and Their Caregivers: A Pilot Randomized Controlled Trial
Phase: NA
Conditions: Glioblastomas, Sarcoma, Astrocytoma, Brain Cancer, Leukemia
Sponsor: National Cancer Institute (NCI)

Abbreviated Title:  EMI Children/YA with  Cancer 
 
 
 
 
 
 
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Version Date: 12/13/2021 
Abbreviated Title: EMI Children/YA with  Cancer 
NIH Protocol #: 18-C-0080 
Version Date: 12/13/2021 
NCT Number: NCT03538587 
Title: Feasibility and Preliminary Efficacy of an Enhanced Mindfulness Intervention for 
Children and Young Adults with High Grade or High-Risk Cancer and Their Caregivers: A Pilot 
Randomized Controlled Trial 
NCI Principal Investigator: Staci Martin, Ph.D. 
Pediatric Oncology Branch (POB) 
National Cancer Institute (NCI) 
National Institutes of Health (NIH) 
9030 Old Georgetown Road 
Bethesda, MD 20892 
Phone: 240-760-6025 
E-mail: martins@mail.nih.gov 
Investigational Agents (or Devices): None 
 
Commerical Agents (or Devices): None 

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PRÉCIS  
Background 
• Children and young adults diagnosed with a high-grade or high-risk cancer (e.g., diffuse 
intrinsic pontine glioma, glioblastoma multiforme, relapsed-refractory leukemia, 
refractory metastatic sarcomas) face a poor prognosis given limited curative options.  
• Recent research has indicated that this population of patients and their parents experience 
elevated stress and poorer health-related quality of life (HRQL) relative to normative 
samples.  
• Recently published psychosocial standards of care in pediatric oncology strongly 
recommend that children diagnosed with cancer and their caregivers receive early and 
continued assessment of their wellbeing and have access to interventions to optimize 
functioning and HRQL. In addition, there is increasing recognition of the importance of 
palliative interventions early in the disease trajectory.  
• Despite this recommendation, minimal research has examined supportive care 
interventions for this population early in the disease trajectory.  
• Mindfulness-based interventions (MBIs) have empirical support for their feasibility and 
efficacy in alleviating emotional distress and physical symptoms in children and adults 
with chronic health conditions, including terminally-ill patients and their caregivers.  
Objectives 
• To assess the feasibility of an enhanced mindfulness intervention (EMI) in children and 
young adults (ages 5-24 years) with a high-grade or high-risk cancer with poor prognosis 
and one of their primary caregivers.  
Eligibility 
• Children and young adults ages 5-24 years and a parent or adult primary caregiver  
• Diagnosis of a high-grade or high-risk cancer with poor prognosis 
• English speaking 
• Must have access to a mobile device or computer with internet. 
• Potential participants will be excluded if there is evidence of pre-morbid severe cognitive 
or psychiatric disability in parent or child that would impair their capacity for 
participation, or if there is evidence of clinical disease progression at the time of referral 
to this study, such that it would prevent the child from engaging in the intervention.  
Design 
• This is a pilot randomized controlled trial that will compare feasibility and preliminary 
efficacy of an 8-week EMI group (n=10 dyads) compared to a psychoeducation control 
group (n=10 dyads).  
• All participants will complete measures of feasibility (primary outcome) and exploratory 
outcomes at baseline and following the 8-week intervention. Exploratory measures will 
include emotional (e.g., depression, anxiety) and physical (e.g., pain, fatigue) wellbeing, 
as well as baseline mindfulness/self-compassion.   
• The 8-week EMI will consist of one initial in-person session with the child and parent, a 
series of at-home assignments, and two “booster” sessions. The psychoeducation group 
will be given educational material about coping with cancer.  
• The psychoeducation group will be offered the opportunity to participate in the EMI 8 
weeks post-baseline. 

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TABLE OF CONTENTS  
PRÉCIS .......................................................................................................................................... 2 
TABLE OF CONTENTS ................................................................................................................ 3 
STATEMENT OF COMPLIANCE ................................................................................................ 5 
1 
INTRODUCTION .................................................................................................................. 6 
1.1 
Study Objectives .............................................................................................................. 6 
1.2 
Background and Rationale ............................................................................................... 6 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT ......................................................... 9 
2.1 
Eligibility Criteria ............................................................................................................ 9 
2.2 
Recruitment Strategies ................................................................................................... 10 
2.3 
Screening Evaluation...................................................................................................... 10 
2.4 
Participant Registration and Status Update Procedures ................................................. 11 
2.5 
Intervention Assignment and Randomization/Stratification Procedures ....................... 11 
2.6 
Baseline Evaluation ........................................................................................................ 12 
3 
STUDY IMPLEMENTATION ............................................................................................ 14 
3.1 
Study Design .................................................................................................................. 14 
3.2 
In-person Session ........................................................................................................... 15 
3.3 
Enhanced Mindfulness Intervention (Immediate Intervention Group) .......................... 17 
3.4 
Cost and Compensation .................................................................................................. 18 
3.5 
Off Study Criteria ........................................................................................................... 19 
4 
DATA COLLECTION AND EVALUATION ..................................................................... 19 
4.1 
Data Collection ............................................................................................................... 19 
4.2 
Data Sharing Plans ......................................................................................................... 20 
4.3 
Toxicity Criteria ............................................................................................................. 20 
5 
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN .. 20 
5.1 
Definitions ...................................................................................................................... 20 
5.2 
OHSRP Office of Compliance and Training / IRB Reporting ....................................... 20 
5.3 
NCI Clinical Director Reporting .................................................................................... 20 
5.4 
NIH Required Data and Safety Monitoring Plan ........................................................... 20 
6 
STATISTICAL CONSIDERATIONS.................................................................................. 20 
6.1 
Statistical Hypothesis ..................................................................................................... 20 
6.2 
Sample Size Determination ............................................................................................ 21 
6.3 
Populations for Analyses ................................................................................................ 21 
6.4 
Statistical Analyses ........................................................................................................ 21 

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HUMAN SUBJECTS PROTECTIONS ............................................................................... 23 
7.1 
Rationale For Subject Selection ..................................................................................... 23 
7.2 
Evaluation of Benefits and Risks/Discomforts .............................................................. 23 
7.3 
Consent and Assent Process and Documentation .......................................................... 23 
8 
REGULATORY AND OPERATIONAL CONSIDERIATIONS ........................................ 25 
8.1 
Study Discontinuation and Closure ................................................................................ 25 
8.2 
Quality Assurance and Quality Control ......................................................................... 26 
8.3 
Conflict of Interest Policy .............................................................................................. 26 
8.4 
Confidentiality and Privacy ............................................................................................ 26 
9 
REFERENCES ..................................................................................................................... 28 
 
 
 

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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 
812)  
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 

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1 
INTRODUCTION 
1.1 
STUDY OBJECTIVES 
1.1.1 Primary Objective 
To assess the feasibility and acceptability of an enhanced mindfulness intervention in children 
(ages 5-17) and young adults (ages 18-24) with a high-grade or high risk cancer and one of their 
primary caregivers. Feasibility and acceptability will be evaluated based on the following: 
A. Proportion of eligible dyads who enroll during a two-year period 
B. Treatment specific retention among all randomized participants, with a target 
retention rate of 70% over the 8 week EMI/control period 
C. Compliance with at-home practices, with a proposed target rate of 4 out of 7 days per 
week on average over the 8 week EMI period 
D. Parent and patient reports of satisfaction on the feasibility questionnaire; for youth 
ages 8+ and caregivers, average item scores >3.0 will be deemed to reflect adequate 
feasibility 
1.1.2 Exploratory Objectives 
1.1.2.1 To assess changes pre- to post-intervention in child anxiety, depression, positive and 
negative affect, stress, pain behavior, fatigue, mindfulness, and health-related quality of 
life compared to children in the psychoeducational control group. 
1.1.2.2 To assess changes pre- to post-intervention in caregiver anxiety, depression, stress, 
fatigue, sleep disturbance, psychological flexibility, mindfulness, and self-compassion 
compared to parents in the psychoeducational control group.  
1.2 
BACKGROUND AND RATIONALE 
A cancer diagnosis in childhood can have an adverse impact on the wellbeing of pediatric 
patients and their parents. Decades worth of research suggests that children diagnosed with 
cancer and their parents experience elevated levels of distress and lower quality of life compared 
to normative samples 1, although only a minority of individuals experience clinically significant 
anxiety or depression 2. Post-traumatic stress symptoms (PTSS), a precursor to post-traumatic 
stress disorder, have been widely reported by pediatric patients and caregivers 3,4 and can persist 
over time when not addressed 5. Children with brain tumors stand out relative to pediatric 
patients with other types of cancer due to their negative social competence as well as poorer 
long-term quality of life, and may require more intensive support and interventions that are 
different in scope, timing, and content than those that may be beneficial for patients with other 
diagnoses 6,7. 
Recent research has specifically examined the needs of children with cancer who do not have a 
high likelihood of cure. For example, a longitudinal study suggests that children with high-grade 
brain tumors exhibit worse physical functioning, increased anxiety, and lower health-related 
quality of life (HRQL) compared to normative samples 8. Further, parents of children with high-
grade brain tumors report high levels of emotional distress 8, which is significantly associated 
with reductions in their child’s HRQL 8,9. Despite these difficult circumstances, minimal 
research has specifically addressed the psychosocial sequelae of these children and their parents 
or offered palliative interventions—defined as efforts to reduce suffering across physical, 
psychological, social, and spiritual domains—early in the disease trajectory.  
Recent psychosocial standards of care in pediatric oncology strongly recommend that children 
diagnosed with cancer and their parents receive access to interventions to mitigate stress and 

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preserve their wellbeing 1. To date, there are no known psychological interventions designed for 
children with a high-grade/high-risk cancer or their parents that address quality of life and stress 
early in the disease trajectory. The literature in this population has overwhelmingly focused on 
end-of-life care, which is at odds with the recent consensus that palliative care be established 
well before progression of disease 10,11. Indeed, a recent review cited strong support from the 
American Society for Clinical Oncology, the Institute of Medicine, and the American Academy 
of Pediatrics that we provide early integration of palliative care for children with all high-risk 
cancers, a standard that is unfortunately not being met.12   
The general psychosocial literature in pediatric oncology (not specific to cancer type) has 
documented a range of supportive psychological protocols for childhood cancer patients 1,13. 
Cognitive-behavioral therapy (CBT) is a commonly cited modality, which includes pragmatic 
skills training (e.g., communication skills) and the development of problem-focused coping skills 
(e.g., identifying and restructuring distorted or “unhelpful” thoughts) for pediatric cancer patients 
13-16. In addition, CBT has been paired with interventions grounded in family systems theory 
that aim to enhance coping, problem solving, and communication among parents and siblings of 
pediatric cancer patients 15-18. Although positive findings are reported in individual studies, a 
meta-analysis of psychological interventions in pediatric oncology revealed only a small effect of 
treatments on parental distress and adjustment and no effect on outcomes in children 19. This 
suggests that many existing psychosocial intervention models are not fully supporting the needs 
of pediatric cancer patients and their families.  
1.2.1 Mindfulness-based interventions 
Mindfulness is a secular meditative practice that aims to cultivate nonjudgmental awareness of 
the present moment. Mindfulness-based interventions (MBIs) entail a diverse set of practices that 
direct an individual’s attention to internal (e.g., physical sensations, cognitions, emotions) and 
external (e.g., sights, sounds) stimuli. These practices can be tailored to alert the participant’s 
attention to condition-specific stimuli (e.g., pain, fatigue) or can be generalized to nonspecific 
stimuli (e.g., nature, music). Among children and adolescents, mindfulness practices often go 
beyond simple mindful breathing and entail more active strategies in order to enhance 
engagement and adherence. MBIs have been trialed with a broad range of populations spanning 
the developmental trajectory (i.e., preschool through old age 20-22), including among patients 
with mental health (e.g., post-traumatic stress, anxiety) and physical health (e.g., chronic pain, 
cancer) conditions 23-28. There is a rapidly growing body of literature documenting the benefits 
of MBIs for symptoms of stress, worry/anxiety, and sadness/depression in clinical and 
nonclinical populations 26,29,30. In addition to psychological benefits, mindfulness practices 
exert physical health benefits. Indeed, research has demonstrated a positive effect of MBIs on 
inflammation, cardiac functioning (e.g., blood pressure, heart rate variability), and 
neuroendocrine functioning (e.g., release of stress hormones such as cortisol) across populations 
31-33.  
The benefits of MBIs are specifically documented in the oncology literature, and there is 
evidence to suggest they would be valuable for youth 34. Meta-analyses report robust effects of 
MBIs on symptoms of anxiety and depression in adult cancer patients on active treatment and 
survivors 30,35. Several studies report reductions in fatigue and pain in cancer patients following 
mindfulness practices 33,36-38. Notably, MBIs have been piloted with adult oncology patients 
with incurable disease and their caregivers with positive initial results: The research suggests 
strong feasibility in addition to lower levels of emotional reactivity, more psychological 
acceptance of difficult events, and reduced caregiving burden in terminally-ill oncology patients 
24,39,40.  

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To date, two studies have examined MBIs in pediatric oncology, specifically with adolescents 
and young adult patients. Both studies utilized traditional Mindfulness-Based Stress Reduction 
(MBSR), a structured group-based protocol consisting of 90-minute sessions for 8 consecutive 
weeks with homework in between 41. One study included a sample of adolescent and young 
adult survivors of cancer, and demonstrated a significant positive effect of the intervention on 
emotional distress and HRQL, in addition to a reduction in negative attitudes toward self 42. The 
second study included a small sample of adolescents (n=7) either in remission or undergoing 
active treatment 43, and results indicated strong acceptance of the intervention model and 
unanimous benefit for handling stress. In this study, however, the researchers indicated barriers 
to recruitment and participation due to the time-heavy and intensive nature of the MBSR 
program, in addition to scheduling challenges inherent to a group-based program. These data 
suggest that MBIs may be suitable and potentially beneficial for youth with high-grade/high-risk 
cancers and/or their parents, but that a time-intensive protocol is likely prohibitive. Although a 
brief MBI has not been examined in pediatric oncology patients, brief protocols have been 
successful in several studies, including adult cancer patients and youth without cancer. These 
studies used protocols consisting of limited in-person contact with the research team and 
primarily relied on at-home practice (i.e., 10 to 20 minutes of daily exercises) or even single 
sessions, and have been associated with multiple positive psychological and physical outcomes 
33,44,45.   
Considerable research has examined the potential mechanisms through which mindfulness exerts 
its effects. Across populations, the aim of mindfulness is to increase attention to the present 
moment and expand openness to, and acceptance of, both desirable and challenging experiences. 
By engaging in this mindset during a single exercise, practitioners experience momentary 
enhancement of personal resources, such as increased cognitive flexibility, positive affect, and 
vagal tone 32,46-48. This is evidenced by patient responses on questionnaires in addition to 
neuroimaging and psychophysiological data 32,49,50. For example, regions of the brain such as 
the anterior cingulate cortex (ACC), which enables executive attention and inter/intrapersonal 
awareness, exhibited increased white matter integrity following a brief mindfulness intervention 
51. In addition, short mindful breathing practices have been associated with relative 
improvements in left prefrontal activation – a region of the brain with self-regulation and 
behavioral flexibility 52. Empirical research has also demonstrated that, over time, a regular 
mindfulness practice can help an individual cultivate durable personal resources that persist 
outside of active practice. In other words, mindfulness does not eliminate feelings of stress, 
worry, or sadness; rather, it increases psychological resources such that individuals have more 
energy to cope with the emotions and stress that accompany a terminal cancer diagnosis and 
associated medical treatment. Given that so much of cancer care is depleting, the capacity to 
restore and cultivate personal resources among patients and caregivers through MBIs is 
noteworthy and has great potential to improve quality of life for these individuals. 
1.2.2 Preliminary Data 
As part of a larger study examining long-term outcomes of pediatric brain tumor patients post-
radiation therapy, we have evaluated psychological sequelae and quality of life among children 
with high-grade and high-risk cancers and their parents. Our unpublished data suggest very 
elevated levels of stress among caregivers, in addition to clinically-elevated difficulties with 
family-based communication and coping. Moreover, HRQL data suggest that approximately 
40% of children experience frequent worries and more than half of parents surveyed report that 
their child’s illness interferes with their child’s happiness to some degree. On measures of 
physical wellbeing, these children and adolescents report significant levels of fatigue compared 
to normative samples. Taken together, these data suggest elevated stress and difficulties coping 

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among parents, coupled with significant fatigue and illness-related impairment in quality of life 
among children with high-grade/high-risk cancers. These preliminary findings support the need 
for supportive psychological interventions in this population. 
1.2.3 Summary and Future Directions 
Interventions that mitigate suffering and enhance wellbeing in children with high-grade and 
high-risk cancers and their parents are sorely needed, given the absence of empirically-supported 
psychological interventions for this population. The proposed project will be the first known 
study to evaluate a supportive psychological intervention in this group of children and parents 
and is well-suited to the NIH Intramural Research Program. It will be the first in a series of 
planned studies. After establishing feasibility and preliminary efficacy, we plan to seek 
additional funding for a larger, sufficiently-powered, randomized controlled trial that allows for 
testing the statistical and clinical efficacy as well as potential mediators and patterns of change 
over longer time periods. Additional future directions include testing the EMI against or 
alongside traditional cognitive behavioral strategies in children with high-grade/high-risk cancers 
and parents, in addition to children and families facing other types of pediatric cancer and those 
undergoing transplant (due to cancer, primary immunodeficiency). Future research also would 
aim to evaluate the efficacy of this intervention when administered by supportive care staff (e.g., 
recreational therapy/child life) or nurses. The ultimate goal of this study is to translate this 
program into a clinical service that has benefits to patients across disease groups.  
In short, the current protocol represents a first-of-its-kind study in an area very much in need of 
empirical attention. It reflects a relatively low cost, simple, and brief intervention that, if proven 
feasible and efficacious, could rapidly translate into clinical practice.  
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT  
2.1 
ELIGIBILITY CRITERIA 
2.1.1 Inclusion Criteria for Patients  
2.1.1.1 Patients diagnosed with a high-risk/high-grade cancer (e.g., high-grade brain tumors, 
relapsed/refractory acute lymphoblastic leukemia, acute myeloid leukemia, high-grade 
sarcoma) characterized by poor prognosis (e.g., estimated 5-year survival rate <30% 
based on scientific consensus in the literature, where available, or by expert physician 
report), as confirmed by medical record review.  
2.1.1.2 Patients with active disease 
2.1.1.3 Age ≥ 5 years and ≤ 24 years of age. 
2.1.1.4 Must be able to speak and understand English. 
2.1.1.5 Must have a parent or adult primary caregiver willing to participate in the study. 
2.1.1.6 Ability of subject or parent/guardian to understand and the willingness to sign a written 
informed consent document. 
2.1.1.7 Must have access to a computer/mobile device and the internet. 
2.1.2 Exclusion Criteria for Patients 
2.1.2.1 Patients will be excluded if there is evidence of pre-morbid severe cognitive or 
psychiatric disability that would impair their capacity for participation or completion of 
evaluations in the judgment of the investigators. 

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2.1.2.2 Evidence of disease progression at the time of referral to this study to the extent that it 
would impede participation or completion of evaluations as determined by the medical 
advisory investigator in conjuction with the study PI/adjunct PI. 
2.1.2.3 Patients with treatment-related sequelae so severe that they would be unable to 
complete the study-related evaluations or intervention (e.g., treatment toxicity) as 
determined by the medical advisory investigator in conjuction with the study PI/adjunct 
PI.  
2.1.3 Inclusion Criteria for Parent or Adult Primary Caregiver 
2.1.3.1 Must be a parent or primary caregiver of a child (age 5 to 24 years of age) who has been 
diagnosed with a high-grade/high risk tumor that carries poor prognosis (as defined 
above); and must live in the same household as the patient for a majority of the time. 
2.1.3.2 Must have a child willing to participate in the study 
2.1.3.3 Must be able to speak and understand English. 
2.1.3.4 Ability of subject to understand and the willingness to sign a written informed consent 
document. 
2.1.3.5 Must have access to a computer/mobile device and the internet. 
2.2 
RECRUITMENT STRATEGIES 
Patients and parents or adult primary caregivers will be referred by principal investigators or 
attending physicians in the Pediatric Oncology Branch at the NCI and other local centers (e.g., 
Johns Hopkins Hospital, CNMC, Sibley Memorial) who provide care for patients with high-
grade or high-risk cancers with poor prognosis. NCI patients and caregivers who may be eligible 
for this study will be approached about the study by a medical team member, and provided with 
preliminary information about the EMI. If interested, they will be referred to the study team who 
will contact them to review the study and informed consent procedures. Patients who are referred 
by community providers will be approached about this study by a member of their clinical team. 
If interested, patients will be given the contact information for the researchers on the EMI 
protocol or authorize their clinical provider to send their contact information to the research 
team. The POB EMI research team will then contact the prospective participants to review the 
study procedures and screen for eligibility. A study flyer and email script are provided in the 
Recruitment Material Package. This protocol may also be abstracted into a plain language 
announcement posted on NIH websites. 
2.3 
SCREENING EVALUATION 
2.3.1 Screening activities performed prior to obtaining informed consent 
Minimal risk activities that may be performed before the subject has signed a consent include the 
following: 
• Review of existing medical records to include H&P, laboratory studies, etc. to confirm 
study eligibility.  The medical/research team will document that the patient participant 
has received a diagnosis of high-grade or high-risk cancer with poor prognosis. 
o The medical advisory investigator (MAI) will be approached to discuss patient 
participant eligibility based on their medical status, including clinical disease 
progression, cognitive ability, and the timing for enrollment on this study. 
• Email, written, in person or telephone communications with prospective subjects.  During 
preliminary discussions with the parent/primary caregiver, the ability to understand the 

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requirements of the study and ability to understand English, and the availability of 
internet access and IT equipment will be evaluated.  
Please see request for waiver of consent for pre-screening activities in Section 7.3.2. 
2.3.2 Screening activities performed after a consent for screening has been signed 
No additional screening activities associated with this study. 
2.4 
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES 
Registration and status updates (e.g., when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant 
Registration & Status Updates found here.  
2.5 
INTERVENTION ASSIGNMENT AND RANDOMIZATION/STRATIFICATION PROCEDURES 
2.5.1 Cohort 
Number 
Name 
Description 
1 
Patients 
Patients with a diagnosis of a high-grade or high-risk cancer 
with active disease and poor prognosis.  
2 
Parents 
Parent or adult primary caregiver of patient participants. 
2.5.2 Arms 
Number 
Name 
Description 
1 
EMI Group 
Participate in an in-person session followed by a series of at-
home assignments, and two “booster” sessions.  
2 
Control Group 
Participants will briefly meet with a member of the research 
team who will assess parent and child coping, and provide 
the child-caregiver dyad educational material about coping 
with cancer 
2.5.3 Stratifications 
Name 
Distinct Options 
Notes 
Adolescents 
Yes: 13-17 years old 
No: 5-12 years old 
 
Young Adults 
Yes: 18-24 years old 
No: > 18 years old 
 
2.5.4 Randomization and Arm Assignment 
Patients, cohort 1, will be randomized between arms 1 and 2 stratifying for age. Once 
randomization of the patient has occured their parent or primary caregiver, cohort 2, will be 
directly assigned to the arm in which their child was assigned. 

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2.6 
BASELINE EVALUATION 
Following parental consent and child assent, the parent/caregiver (see Table 1) and the 
participant (see Table 2) will complete a baseline assessment (Time 1) including questionnaires 
that assess their stress, emotional (e.g., depression, anxiety) and physical (e.g., pain, fatigue) 
wellbeing, in addition to baseline mindfulness/self-compassion. Disease parameters (e.g., cancer 
type and location, treatment history and radiation/chemotherapy doses, steroid use) will be 
abstracted from medical records. Participants will then be randomized to the enhanced 
mindfulness intervention (n=10 dyads) or a psychoeducation control group (n=10 dyads). The 
experimental design is depicted in Figure 1. 
 
 Figure 1 (See the Study Instrument 1 for descriptions of the measures). 
2.6.1 Measures assessing caregiver (parent) functioning: 
1. Demographic Questionnaire (5 minutes) 
(see Study Instrument 1 for additional information regarding measures)  
Table 1: Measures assessing parent functioning  
Study Variable 
Measure 
Time 
Point 
Time to 
Complete 
(approximate) 
Self-compassion 
The Self-Compassion Scale  
All 
10 minutes 
Acceptance 
Illness Cognition Questionnaire 
All 
< 5 minutes 

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Study Variable 
Measure 
Time 
Point 
Time to 
Complete 
(approximate) 
Mindfulness skills 
Mindful Attention and Awareness 
Scale (MAAS) 
All 
 5 minutes 
Emotional well-
being 
PROMIS Emotional Distress: Anxiety 
and Depression, Short Forms 8a 
All 
5 minutes 
Physical well-being 
PROMIS Fatigue and Sleep 
Disturbance, Short Forms 6a 
All 
< 5 minutes 
each 
Affect 
Positive and Negative Affect Scale 
All 
5 minutes 
Coping 
Coping Inventory 
All 
<5 minutes 
Feasibility 
Feasibility Survey 
Post-EMI 
5 minutes 
Total amount of time at each assessment 
~ 35 minutes 
2.6.2 Measures assessing Patient Functioning 
(see Study Instrument 1 for additional information regarding measures)  
Table 2: Measures assessing patient functioning 
Study Variable 
Measure 
Time 
Point 
Time to 
Complete 
(approximate) 
HRQL 
Impact of Pediatric Illness (IPI), self- 
and caregiver-report (ages 5+) 
All 
10 minutes 
Mindfulness skills 
Child and Adolescent Mindfulness 
Measure (CAMM), self-report (ages 
8+) 
All 
5 minutes 
Emotional wellbeing 
PROMIS Emotional Distress: Anxiety 
and Depression, self-report (ages 8+) 
and caregiver report (ages 5+) 
All 
< 5 minutes 
Physical wellbeing 
PROMIS Pain Behavior, Short form 
8a, self-report (ages 8+) and caregiver 
report (ages 5+) 
All 
< 5 minutes 
Physical wellbeing 
Neuro-Qol Fatigue, short form, self-
report (ages 8+)  
All 
< 5 minutes 
Physical wellbeing 
PROMIS \Fatigue, short form 8a, 
caregiver report (ages 5+) 
All 
<5 minutes 
Affect 
Positive and Negative Affect Scale – 
Child Shortened version 
All 
<5 minutes 

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Feasibility 
Feasibility Survey, self- and 
caregiver-report (ages 5+) 
• 
Patient participant ages 5-7 
(interview with 3-point Likert 
scale) 
• 
Patient participant ages 8+     
(5 point Likert scale) 
Post-EMI 
5 minutes 
Total amount of time at each assessment for child participants ages 8+ 
Total amount of time at each assessment for child participants ages 5-7 
Total amount of time at each assessment for caregiver-proxy report 
~ 30-35 minutes 
~ 10-15 minutes 
~20-25 minutes 
3 
STUDY IMPLEMENTATION 
3.1 
STUDY DESIGN 
This is a pilot trial that principally aims to evaluate the feasibility of a novel EMI for children 
and young adults with high-grade/high-risk cancers and their caregivers. Secondarily, through 
the use of a pilot randomized-controlled design, this trial will examine the preliminary efficacy 
of the EMI (n=10 dyads [patient participant and parent/primary caregiver]) compared to a 
psychoeducation control (n=10 dyads). This study design was chosen because randomized pilots 
provide both feasibility and preliminary efficacy data, which are essential for justifying larger 
trials and/or evaluating limitations of the intervention.  
At baseline, all participants will complete a series of measures assessing their functioning 
including emotional (e.g., depression, anxiety, stress) and physical (e.g., pain, fatigue) wellbeing, 
positive and negative affect, coping, and mindfulness/self-compassion.  
Patient-parent/caregiver dyads will be randomized to one of two groups: the EMI group or the 
psychoeducation control group. The EMI group will participate in an in-person session followed 
by a series of at-home assignments, and two “booster” sessions. At the conclusion of the EMI, 
measures will be repeated (8 weeks post-baseline: Time 2), and again at 16-weeks post-baseline 
(Time 3). At the 8 week timepoint, the EMI group will also complete a measure of feasibility, 
which is a primary outcome for this study. Measures will be administered either with paper 
forms or electronically via iPads in clinic, or from participants’ home computer. Caregiver forms 
will take approximately 30-35 minutes to complete. For children ≥ 8 years old and young adults, 
questionnaires will take approximately 30-35 minutes to complete. Children 5-7 years old will 
complete an abbreviated set of questionnaires (i.e., 10-15 minutes), given the limited availability 
and reliability of self-report measures in this age group.   
Upon randomization to the psychoeducation group, patient participants and their parent/primary 
caregiver will briefly meet with a member of the research team who will assess parent and child 
coping, and provide the child-caregiver dyad educational material about coping with cancer (see 
Study Instrument 2). One of the psychologists will call or videochat with the family at 1 week 
and 3 weeks post-baseline to be consistent with the EMI group, although these phone contacts 
are not expected to take as long as in the EMI group. If more intensive services are needed, the 
patient will be taken off study and the research team will continue to provide more frequent 
mental health services as needed. At the conclusion of 8 weeks and completion of the measures 
(Time 2), the psychoeducation group will be offered the opportunity to participate in the EMI. If 

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participants in the psychoeducation group would like to participate in the EMI but travel to the 
NIH presents a hardship, the option will be made available to complete the EMI training via 
videochat and materials will be sent via postal mail.  
The final set of questionnaires (i.e., Time 3) will be administered to parents and children in both 
the EMI and the psychoeducation group 16-weeks post-baseline. This time point will be used to 
evaluate the longer-term outcomes among patients and caregivers and to track functioning over 
time. It will also provide additional post-EMI data for any dyads from the control condition that 
electively enrolled in the EMI at Time 2. If a participant in either the EMI group or control group 
exhibits significant clinical disease progression after enrollment, such that they are no longer 
able to participate in the intervention and/or complete study-related questionnaires, they will be 
taken off study. If this were to occur, caregivers would be offered the option of remaining on 
study to complete the intervention. If patients are taken off-study before the 8-week time point 
due to disease progression and cannot be evaluated, they will not be included in the target N and 
can be replaced by a new participant.   
3.2 
IN-PERSON SESSION 
3.2.1 Enhanced Mindfulness Intervention Group 
The in-person session for the EMI group will be scheduled to coincide with an already scheduled 
clinic visit whenever possible. Dyads assigned to participate in the mindfulness intervention will 
be paired with two members of the clinical research team (i.e., two psychologists/psychology 
associates trained in mindfulness-based interventions, referred to as “mindfulness coaches”). 
Following completion of the baseline measures, the child participant will meet with one member 
of the research team for an initial training session, while the parent participant will have a 
concurrent training session with the second member of the research team.  
The initial in-person session will last 75-90 minutes, and child and parent sessions will follow 
the same format. Specifically, the session will include a brief interview to build rapport and to 
further assess overall wellbeing, sources of stress (related and unrelated to cancer), and existing 
coping strategies (15-20 minutes). Subsequently, using developmentally-appropriate language 
and exercises, mindfulness will be introduced and practiced (30 minutes), followed by a 
discussion of personally-relevant values and goals (20 minutes) in which the mindfulness 
practice can be contextualized and individualized for each participant.  
The parent and child participant will come together for the final 15 to 20 minutes of the training 
session. This time will afford an opportunity to teach parents about the mindfulness practices 
assigned to their children and allow dyads to participate in a joint mindfulness exercise.  
Given the broad age range of this intervention, the interview style and exercises utilized for the 
in-person training sessions will be unique for each age group of young children, adolescents, and 
parents (separate semi-structured manuals will be used to guide in-person sessions for children 
ages 5-7, 8-12, 13-24 years old, and parents, while maintaining consistency in the format across 
age groups). For example, the mindfulness coach will rely on interactive exercises and playful 
language to ascertain information from younger children during the interview (e.g., use 
caricatures to represent feelings when talking about stress) and to introduce mindfulness (e.g., 
create a “mindfulness jar” to represent the concept of mindfulness). In contrast, with adolescents 
and parents, the sessions may be more heavily weighted toward traditional verbal 
discussion/instruction. Flexibility will be permitted to adapt explanations based on a participant’s 
developmental stage and breaks will be offered when needed. Note: While mindfulness practices 
will be based on age/development, they will be standardized in length (i.e., approximately 15 

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minutes) and will utilize similar themes (e.g., mindful breathing, body awareness) across 
participants. 
Following the in-person session, parents and children will be asked to practice mindfulness 
exercises at least 4 out of 7 days per week (see Section 3.3 for Home-Based Mindfulness 
Exercises). To facilitate at-home practice, each child and parent participant will receive a series 
of 4 exercises, lasting approximately 15 minutes each. Participants are given leeway to choose 
among these exercises throughout the duration of the intervention and the research team will 
track which exercises are practiced throughout the week. For parents, at-home practice will 
consist of .mp3 audio files with guided mindfulness practices. Youth participants will receive 
multiformat exercises (e.g., age-appropriate .mp3 audio files, art-based exercises, interactive 
games that can be done with the assistance of a caregiver or sibling). Several mindfulness 
practitioners and researchers have developed exercises that are for the mutual benefit of parents 
and children 53,54, which can be practiced together. Adaptations of these exercises will be 
provided to families of younger children (i.e., <8 years old), so as not to overburden a parent 
with independent practice and their child’s practice separately. Children who are nonverbal (i.e., 
cannot express themselves verbally) due to their disease and/or treatment will have access to 
appropriate interventions that do not entail verbal skills.  
Approximately one week and three weeks after the initial in-person training session, a brief (i.e., 
30 minute) follow-up sessions will take place with the two-person research team. We anticipate 
that the majority of participants in this study will be staying at or nearby the NIH during this time 
period, or will be visiting the NIH frequently (e.g., receiving radiation treatment through other 
protocols at the NIH Intramural Research Program), which will make it possible to schedule 
follow-ups in person. For in-person follow-up, caregivers and children will each meet separately 
with their mindfulness coach, and then come together at the end of the follow-up for a joint 
meeting. If participants are not available for an in-person follow-up, sessions will take place via 
video chat (e.g., Skype, FaceTime) or telephone if video chat is unavailable. The literature 
suggests comparable efficacy between in person and teletherapy, which makes this a valid option 
55. The purpose of these follow-up sessions is to troubleshoot any challenges that arise (e.g., 
difficulty finding time to practice) and to engage in a clinician-guided practice. Depending on the 
age and functional limitations of the child, remote follow-up sessions will take place jointly with 
the parent/child or separately. Attendance in follow-up sessions will be systematically tracked 
and will be evaluated as part of the feasibility of this intervention. 
Throughout the intervention, weekly text messages (or emails when text is not an option) will be 
sent to parent participants and youth with a personal cell phone, in which we will ask individuals 
to indicate the number of days practiced in the past week. The following script will be used as a 
guideline: “Hello. Just checking in to ask how many days you have practiced mindfulness over 
the past week (since INSERT DATE). Please reply by text (or email) with your response.”  The 
weekly interval will mitigate concerns regarding inaccurate recall 56,57, without overburdening 
families. Among younger children who do not have a personal cell phone, compliance data will 
be collected through parents, or children (>7 years old) will be loaned an iPod (with parental 
permission) from the study team through which compliance data can be obtained. All 
participants will also be provided with an optional tracking sheet, on which they can keep track 
of practice days and note the specific exercises completed (Study Instrument 3).  
3.2.2 Psychoeducation Group (Control group):  
After completing baseline questionnaires, dyads randomized to the psychoeducation group will 
meet for a brief in-person session, which will include an interview to further assess overall 
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(approximately 30 minutes). This is consistent with the EMI group. Subsequently, participants 
will receive a handout providing information on coping in the context of cancer. This will 
include specific information for pediatric patients and, separately, parents, which will be briefly 
reviewed with families (15 minutes). This sheet has been adapted using existing informational 
sheets available through the NIH and the American Cancer Society (Study Instrument 2).  
Approximately one week and three weeks after the initial in-person session, a brief (10 minute) 
the trainer will attempt to check-in with participants in the psychoeducation group, typically by 
phone. The purpose is to assess ongoing coping and ensure there are not clinically-relevant 
concerns that warrant additional support. If significant clinical concerns arise, the research team 
will have a discussion with patients and caregivers about coming off study and receiving more 
consistent and personalized therapeutic support by a member of the Health Psychology Group or 
a therapist in their community. In the event of a community referral, the research team will work 
with the family to identify potential providers. 
Within a year following the baseline session (i.e., Time 2), parents and children in the control 
group will be asked to complete a second set of questionnaires assessing their quality of life, 
emotional and physical wellbeing, and state of mindfulness (See Table 1) if there are no major 
changes to their health status (including psychiatric and physical wellbeing). In addition, all 
participants in the EMI group will be asked to complete a feasibility questionnaire assessing their 
impression of the intervention. At this point, individuals initially assigned to the control 
condition will be offered an opportunity to participate in the EMI.  
3.3 
ENHANCED MINDFULNESS INTERVENTION (IMMEDIATE INTERVENTION GROUP) 
After patients and their caregivers complete the in-person session (see Experimental Design in 
the Research Project Narrative for additional details), they will be provided with structured 
mindfulness exercises to practice at home. They will be asked to practice at least one 
mindfulness activity (out of 5 primary choices) at least 4 out of 7 days per week, with an ideal 
goal of daily practice. The home-based practices are tailored based on the participant’s 
developmental stage, though each age group shares three common practices (i.e., Loving 
Kindness, Body Scan, and Mindful Breathing). Below is a brief description of the at-home 
practices that will be offered to participants, arranged by age group. Flexibility is permitted 
within the intervention protocol to adapt exercises or offer alternative practices for patients when 
needs arise (e.g., cognitive and/or verbal limitations, physical limitations). This will be addressed 
on a case-by-case basis with participants during the initial in-person session, at which point 
adaptations/alternatives will be provided. Patients and caregivers will be allowed to choose 
among the mindfulness exercises provided (the research team will track their choices via a 
tracking sheet). All materials needed to complete these exercises will be provided to participants. 
3.3.1 Home-Based Mindfulness Practices for Caregivers 
Home-based practices for caregivers will primarily consist of guided mindfulness meditations 
via audio recordings. This will include brief (i.e., 5-minute) and extended (i.e., 15-20-minute) 
formats. Audio files (.mp3 files) will be provided to caregivers immediately following or during 
the in-person session and can be downloaded to a smart phone, tablet, or computer. Mp3 players 
will be available for any participant who does not have access to a personal device through 
which these files can be accessed. Descriptions of these exercises are available in Study 
Instrument 4. 
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Home-based practices for adolescents will be multi-format in nature. Exercises aim to increase 
awareness of emotional and physical experiences, and enhance attunement to environmental 
stimuli. Although each of these exercises can be completed independently, they can also be 
completed with the company of a caregiver. Descriptions of these exercises are in Study 
Instrument 5.  
3.3.3 Home-Based Mindfulness Practices for Youth (8-12 years old) 
Home-based practices for pre-adolescent youth will be multi-format in nature. Exercises aim to 
increase awareness of emotional and physical experiences, and enhance attunement to 
environmental stimuli. Exercises are completed independently or with a caregiver. 
Reinforcement (e.g., tangible items like stickers, praise, positive attention) can be paired with 
these exercises to increase engagement in this age group. Descriptions of these exercises can be 
found in Study Instrument 6. 
3.3.4 Home-Based Mindfulness Practices for Children (5-7 years old) 
Mindfulness practices for young children are interactive and engaging. These exercises are 
intentionally game-like and utilize reinforcers (e.g., tangible items, positive caregiver attention) 
to help sustain participation and patient enjoyment. Tangible reinforcers (e.g., stickers) will be 
provided in the mindfulness toolkit. All exercises should be completed with a caregiver and offer 
mutual benefit such that a caregiver would not have to complete a separate practice. Descriptions 
of these exercises are in Study Instrument 7.  
3.4 
COST AND COMPENSATION 
3.4.1 Costs 
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center.  If some tests and procedures performed 
outside the NIH Clinical Center, participants may have to pay for these costs if they are not 
covered by insurance company.  Medicines that are not part of the study treatment will not 
generally be provided or paid for by the NIH Clinical Center. 
3.4.2 Compensation 
Participants (each child and each parent/caregiver) will receive compensation ($20) for 
completing each set of questionnaires to thank them for their time and effort spent participating 
in this study.  The maximum compensation that any participant can receive is $60 
(questionnaires at baseline, 8 weeks and 16 weeks). Funds will be distributed in accordance with 
the Clinical Center’s Research Volunteer system, such that participants can have the money 
directly deposited to a bank account or have a check mailed to them.  
In addition, each parent-child dyad will receive a mindfulness toolkit as part of this study, which 
will provide them with all the necessary supplies to practice the mindfulness exercises outside 
the clinic. Because we anticipate that some families will be away from their home environment 
while they participate in this project, it is essential that all equipment be provided to families. 
This will include pragmatic supplies to complete exercises (e.g., art supplies for art-based 
mindfulness exercises such as Mandalas, bubbles, copyrighted audio files, headphones) in 
addition to tools to enhance their experience (e.g., eye pillow, meditation mat). Collectively, 
these supplies will cost approximately $100 per dyad. These costs are covered by a grant through 
the St. Baldrick’s Foundation, awarded to Dr. Allen in support of this study.  
3.4.3 Reimbursement 
This study does not offer reimbursement for, or payment of, travel, lodging or meals. 

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3.5 
OFF STUDY CRITERIA 
Subjects will be removed from the study for any of the following: 
• Completed study follow-up period (16 weeks) 
• Participant requests to be withdrawn from study 
• Participant becomes too ill to continue participation 
• Participant is in need of additional psychotherapeutic support due to significant mental 
health concerns (e.g., moderate to severe depression or anxiety) 
• Inability to consent / loss of capacity 
• Lost to follow-up 
• Investigator discression 
• Death 
3.5.1 Lost to Follow-up 
A participant will be considered lost to follow-up if he or she fails to respond to 2 or more 
timepoint check ins and is unable to be contacted by the study site staff.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site will attempt to contact the participant and reschedule the missed visit within one 
week and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, an IRB approved certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented in 
the participant’s medical record or study file.  
• Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.. 
4 
DATA COLLECTION AND EVALUATION  
4.1 
DATA COLLECTION 
The PI/adjunct PI will be responsible for overseeing entry of data into an in-house password 
protected electronic system (Labmatrix) and ensuring data accuracy, consistency and timeliness. 
The principal investigator, adjunct principal investigator, associate investigators/research nurses 
and/or a contracted data manager will assist with the data management efforts.  Primary and final 
analyzed data will have identifiers so that research data can be attributed to an individual human 
subject participant. 
End of study procedures: Data will be stored according to HHS, FDA regulations and NIH 
Intramural Records Retention Schedule as applicable.  
Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, this will be reported expeditiously per 
requirements in section 5.2.1.. 

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4.2 
DATA SHARING PLANS 
4.2.1 Human Data Sharing Plan 
Identified or coded, linked data will be shared with approved outside collaborators under 
appropriate agreements; and de-identified data will be shared at the time of publication and or 
public presentation. 
4.3 
TOXICITY CRITERIA 
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 
5.0.  A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).  
5 
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN 
5.1 
DEFINITIONS 
Please refer to definitions provided in Policy 801: Reporting Research Events found here. 
5.2 
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING 
5.2.1 Expedited Reporting 
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found here.  
5.3 
NCI CLINICAL DIRECTOR REPORTING 
Problems expeditiously reported to the OHSRP in iRIS will also be reported to the NCI Clinical 
Director.  A separate submission is not necessary as reports in iRIS will be available to the 
Clinical Director. 
5.4 
NIH REQUIRED DATA AND SAFETY MONITORING PLAN 
5.4.1 Principal Investigator/Research Team  
The clinical research team will meet on a regular basis when patients are participating in the 
intervention period on the trial to discuss each dyad.  All data will be collected in a timely 
manner and reviewed by the principal investigator or medical advisory investigator. Events 
meeting requirements for expedited reporting as described in section 5.2.1 will be submitted 
within the appropriate timelines.  
The principal investigator and medical advisory investigator (when indicated) will review 
adverse event and study data on each patient to ensure safety and data accuracy. The principal 
investigator will personally conduct or supervise the investigation and provide appropriate 
delegation of responsibilities to other members of the research staff. 
6 
STATISTICAL CONSIDERATIONS   
6.1 
STATISTICAL HYPOTHESIS 

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The current protocol is a pilot study, and therefore its primary aim does not include hypothesis 
testing. Components of feasibility (as described in section 6.1.1) will be evaluated during the 
recruitment phase (i.e., proportion of eligible dyads who enroll) and following the 8-week 
EMI/psychoeducation period.  
6.1.1 Primary Objective 
The primary objective of this study is to assess the feasibility and acceptability of an enhanced 
mindfulness intervention in children and young adults (ages 5-24) with a high-grade or high-risk 
cancer and one of their primary caregivers. Feasibility and acceptability will be evaluated based 
on the following: 
1. Proportion of eligible dyads who enroll during a two-year period 
2. Treatment specific retention among all randomized participants, with a target retention rate 
of 70% over the 8 week EMI/control period 
3. Compliance with at-home practices, with a proposed target rate of 4 out of 7 days per week 
on average over the 8 week EMI period 
4. Parent and child reports of satisfaction on the feasibility questionnaire; for youth ages 8+ and 
caregivers, average item scores >3.0 will be deemed to reflect adequate feasibility 
Of note, because the sample size of this study is very limited, even the results of the comparisons 
tested using statistical methods and identified within the primary objective will be considered 
descriptive and hypothesis generating.  
6.2 
SAMPLE SIZE DETERMINATION 
Sample size determination was not undertaken for this protocol because it is a small pilot 
intervention primarily aiming to test the feasibility of the proposed EMI. We specifically aimed 
to recruit 10 dyads per arm because this sample size would provide enough subjects to yield data 
appropriate for a pilot study. It is also anticipated that this sample can be recruited within a 
reasonable amount of time, over a 2 year period (1 to 2 dyads per month, on average). The 
proposed sample size will likely limit the ability to evaluate preliminary efficacy, which is an 
exploratory aim.  
6.3 
POPULATIONS FOR ANALYSES 
For the primary outcome of feasibility, all randomized participants will be included. In addition, 
as described below in section 6.4.2, we will track total number of eligible individuals approached 
about the intervention (prior to randomization/enrollment), which will allow us to evaluate the 
proportion of eligible dyads who enroll. To evaluate exploratory aims, a modified intent-to-treat 
dataset will be used and will include all participants who, at a minimum, complete the initial in-
person training (across EMI and psychoeducation conditions) and questionnaires at Time 1 
(baseline) and Time 2 (8 weeks). 
6.4 
STATISTICAL ANALYSES 
6.4.1 General Approach 
For descriptive statistics, categorical data will be presented as percentages. Continuous data will 
be presented as means with standard deviations and ranges. For inferential statistics, statistical 
significance will be declared if =0.05 and tests will be two-tailed; results will be interpreted in 
the context of a pilot study in which statistical testing is for descriptive purposes. For exploratory 
analyses, checks of assumptions will be conducted and corrective procedures will be applied 
accordingly (e.g., transformation of non-normal data or nonparametric tests will be substituted).    

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6.4.2 Analysis of the Primary Endpoints 
Planned analysis: For the primary feasibility aim, descriptive and summary statistics will be 
used to report parent and child rates of intervention completion, as well as ratings of satisfaction 
with the intervention via responses on a feasibility questionnaire. A Z-test for binomial 
proportion with continuity correction will be used to examine whether the retention rate and at-
home practice compliance rate are lower than the target (i.e., respectively, a target of 70% 
participants retained over 8 weeks and a practice rate of 4 out of 7 days per week on average 
over 8 weeks). Retention rate will be evaluated across the experimental and control groups, and 
separately for each. In addition, descriptive and summary statistics will be used to detail the total 
number of patients screened, determine rates and reasons for non-eligibility and patient refusal, 
the number and type of adverse events (if any), and the number of days practiced (obtained via 
text/email) by each participant. A series of t-tests (for continuous variables) and Chi-square tests 
(for non-continuous variables) will be used to examine potential differences between eligible 
patients who accept or decline study participation; between participants who meet (versus do not 
meet) the target practice rate (i.e., 4 out of 7 days completed); and for other medical, 
psychological, and contextual factors. Nonparametric models will be used if data do not meet 
assumption checks.     
6.4.3 Sub-Group Analyses 
As described in section 2.5.3, randomization will be stratified by child age for youth ages 5-12, 
13-17, and 18-24 years old. Caregivers will be directly assigned to the child’s randomization 
group (i.e., EMI or psychoeducation control). From a feasibility perspective, stratification will 
allow us to evaluate enrollment/retention data per age group across conditions (reducing the bias 
associated with enrollment/retention in a single arm treatment study), which will be useful to 
inform larger RCTs in the future. Stratification across ages will also better allow us to assess 
exploratory efficacy aims (see 6.4.5) among developmental cohorts.  
 
Further, as described in 6.4.2, we will evaluate demographic and medical/disease-related factors 
that are associated with components of feasibility. 
6.4.4 Tabulation of individual Participant Data 
Individual participant data will be listed by measure and time point.  
6.4.5 Exploratory Analyses 
Given the small sample, there may be limited power to detect changes on all exploratory 
outcome measures. Descriptive and summary statistics will be used to summarize secondary 
outcome measures between the EMI and control groups. Bivariate analyses (i.e., correlations, 
chi-square analysis as appropriate) will then be conducted to identify potential covariates for 
subsequent analyses. Dependent samples t-tests will assess changes pre- to post-intervention in 
child anxiety, depression, pain behavior, fatigue, mindfulness, and health-related quality of life 
among youth in the EMI group and also youth in the psychoeducational control group.  
In addition, using dependent samples t-tests, we will explore changes pre- to post-intervention in 
caregiver anxiety, depression, stress, fatigue, sleep disturbance, psychological flexibility, 
mindfulness, and self-compassion among the intervention group and also parents in the 
psychoeducational control group. Given the small sample, these analyses will be considered 
hypothesis generating.  
Linear regression models using the 8-week or 16-week assessment as the outcome will be 
considered in an effort to preliminarily estimate the effect size of the intervention, with 

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adjustment for potential confounders including scores at baseline. We will assess which 
demographic (e.g., age), medical, psychological, and environmental factors are related to 
preliminary efficacy of the intervention.  
7 
HUMAN SUBJECTS PROTECTIONS  
7.1 
RATIONALE FOR SUBJECT SELECTION 
7.1.1 Participation of Children 
The age range of patients eligible for this trial is at least 5 years of age and less than or equal to 
24 years of age. Physicians, nurses, and multidisciplinary support teams of the POB, NCI and 
Clinical Center will provide patient care.  The staff of the POB has expertise in the management 
of children with complex oncologic disorders, neurocognitive testing in children and 
complications of all types of oncologic conditions.  Full pediatric support and subspecialty 
services are available at the NIH Clinical Center. 
This study will be limited to English speaking subjects and their parent or primary caregive. The 
rationale for this is that the at-home intervention materials currently only available in English as 
well as many of the outcome measures have only been validated in English.  
7.2 
EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS 
7.2.1 Risks for parents/caregivers 
For parents or caregivers helping their child participate in this study, there is the risk of the time 
commitment involved in the initial one on one session, the time required to complete the 
questionnaires at 3 time points, check their study emails/texts, participate in the home-based 
practices for themselves, and to encourage their child and review the activities and progress with 
their child. 
7.2.2 Risks for patient participants 
Similarly, the major risk for participants is the time commitment of participation.  The content 
and context of the program is specifically tailored for the targeted age group, and the interview 
style and exercises utilized for the in-person training sessions will be unique for each age group, 
young children, adolescents and young adults in an attempt to maintain interest, keep the 
participant engaged and involved in active participation. 
7.3 
CONSENT AND ASSENT PROCESS AND DOCUMENTATION 
The informed consent document will be provided as a physical or electronic document to the 
participant or cosent designee(s) as applicable for review prior to consenting.  A designated study 
investigator will carefully explain the procedures and tests involved in this study, and the 
associated risks, discomforts and benefits. In order to minimize potential coercion, as much time 
as is needed to review the document will be given, including an opportunity to discuss it with 
friends, family members and/or other advisors, and to ask questions of any designated study 
investigator. A signed informed consent document will be obtained prior to entry onto the study. 
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms used in compliance with 
polices, including HRPP Policy 303) per discretion of the designated study investigator and with 
the agreement of the participant/consent designee(s). Whether in person or remote, the privacy of 
the subject will be maintained. Consenting investigators (and participant/consent designee, when 
in person) will be located in a private area (e.g., clinic consult room). When consent is conducted 

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remotely, the participant/consent designee will be informed of the private nature of the 
discussion and will be encouraged to relocate to a more private setting if needed. 
Consent will be documented with required signatures on the physical document (which includes 
the printout of an electronic document sent to participant) or as described below, with a manual 
(non-electronic) signature on the electronic document.  When required, witness signature will be 
obtained similarly as described for the investigator and participant. 
Manual (non-electronic) signature on electronic document: 
When a manual signature on an electronic document is used for the documentation of consent 
at the NIH Clinical Center, this study will use the following to obtain the required signatures: 
• 
Adobe platform (which is not 21 CFR Part 11 compliant); or,   
• 
iMedConsent platform (which is 21 CFR Part 11 compliant) 
During the consent process, participants and investigators will view individual copies of the 
approved consent document on screens at their respective locations (if remote consent); the 
same screen may be used when in the same location but is not required.   
Both the investigator and the participant will sign the document using a finger, stylus or mouse.  
Note: Refer to the CCR SOP PM-2, Obtaining and Documenting the Informed Consent 
Process for additional information (e.g., verification of participant identity when obtaining 
consent remotely) found here. 
7.3.1 Consent Process for Minors 
Consent will be obtained from parent(s)/guardians of minor children as described in Section 7.3. 
Where deemed appropriate by the clinician and the child’s parent(s) or guardian, the child will 
also be included in all discussions about the trial and age-appropriate language will be used to 
describe the procedures and tests involved in this study, along with the risks, discomforts and 
benefits of participation.  The assent process will take place in conjunction with consent; 
therefore, in person and remote assent are permitted under the same circumstances as in person 
and remote consent. Verbal assent will be obtained as appropriate for children ages 5-11. The 
assent document will be used to guide this discussion. Should a child in this age group (5-11) 
choose to sign the assent document they will not be discouraged; however it is not required. 
Children under the age of 18, but who are age 12 or older will be asked to sign an age 
appropriate assent form. The consent/assent process will be documented in the child’s medical 
record, including the assessment of the child’s ability to provide assent (verbal versus written) as 
applicable. All children will be contacted after they have reached the age of 18 to determine 
whether they wish to continue on the trial and informed consent will be obtained from them at 
that time.    
7.3.2 Request for Waiver of Consent for Screening Activities 
Prior to the subject signing the consent for this study pre-screening activities listed in section 2.3 
may be performed.  
We request a waiver of consent for these activities as they involve only minimal risk to the 
subjects.  A waiver will not adversely affect the rights and welfare of the subjects given that the 
activities are only intended to determine suitability for screening for participation in research 
protocols.  These activities could not practicably be carried out without the wavier as central 
recruiting services, utilized in the NIH Clinical Center, perform pre-screening activities for 
multiple studies and obtaining consent for each one is beyond their resources.  The subjects will 

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be provided with additional pertinent information after participation as they will be informed 
whether are not they are eligible to sign a consent for additional screening. 
7.3.3 Consent for minors when they reach the age of majority  
When a pediatric subject reaches age 18, continued participation (including ongoing interactions 
with the subject or continued analysis of identifiable data) will require that consent be obtained 
from the now adult with the standard protocol consent document to ensure legally effective 
informed consent has been obtained. Given the length of time that has transpired for some of the 
subjects since their last visit for this study, we request waiver of informed consent for those 
individuals who have completed their participation in the research study and have met the off-
study criteria defined in section 3.5. 
Requirements for Waiver of Consent consistent with 45 CFR 46.116 (d): 
(1) The research involves no more than minimal risk to the subjects. 
a. Analysis of samples and data from this study involves no additional risks to 
subjects. 
(2) The waiver or alteration will not adversely affect the rights and welfare of the 
subjects. 
a. Retention of these samples or data does not affect the welfare of subjects.  
(3) The research could not practicably be carried out without the waiver or alteration. 
a. Considering the length of time between the minor’s last contact with the 
research team and their age of majority, it will likely be very difficult to locate 
them again.  A significant reduction in the number of samples analyzed is 
likely to impact the quality of the research.  
(4) Whenever appropriate, the subjects will be provided with additional pertinent 
information after participation. 
a. We do not anticipate that any information generated by these studies would be 
pertinent in any way to the health and treatment of these research subjects.  
However, if such information is generated, and we are able to locate the 
research subject(s), we would provide the information to them.  The subjects 
who are provided the data will not be contacted by anyone connected with the 
research without prior approval by the IRB. 
8 
REGULATORY AND OPERATIONAL CONSIDERIATIONS 
8.1 
STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigator, funding agency and regulatory authorities.  If the study is prematurely terminated or 
suspended, the Principal Investigator (PI) will promptly inform study participants and the 
Institutional Review Board (IRB) and will provide the reason(s) for the termination or 
suspension.  Study participants will be contacted, as applicable, and be informed of changes to 
study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping    

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• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the IRB. 
8.2 
QUALITY ASSURANCE AND QUALITY CONTROL 
The clinical site will perform internal quality management of study conduct, data collection, 
documentation and completion. An individualized quality management plan will be developed to 
describe a site’s quality management. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted, and data are generated, documented (recorded), and reported in 
compliance with the protocol, International Conference on Harmonisation Good Clinical Practice 
(ICH GCP), and applicable regulatory requirements.  
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing, and inspection by local and regulatory 
authorities. 
8.3 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any 
actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, 
or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a 
perceived conflict of interest will be required to have such conflicts managed in a way that is 
appropriate to their participation in the design and conduct of this trial.  The study leadership in 
conjunction with the National Cancer Institute has established policies and procedures for all 
study group members to disclose all conflicts of interest and will establish a mechanism for the 
management of all reported dualities of interest. 
8.4 
CONFIDENTIALITY AND PRIVACY 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s). This confidentiality is extended to cover the clinical information 
relating to participants. Therefore, the study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the study, or 
the data will be released to any unauthorized third party without prior written approval of the 
sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study monitor, representatives of the Institutional Review Board (IRB), and/or regulatory 
agencies may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) for the participants in 
this study. The clinical study site will permit access to such records. 

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The study participant’s contact information will be securely stored at the/each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB or Institutional policies. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored at the NCI CCR. This will not include the 
participant’s contact or identifying information. Rather, individual participants and their research 
data will be identified by a unique study identification number. The study data entry and study 
management systems used by the clinical site and by NCI CCR research staff will be secured, 
and password protected. At the end of the study, all study databases will be archived at the NCI 
CCR: NIH. 
To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve 
the research objectives and promote participation in studies by helping assure confidentiality and 
privacy to participants. 
 

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9 
REFERENCES  
1. 
Steele AC, Mullins LL, Mullins AJ, Muriel AC. Psychosocial Interventions and 
Therapeutic Support as a Standard of Care in Pediatric Oncology. Pediatr Blood Cancer 2015;62 
Suppl 5:S585-618. 
2. 
Myers RM, Balsamo L, Lu X, et al. A prospective study of anxiety, depression, and 
behavioral changes in the first year after a diagnosis of childhood acute lymphoblastic leukemia: 
a report from the Children's Oncology Group. Cancer 2014;120:1417-25. 
3. 
Patino-Fernandez AM, Pai AL, Alderfer M, Hwang WT, Reilly A, Kazak AE. Acute 
stress in parents of children newly diagnosed with cancer. Pediatr Blood Cancer 2008;50:289-92. 
4. 
Kaplan LM, Kaal KJ, Bradley L, Alderfer MA. Cancer-related traumatic stress reactions 
in siblings of children with cancer. Fam Syst Health 2013;31:205-17. 
5. 
Ljungman L, Hoven E, Ljungman G, Cernvall M, von Essen L. Does time heal all 
wounds? A longitudinal study of the development of posttraumatic stress symptoms in parents of 
survivors of childhood cancer and bereaved parents. Psycho-oncology 2015;24:1792-8. 
6. 
Barrera M, Shaw AK, Speechley KN, Maunsell E, Pogany L. Educational and social late 
effects of childhood cancer and related clinical, personal, and familial characteristics. . Cancer 
2005;104:1751–60. 
7. 
Salley CG, Hewitt LL, Patenaude AF, et al. Temperament and social behavior in 
pediatric brain tumor survivors and comparison peers. . Journal of Pediatrric Psychology 
 2015;40:297–308. 
8. 
Mandrell BN, Baker, J, Levine, D. Gattuso, J., West, N., Sykes, A., Gajjar, A., & 
Broniscer, A. Children with minimal chance for cure: Parent proxy of the child's health-related 
quality of life and the effect on parental physical and mental health during treatment. Journal of 
Neurooncology 2016;129:373-81. 
9. 
Rosenberg AR, Dussel, V., Kang, T., Geyer, R., Gerhardt, C.A.,Feudtner, C., & Wolfe, J. 
Psychological distress in parents of children with advanced cancer. JAMA Pediatrics 
2013;167:537-43. 
10. 
Levine DR, Mandrell BN, Sykes A, et al. Patients' and Parents' Needs, Attitudes, and 
Perceptions About Early Palliative Care Integration in Pediatric Oncology. JAMA Oncol 2017. 
11. 
Weaver MS, Heinze KE, Kelly KP, et al. Palliative Care as a Standard of Care in 
Pediatric Oncology. Pediatr Blood Cancer 2015;62 Suppl 5:S829-33. 
12. 
Kaye EC, Friebert S, Baker JN. Early Integration of Palliative Care for Children with 
High-Risk Cancer and Their Families. Pediatric blood & cancer 2016;63:593-7. 
13. 
Kazak AE. Evidence-based interventions for survivors of childhood cancer and their 
families. J Pediatr Psychol 2005;30:29-39. 
14. 
Kirby ED, Williams VP, Hocking MC, Lane JD, Williams RB. Psychosocial benefits of 
three formats of a standardized behavioral stress management program. Psychosom Med 
2006;68:816-23. 
15. 
Kazak AE, Simms S, Barakat L, et al. Surviving cancer competently intervention 
program (SCCIP): a cognitive-behavioral and family therapy intervention for adolescent 
survivors of childhood cancer and their families. Family process 1999;38:175-91. 

Abbreviated Title:  EMI Children/YA with  Cancer 
 
 
 
 
 
 
29 
Version Date: 12/13/2021 
16. 
Kazak AE, Alderfer MA, Streisand R, et al. Treatment of posttraumatic stress symptoms 
in adolescent survivors of childhood cancer and their families: a randomized clinical trial. 
Journal of family psychology : JFP : journal of the Division of Family Psychology of the 
American Psychological Association (Division 43) 2004;18:493-504. 
17. 
Stehl ML, Kazak AE, Alderfer MA, et al. Conducting a randomized clinical trial of an 
psychological intervention for parents/caregivers of children with cancer shortly after diagnosis. 
J Pediatr Psychol 2009;34:803-16. 
18. 
Salem H, Johansen C, Schmiegelow K, et al. FAMily-Oriented Support (FAMOS): 
development and feasibility of a psychosocial intervention for families of childhood cancer 
survivors. Acta Oncol 2017;56:367-74. 
19. 
Pai AL, Drotar D, Zebracki K, Moore M, Youngstrom E. A meta-analysis of the effects 
of psychological interventions in pediatric oncology on outcomes of psychological distress and 
adjustment. J Pediatr Psychol 2006;31:978-88. 
20. 
Lo HH, Wong SY, Wong JY, Wong SW, Yeung JW. The effect of a family-based 
mindfulness intervention on children with attention deficit and hyperactivity symptoms and their 
parents: design and rationale for a randomized, controlled clinical trial (Study protocol). BMC 
Psychiatry 2016;16:65. 
21. 
Flook L, Goldberg SB, Pinger L, Davidson RJ. Promoting prosocial behavior and self-
regulatory skills in preschool children through a mindfulness-based Kindness Curriculum. Dev 
Psychol 2015;51:44-51. 
22. 
Kishita N, Takei Y, Stewart I. A meta-analysis of third wave mindfulness-based 
cognitive behavioral therapies for older people. Int J Geriatr Psychiatry 2016. 
23. 
Bethell C, Gombojav N, Solloway M, Wissow L. Adverse Childhood Experiences, 
Resilience and Mindfulness-Based Approaches: Common Denominator Issues for Children with 
Emotional, Mental, or Behavioral Problems. Child Adolesc Psychiatr Clin N Am 2016;25:139-
56. 
24. 
Tsang SC, Mok ES, Lam SC, Lee JK. The benefit of mindfulness-based stress reduction 
to patients with terminal cancer. J Clin Nurs 2012;21:2690-6. 
25. 
Whittingham K, Sanders M, McKinlay L, Boyd RN. Interventions to reduce behavioral 
problems in children with cerebral palsy: an RCT. Pediatrics 2014;133:e1249-57. 
26. 
Hilton L, Maher AR, Colaiaco B, et al. Meditation for Posttraumatic Stress: Systematic 
Review and Meta-analysis. Psychol Trauma 2016. 
27. 
Hilton L, Hempel S, Ewing BA, et al. Mindfulness Meditation for Chronic Pain: 
Systematic Review and Meta-analysis. Ann Behav Med 2016. 
28. 
Gotink RA, Chu P, Busschbach JJ, Benson H, Fricchione GL, Hunink MG. Standardised 
mindfulness-based interventions in healthcare: an overview of systematic reviews and meta-
analyses of RCTs. PLoS One 2015;10:e0124344. 
29. 
Kuyken W, Warren FC, Taylor RS, et al. Efficacy of Mindfulness-Based Cognitive 
Therapy in Prevention of Depressive Relapse: An Individual Patient Data Meta-analysis From 
Randomized Trials. JAMA psychiatry 2016;73:565-74. 
30. 
Piet J, Wurtzen H, Zachariae R. The effect of mindfulness-based therapy on symptoms of 
anxiety and depression in adult cancer patients and survivors: a systematic review and meta-
analysis. Journal of consulting and clinical psychology 2012;80:1007-20. 

Abbreviated Title:  EMI Children/YA with  Cancer 
 
 
 
 
 
 
30 
Version Date: 12/13/2021 
31. 
Grossman P, Niemann L, Schmidt S, Walach H. Mindfulness-based stress reduction and 
health benefits. A meta-analysis. Journal of psychosomatic research 2004;57:35-43. 
32. 
Kok BE, Coffey KA, Cohn MA, et al. How positive emotions build physical health: 
perceived positive social connections account for the upward spiral between positive emotions 
and vagal tone. Psychological science 2013;24:1123-32. 
33. 
Soo MS, Jarosz JA, Wren AA, et al. Imaging-Guided Core-Needle Breast Biopsy: Impact 
of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue. Journal of the 
American College of Radiology : JACR 2016;13:526-34. 
34. 
Jones P, Blunda M, Biegel G, Carlson LE, Biel M, Wiener L. Can mindfulness-based 
interventions help adolescents with cancer? Psycho-oncology 2013;22:2148-51. 
35. 
Ledesma D, Kumano H. Mindfulness-based stress reduction and cancer: a meta-analysis. 
Psycho-oncology 2009;18:571-9. 
36. 
Zhang J, Xu R, Wang B, Wang J. Effects of mindfulness-based therapy for patients with 
breast cancer: A systematic review and meta-analysis. Complementary therapies in medicine 
2016;26:1-10. 
37. 
Johannsen M, O'Connor M, O'Toole MS, Jensen AB, Hojris I, Zachariae R. Efficacy of 
Mindfulness-Based Cognitive Therapy on Late Post-Treatment Pain in Women Treated for 
Primary Breast Cancer: A Randomized Controlled Trial. Journal of clinical oncology : official 
journal of the American Society of Clinical Oncology 2016;34:3390-9. 
38. 
Reich RR, Lengacher CA, Alinat CB, et al. Mindfulness-Based Stress Reduction in Post-
treatment Breast Cancer Patients: Immediate and Sustained Effects Across Multiple Symptom 
Clusters. Journal of pain and symptom management 2017;53:85-95. 
39. 
Eyles C, Leydon GM, Hoffman CJ, et al. Mindfulness for the self-management of 
fatigue, anxiety, and depression in women with metastatic breast cancer: a mixed methods 
feasibility study. Integrative cancer therapies 2015;14:42-56. 
40. 
van den Hurk DG, Schellekens MP, Molema J, Speckens AE, van der Drift MA. 
Mindfulness-Based Stress Reduction for lung cancer patients and their partners: Results of a 
mixed methods pilot study. Palliative medicine 2015;29:652-60. 
41. 
Kabat-Zinn J. Full Catastrophe Living. New York: Bantam Books; 2013. 
42. 
Van der Gucht K, Keisuke, T., Labarque, V., Vandenabeele, K., Nolf, N., Kuylen, S., 
Cosyns, V., Van Broeck, N., Kuppens, P., Raes, F. A mindfulness-based intervention for 
adolescents and young adults after cancer treatment: Effects on quality of life, emotional distress, 
and cognitive vulnerability. Journal of Adolescent and Young Adult Oncology 2016;00. 
43. 
Malboeuf-Hurtubise C, Achille, M., Mulse, L., Beaugregard-Lacroix, R., Vadnais, M., 
Lacourse, E. A mindfulness-based meditation pilot study: Lessons learned on acceptability and 
feasibility in adolescents with cancer. Journal of Child and Family Studies 2016;25:1168-77. 
44. 
Stafford L, Thomas N, Foley E, et al. Comparison of the acceptability and benefits of two 
mindfulness-based interventions in women with breast or gynecologic cancer: a pilot study. 
Supportive care in cancer : official journal of the Multinational Association of Supportive Care 
in Cancer 2015;23:1063-71. 
45. 
Hilt LMP, S. D. Getting Out of Rumination: Comparison of Three Brief Interventions in 
a Sample of Youth. Journal of Abnormal Child Psychology 2012;40:1157-65. 

Abbreviated Title:  EMI Children/YA with  Cancer 
 
 
 
 
 
 
31 
Version Date: 12/13/2021 
46. 
Garland EL, Fredrickson B, Kring AM, Johnson DP, Meyer PS, Penn DL. Upward 
spirals of positive emotions counter downward spirals of negativity: insights from the broaden-
and-build theory and affective neuroscience on the treatment of emotion dysfunctions and 
deficits in psychopathology. Clinical psychology review 2010;30:849-64. 
47. 
Garland EL, Geschwind N, Peeters F, Wichers M. Mindfulness training promotes upward 
spirals of positive affect and cognition: multilevel and autoregressive latent trajectory modeling 
analyses. Frontiers in psychology 2015;6:15. 
48. 
Grecucci A, Pappaianni E, Siugzdaite R, Theuninck A, Job R. Mindful Emotion 
Regulation: Exploring the Neurocognitive Mechanisms behind Mindfulness. BioMed research 
international 2015;2015:670724. 
49. 
Batink T, Peeters F, Geschwind N, van Os J, Wichers M. How does MBCT for 
depression work? studying cognitive and affective mediation pathways. PloS one 2013;8:e72778. 
50. 
Ives-Deliperi VL, Howells F, Stein DJ, Meintjes EM, Horn N. The effects of 
mindfulness-based cognitive therapy in patients with bipolar disorder: a controlled functional 
MRI investigation. Journal of affective disorders 2013;150:1152-7. 
51. 
Tang YY, Lu Q, Geng X, Stein EA, Yang Y, Posner MI. Short-term meditation induces 
white matter changes in the anterior cingulate. Proceedings of the National Academy of Sciences 
2010;107:15649–52. 
52. 
Barnhofer T, Chittka T, Nightingale H, Visser C, Crane C. State Effects of Two Forms of 
Meditation on Prefrontal EEG Asymmetry in Previously Depressed Individuals. Mindfulness 
2010;1:21-7. 
53. 
Snel EK-Z, M. Sitting Still Like a Frog: Mindfulness Exercises for Kids. Boston, MA: 
Shambhala; 2010. 
54. 
Greenland SK. Mindful Games. Boulder, CO: Shambhala Publications Inc; 2016. 
55. 
Stubbings DR, Rees CS, Roberts LD, Kane RT. Comparing in-person to 
videoconference-based cognitive behavioral therapy for mood and anxiety disorders: randomized 
controlled trial. Journal of medical Internet research 2013;15:e258. 
56. 
Nieuwkerk PT, Oort FJ. Self-reported adherence to antiretroviral therapy for HIV-1 
infection and virologic treatment response: a meta-analysis. Journal of acquired immune 
deficiency syndromes (1999) 2005;38:445-8. 
57. 
Simoni JM, Kurth AE, Pearson CR, Pantalone DW, Merrill JO, Frick PA. Self-report 
measures of antiretroviral therapy adherence: A review with recommendations for HIV research 
and clinical management. AIDS and behavior 2006;10:227-45. 
58. 
Neff KD. Development and validation of a scale to measure self-compassion. . Self and 
Identity 2003;2:223-50. 
59. 
Sint Nicolaas SM, Schepers SA, van den Bergh EMM, et al. Illness cognitions and family 
adjustment: psychometric properties of the Illness Cognition Questionnaire for parents of a child 
with cancer. Supportive Care in Cancer 2016;24:529-37. 
60. 
Brown KW, Ryan RM. The benefits of being present: Mindfulness and its role in 
psychological well-being.  
. Journal of Personality and Social Psychology 2003;84:822-48. 

Abbreviated Title:  EMI Children/YA with  Cancer 
 
 
 
 
 
 
32 
Version Date: 12/13/2021 
61. 
Watson D, Clark LA, Tellegen A. Development and validation of brief measures of 
positive and negative affect: the PANAS scales. . Journal of personality and social psychology 
1988;54:1063. 
62. 
Wolters PL, Martin S, Toledo-Tamula MA, Gillespie A, Baldwin A, Widemann B. 
Quality of life of adolescents with neurofibromatosis type 1 (NF1) and plexiform neurofibromas 
(PNs):  Reliability and validity of the Impact of Pediatric Illness (IPI) Scale self-report form.  
The National Conference in Pediatric Psychology; 2013; New Orleans, LA. 
63. 
Greco L, Baer RA, Smith GT. Assessing mindfulness in children and adolescents: 
Development and validation of the child and adolescent mindfulness measure (CAMM). . 
Psychological Assessment 2011;23:606-14. 
64. 
Ebesutani C, Regan J, Smith A, Reise S, Higa-McMillian C, Chorpita BF. The 10-Item 
Positive and Negative Affect Schedule for Children, Child and Parent Shortened Versions: 
Application of Item Response Theory for More Efficient Assessment. Journal of 
Psychopathology and Behavioral Assessment 2012;34:191-203.