A Review of Health Behaviors in Childhood and Adolescent Cancer Survivors: Toward Prevention of Second Primary Cancer

Abstract

Purpose:

Survival of children and adolescents and young adults (AYAs) treated for cancer has increased with improved treatments. However, there is still an increased risk of second primary cancer (SPC) in the long term compared with the same-age population, especially related to treatments. The follow-up of this population and the prevention of SPC are important issues. Therefore, this study aimed to review the available literature on cancer risk factors (lifestyle and occupational exposures) in children and AYAs previously treated for cancer in order to identify interventions that might be implemented to improve healthy behaviors in this population.

Methods:

PubMed was searched using the following terms: “cancer[Tiab] AND young adult[Tiab] or teen[Tiab] or childhood[Tiab] AND prevention[Tiab] AND survivors[Meshterm].”

Results:

Twenty-seven articles were included. Children and AYA survivors of cancer have similar risk behaviors to their peers regarding tobacco, diet, and sun exposure. However, they have lower physical activity. Few studies on prevention strategies in this population were identified. Results of available studies remain inconclusive. No publications were found on occupational exposure and risk of second cancer.

Conclusion:

Children and AYAs treated for cancer are a population at risk and require specific effective prevention strategies.

Survival rates for children and adolescents and young adults (AYAs) with cancer have improved due to new treatments. For all cancers, 5-year survival rates are around 80%.¹ Alongside these improvements, the long-term consequences of the disease and its treatment are substantial. Cancer treatments in children and AYAs lead to long-term adverse effects, including endocrine dysfunction, cardiovascular disease, metabolic syndromes, decreased fertility, and impaired quality of life. Radiotherapy and chemotherapy significantly increase the risk of second malignancies.^1,2 The latter represent the most common cause of treatment-related death in long-term survivors of childhood cancer.¹ Cancers in children and AYAs represent a heterogeneous disease group that vary widely in incidence, age at diagnosis, type of treatment, survival, and most probably etiology.³ The definition of age limits for AYAs in the literature varies widely across studies, publication periods, and countries. While most authors consider 15 years as the lower boundary, the upper age cutoffs range from 24 to 29 and sometimes 39 years.⁴ Survivors of cancer younger than 17 years of age at initial diagnosis are six times more likely to develop a second cancer compared with the general population of the same age.³ This risk is two to three times that of people treated for cancer aged 18–39 years at initial diagnosis.³ The cumulative incidence of second malignancies in the Childhood Cancer Survivor Study (CCSS) at 30 years after initial cancer diagnosis was 21% for all subsequent neoplasms, 9% for non-melanoma skin cancer, and 11% for second malignant neoplasms (excluding non-melanoma skin cancer). Excess risk was observed for all primary cancer localizations. The 10 most frequent second malignant neoplasms (excluding non-melanoma skin cancer) observed in the CCSS (median follow-up of 23 years) were breast cancers (23%), thyroid cancers (15%), central nervous system (CNS) tumors (10%), soft-tissue sarcomas (9%), melanomas (6%), bone cancers (6%), head and neck cancers (5%), osteosarcomas (4%), lymphomas (4%), and small intestine and colorectal cancers (3%), with a mean age of 29.5 years at subsequent neoplasm diagnosis. A significantly increased incidence with a 2–30-fold standardized incidence ratio (SIR) was observed for all localizations compared with the general population, including a 3–10-fold SIR for cancers that are more typical of cancers in older adults, such as breast cancer, small intestine cancer, head and neck cancer, CNS tumors, lung cancer, and leukaemia.⁵

Female sex, older age at diagnosis, earlier treatment era, and radiation therapy were associated with increased risk of subsequent neoplasms. Differential exposure to cancer risk factors such as lifestyle (tobacco, diet, physical activity) may also be associated with increased risk of second malignancies, but this has been poorly studied in AYAs. To improve the prevention of second malignancies, the available literature was searched on cancer risk factors (lifestyle and occupational exposures) in children and AYAs previously treated for cancer. This study also reviewed the interventions that can be implemented to improve healthy behaviors in this population. The study focused on cancer risk factors known to be associated with the cancer types having shown an increased incidence in children and AYAs previously treated with cancer: smoking (lung cancer, breast cancer, colorectal cancer, leukemia)⁶; diet, nutrition, and physical activity (colon cancer, rectal cancer, breast cancer, skin)⁷; sun exposure (skin cancer); alcohol (breast cancer, colorectal cancer); and occupational exposures (lung cancer, leukemia, skin cancer, bone sarcomas, CNS tumors).^8,9

Methods

PubMed was searched until June 2014, with no restriction on the earliest date of the publications, using the terms “cancer[Tiab] AND young adult[Tiab] or teen[Tiab] or childhood[Tiab] AND prevention[Tiab] AND survivors[Meshterm],” and limiting the search to articles in English and French. The search was completed using online data from the Public Health data bank, International Agency for Research on Cancer (IARC) website, and various websites (sanitary, occupational, and environmental agencies) and consensus conferences. The reference lists of related articles were also searched.

The articles (epidemiological studies, intervention studies, and literature reviews) were selected on their summary and further through the full article. Articles dealing with the risk of second malignancies associated with life style factors or occupational exposures as well as articles on cancer prevention strategies for the malignancies seen as second cancers after childhood and AYA cancer were selected. To take into account the substantial variability in the age ranges used by authors across studies and to facilitate the analyses of available publications, a predefined age range for this population was no applied. Articles dealing with second cancers related to genetic predisposition or psychosocial consequences of second malignancies, screening, and surveillance practices were not included. Articles dealing specifically with the risk of second malignancies associated with treatment of a first cancer were also excluded, as extensive reviews of the literature have been published previously on this topic.^2,5

Results

Of the 105 articles identified by the search, 27 articles were included of which 14 dealt with behavioral risk factors and 13 with health promotion, including preventing risk factors for second cancers (see Fig. 1). Fifty-seven articles were excluded after reviewing the full publication because they did not match the eligibility criteria. Fifteen of the articles were unavailable through the authors' library or interlibrary services within the review time scope. Fifteen of the articles were excluded after full reviewing by two reviewers (J.C. and S.D.), who considering them to be outside the scope. Table 1 provides a detailed description of the main studies included in our search.

FIG. 1.

Flow diagram for the search.

Table 1.

Description of the Main Clinical and Epidemiological Studies Included

First author, year of publication	Type of article	Number of subjects	Age at diagnosis	Objectives	Source of data	Key results
Reulen, 2011⁸	Multicentric retrospective cohort study	17,981 cancer survivors	<15 years	(1) To investigate the long-term risks of subsequent primary neoplasms in survivors of childhood cancer; (2) to identify subsequent primary neoplasm types that contribute most to the long-term excess risk; (3) to identify subgroups of survivors at substantially increased risk of particular subsequent primary neoplasms who may require specific interventions.	The British Childhood Cancer Survivor Study; 5-year cancer survivors	Cumulative incidence of colorectal cancer for survivors treated with direct abdominopelvic irradiation 1.4% by age 50 years, comparable with the 1.2% risk in individuals with at least two first-degree relatives affected by colorectal cancer. The absolute excess risks (AERs) in survivors older than 40 years of age are highest for digestive subsequent primary neoplasms (AER = 5.9; 95% CI: 2.5–9.3 per 10,000 person-years) and genito-urinary subsequent primary neoplasms (AER = 6.0; 95% CI: 2.3–9.6 per 10 000 person-years); these patients may require specific interventions (prevention, screening).
Bauld, 2005¹¹	Comparison study	153 cancer survivors; sample of 6377 healthy peers to match the adolescent survivor age range 13–17 years, and sample of 465 participants aged 8–24 years to match with older survivors	13–24 years	To investigate smoking, alcohol use, illicit drug use, and sexual risk in adolescent survivors of childhood cancer	Adolescent cancer survivors off treatment for 12 months or more, recruited through the Royal Children's Hospital, Melbourne, Australia, compared with age-matched healthy adolescents drawn from one of two Australian population-based surveys of adolescent health	Among participants, the most prevalent cancer diagnoses were leukemia (53%), bone cancer (14%), Wilms tumor (10%), and non-Hodgkin lymphoma (7%). Compared with their healthy peers, younger survivors (13–17 years) were at a decreased risk of reporting alcohol use (OR = 0.44; 95% CI: 0.39–0.49), binge drinking (OR = 0.20; 95% CI: 0.18–0.23), current tobacco use (OR = 0.38; 95% CI: 0.34–0.43), cannabis use (OR = 0.25; 95% CI: 0.22–0.29), and other illicit drug use (OR = 0.31; 95% CI: 0.27–0.35), but at increased risk of reporting pain reliever use (OR = 2.1; 95% CI: 1.8–2.4). Older adolescent survivors (18–24 years) reported increased alcohol use (OR = 1.5; 95% CI: 1.0–2.2), lower cannabis use (OR = 0.27; 95% CI: 0.20–0.36), other illicit drug use (OR = 0.44; 95% CI: 0.35–0.55), and current tobacco use (OR = 0.47; 95% CI: 0.37–0.60). Survival analysis showed a later age of onset of smoking for cancer survivors (HR = 0.65). There was no association between health-risk behaviors and disease characteristics, patients' demographics (i.e., age at diagnosis, time on treatment, and time off treatment), suggesting that alcohol use, binge drinking, smoking, and drug use are mediated by factors outside the illness and treatment.
Carswell, 2008¹²	Comparative national, multicenter, population-based study	1263 cancer survivors; 1422 controls from provincial health insurance agencies	<20 years	(1) To describe the prevalence of smoking and binge drinking among survivors of childhood and adolescent cancer, comparison with age- and sex-matched healthy controls. (2) To identify factors associated with these behaviors.	Late Effects study, part of the Canadian Childhood Cancer Surveillance and Control Program. Patients who survived at least 5 years after diagnosis.	Survivors were less likely to be current smokers (OR_adj = 0.65; 95% CI: 0.54–0.77) and binge drinkers (OR_adj = 0.66, 95% CI: 0.55–0.78) than controls were. Survivors' smoking (23%) and binge drinking (25%) did not vary according to clinical factors.
Tercyak, 2006¹³	Randomized controlled trial of health-promotion intervention	75 cancer survivors	11–21 years	To test the efficacy of health education and health behavior counseling (cigarette use, insufficient physical activity, and non-adherence to sun protection recommendations) among adolescent survivors of childhood cancer. Focus on the prevalence and co-occurrence of three behavioral risk factors.	Telephone-based assessment of health behaviors and stress; behavioral record of the past 7 days.	28% of patients reported one of three risk factors, 12% reported two of three risk factors, and 7% reported all three risk factors. Non-adherence to sun protection was the single most common risk factor; physical inactivity and non-adherent sun protection were the most common co-occurring risk factors. Greater age and stress were significantly associated with the presence of more than one behavioral risk factors.
Kahalley, 2012¹⁴	Multicentric cohort study	307 cancer survivors; 97 healthy siblings	<21 years; 14–20 years (healthy siblings)	To estimate the rate of smoking, and to identify factors associated with smoking in adolescent survivors	The Childhood Cancer Survivor Study cohort^a. Participants completed a self-report survey of health, quality of life, and health behaviors	Survivors: 28% ever smokers; 10% recent smokers. Sibling groups: 33% ever smokers; 9% recent smokers. Ever smoking was significantly associated with purging (RR = 2.49; 95% CI: 1.60–3.88; p < 0.001), binging (RR = 1.57; 95% CI: 1.08–2.31; p < 0.05), suicidal behavior (RR = 2.12; 95% CI:1.47–3.07; p < 0.001), peer smoking (RR = 3.21; 95% CI: 2.35–4.38; p < 0.001), having smokers in the household (RR = 1.73; 95% CI: 1.22–2.46; p < 0.01), and having no history of cranial radiation therapy (RR = 1.92; 95% CI:1.05–3.45, p < 0.05). Recent smoking was significantly associated with purging (RR = 4.44; 95% CI: 2.08–9.50; p < 0.001), binging (RR = 2.55; 95% CI: 1.32–4.90; p < 0.01), suicidal behavior (RR = 3.61; 95% CI: 1.89–6.89; p < 0.001), emotional discomfort (RR = 2.75; 95% CI: 1.38–5.49; p < 0.01), peer smoking (RR = 7.18; 95% CI: 3.85–13.40; p < 0.001), and having smokers in the household (RR = 3.03; 95% CI: 1.58–5.82; p < 0.01).
Tyc, 2009¹⁵	Multicentric case-control study	94 patients undergoing cancer treatment	8–11 years	To compare preadolescents treated for cancer to their healthy peers on a number of tobacco-related risk factors	The 94 preadolescents undergoing treatment for cancer and a matched comparison sample of 190 participants without cancer completed questionnaires about their smoking habits, intentions to smoke, and tobacco-related psychosocial risk factors.	There were no current smokers in the cancer cohort and only two current (0.5%) in the original school sample. Healthy preadolescents were more likely to report future intentions to smoke (34.1%) relative to preadolescents with cancer (14.0%, p < 0.001). Healthy preadolescents were more likely to have at least one close friend who smoked (16.8%) compared with those with cancer (7.5%, p = 0.030). Compared with those without cancer, preadolescents with cancer had higher tobacco-related knowledge (p = 0.001), perceived themselves to be more vulnerable to tobacco-related illness (p < 0.001), were more optimistic (p < 0.001), and attributed more value to overall health (p = 0.001). They also perceived themselves to be more vulnerable to general health problems (p < 0.001), and had lower levels of rebelliousness/risk taking (p = 0.001), as well as perceived instrumental value of smoking (p = 0.002). Multivariable analyses suggest that the ages of 8–11 years may be a critical period for a child's development of attitudes about smoking in that every year of age conferred approximately a 50% increase in the odds of intending to smoke.
Emmons, 2002¹⁶	Multicentric retrospective cohort study	9709 cancer survivors	≥18 years	To examine smoking behaviors and to evaluate predictors of cigarette smoking initiation and cessation	The Childhood Cancer Survivor Study^a	Ever smoking: 28%; current smokers: 17%. Factors independently associated with a statistically significant relative risk of smoking initiation included older age at cancer diagnosis, lower household income, less education, not having had pulmonary-related cancer treatment, and not having had brain radiation. Blacks were less likely to start smoking. The frequency of smoking initiation was significantly lower among survivors.
Green, 2012¹⁷	Multicentric retrospective cohort study	9284 cancer survivors	≥18 years	To evaluate the potential contribution of demographic, lifestyle, treatment, and intrapersonal factors and self-reported pharmaceutical use to obesity	The Childhood Cancer Survivor Study^a	The risk of obesity (BMI^b >30 kg/m²) was increased among those aged 5–9 years at diagnosis (RR = 1.12; 95% CI: 1.01–1.24; p = 0.03), those who received 20–30 Gy of hypothalamic/pituitary radiation dose (RR = 1.17; 95% CI: 1.05–1.30; p = 0.01), and those with abnormal SF-36 physical function (RR = 1.19; 95% CI: 1.06–1.33; p = 0.001). The risk of obesity was decreased among those who met the US Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR = 0.90; 95% CI: 0.82–0.97; p = 0.01) and among those with a medium amount of cancer-related anxiety (RR = 0.86; 95% CI: 0.75–0.99; p = 0.04). Of the pharmaceuticals evaluated, only paroxetine (antidepressant) was independently associated with an increased risk for obesity (RR = 1.29; 95% CI: 1.08–1.54; p = 0.01).
Robien, 2008¹⁹	Clinical study	72 cancer survivors	≤20 years	(1) To evaluate the typical dietary intake of adult survivors of childhood acute lymphocytic leukemia (ALL) and to compare these data with major dietary recommendations related to cancer and cardiovascular disease prevention; (2) to evaluate whether adherence with dietary guidelines was associated with BMI^b and waist circumference among adult survivors of childhood ALL.	The Childhood Cancer Survivor Study Cohort^a	Half the participants met minimal goals for fruit and vegetable intake: this is significantly greater than the population median percentage of adults nationwide (23.2%) and those in the state of Minnesota (24.5%); and half the participants met minimal goals for dietary fat restrictions. Participants reported dietary sodium and added sugar intake in excess of recommendations, and suboptimal consumption of dietary fiber. 18% of participants met recommendations for 30 minutes of physical activity, 5 days/week.
Gurney, 2003²⁰	Retrospective cohort study	921 childhood brain cancer survivors	≤20 years	(1) To compare final height and BMI^b between adult survivors of childhood brain cancer and age- and sex-matched population norms; (2) to quantify the effects of treatment and cancer-related factors on the risk of final height below the 10th percentile (adult short stature) or having a BMI^b of ≥30 kg/m² (obesity).	The Childhood Cancer Survivor Study Cohort^a	40% of participants were very short in stature: <10th percentile for height. The strongest risk factors for short adult stature: young age at diagnosis and radiation treatment involving the hypothalamic–pituitary axis. Obesity risk factor: younger age and cranial radiation in females.
Buchanan, 2009²³	Retrospective cohort study	9298 childhood cancer survivors; 2950 sibling controls	≤20 years	To determine the current sun protection behaviors of childhood cancer survivors, and to compare these behaviors to a sibling population. Secondary objective: to determine whether survivors who are at higher risk of skin cancer because of previous radiation therapy have improved sun protection behavior.	The Childhood Cancer Survivor Study Cohort^a	66% of siblings and 67% of cancer survivors practiced at least some sunscreen use in the past summer. Childhood cancer survivors were less likely to have sunbathed in the past year (none vs. any: RR = 0.92; 95% CI: 0.89–0.95) or use artificial tanning methods in the past year (none vs. any: RR = 0.76; 95% CI: 0.70–0.83). Factors associated with survivor's sunscreen use in the previous year: exposure to therapeutic radiation, being female, having lighter skin complexions, having previously examined for skin cancer, and higher predisposition to sunburn. Variables associated with increased sunbathing in the previous year among survivors: no previous radiation, being female, younger age (≤45 years), the number of years post-diagnosis (≤30 years), darker skin color, and lower predisposition to sunburn. Subjects with a prior skin cancer were more likely to use sunscreen (RR = 1.12; 95% CI: 1.06–1.18) and less likely to sunbathe (RR = 0.87; 95% CI: 0.79–0.96).
Keats, 2006²⁴	Cross-sectional survey	97 adolescent cancer survivors	11–19 years	To investigate the impact of a cancer diagnosis on adolescent physical activity behaviors across the cancer experience (i.e., pre-diagnosis, during treatment, and post-treatment)	Participants residing in Western Canada (15–20 years old at the time of initial study recruitment) completed a mailed, self-administered questionnaire (measures of physical activity at three time points).	Three most common diagnoses included some form of lymphoma or Hodgkin disease (29.9%), leukemia (27.8%), and tumors of the central nervous system (14.4%). Based on the 27 MET (metabolic equivalent) criterion (selected as criterion for “active”): 84.5% were active pre-diagnosis, 26.4% were active during treatment, 73.6% were active post-treatment. The decline in physical activity persisted following the completion of treatment. No systematic differences or relationships between the measured demographic/medical characteristics and physical activity behaviors during or post-treatment.
Upadhyaya, 2004²⁵	Open-label pilot study	16 adolescents without history of cancer	12–19 years	To examine the feasibility and preliminary tolerability of bupropion SR in adolescents with nicotine dependence	Adolescents were titrated over 1 week to bupropion SR 150 mg b.i.d and maintained at this dosage for 6 weeks. Participants also received two 30-minute individual smoking cessation counseling sessions.	Nine participants received at least 4 weeks of medication: significant decrease in the average number of cigarettes smoked and carbon monoxide levels. 31.25% of the adolescents were abstinent after 4 weeks of taking bupropion SR. Bupropion SR along with counseling may be safe and potentially efficacious for this population. Lack of weight gain among participants during the smoking cessation effort. Possibility that bupropion might have a harm reduction effect due to reduction of the number of cigarettes smoked.
Killen, 2004²⁶	Smoking cessation randomized clinical trial	211 adolescent smokers, without history of cancer	15–18 years	To examine the efficacy of a treatment for adolescent smokers that combines nicotine patches with bupropion	Randomization to one of two groups: (1) nicotine patch + bupropion SR (2) nicotine patch + placebo. Participants met weekly in 45-minute session (group skills training).	Percentage abstinent assessed by time and treatment group: (1) nicotine patch + bupropion SR: 23% week 10, 8% week 26; (2) nicotine patch + placebo: 28% week 10, 7% week 26. Bupropion might have failed to improve abstinence rates because of the dosage used in this study (150 mg/day, whereas the recommended dosage for adult smokers is 300 mg/day). The medication appeared to be safe and were well tolerated. The large majority of adolescents in both treatment groups reduced their consumption to a few cigarettes per day or less.
Hollen, 1999²⁷	Prospective clinical trial	64 cancer survivors	13–21 years	To test the hypothesis that teen survivors who receive education to enhance decision-making skills will report increased quality decision making and maintained or lowered risk-behavior status (in smoking, alcohol use, or illicit drug use) at 1, 6, and 12 months post-intervention more than the comparison group	Intervention group with 21 participants who attended a workshop, and comparison group with 43 survivors who did not attend the workshop. The intervention included three components: five 1-hour educational units administered in 1 day, three short videocassettes (one on decision making, two on alcohol use), and four weekly home assignments given during the first post-intervention month.	Effect of the intervention for improving decision-making knowledge, and decision making was significant at 1 month post-intervention, and highly significant at 12 months post-intervention. The intervention did not affect smoking risk motivation at any of the three time points. The intervention had a significant effect on motivation for engaging in alcohol use at 1 month post-intervention, and a marginally significant effect at 6 months, but no effect at 12 months. Home assignments for remediation with cancer-surviving adolescents most likely need to be expanded over a longer follow-up period to obtain a lasting effect for risk behaviors.
Tyc, 2003²⁸	Randomized controlled trial	103 cancer survivors	10–18 years	To evaluate the efficacy of a tobacco risk counseling intervention on knowledge, perceived vulnerability, and future intentions to smoke among preadolescents and adolescents cancer survivors compared with a standard care control condition	Participants from St. Jude Children's Research Hospital, were randomized in two groups: standard care control group (standard advice about the risks of tobacco use), and tobacco intervention group (with more intensive late effects risk counseling in addition to an educational video, goal setting, written physician feedback, smoking literature, follow-up telephone counseling).	Compared with the standard care control group, intervention group's participants had significantly higher knowledge scores, higher perceived vulnerability scores, and lower intention scores at 12 months following the intervention. No significant differences between the two groups at 6 months, across all measures, were found. Participants whose parents used tobacco had significantly higher intentions scores at 12 months compared with scores obtained at 6 months and baseline. Participants whose parents were non-tobacco users and who received the intervention reported significantly lower intention scores than the control group patients. Informing adolescent cancer survivors about their personal susceptibility to negative health outcomes can play a role in promoting tobacco abstinence in this vulnerable population. Modifying young survivors' perceptions of risk and intentions to use tobacco may reflect a process that evolves over time.
Smith, 1996³¹	Non-randomized open-label clinical trial	22 adolescent smokers	13–17 years	To evaluate the safety, tolerance, and efficacy of 24-hour nicotine patch therapy in adolescent smokers with current smoking rate of ≥20 cigarettes/day, who were trying to stop smoking	The intervention was a daily nicotine patch therapy for 8 weeks (22 mg/day for 6 weeks followed by 11 mg/day for 2 weeks). Weekly individual behavioral counseling and group support continued for 8 weeks with follow up visits at 3 and 6 months, and a mailed survey at 1 year.	82% experienced at least one adverse event during the 8-week patch phase; 68% reported some kind of skin reaction; 55% reported erythema only; 32% reported no skin reactions (common adverse events also reported with patch use adult smokers in the literature). 14% of the participants reported not smoking during week 8. Patch is safe to use in this population, and is well tolerated as an adjunct to a smoking cessation program.
Moolchan, 2005³²	Double-blind, double dummy, randomized three-arm trial	120 adolescents without history of cancer	13–17 years	To determine the safety and efficacy of the nicotine patch and gum for adolescents who smoked ≥10 cigarettes/day and who want to quit smoking	Participants received 12 weeks of nicotine patch or gum therapy with cognitive–behavioral therapy, with a follow-up visit at 6 months. They were randomized into three groups: nicotine patch 21 mg (34 participants), nicotine gum 2 and 4 mg (46 participants), placebo patch and gum (40 participants).	Mean compliance across groups was higher for the patch than for the gum. Both patch and gum were well tolerated, and adverse events were similar to those reported in adult trials. No significant effect of patch versus gum placebo on cessation outcomes. Significant difference between the active patch and placebo arms with prolonged abstinence rates: 18% for the active patch group, 2.5% for the placebo group. The nicotine patch was significantly more effective than placebo in helping dependent adolescent smoking receiving cognitive–behavioral therapy quit smoking (prolonged abstinence).
Hudson, 2002³³	Behavioral health promotion study	266 cancer survivors	12–18 years	To assess the impact of a multicomponent behavioral intervention on changing health knowledge, health perceptions (perceived susceptibility, perceived seriousness, perceived benefits, perceived barriers), and health behavior practices	From a childhood cancer survivor cohort attending the St. Jude Children's Research Hospital after completion of therapy clinic for annual evaluation, in remission ≥2 years after completion of cancer therapy; randomly assigned to a control-arm (standard care, n = 135) or treatment-arm (standard care plus the multi-behavioral intervention, n = 131). 251 participants were evaluated at both time points for the calculation of change scores.	Baseline evaluation: no significant differences in health practices, perceptions or knowledge. 52% reported to be unaware of the potential risk of second cancer which was the most concerning potential treatment sequelae in 48% of participants. No significant differences in the change scores between the standard care group and the intervention group at 1 year follow-up. Perceptions of seriousness for risks factors secondary to the cancer treatment of adolescent cancer patients were increased as a result of the intervention. On selected patient subgroups: significant differences between males and females in change scores for health knowledge, with females in the cohort demonstrating greater improvement in knowledge at 12 months among females randomized to the intervention group.

The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study of 14,359 survivors of childhood cancer diagnosed prior to 21 years of age between January 1, 1970, and December 31, 1986, with a longitudinal follow-up of 5-year survivors of childhood cancer treated in 26 institutions in the United States and Canada. Eligible cancer diagnoses included leukemia, central nervous system malignancy, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumor, neuroblastoma, soft-tissue sarcoma, and bone tumors.

Body mass index (BMI) is a measure of body fat based on height and weight that applies to men and women.

AERs, absolute excess risks; ALL, acute lymphoblastic leukemia; CI, confidence interval; HR, hazard ratio; RR, relative risk; SIR, standardized incidence ratio.

Behavioral factors

Overall, 14 publications addressed lifestyle factors, such as smoking, cannabis use, alcohol consumption, sun exposure, physical activity, and nutrition. Four focused especially on AYAs previously treated for cancer.^10–13 Three articles focused exclusively on smoking,^14–16 and six on physical activity and nutrition.^17–22 One publication dealt with sun exposure in AYAs who had previously been treated for cancer.²³

Tobacco

Overall, five studies focused on smoking in young cancer survivors.^{11,12,14–16} Smoking prevalence in survivors varied between 10% and 29%. Two studies found a significantly lower prevalence of smoking in survivors of AYA cancers compared with the general AYA population.^11,12

Kahalley et al. studied factors associated with smoking in 307 adolescents from the CCSS.¹⁴ In this study, the percentages of current smokers (10%) and past adolescent smokers (28%) were similar to those in the general population (9% and 33%, respectively). Factors associated with increased prevalence of recent smoking (having smoked in the week before the survey) were eating disorders (bulimia, anorexia), psychiatric problems (e.g., suicidal behavior), emotional distress, having friends who smoke, and having smokers in their household. Tyc et al. studied the factors associated with starting smoking in 94 preadolescents with cancer and in 190 preadolescents without cancer.¹⁵ In this study, no preadolescents with cancer and only 0.5% of preadolescents without cancer reported current smoking (a non-significant difference). Preadolescents without cancer were more likely to report future intent to smoke compared with preadolescents with cancer (34.1% vs. 14%; p < 0.001). They were also more likely to have a close friend who smoked (16.8 vs. 7.5%, p = 0.03). Preadolescents with cancer had a better knowledge of the risks related to tobacco smoking in general (p = 0.001) and of their own specific risks (p < 0.001). They attributed more value to overall health (p = 0.001). Intent to smoke was significantly associated with age, sex (male being at greater risk), the absence of cancer, having parents or friends who smoke, and perceived vulnerability to tobacco-related illnesses.¹⁵

Regarding cannabis smoking, an Australian study showed that cannabis use was significantly lower among the 153 adolescents treated for cancer than in the age-matched healthy population.¹¹

Tercyak et al. evaluated the prevalence of three behavioral risk factors (smoking, insufficient physical activity, and non-compliance with recommendations on sun exposure) in adolescents aged 11–22 years of age who had had childhood cancer. Regarding smoking, 50% of the participants smoked, whereas 53% declared not having any of these risk behaviors, 28% declared one of the three risk behaviors, 12% having two of the three risk behaviors, and 7% having all three (see Table 1).¹³

Alcohol

Two studies showed significantly lower alcohol consumption among childhood or adolescent cancer survivors compared to the age-matched healthy population.^11,12 Compared to their healthy peers, younger survivors (13 to 17-years) less frequently reported alcohol use (odds ratio [OR] = 0.44; 95% confidence interval [CI]: 0.39–0.49); whereas older adolescent survivors (18–24 years of age) more frequently reported alcohol use (OR = 1.5; 95% CI: 1.0–2.2; see Table 1).¹¹

Overweight, obesity

Seven studies investigated factors associated with unhealthy lifestyle, overweight, and obesity in people who had had cancer as children or AYAs. Three studies reported a relationship between obesity and cancer treatment.^20,21,24 Children with acute lymphoblastic leukemia who received a dose of radiotherapy to the brain greater than 20 Gy before 4 years of age had a fourfold increased risk of obesity; this was especially true for women.²⁴ The risk of obesity in women treated for a brain tumor was higher if they were younger than 4 years old at diagnosis.²⁰ A review of the literature reported a low rate of physical activity, little motivation to undertake sports, and difficulties meeting nutritional recommendations among childhood cancer survivors.¹⁸ However, the proportion was similar to the healthy age-matched population, with adolescents having a less healthy lifestyle in general (eating at fast-food outlets, decreased physical activity).²²

Sun exposure

Buchanan et al. studied sun exposure in 9298 survivors of childhood cancer, diagnosed prior to 21 years of age, from the CCSS cohort. Compared with the 2950 matched controls (who were siblings of the cases), cancer survivors exposed themselves significantly less to the sun, used significantly less artificial tanning devices, and had used more sunscreen the previous summer.²³

Results from Tercyak et al.'s study showed that 37% of the participants did not follow recommendations on sun exposure. Among the 28% of participants reporting only one risk behavior, non-compliance with recommendations on sun exposure was the most common (17%; see Table 1).¹³

Determinants of behavioral risk factors

Overall, five studies investigated factors associated with increased prevalence of behavioral risk factors. Emmons et al. studied the factors associated with starting or quitting smoking in 9709 subjects from the CCSS.¹⁶ Factors associated with a reduced likelihood of smoking were younger age at diagnosis (younger than 10 years old), history of brain radiotherapy, and pulmonary-related cancer treatment. Factors associated with an increased likelihood of smoking were lower education level (below bachelor level), lower annual income (<US$20,000), and not having black skin color. Furthermore, lower education level, male sex, lesser satisfaction with life, and stressful events were associated with excessive alcohol consumption in AYA cancer survivors.¹² Green et al. analyzed the factors associated with obesity in 9284 adults (older than 18 years of age) from the CCSS. Age at diagnosis (between 5 and 9 years old) and radiation dose to the hypothalamus and the pituitary (between 20 and 30 Gy) were significantly associated with obesity. Meeting US Center for Disease Control and Prevention guidelines on vigorous physical activity and a medium amount of cancer-related anxiety were significantly associated with a decreased risk of obesity. Use of paroxetine was significantly associated with an increased risk of obesity compared with other drugs (see Table 1).¹⁷ Buchanan et al. found that factors associated with regular sunscreen use in the past summer in survivors of childhood cancer were female sex, having fair skin, having previously been screened for skin cancer, and being prone to sunburn (see Table 1).²³ Older age and stress were significantly associated with the presence of more than one risk behaviors (smoking, insufficient physical activity and non-compliance with recommendations on sun exposure) in Tercyak et al.'s study.¹³

Occupational exposures

Charbotel et al. have recently reviewed occupational carcinogenic agents associated with rare tumors, including the most frequent tumors is children and AYAs.⁹ However, the search did not find any study in the literature investigating the risk of relapse or the risk of second malignancies associated with occupational exposures.

Prevention strategies to reduce unhealthy behaviors in childhood and AYA cancer survivors

Five articles addressed the problem of prevention of second cancers associated with avoidable risk factors, such as smoking, obesity, and lack of physical activity in children and AYAs who had had cancer.^{14,15,17–19}

Smoking cessation^10,25–32

Several studies on smoking cessation were identified. Tyc et al. compared an educational program with follow-up telephone counseling on the risks associated with smoking to standard advice on smoking in 94 pre-adolescents and adolescents who had had cancer. Participants were 10–18 years of age, and mean time from diagnosis was 6.3 years. At 12 months, participants in the intervention group had better knowledge of tobacco, had better perception of their vulnerability, and were less likely to want to smoke (differences not statistically significant).²⁸

A case-control study of 21 young cancer survivors and 43 controls cancer survivors (age range 13–21 years) looked at the impact of a decision-making and risk-education intervention and showed a marginal significant reduction in smoking among smokers at 6 months after the intervention (see Table 1).²⁷

No studies on nicotine replacement therapy (NRT) in adolescents with cancer were identified. Recent updates of recommendations propose the use of long-lasting bupropion or NRT in healthy adolescents who have a high dependency on nicotine and who wish to quit smoking.³⁰ However, recommending their use in children or adolescents who have had cancer seems premature in the absence of safety and efficacy data in this population.³⁰ Bupropion is contraindicated in people with a history of CNS tumor due to an increased risk of seizures, thereby limiting its usefulness in adult oncology populations.²⁹

Smith et al. studied the benefit of NRT combined with individual or group behavioral counseling in healthy adolescents.³¹ Fourteen percent had stopped smoking at week 8, but only 5% continued to be smoke free at 6 months. Moolchan et al. evaluated the efficacy of different NRTs combined with cognitive–behavioral group therapy.³² The three groups included (1) active patch (21 mg), (2) active gum (2 and 4 mg), and (3) gum and placebo patch. The proportions of participants who achieved prolonged abstinence at 3 months were 17.6% in the active patch group, 6.5% in the gum group, and 2.5% in the placebo group. The difference was statistically significant between patch and placebo, but not between gum and placebo nor between patch and gum.

Killen et al. performed a randomized clinical trial in 211 healthy adolescent smokers comparing nicotine patch plus bupropion sustained release (150 mg/day) versus nicotine patch placebo. There was no significant difference between both groups, but a majority of adolescents in both groups reduced their consumption to a few cigarettes per day or less and maintained this reduction over time (26-week assessment).²⁶ The authors explained the lack of difference by a suboptimal dose of bupropion, usually given at 300 mg/day in adults.

Diet, weight, and physical activity

Stolley et al. reviewed the descriptive and intervention studies that included survivors of childhood cancers and a measurement of diet and physical activity. They highlighted that childhood cancer survivors engaged in health-promoting activities at rates comparable to the general population. Authors pointed that the dietary research in childhood cancer survivors is methodologically weak and that behavioral interventions have mostly targeted physical activity.¹⁸

The clinical study of Robien et al. with adult survivors of childhood acute lymphoblastic leukemia (ALL) suggested that in general dietary intake was not consistent with dietary recommendations: 50% of the participants met minimal goals for fruit and vegetable intake, and 50% met minimal goals for dietary fat restrictions. Eighteen percent met recommendations for 30 minutes of physical activity 5 days/week.¹⁹ In the multicentric retrospective cohort study from the CCSS, Green et al. showed that the risk of obesity was decreased among those who met the US Centers for Disease Control and Prevention guidelines for vigorous physical activity (relative risk [RR] = 0.90; 95%CI: 0.82–0.97; see Table 1).¹⁷

Promoting health protective behaviors

In a behavioral health promotion study of 266 childhood cancer survivors aged 12–18 years of age from the St. Jude Children's Research Hospital, Hudson et al. assessed the impact of a multicomponent behavioral intervention on changing health knowledge, health perceptions (perceived susceptibility, perceived seriousness, perceived benefits, perceived barriers), and health behavior practices. In this study, more than half of the participants (52%) did not know that cancer treatments could be associated with a risk of second cancer; 48% of the participants considered this risk as the most concerning potential treatment sequelae (see Table 1).³³ Due to lack of knowledge about the long-term side effects of treatments and about the risk associated with some behaviors, AYAs may not adopt healthy behaviors. New internet technologies (“ehealth”) seem to be useful in promoting healthy behaviors in children and AYAs who have had cancer.³⁴

Discussion

The aim of this article was to review the available literature on cancer risk factors (lifestyle and occupational exposures) in children and AYAs previously treated for cancer. The article also reviews the interventions that can be implemented to improve healthy behaviors in this population.

It seems that the behavior of cancer survivors toward a healthy lifestyle is similar to that of the healthy population of the same age, particularly regarding tobacco smoking, diet, and to a lesser extent sun exposure. Although AYA cancer survivors seem to engage in less physical activity than their peers, these results are consistent with previous literature that reported a significantly higher prevalence of current smoking, obesity, and chronic conditions in this population compared with individuals who have no history of cancer.³⁵

Overall, there are few studies that investigate the risk factors associated with second malignancies, except for long-term side effects of cancer treatments, which are the most important risk factors. However, the increased incidence of second malignancies in this population, of all cancers and in particular of cancers not associated with primary treatment, suggests a potential role of and synergies with other cancer risk factors, such as lifestyle and occupational exposures. The role of the latter in the development of second malignancies remains widely unknown.

Smoking in children and AYA cancer survivors may increase the risk of lung cancer, breast cancer, colorectal cancer, and leukemia.⁶ Smoking is one of the most preventable risk factors implicated in cancer development. While survivors of childhood cancer have similar smoking rates to their peers, the former seem to have a better knowledge of the health risks associated with smoking. Tobacco has not only a carcinogenic effect per se, but also enhances radiation effects. For example, smoking has been shown to increase the risk of radiotherapy-induced lung cancer in patients treated for Hodgkin disease.³⁴ While few studies have assessed the usefulness of smoking cessation programs in young cancer survivors, short-term results are quite disappointing, and there is no long-term evaluation.^27,28 The use of NRTs in this population seems premature.³⁰ This means that it is important to improve our knowledge on the role of tobacco in the occurrence of second malignancies, to implement specific interventions to reduce tobacco consumption, and to prevent young people from starting smoking.¹⁰ This may equally apply to the use of cannabis.

Alcohol consumption appears to contribute substantially to the worldwide cancer burden, although light-to-moderate alcohol consumption has been associated with some benefits related to heart disease, stroke, and diabetes (benefits that are reversed with occasional or regular heavy drinking), as highlighted by Cogliano et al.³⁶ Alcohol consumption is associated with an increased risk of second malignancy in adults treated for cancers of the upper aerodigestive tract.³⁷ Even if alcohol consumption seems lower in childhood or adolescent survivors of cancer compared with the healthy age-matched population,^11,12 it may contribute to an increased risk of second malignancies. However, no study has specifically evaluated the impact of alcohol consumption on the risk of second malignancy in that population.

Obesity and lack of physical activity are known risk factors for cancers frequently found in childhood or adolescent cancer survivors, such as breast cancer, colorectal cancer, and lung cancer.³⁷ Furthermore, weight gain associated with cancer-related treatments (steroids or brain radiotherapy) can be amplified by an unhealthy diet and lack of physical activity.³⁸ However, no studies were found specifically investigating their impact on second malignancies in childhood and AYA cancer survivors. Yet, prevention programs focusing on diet and physical activity have shown long-term efficacy in young people without cancer.³⁹ It would be pertinent to study the impact of treatment-related weight gain and its active management on second malignancies.

The literature suggests greater proportions of childhood and AYA cancer survivors with appropriate behavior toward UV exposure. However, there is still progress to be made regarding the use of artificial tanning devices. Information on the risk of skin cancer associated with inappropriate sun exposure and artificial UV exposure should be given to these patients.^23,40 Such information should also explain the importance of balancing natural sunlight exposure to avoid its damaging effects and meet sun protection guidelines with vitamin D requirements. The latter, produced by natural sun exposure, may have a protective effect against certain types of cancer.⁴¹

Although AYAs are about to enter the workforce in most cases, there are no studies about the impact of occupational exposures on the risk of relapse of the first primary and on the risk of second malignancies. However, some of the tumors that occur in childhood cancer survivors (such as lung and respiratory subsequent primary neoplasms)^5,8 are also known to be related to carcinogens present in the occupational environment. According to the periodical cross-sectional French medical survey on exposure to occupational risks (SUMER), young apprentices and young workers are the most exposed to carcinogens at work.⁴² Therefore, as a precautionary measure, they should be advised to talk about their medical history with an occupational physician when thinking about their professional orientation. There are no jobs contraindicated in cancers survivors. However, applying a precautionary principle, specific attention should be paid in this population to avoid occupational exposure to carcinogens.

While the awareness of cancer risk among survivors of cancer in childhood and adolescence is higher than it is in the general population, a large proportion of the former seems unaware of their increased risk of second malignancies.³³ Various studies emphasize the need to implement specific prevention programs for this population to increase awareness, in particular with regard to the risks associated with certain lifestyle factors and to try to reduce them.³⁰

While there are no data on the timing of preventive information and interventions, patients request such information from their clinical team.^15,43 International and national guidelines on prevention for this population, including screening guidelines, have been published.⁴⁴ It is important that this information be communicated and discussed several times throughout follow-up. General practitioners (GPs) have also a key role in providing these guidelines, as less than 20% of adults who have had a tumor in their childhood are followed in a specialized center or by an oncologist.⁴⁵ This percentage even decreases over time. Thus, GPs are in the front line to implement prevention and screening procedures and to detect second malignancies for which late diagnosis is a poor prognostic factor.⁴⁵ However, GPs often do not feel comfortable following up childhood and AYA cancer survivors, as they lack information on long-term side effects and appropriate follow-up schedules.⁴⁵

A recent workshop at the Institute of Medicine emphasized the importance of improving AYA cancer survivorship care based on “a systematic plan for screening, surveillance, and prevention that incorporates risks based on the previous cancer, cancer therapy, genetic predispositions, lifestyle behaviors, and comorbid health conditions should be developed for all AYA cancer survivors.”⁴⁶

It may be timely to develop and implement specific prevention approaches in this population, such as lifestyle intervention programs, and to evaluate their benefits, especially since many lifestyles risk behaviors cluster together.⁴⁷ The development of evidence-based programs such as those developed and tested by Emmons et al. to address substance abuse among AYA cancer survivors⁴⁶ should be encouraged to be widely implemented in other countries.

It seems relevant to study how to improve adherence of children and AYA cancer survivors to these prevention guidelines. Adolescents seem more receptive to messages given by people of their own age. Newer information and communication techniques (such as social networks, games, text messages, or smartphone applications) could be used to deliver the information and some of the interpersonal interactions required. As noted by Elliot et al., health promotion strategies in childhood ALL survivors relate to strategies similar to those applicable to improving healthy behaviors in the general population, and strategies using eHealth technologies are promising.³⁴ In a recent survey in 25 European countries on more than 25,000 children aged 9–16 years old, 93% surf the internet at least once a week and 60% every day or nearly. They spend at least 1.5 hours per day on the internet. Half of them say “they feel more themselves” in relationships on the net than face-to-face. Adolescents qualify the net as being the first source of information concerning health.⁴⁸ Therefore, this technology, with games or online quizzes, may be a good way to convey messages on prevention and healthy lifestyles (cannabis, drug abuse, sexuality, diet, physical activity, etc.).^49,50 These tools may be also useful for social support and sharing experiences to reinforce motivation. They are also a great opportunity for new interdisciplinary public health approaches to prevention.

Conclusions and Perspectives

The risk of second malignancies after a childhood or AYA cancer is an important issue in this population and should be addressed in follow-up programs. Appropriate communication between oncologists and GPs is very important in this context. Patients (and their GPs) should have all the information on the course of the disease, the treatment received, the possible late side effects, the follow-up plan, and the screening plan. This plan should be adapted to the individual's risks and the evolution of risky exposures and behaviors.

The present review underscores the need to improve our knowledge on the impact of these behaviors (tobacco, alcohol, diet, and physical activity) on second malignancies and their interaction with the effects related to treatment.

It is important to implement specific prevention strategies in this population and to evaluate these interventions and the factors that could contribute to adhesion to health-promoting messages relying in particular on research on health-risk behaviors that are commonly initiated during pre-adolescence and adolescence and that have importance for adult risk of second primary cancers.

The conclusions of this review may evolve as new data become available.

Footnotes

Acknowledgments

Thanks to Nicole Falette, PhD, Aude-Marie Foucaut, PhD, and Aurélie Danjou, PhD student, for their participation in the review of the manuscript. The research leading to these results has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. HEALTH-F2-2011-261474.

Author Disclosure Statement

No competing financial interests exist.

References

Morton

, Onel

, Curtis

, et al. The rising incidence of second cancers: patterns of occurrence and identification of risk factors for children and adults. Am Soc Clin Oncol Educ Book. 2014; e57–e67.

Demoor-Goldschmidt

, Fayech

, Girard

, Plantaz

. Tumeurs secondaires: incidence, facteurs de risque et recommandations de prévention. Bull Cancer. 2015 Apr 23. pii: S0007-4551(15)00129-0.

Curtis

, Freedman

, Ron

, et al. New malignancies among cancer survivors: SEER cancer registries, 1973–2000 (NIH Pub. No. 05-5302). Bethesda, MD: National Cancer Institute, 2006.

Geiger

, Castellino

. Delineating the age ranges used to define adolescents and young adults. J Clin Oncol. 2011; 29(16):e492–3.

Friedman

, Whitton

, Leisenring

, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010; 102(14):1083–95.

International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans IARC Monographs, Volume 100 (E); 2012.

World Cancer Research Fund (WCRF), Continuous Update Project (CUP) Matrix Summary of strong evidence from our analysis of worldwide research on diet, nutrition, physical activity and preventing cancer. Accessed September 9, 2015 from: www.wcrf.org

Reulen

, Frobisher

, Winter

, et al. Long-term risks of subsequent primary neoplasms among survivors of childhood cancer. JAMA. 2011; 305(22):2311–19.

Charbotel

, Fervers

, Droz

. Occupational exposures in rare cancers: a critical review of the literature. Crit Rev Oncol Hematol. 2014; 90(2):99–134.

10.

Hudson

, Findlay

. Health-risk behaviors and health promotion in adolescent and young adult cancer survivors. Cancer. 2006; 107(7 Suppl):1695–701.

11.

Bauld

, Toumbourou

, Anderson

, et al. Health-risk behaviours among adolescent survivors of childhood cancer. Pediatr Blood Cancer. 2005; 45(5):706–15.

12.

Carswell

, Chen

, Nair

, et al. Smoking and binge drinking among Canadian survivors of childhood and adolescent cancers: a comparative, population-based study. Pediatr Blood Cancer. 2008; 51(2):280–7.

13.

Tercyak

, Donze

, Prahlad

, et al. Multiple behavioral risk factors among adolescent survivors of childhood cancer in the Survivor Health and Resilience Education (SHARE) program. Pediatr Blood Cancer. 2006; 47(6):825–30.

14.

Kahalley

, Robinson

, Tyc

, et al. Risk factors for smoking among adolescent survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2012; 58(3):428–34.

15.

Tyc

, Klosky

, Lensing

, et al. A comparison of tobacco-related risk factors between preadolescents with and without cancer. J Cancer Surviv. 2009; 3(4):251–9.

16.

Emmons

, Li

, Whitton

, et al. Predictors of smoking initiation and cessation among childhood cancer survivors: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2002; 20(6):1608–16.

17.

Green

, Cox

, Zhu

, et al. Risk factors for obesity in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2012; 30(3):246–55.

18.

Stolley

, Restrepo

, Sharp

. Diet and physical activity in childhood cancer survivors: a review of the literature. Ann Behav Med. 2010; 39(3):232–49.

19.

Robien

, Ness

, Klesges

, et al. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2008; 30(11):815–22.

20.

Gurney

, Ness

, Stovall

, et al. Final height and body mass index among adult survivors of childhood brain cancer: Childhood Cancer Survivor Study. J Clin Endocrinol. Metab, 2003; 88(10):4731–9.

21.

Lughetti

, Bruzzi

, Predieri

, Paolucci

. Obesity in patients with acute lymphoblastic leukemia in childhood. Ital J Pediatr. 2012; 38:4.

22.

Holman

, White

. Dietary behaviors related to cancer prevention among pre-adolescents and adolescents: the gap between recommendations and reality. Nutr J. 2011; 10:60.

23.

Buchanan

, Leisenring

, Mitby

, et al. Behaviors associated with ultraviolet radiation exposure in a cohort of adult survivors of childhood and adolescent cancer: a report from the Childhood Cancer Survivor Study. Cancer. 2009; 115(18 Suppl):4374–84.

24.

Keats

, Culos-Reed

, Courneya

, McBride

. An examination of physical activity behaviors in a sample of adolescent cancer survivors. J Pediatr Oncol Nurs. 2006; 23(3):135–42.

25.

Upadhyaya

, Brady

, Wang

. Bupropion SR in adolescents with comorbid ADHD and nicotine dependence: a pilot study. J Am Acad Child Adolesc Psychiatry. 2004; 43(2):199–205.

26.

Killen

, Robinson

, Ammerman

, et al. Randomized clinical trial of the efficacy of bupropion combined with nicotine patch in the treatment of adolescent smokers. J Consult Clin Psychol. 2004; 72(4):729–35.

27.

Hollen

, Hobbie

, Finley

. Testing the effects of a decision-making and risk-reduction program for cancer-surviving adolescents. Oncol Nurs Forum. 1999; 26(9):1475–86.

28.

Tyc

, Rai

, Lensing

, et al. Intervention to reduce intentions to use tobacco among pediatric cancer survivors. J Clin Oncol. 2003; 21(7):1366–72.

29.

Klosky

, Tyc

, Garces-Webb

, et al. Emerging issues in smoking among adolescent and adult cancer survivors: a comprehensive review. Cancer. 2007; 110(11):2408–19.

30.

Fiore

. Treating tobacco use and dependence: 2008 update U.S. Public Health Service Clinical Practice Guideline executive summary. Respir Care. 2008; 53(9):1217–22.

31.

Smith

, House

Jr , Croghan

, et al. Nicotine patch therapy in adolescent smokers. Pediatrics. 1996; 98(4 Pt 1):659–67.

32.

Moolchan

, Robinson

, Ernst

, et al. Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Pediatrics. 2005; 115(4):e407–14.

33.

Hudson

, Tyc

, Srivastava

, et al. Multi-component behavioral intervention to promote health protective behaviors in childhood cancer survivors: the protect study. Med Pediatr Oncol. 2002; 39(1):2-1.

34.

Elliot

, Lindemulder

, Goldberg

, et al. Health promotion for adolescent childhood leukemia survivors: building on prevention science and ehealth. Pediatr Blood Cancer. 2013; 60(6):905–10.

35.

Tai

, Buchanan

, Townsend

, et al. Health status of adolescent and young adult cancer survivors. Cancer. 2012; 118(19):4884–91.

36.

Cogliano

, Baan

, Straif

, et al. Preventable exposures associated with human cancers. J Natl Cancer Inst. 2011; 103(24):1827–39.

37.

Travis

, Gospodarowicz

, Curtis

, et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. J National Cancer Inst. 2002; 94(3):182–92.

38.

Sunga

, Eberl

, Oeffinger

, et al. Care of cancer survivors. Am Fam Physician. 2005; 71(4):699–706.

39.

Simon

, Wagner

, Platat

, et al. ICAPS: a multilevel program to improve physical activity in adolescents. Diabetes Metab. 2006 Feb; 32(1):41–9.

40.

Pappo

, Armstrong

, Liu

, et al. Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2013; 60(3):461–6.

41.

International Agency for Research on Cancer. Vitamin D and Cancer. IARC Working Group Reports Vol. 5, International Agency for Research on Cancer, Lyon, November 25, 2008.

42.

Direction de l'Animation de la Recherche, des Etudes et des Statistiques. Les expositions aux produits chimiques cancérogènes en 2010. DARES Analyses, Septembre 2013, no. 054.

43.

Institut National du Cancer (INCa). Identifier et prévenir les risques de second cancer primitif chez l'adulte, collection état des lieux et des connaissances ouvrage collectif édité par l'INCa, Boulogne-Billancourt, décembre 2013.

44.

Children's Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescents and young adult cancers, version 4.0. Monrovia, CA: Children's Oncology Group; 2013.

45.

Shad

, Myers

, Hennessy

. Late effects in cancer survivors: “the shared care model.”. Curr Oncol Rep. 2012; 14(2):182–90.

46.

Nass

, Beaupin

, Demark-Wahnefried

, et al. Identifying and addressing the needs of adolescents and young adults with cancer: summary of an Institute of Medicine workshop. Oncologist. 2015; 20(2):186–95.

47.

Santelli

, Sivaramakrishnan

, Edelstein

, et al. Adolescent risk-taking, cancer risk, and life course approaches to prevention. J Adolesc Health. 2013; 52(5 Suppl);S41–4.

48.

EU Kids Online. Accessed November 17, 2014 from: www.lse.ac.uk/media@lse/research/EUKidsOnline/Home.aspx

49.

Biddiss

, Irwin

. Active video games to promote physical activity in children and youth: a systematic review. Arch Pediatr Adolesc Med. 2010; 164(7):664–72.

50.

Hyden

, Cohall

. Innovative approaches to using new media and technology in health promotion for adolescents and young adults. Adolesc Med State Art Rev. 2011; 22(3):498–xii.

A Review of Health Behaviors in Childhood and Adolescent Cancer Survivors: Toward Prevention of Second Primary Cancer

Abstract

Purpose:

Methods:

Results:

Conclusion:

Methods

Results

Behavioral factors

Tobacco

Alcohol

Overweight, obesity

Sun exposure

Determinants of behavioral risk factors

Occupational exposures

Prevention strategies to reduce unhealthy behaviors in childhood and AYA cancer survivors

Smoking cessation10,25–32

Diet, weight, and physical activity

Promoting health protective behaviors

Discussion

Conclusions and Perspectives

Footnotes

Acknowledgments

Author Disclosure Statement

References

Smoking cessation^10,25–32