Fit4Life: A weight management program for young cancer survivors Jeannie Huang, MD, MPH University of California San Diego October, 2014
Disclosures I have no relevant disclosures
Objectives To review the prevalence of weight issues in pediatric cancer survivors To review the current recommendations regarding treatment/management of overweight/obesity in pediatric cancer survivors To review our experience related to treatment/management of overweight and obesity in pediatric cancer survivors
Obesity and Pediatric Cancer Survivors Tremendous advances in treatment of pediatric cancer, ALL in particular such that 5 year cure rates >90% Survivorship common Prior studies have demonstrated increased overweight/obesity prevalence in this at-risk population; rates vary by cohort (as high as 57%) Generally higher rates than the general population Pui CH et al. NEJM 2009; Baillargeon J et al Cancer 2005; Didi M et al. J Pediatr 2005; Meacham LR et al. Cancer 2005; Odame I et al. Arch Dis Child 1994; Oeffinger KC et al. J clin Oncol 2003; Reilly JJ et al. J Clin Endocrinol Metab 2001; Rogers PC et al. Pediatr Blood Cancer 2005; Sklar CA et al. Med Pediatr Oncol 2000; Zee P et al. Pediatr Hematol Oncol 1986.
Obesity and Pediatric ALL Systemic literature review, meta-analysis Medline from inception to 2013 Study Inclusion: >=10 survivors pediatric ALL, assessed prevalence of obesity, compared obesity in survivors to reference population or external control group. 47 studies; heterogeneity Mean BMI Z-score 0.83 (0.6-1.06) corresponding to 80% BMI % - higher than reference population. High BMI Z-score controlling for CRT, gender, age at diagnosis Zhang FF, et al. Pediatrics 2014.
Metabolic syndrome Nottage et al. 784 adult childhood ALL survivors (median age 32 years) compared to 777 age, sex, race matched controls from NHANES Metabolic syndrome (MetS) identified in 259 survivors (34%) and associated with older age, and prior CRT ALL v. controls RR MetS (RR 1.43 (1.22-1.69)) and obesity (1.45 (1.29-1.68) Nottage KA, et al. Br J Haematol 2014.
Cardiovascular risk Mertens et al. 20483 5-year survivors of childhood and adolescent cancer dx (1970-1986) followed for deaths occurring (1979-2002) 2821 5-year survivors died Absolute excess risk of death 7.36 deaths/1000 person years Increases in cause-specific mortality seen for 2ndary malignancy (15.2 (13.9-16.6) SMR) and cardiac (7.0 (5.9-8.2)) Mertens AC et al. J Natl Cancer Inst 2008.
Obesity/OW in Children after ALL therapy Sklar et al. Cohort of 126 survivors of ALL; 59 males followed from diagnosis until pubertal maturity (final height) Spectrum of therapies; 38 IT chemo; 35 CRT Mean BMI Z-score increased significantly between diagnosis (-0.18 + 0.08) and end of therapy (0.41 + 0.09) with no significant change thereafter Greater in 24 Gy v. 18 Gy group and CRT independent predictor of being overweight at time of pubertal maturity (final height) Sklar CA, et al. Med Pediatr Oncol 2000.
Obesity and Pediatric ALL Survivors Zhang et al. Retrospective evaluation of 83 patients with ALL diagnosed between 1985-2010 At diagnosis 21% overweight or obese At end of treatment and 5 years post treatment, 40% overweight or obese Weight gain during treatment was associated with being overweight or obese 5 years post treatment Zhang FF et al. Pediatr Blood Cancer 2014.
ALL Outcomes and Obesity Butturini et al. Retrospective analysis of 4260 pts with newly diagnosed ALL 1988-1995 (5 COG studies); also in 2 nd cohort 1733 patients 1996-2002 (6 th study) 343 obese; 3971 nonobese patients 5-year event free survival rate and risk of relapse: 72 + 2.4% v. 77 + 0.6% and 26 + 2.4% v. 20 + 0.6%, obese v. nonobese, p=0.02 (both) Hazard ratios events & relapses (1.36 (1.04-1.77) & 1.29 (1.02-1.56)) Higher in 10 and older at diagnosis HRs events & relapses (1.5 (1.1-2.1) and 1.5 (1.2, 2.1)) Butturini AM et al. J Clin Oncol 2007
ALL Outcomes and Obesity Gelelete et al. Retrospective analysis 181 newly diagnosed ALL (1990-2009) Most children <10 yr Overweight/obesity independent predictor of relapse risk, mainly in intermediate and high risk groups Gelelete CB et al. Obesity 2011
ALL Outcomes and Obesity Orgel et al. 2008 children high-risk ALL in COG Determine effects of event-free survival of cumulative time receiving tx while obese or underweight between end of induction and start of maintenance Being obese/underweight at diagnosis and for >=50% time between induction and start of maintenance resulted in inferior EFS (P<0.001) v. not. Normalization of weight during end of induction and start of maintenance resulted in mitigation of risk comparable to never being obese/underweight Obese and underweight at start of each treatment course was significantly associated with treatment related toxicity. Orgel E et al. J Clin Oncol 2014
Weight and ALL Outcomes Youth with ALL increased risk for OB/OW Concomitant metabolic and cardiovascular risks Develops over treatment period Increased risk for relapse Problems with treatment toxicities?dosing issues pharmacokinetics and metabolic effects of obesity Tolbert J et al. Arch Dis Child 2014
Energy Expenditure 20 children (9 boys, 11 girls; mean age 11 yrs) treated for ALL with overweight 16 completed treatment; 4 within 2 nd year therapy Gender-and-age-matched with 20 healthy controls Measured TEE with doubly-labeled water method, REE, energy expended on PA and energy intake TEE higher in controls (mean paired difference ~282 kcal/d) REE also lower in patients (mean paired difference 76 kcal/d) Energy intake also lower in patients (238 kcal/d) Reilly, JJ et al. Pediatr Res. 1998
Increased energy intake v. Decreased PA? Jansen et al. 16 ALL pts on maintenance therapy v. 17 healthy controls In pts, increased energy intake on Dexamethasone (Dexa) (2100 v. 1775 kcal/d) but lower off Dexa (1300 v. 1775 kcal/d) v. controls PA lower on Dexa (30 v. 5 kcal/kg/d) but similar off Dexa v. controls Jansen H, et al. Support Care Cancer 2009.
Eating Behavior and OW/Obesity in Pediatric Cancer Survivors Hansen et al. 98 cancer survivors (50 acute lymphoblastic leukemia, 48 brain tumor), aged 12 to 17 years and 12 months post-treatment from a large pediatric oncology hospital. 52% ALL survivors and 42% brain tumor were overweight/obese Overweight/obesity status was associated with higher cognitive restraint (odds ratio = 1.03; 95% confidence interval = 1.01-1.06). Hansen JA et al. J Pediatr Oncol Nurs 2014.
Synopsis Contributors to obesity: Treatment, Dietary and PA behaviors, Psychological Opportunities for treatment Lifestyle changes
ACS Recommendations Active treatment Nutrition Focus to prevent/resolve nutrient deficiencies Achieve/maintain healthy weight PA Safe and feasible during cancer treatment, maintain as much as possible After treatment Nutrition Diet high in vegetables, fruits, whole grains (guidelines on cancer prevention) If OW/OB, limit consumption of high calorie foods and beverages PA Regular PA essential to aid recovery and improve fitness, Avoid inactivity If OW/OB, increase PA to promote weight loss Aim to exercise 150 min/week with strength training at least 2 days per week. Rock CL et al. CA Cancer J Clin 2012
AAP Guidance in Long-term Follow-up Care for Pediatric Cancer Survivors www.survivorshipguidelines.org Adults and children Healthy Diet >=5 servings fruits/vegetables High-fiber foods Limit red meat, fried, high-fat foods, refined CHO Avoid salted, smoked, pickled foods AAP Section Hematology/Oncology COG. Pediatr 2009.
AAP Guidance in Long-term Follow-up Care for Pediatric Cancer Survivors Exercise 60 minutes per day MVPA 5 d/week May need PT or OT to help adapt activities for success in exercise AAP Section Hematology/Oncology COG. Pediatr 2009.
Issues When is the best time to intervene? During initial therapy Maintenance After therapy How best to intervene? Standard Tailored/specialized
Why tailor? Need to take into account and address cancer survivorship issues Physical (compromised pulmonary and exercise capacity, reduced physical fitness/fatigue, skeletal morbidity) Psychological (post-traumatic stress, information processing difficulties, alterations in behavior and mood, and impaired relationships and coping skills). Tailoring has been shown to be effective in reducing weight among adult breast cancer survivors
Fit4Life Intervention 4 month intervention including the following components: Web/online educational sessions on diet, physical activity, weight management Telephone counseling sessions (1 st month weekly; 2-4 mos 2x/mo) Mailed educational materials Cellphone/texting based components Parental involvement Content based on behavioral modification theory and proven weight management interventions Huang JS et al. Pediatr Blood Cancer 2014
Your Fit4Life Goals are always: Eat Healthy and B Active!
Fit4Life Randomized, controlled trial 38 child and adolescent males and females who have survived childhood ALL (off therapy for >2 years without disease relapse) 7-18 years old BMI >85th percentile BMI-for-age and gender exclude patients unable to perform moderate-level physical activity recommendations (i.e., brisk walking without mechanical aids) or who are on any weightaltering therapies (including antidepressants, steroids) Huang JS et al. Pediatr Blood Cancer 2014
Comparison Condition Enhanced Standard Intervention Proven adolescent weight management intervention also including telephone counseling and mailed materials Program without tailoring to cancer survivor issues Huang JS et al. Pediatr Blood Cancer 2014
Fit4Life Huang JS et al. Pediatr Blood Cancer 2014
Fit4Life Baseline Characteristics Characteristic Fit4Life Control Age 13 (10, 16) 13 (10,16) <14:>=14 years 10:9 12:7 Gender (M:F) 12:7 11:8 Ethnicity Hispanic 17 Hispanic 17 Age at diagnosis (yrs) 5 (3, 10) 4 (3, 6) Time since last therapy (y) 5 (3, 7) 6 (3, 8) Weight (kg) 63.9 (48.4, 84.4) 65 (53.4, 86.1)
Fit4Life Intervention Outcomes Baseline v. 4 months Weight, height Behaviors Nutrition (YAQ) PA (Accelerometer) QOL Depression Huang JS et al. Pediatr Blood Cancer 2014
Fit4Life RCT Results Weight and weight status Fit4Life participants generally maintained their weight while controls increased their weight (65.6 to 65.5 kg v. 70 to 71.4 kg, Fit4Life v. control, p=0.06) and had greater reductions in BMI-Z over time (1.84 to 1.77 v. 2 to 1.99, p=0.13) Not significantly In older children (>=14 years), did meet significance, (82.7 to 82.1 kg v. 80.3 to 83.1 kg, Fit4Life v. control, p=0.05) Huang JS et al. Pediatr Blood Cancer 2014
Fit4Life RCT Results PA No differences in minutes of moderate to vigorous activities over time by group MVPA increased among older Fit4Life participants as compared to control counterparts (P = 0.009) Nutrition No differences in caloric intake over time by group (2002 to 1748 kcal/d (Fit4Life) v. 1775 v. 1784 (control), p=0.24) Psychological Notable improvements in negative mood in the Fit4Life group v. control over time (p=0.01) Huang JS et al. Pediatr Blood Cancer 2014
Fit4Life Results Preliminary efficacy of a cancer survivortailored phone and tech-disseminated WMI to improve weight status in older overweight/obese children who survived ALL Offers some evidence for tailored v. standard WMI Huang JS et al. Pediatr Blood Cancer 2014
Limitations Weight Not ideal outcome given potential changes in height However, no significant changes in height across older youth Self-report data Nutrition, likely underreporting Limited study Number of participants Time of follow-up Huang JS et al. Pediatr Blood Cancer 2014
Limitations Contact frequency?reason for improved outcomes is increased contact frequency Personal contact did appear to help with compliance and with follow-up in the Fit4Life group Compliance Across all modalities, Fit4Life recipients received 80% (70%, 100%) [median (IQR)] of the curriculum (web, text, phone) Controls: 50% (40%, 65%) of scheduled counseling calls
Promise Use of technology offers feasible, relatively low-cost alternative in at-risk but sparse population Can be distributed across time and geography Huang JS et al. Pediatr Blood Cancer 2014
Summary Obesity is prevalent in youth with ALL Important to treat given effects on disease outcomes and metabolic, cardiovascular outcomes Evidence to date suggests that weight management should start even during treatment Some evidence to suggest that tailored interventions may be more effective v. standard interventions More data is needed to improve evidence based recommendations
Acknowledgements Kevin Patrick, MD, MS Jerry Finklestein, MD Maria C. Swartz, MPH, RD Lynn Schubert, RN/William Roberts, MD Funders: NIH, American Cancer Society