Voices of children and adolescents on phase 1 or phase 2 cancer trials: A new trial endpoint?

BACKGROUND: Pediatric participants on phase 1 or phase 2 clinical trials for incurable cancer are at risk of experiencing toxicities (adverse events [AEs]) related to trial participation. Multiple AEs are subjective; thus, the real impact of trial treatment cannot be known unless patient subjective reports are solicited. METHODS: The authors assessed the feasibility and acceptability of soliciting symptom, function, and quality of life (QOL) reports from participants aged 8 to 18 years who were enrolled on phase 1/2 clinical trials at 4 cancer centers during the first course of chemotherapy. The authors also assessed the reliability and validity of 6 self-report Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric measures and 4 open-ended interview questions at 2 time points (at the time of trial enrollment [T1] and 3 to 4 weeks later [T2]). RESULTS: The enrollment rate of 75.9% (20 participants) exceeded the feasibility criterion, and missingness of measures by person, measure, and items at T1 and T2 were lower than the acceptability criteria. New QOL themes were limited to the impact of treatment on families and being away from home, family, and friends for treatment. All but one measure at T1 met the reliability criterion and all measures did so at T2. Validity support was limited however because as theorized, mobility decreased and fatigue increased as AEs increased. CONCLUSIONS: Soliciting and documenting symptom, function, and QOL reports from patients aged 8 to 18 years who are enrolled on a phase 1/2 clinical trial is feasible and acceptable to participants, particularly when embedded in trials. Reliable and valid findings can result, making patient self-reported outcomes a possible new trial endpoint. Cancer 2017;123:3799-3806. © 2017 American Cancer Society.

Adolescent and Young Adult Patient Engagement and Participation in Survey-Based Research: A Report From the "Resilience in Adolescents and Young Adults With Cancer" Study.

Conducting patient-reported outcomes research with adolescents and young adults (AYAs) is difficult due to low participation rates and high attrition. Forty-seven AYAs with newly diagnosed cancer at two large hospitals were prospectively surveyed at the time of diagnosis and 3-6 and 12-18 months later. A subset participated in 1:1 semistructured interviews. Attrition prompted early study closure at one site. The majority of patients preferred paper-pencil to online surveys. Interview participants were more likely to complete surveys (e.g., 93% vs. 58% completion of 3-6 month surveys, P = 0.02). Engaging patients through qualitative methodologies and using patient-preferred instruments may optimize future research success.

Promoting Resilience in Stress Management: A Pilot Study of a Novel Resilience-Promoting Intervention for Adolescents and Young Adults With Serious Illness.

OBJECTIVE: To examine the feasibility and format of the Promoting Resilience in Stress Management (PRISM) intervention among two groups of adolescents and young adults (AYAs) at-risk for poor outcomes: those with Type 1 diabetes (T1D) or cancer. METHODS: PRISM consists of two long or four short skills-based modules. English-speaking patients 12-25 years old were eligible if they had T1D for >6 months or cancer for >2 weeks. Feasibility was defined as an 80% completion rate and high satisfaction. Ongoing monitoring shaped iterative refinement of disease-specific approach. RESULTS: 12 of 15 patients with T1D (80%) completed the two-session intervention. 3 of 15 patients with cancer declined to complete the two-session version, citing prohibitive length of individual sessions. 12 (80%) completed the four-session version. Patient-reported satisfaction was high across groups. CONCLUSIONS: The PRISM intervention is feasible and well-accepted by AYAs with cancer or T1D. Differences in patient populations warrant differences in approach.

Glucocorticoids and insulin resistance in children with acute lymphoblastic leukemia.

BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) are more likely to become overweight. Prolonged exposure to high-dose glucocorticoids may cause insulin resistance and facilitate development of this phenotype. PROCEDURE: Body mass indices (BMI) and insulin resistance (homeostatic model assessment [HOMA]-IR) were prospectively measured among on- (n = 31) and off-therapy participants (n = 29). On-therapy participants were assessed prior to and while on glucocorticoids (5 days of prednisone 40 mg m(-2) or dexamethasone 6 mg m(-2)) given as part of routine maintenance chemotherapy, with a subset (n = 10) receiving an intravenous glucose tolerance test (IVGTT) while on glucocorticoids. RESULTS: Baseline HOMA-IR values among on- and off-therapy participants were similar, but among on-therapy participants, HOMA-IR increased significantly with glucocorticoid exposure (median 3.39 vs. 1.26; P < 0.01) with 45.2% of participants having values >4.39 (upper 2.5th percentile among normal weight adolescents). Although baseline HOMA-IR was significantly correlated with current BMI (r = 0.48, P < 0.01), change in HOMA-IR following steroid exposure was not correlated with any demographic or treatment characteristic including current BMI. Among those with IVGTT data, HOMA estimates in general correlated with values derived from a minimal model analysis (r ~ 0.7). CONCLUSIONS: High-dose glucocorticoids given as part of routine chemotherapy were associated with a significantly increased insulin resistant state. Given the amount and duration of glucocorticoids children with ALL experience, these physiologic changes could be an important contributor to the development of therapy-related obesity.

Provider Perspectives on Use of Medical Marijuana in Children With Cancer.

BACKGROUND: Although medical marijuana (MM) may have utility in the supportive care of children with serious illness, it remains controversial. We investigated interdisciplinary provider perspectives on legal MM use in children with cancer. METHODS: We sent a 32-item, cross-sectional survey to 654 pediatric oncology providers in Illinois, Massachusetts, and Washington characterizing MM practices, knowledge, attitudes, and barriers. Forty-eight percent responded; 44% (n = 288) were included in analyses. Providers were stratified by status as legally eligible to certify (ETC) for MM. We used Fisher's exact and Wilcoxon rank tests and univariate and multivariate logistic regression models for group comparisons. RESULTS: The provider median age was 35 years (range 22-70 years); 33% were ETC (83 physicians; 13 Washington state advance practice providers). Thirty percent of providers received ≥1 request for MM in the previous month. Notably, only 5% of all providers knew state-specific regulations. ETC providers were more likely to know that MM is against federal laws (P < .0001). Whereas most providers (92%) reported willingness to help children with cancer access MM, in adjusted models, ETC providers were less likely to indicate approval of patient MM use by smoking, oral formulations, as cancer-directed therapy, or to manage symptoms (P < .005 for all). Forty-six percent of all providers cited the absence of standards around formulations, potency, or dosing to be the greatest barrier to recommending MM. CONCLUSIONS: Most pediatric oncology providers are willing to consider MM use in children with cancer and receive frequent inquiries. However, ETC providers endorse less favorable attitudes overall. The absence of standards is an important barrier to recommending MM.

Promoting Resilience in Stress Management for Parents (PRISM-P): An intervention for caregivers of youth with serious illness.

INTRODUCTION: It is well-known that parental stress and coping impacts the well-being of children with serious illness. The current study aimed to evaluate the feasibility and satisfaction of a novel resilience promoting intervention, the Promoting Resilience in Stress Management Intervention for Parents (PRISM-P) among parents of adolescents and young adults with Type 1 diabetes or cancer. Secondary analyses explored the effect of the PRISM-P on parent-reported resilience and distress. METHOD: The PRISM-P includes 4 short skills-based modules, delivered in either 2 or 4 separate, individual sessions. English-speaking parents of adolescents with cancer or Type 1 diabetes were eligible. Feasibility was conservatively defined as a completion rate of 80%; satisfaction was qualitatively evaluated based upon parent feedback regarding intervention content, timing, and format. Resilience and distress were assessed pre- and postintervention with the Connor Davidson Resilience Scale and the Kessler-6 Psychological Distress Scale. RESULTS: Twelve of 24 caregivers of youth with diabetes (50%) and 13 of 15 caregivers of youth with cancer (87%) agreed to participate. Nine of 12 (75%) and 9 of 13 (64%) completed all PRISM-P modules, respectively. Among those who completed the intervention, qualitative satisfaction was high. Parent-reported resilience and distress scores improved after the intervention. Effect sizes for both groups indicated a moderate intervention effect. DISCUSSION: Ultimately, the PRISM-P intervention was well accepted and impactful among parents who completed it. However, attrition rates were higher than anticipated, suggesting alternative or less time-intensive formats may be more feasible. (PsycINFO Database Record

Intimacy, Substance Use, and Communication Needs During Cancer Therapy: A Report From the "Resilience in Adolescents and Young Adults" Study.

PURPOSE: The prevalence of intimacy and substance use among adolescents and young adults during cancer therapy has not been well described. METHODS: The "Resilience in Adolescents and Young Adults with Cancer" study was a prospective, multicenter, mixed-methods cohort study. English-speaking patients 14-25 years old with newly diagnosed cancer were invited to complete a comprehensive survey at the time of enrollment (T1) and 3-6 months later (T2). Intimate relationships and health behaviors were assessed with questions adapted from the Guidelines for Adolescent Preventative Services assessment. Descriptive statistics characterized the prevalence of sexual and substance-related behaviors at each time point. RESULTS: Of 42 eligible and enrolled participants, 35 (83%) and 25 (59%) completed T1 and T2 surveys, respectively. Their mean age was 17.6 years (standard deviation 2.3), 57% were male, and the most common diagnoses were sarcoma and acute leukemia. Over a third of participants reported dating at each time point; 26% were sexually active at T1, and 32% at T2. Of those endorsing sexual activity, fewer than half reported consistent birth control or condom use and 4 reported their first sexual intercourse during our observation. In addition, 46% (T1) and 44% (T2) reported alcohol use and 23% (T1) and 26% (T2) reported illicit drug use. Despite these activities, fewer than 10% endorsed a worry or need to discuss these behaviors with oncology providers. CONCLUSIONS: Intimacy and substance use among adolescents and young adults are common during cancer therapy. Clinical and research implications include the identification of optimal communication and patient-centered supports.

The Benefits and Burdens of Cancer: A Prospective Longitudinal Cohort Study of Adolescents and Young Adults.

BACKGROUND: Adolescents and early young adults (AYAs) with cancer are at high risk for poor outcomes. Positive psychological responses such as benefit-finding may buffer the negative impacts of cancer but are poorly understood in this population. OBJECTIVE: We aimed to prospectively describe the content and trajectory of benefit- and burden-finding among AYAs to develop potential targets for future intervention. PATIENTS AND METHODS: One-on-one semistructured interviews were conducted with English-speaking AYA patients (aged 14-25 years) within 60 days of diagnosis of a noncentral nervous system malignancy requiring chemotherapy, 6-12 and 12-18 months later. Interviews were coded using directed content analyses with a priori schema defined by existing theoretical frameworks, including changed sense of self, relationships, philosophy of life, and physical well-being. We compared the content, raw counts, and ratios of benefit-to-burden by patient and by time point. SETTING/SUBJECTS: Seventeen participants at one tertiary academic medical center (mean age 17.1 years, SD = 2.7) with sarcoma (n = 8), acute leukemia (n = 6), and lymphoma (n = 3) completed 44 interviews with >100 hours of transcript-data. RESULTS: Average benefit counts were higher than average burden counts at each time point; 68% of interviews had a benefit-to-burden ratio >1. Positive changed sense-of-self was the most common benefit across all time points (44% of all reported benefits); reports of physical distress were the most common burden (32%). Longitudinal analyses suggested perceptions evolved; participants tended to focus less on physical manifestations and more on personal strengths and life purpose. CONCLUSIONS: AYAs with cancer identify more benefits than burdens throughout cancer treatment and demonstrate rapid maturation of perspectives. These findings not only inform communication practices with AYAs but also suggest opportunities for interventions to potentially improve outcomes.

Contributors and Inhibitors of Resilience Among Adolescents and Young Adults with Cancer.

Purpose: Self-perceived resilience may enable coping and mitigate poor psychosocial outcomes among adolescent and young adult (AYA) patients with cancer. In order to inform the development of resilience-promoting interventions, we aimed to: (1) describe AYA patient-reported resilience and (2) identify AYA patient-reported contributors and inhibitors of resilience. Methods: The "Resilience in Adolescents and Young Adults with Cancer" study was a prospective longitudinal mixed-methods study. Consecutive Caucasian patients aged 14-25 years old enrolled 14-60 days following their diagnosis of cancer and completed one-on-one semi-structured interviews both at the time of enrollment and 3-6 months later. Constant comparative analyses identified salient themes describing modifiable contributors and inhibitors to patient-perceived resilience. Results: Seventeen patients (85% of those approached) enrolled in the study. The mean age was 17 years (SD=2.6) and 53% were female. All patient definitions of resilience inferred an ability to handle adversity. Five themes emerged as predominant contributors or inhibitors of resilience: (1) stress and coping; (2) goals, purpose, and planning; (3) optimism; (4) gratitude and meaning; and (5) connection and belonging. Merged analyses suggested that AYA resilience was a balance that may be enabled by promoting certain skills. Conclusion: AYA patients with cancer perceive resilience as a balance. Learned skills in stress management, goal-setting, and benefit-finding may empower AYAs during their cancer experience, in turn improving long-term psychosocial outcomes.