Characterization of chronic pain, pain interference, and daily pain experiences in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

ABSTRACT: Although survivors of childhood cancer are at an increased risk, little is known about the prevalence of chronic pain, associated interference, and daily pain experiences. Survivors (N = 233; mean age = 40.8 years, range 22-64 years; mean time since diagnosis = 32.7 years) from the Childhood Cancer Survivor Study completed pain and psychosocial measures. Survivors with chronic pain completed 2-week, daily measures assessing pain and psychological symptoms using mHealth-based ecological momentary assessment. Multivariable-modified Poisson and linear regression models estimated prevalence ratio estimates (PR) and mean effects with 95% confidence intervals (CI) for associations of key risk factors with chronic pain and pain interference, respectively. Multilevel mixed models examined outcomes of daily pain and pain interference with prior day symptoms. Ninety-six survivors (41%) reported chronic pain, of whom 23 (24%) had severe interference. Chronic pain was associated with previous intravenous methotrexate treatment (PR = 1.6, 95% CI 1.1-2.3), respiratory (PR = 1.8, 95% CI 1.2-2.5), gastrointestinal (PR = 1.6, 95% CI 11.0-2.3), and neurological (PR = 1.5, 95% CI 1.0-2.1) chronic health conditions, unemployment (PR = 1.4, 95% CI 1.0-1.9) and clinically significant depression and anxiety (PR = 2.9, 95% CI 2.0-4.2), as well as a diagnosis of childhood Ewing sarcoma or osteosarcoma (PR = 1.9, 95% CI 1.0-3.5). Higher pain interference was associated with cardiovascular and neurological conditions, unemployment and clinical levels of depression and/or anxiety, and fear of cancer recurrence. For male, but not female survivors, low sleep quality, elevated anxiety, and elevated depression predicted high pain intensity and interference the next day. A substantial proportion of childhood cancer survivors experience chronic pain and significant associated interference. Chronic pain should be routinely evaluated, and interventions are needed.

Adverse Childhood Experiences, Resilience, and Cardiovascular Disease in Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

BACKGROUND: The impact of Adverse Childhood Experiences (ACEs: e.g., abuse, neglect and/or household dysfunction experienced before age 18) and resilience on risk for cardiovascular disease (CVD) has not previously been investigated in adult survivors of childhood cancer. METHODS: We conducted a nested case-control study among long-term, adult-aged survivors of childhood cancer from the Childhood Cancer Survivor Study (CCSS). Self-report questionnaires ascertained ACEs and resilience, and scores were compared between cases with serious/life-threatening CVD and controls without CVD matched on demographic and cardiotoxic treatment factors. RESULTS: Among 95 cases and 261 controls, the mean ACE score was 1.4 for both groups; 53.4% of survivors endorsed ≥1 ACE. There was no association between ACEs or resilience and CVD in adjusted models. CONCLUSIONS: ACEs and resilience do not appear to contribute to CVD risk for adult survivors of childhood cancer with cardiotoxic treatment exposures. IMPACT: Although not associated with CVD in this population, ACEs are associated with serious health issues in other populations. Therefore, future studies could investigate effects of ACEs on other health outcomes affecting childhood cancer survivors.

Exercise and QUality diet After Leukemia (EQUAL): A randomized weight loss trial among adult survivors of childhood leukemia in the Childhood Cancer Survivor Study.

BACKGROUND: Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity. METHODS: In this phase 3 efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with body mass index (BMI)≥25 kg/m2 were randomized to a remotely-delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy (CRT). The primary endpoint was the difference in weight loss at 24-months in an intent-to-treat analysis. Analyses were performed using linear mixed effects models. RESULTS: Among 358 survivors (59% female, median attained age: 37 years, IQR: 33-43), baseline mean (SD) weight was 98.6 kg (24.0) for the intervention group (n=181) and 94.9 kg (20.3) for controls (n=177). Adherence to the intervention was poor; 15% of individuals in the intervention completed 24/30 planned coaching calls. Weight at 24-months was available for 274 (77%) participants. After controlling for CRT, sex, race/ethnicity, and age, the mean (SE) change in weight from baseline to 24-months was -0.4 kg (0.8) for intervention and 0.2 kg (0.6) for control participants (p=0.59). CONCLUSIONS: A remote weight-loss intervention that was successful among adults with CV conditions did not result in significant weight loss among adult survivors of childhood ALL. IMPACT: Future interventions in this population must be tailored to the unique needs of survivors to encourage engagement and adherence.

Health Insurance Navigation Tools Intervention: A Pilot Trial Within the Childhood Cancer Survivor Study.

PURPOSE: Childhood cancer survivors are at increased risk for underinsurance and health insurance-related financial burden. Interventions targeting health insurance literacy (HIL) to improve the ability to understand and use health insurance are needed. METHODS: We codeveloped a four-session health insurance navigation tools (HINT) intervention, delivered synchronously by a patient navigator, and a corresponding booklet. We conducted a randomized pilot trial with survivors from the Childhood Cancer Survivor Study comparing HINT with enhanced usual care (EUC; booklet). We assessed feasibility, acceptability, and preliminary efficacy (HIL, primary outcome; knowledge and confidence with health insurance terms and activity) on a 5-month survey and exit interviews. RESULTS: Among 231 invited, 82 (32.5%) survivors enrolled (53.7% female; median age 39 years, 75.6% had employer-sponsored insurance). Baseline HIL scores were low (mean = 28.5; 16-64; lower scores better); many lacked knowledge of Affordable Care Act (ACA) provisions. 80.5% completed four HINT sessions, and 93.9% completed the follow-up survey. Participants rated HINT's helpfulness a mean of 8.9 (0-10). Exit interviews confirmed HINT's acceptability, specifically its virtual and personalized delivery and helpfulness in building confidence in understanding one's coverage. Compared with EUC, HINT significantly improved HIL (effect size = 0.94. P < .001), ACA provisions knowledge (effect size = 0.73, P = .003), psychological financial hardship (effect size = 0.64, P < .006), and health insurance satisfaction (effect size = 0.55, P = .03). CONCLUSION: Results support the feasibility and acceptability of a virtual health insurance navigation program targeted for childhood survivors to improve HIL. Randomized trials to assess the efficacy and sustainability of health insurance navigation on HIL and financial burden are needed.

The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.

BACKGROUND: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. The ENGaging and Activating cancer survivors in Genetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing. METHODS: The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services. DISCUSSION: With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.

Improved Cardiomyopathy Risk Prediction Using Global Longitudinal Strain and N-Terminal-Pro-B-Type Natriuretic Peptide in Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy.

PURPOSE: To leverage baseline global longitudinal strain (GLS) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) to identify childhood cancer survivors with a normal left ventricular ejection fraction (LVEF) at highest risk of future treatment-related cardiomyopathy. METHODS: St Jude Lifetime Cohort participants ≥5 years from diagnosis, at increased risk for cardiomyopathy per the International Guideline Harmonization Group (IGHG), with an LVEF ≥50% on baseline echocardiography (n = 1,483) underwent measurement of GLS (n = 1,483) and NT-proBNP (n = 1,052; 71%). Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs for postbaseline cardiomyopathy (modified Common Terminology Criteria for Adverse Events ≥grade 2) incidence in association with echocardiogram-based GLS (≥-18) and/or NT-proBNP (>age-sex-specific 97.5th percentiles). Prediction performance was assessed using AUC in models with and without GLS and NT-proBNP and compared using DeLong's test for IGHG moderate- and high-risk individuals treated with anthracyclines. RESULTS: Among survivors (median age, 37.6; range, 10.2-70.4 years), 162 (11.1%) developed ≥grade 2 cardiomyopathy 5.1 (0.7-10.0) years from baseline assessment. The 5-year cumulative incidence of cardiomyopathy for survivors with and without abnormal GLS was, respectively, 7.3% (95% CI, 4.7 to 9.9) versus 4.4% (95% CI, 3.0 to 5.7) and abnormal NT-proBNP was 9.9% (95% CI, 5.8 to 14.1) versus 4.7% (95% CI, 3.2 to 6.2). Among survivors with a normal LVEF, abnormal baseline GLS and NT-proBNP identified anthracycline-exposed, IGHG-defined moderate-/high-risk survivors at a four-fold increased hazard of postbaseline cardiomyopathy (HR, 4.39 [95% CI, 2.46 to 7.83]; P < .001), increasing to a HR of 14.16 (95% CI, 6.45 to 31.08; P < .001) among survivors who received ≥250 mg/m2 of anthracyclines. Six years after baseline, AUCs for individual risk prediction were 0.70 for models with and 0.63 for models without GLS and NT-proBNP (P = .022). CONCLUSION: GLS and NT-proBNP should be considered for improved identification of survivors at high risk for future cardiomyopathy.

Advancing Survivors Knowledge (ASK Study) of Skin Cancer Surveillance After Childhood Cancer: A Randomized Controlled Trial in the Childhood Cancer Survivor Study.

PURPOSE: To improve skin cancer screening among survivors of childhood cancer treated with radiotherapy where skin cancers make up 58% of all subsequent neoplasms. Less than 30% of survivors currently complete recommended skin cancer screening. PATIENTS AND METHODS: This randomized controlled comparative effectiveness trial evaluated patient and provider activation (PAE + MD) and patient and provider activation with teledermoscopy (PAE + MD + TD) compared with patient activation alone (PAE), which included print materials, text messaging, and a website on skin cancer risk factors and screening behaviors. Seven hundred twenty-eight participants from the Childhood Cancer Survivor Study (median age at baseline 44 years), age > 18 years, treated with radiotherapy as children, and without previous history of skin cancer were randomly assigned (1:1:1). Primary outcomes included receiving a physician skin examination at 12 months and conducting a skin self-examination at 18 months after intervention. RESULTS: Rates of physician skin examinations increased significantly from baseline to 12 months in all three intervention groups: PAE, 24%-39%, relative risk [RR], 1.65, 95% CI, 1.32 to 2.08; PAE + MD, 24% to 39%, RR, 1.56, 95% CI, 1.25 to 1.97; PAE + MD + TD, 24% to 46%, RR, 1.89, 95% CI, 1.51 to 2.37. The increase in rates did not differ between groups (P = .49). Similarly, rates of skin self-examinations increased significantly from baseline to 18 months in all three groups: PAE, 29% to 50%, RR, 1.75, 95% CI, 1.42 to 2.16; PAE + MD, 31% to 58%, RR, 1.85, 95% CI, 1.52 to 2.26; PAE + MD + TD, 29% to 58%, RR, 1.95, 95% CI, 1.59 to 2.40, but the increase in rates did not differ between groups (P = .43). CONCLUSION: Although skin cancer screening rates increased more than 1.5-fold in each of the intervention groups, there were no differences between groups. Any of these interventions, if implemented, could improve skin cancer prevention behaviors among childhood cancer survivors.

Underdiagnosis and Undertreatment of Modifiable Cardiovascular Risk Factors Among Survivors of Childhood Cancer.

Background Determine the prevalence and predictors associated with underdiagnosis and undertreatment of modifiable cardiovascular disease (CVD) risk factors (hypertension, dyslipidemia, glucose intolerance/diabetes) among adult survivors of childhood cancer at high risk of premature CVD. Methods and Results This was a cross-sectional study of adult-aged survivors of childhood cancer treated with anthracyclines or chest radiotherapy, recruited across 9 US metropolitan regions. Survivors completed questionnaires and in-home clinical assessments. The comparator group was a matched sample from the National Health and Nutrition Examination Survey. Multivariable logistic regression estimated the risk (odds ratios) of CVD risk factor underdiagnosis and undertreatment among survivors compared with the National Health and Nutrition Examination Survey. Survivors (n=571; median age, 37.7 years and 28.5 years from cancer diagnosis) were more likely to have a preexisting CVD risk factor than the National Health and Nutrition Examination Survey (n=345; P<0.05 for all factors). While rates of CVD risk factor underdiagnosis were similar (27.1% survivors versus 26.1% National Health and Nutrition Examination Survey; P=0.73), survivors were more likely undertreated (21.0% versus 13.9%, P=0.007; odds ratio, 1.8, 95% CI, 1.2-2.7). Among survivors, the most underdiagnosed and undertreated risk factors were hypertension (18.9%) and dyslipidemia (16.3%), respectively. Men and survivors who were overweight/obese were more likely to be underdiagnosed and undertreated. Those with multiple adverse lifestyle factors were also more likely undertreated (odds ratio, 2.2, 95% CI, 1.1-4.5). Greater health-related self-efficacy was associated with reduced undertreatment (odds ratio, 0.5; 95% CI, 0.3-0.8). Conclusions Greater awareness of among primary care providers and cardiologists, combined with improving self-efficacy among survivors, may mitigate the risk of underdiagnosed and undertreated CVD risk factors among adult-aged survivors of childhood cancer. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03104543.

Implementing a mHealth intervention to increase colorectal cancer screening among high-risk cancer survivors treated with radiotherapy in the Childhood Cancer Survivor Study (CCSS).

BACKGROUND: Cancer survivors treated with any dose of radiation to the abdomen, pelvis, spine, or total body irradiation (TBI) are at increased risk for developing colorectal cancer (CRC) compared to the general population. Since earlier detection of CRC is strongly associated with improved survival, the Children's Oncology Group (COG) Long-Term Follow-Up Guidelines recommend that these high-risk cancer survivors begin CRC screening via a colonoscopy or a multitarget stool DNA test at the age of 30 years or 5 years following the radiation treatment (whichever occurs last). However, only 37% (95% CI 34.1-39.9%) of high-risk survivors adhere to CRC surveillance. The Activating cancer Survivors and their Primary care providers (PCP) to Increase colorectal cancer Screening (ASPIRES) study is designed to assess the efficacy of an intervention to increase the rate of CRC screening among high-risk cancer survivors through interactive, educational text-messages and resources provided to participants, and CRC screening resources provided to their PCPs. METHODS: ASPIRES is a three-arm, hybrid type II effectiveness and implementation study designed to simultaneously evaluate the efficacy of an intervention and assess the implementation process among participants in the Childhood Cancer Survivor Study (CCSS), a North American longitudinal cohort of childhood cancer survivors. The Control (C) arm participants receive electronic resources, participants in Treatment arm 1 receive electronic resources as well as interactive text messages, and participants in Treatment arm 2 receive electronic educational resources, interactive text messages, and their PCP's receive faxed materials. We describe our plan to collect quantitative (questionnaires, medical records, study logs, CCSS data) and qualitative (semi-structured interviews) intervention outcome data as well as quantitative (questionnaires) and qualitative (interviews) data on the implementation process. DISCUSSION: There is a critical need to increase the rate of CRC screening among high-risk cancer survivors. This hybrid effectiveness-implementation study will evaluate the effectiveness and implementation of an mHealth intervention consisting of interactive text-messages, electronic tools, and primary care provider resources. Findings from this research will advance CRC prevention efforts by enhancing understanding of the effectiveness of an mHealth intervention and highlighting factors that determine the successful implementation of this intervention within the high-risk cancer survivor population. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (identifier NCT05084833 ) on October 20, 2021.

Impact of COVID-19 pandemic on a large cohort of adult survivors of childhood cancer.

Childhood cancersurvivors may be differentially impacted by coronavirus disease 2019 (COVID-19). From April to June of 2020, we examined psychosocial/health concerns in 4148 adult survivors and 571 siblings. Although more survivors reported concerns about getting sick (p = .002) and needing hospitalization (p = .003) in general, survivors and siblings were comparably concerned about being infected with and the consequences of COVID-19. Cranial radiation was associated with social isolation (relative risk [RR] = 1.3, CI = 1.1-1.7), and central nervous system (CNS) tumors were associated with unemployment due to COVID-19 (RR = 1.7, CI = 1.2-2.2). Some survivors appear more vulnerable and may require more support to meet health care and vocational needs during COVID-19, though siblings also perceive substantial risk.

Wearable Respiratory Monitoring and Feedback for Chronic Pain in Adult Survivors of Childhood Cancer: A Feasibility Randomized Controlled Trial From the Childhood Cancer Survivor Study.

PURPOSE: Approximately 40% of childhood cancer survivors experience chronic pain, with many also reporting pain-related disability. Given associations established in the general population among respiration, anxiety, and pain, continuous tracking and feedback of respiration may help survivors manage pain. METHODS: A feasibility, nonblinded, randomized controlled trial (RCT) comparing wearable respiratory monitoring with a control group examined feasibility, acceptability, and preliminary efficacy among survivors of childhood cancer with chronic pain who were ≥ 18 years of age, able to speak and read English, lived in the United States, and had access to a smartphone and the Internet. The primary outcomes were pain interference, pain severity, anxiety, negative affect, and perceived stress. The intervention group (n = 32) received a wearable respiratory monitor, used the device, and completed an in-application breathing exercise daily for 30 days. The control group (n = 33) received psychoeducation after completion of the study. RESULTS: Almost all participants in the intervention group (n = 31 of 32) and control group (n = 32 of 33) completed the study. Of those who completed the intervention, 90.3% wore the device for ≥ 50% of the trial. Posttreatment improvement for negative affect (Cohen d = 0.59; 95% CI, 0.09 to 1.10) was significantly greater in the intervention group compared with the control group. A follow-up study (n = 24) examined acceptability and feasibility of a second-generation device among those who completed the RCT. Most survivors (81.0%) wore the device daily during the trial and 85.7% reported satisfaction with the device and the application. CONCLUSION: The results of this pilot study support the acceptability and feasibility of wearable respiratory monitoring among survivors of childhood cancer. Larger randomized trials are needed to assess efficacy and maintenance of this intervention for chronic pain.

Communicating health information and improving coordination with primary care (CHIIP): Rationale and design of a randomized cardiovascular health promotion trial for adult survivors of childhood cancer.

BACKGROUND: Long-term survival for children diagnosed with cancer exceeds 80%. Notably, premature cardiovascular disease has become the leading non-cancer cause of late mortality among these survivors. METHODS/DESIGN: This randomized controlled trial (RCT; NCT03104543) focuses on adult participants in the Childhood Cancer Survivor Study identified as high risk for ischemic heart disease or heart failure due to their cancer treatment. Participants undergo a home-based evaluation of blood pressure and laboratory tests to determine the prevalence of undiagnosed and/or undertreated hypertension, dyslipidemia, and diabetes. Those with abnormal values are then enrolled in an RCT to test the efficacy of a 12-month personalized, remotely delivered survivorship care plan (SCP) intervention designed to reduce undertreatment of these three target conditions. The intervention approximates a clinical encounter and is based on chronic disease self-management strategies. RESULTS: With a goal of 750, currently 342 out of 742 eligible participants approached have enrolled (46.1%). Initially, we randomized participants to different recruitment strategies, including shorter approach packets and a tiered consent, but did not find significant differences in participation rates (40.7% to 42.9%; p = .95). Subsequently, slightly greater participation was seen with larger upfront unconditional incentive checks ($50 vs. $25: 50.7% vs. 44.1%; p = .10). Overall, the financial impact of the $50 upfront incentive was cost neutral, and possibly cost-saving, vs. a $25 upfront incentive. CONCLUSION: The overall study will determine if a National Academy of Medicine-recommended SCP intervention can improve cardiovascular outcomes among long-term survivors of childhood cancer. Modifications to the recruitment strategy may improve participation rates over time.

Promoting Breast Cancer Surveillance: The EMPOWER Study, a Randomized Clinical Trial in the Childhood Cancer Survivor Study.

PURPOSE: The aim of the current study was to increase the uptake of screening mammography among high-risk women who were treated for a childhood cancer with chest radiotherapy. PATIENTS AND METHODS: Two hundred four female survivors in the Childhood Cancer Survivor Study who were treated with chest radiotherapy with 20 Gy or greater, age 25 to 50 years, and without breast imaging in the past 24 months were randomly assigned 2:1 to receive a mailed informational packet followed by a tailored telephone-delivered brief motivational interview (intervention) versus an attention control. Primary outcome was the difference in the proportion of participants who completed a screening mammogram by 12 months as evaluated in an intent-to-treat analysis. Stratum-adjusted relative risk (RR) and 95% CI were estimated using the Cochran-Mantel-Haenszel method. Secondary outcomes included the completion of screening breast magnetic resonance imaging (MRI) and barriers to screening and moderating factors. RESULTS: Women in the intervention group were significantly more likely than those in the control group to report a mammogram (45 [33.1%] of 136 v 12 [17.6%] of 68; RR, 1.9; 95% CI, 1.1 to 3.3). The intervention was more successful among women age 25 to 39 years (RR, 2.2; 95% CI, 1.1 to 4.7) than among those age 40 to 50 years (RR, 1.4; 95% CI, 0.6 to 3.2). The proportion of women who reported a breast MRI at 12 months was similar between the two groups: 16.2% (intervention) compared with 13.2% (control; RR, 1.2; 95% CI, 0.6 to 2.5). Primary barriers to completing a screening mammogram and/or breast MRI included lack of physician recommendation, deferred action by survivor, cost, and absence of symptoms. CONCLUSION: Use of mailed materials followed by telephone-delivered counseling increased mammography screening rates in survivors at high risk for breast cancer; however, this approach did not increase the rate of breast MRI. Cost of imaging and physician recommendation were important barriers that should be addressed in future studies.

Skin Cancer Early Detection Practices among Adult Survivors of Childhood Cancer Treated with Radiation.

Because rates of skin cancer are greater among adult survivors of childhood cancer who received radiation therapy than among the general population, the National Cancer Institute recommends skin self-examinations and annual physician examination. There has been no comprehensive assessment of survivors' adherence to the skin cancer screening guidelines associated with skin self-examination (SSE) and physician whole-body skin examination (PSE). We conducted a cross-sectional survey of radiation-treated, adult 5-year survivors of childhood cancer, diagnosed between 1970 and 1986, in the Childhood Cancer Survivor Study cohort. Multivariate multinomial logit regression investigated the association between demographic, cancer diagnosis, patient activation, cancer treatment characteristics, and skin cancer screening practice. Among 728 survivors, 13.1% reported performing SSE in the prior 2 months plus receiving PSE in the prior 12 months, and 16.4% and 11.0% reported performing only an SSE or a PSE, respectively; 59.5% of survivors reported having had neither. Participants at the highest patient activation score were most likely to report SSE plus PSE compared with neither (adjusted relative risk ratio = 4.16, 95% confidence interval = 1.34-12.85). Most adult survivors of childhood cancer who had radiation therapy do not practice strategies that promote early detection of skin cancer. Interventions designed to activate survivors to increase their participation in screening are needed.

Advancing Survivors' Knowledge (ASK) about skin cancer study: study protocol for a randomized controlled trial.

BACKGROUND: Advances in treatment have increased childhood cancer 5-year survival rates to greater than 80%. However, children previously treated with radiation are at significantly increased risk of developing subsequent neoplasms, the most common of which are skin cancers. The National Cancer Institute and Children's Oncology Group have issued recommendations for survivors treated with radiation to perform monthly skin self-examinations and receive a physician skin examination at least annually, as early detection has demonstrated markedly improved outcomes in the diagnosis and treatment of skin cancers. The goal of the present study is to increase rates of skin self-examinations and clinical skin examinations among adult survivors of childhood cancer treated with radiation. METHODS/DESIGN: This randomized controlled trial uses a 3-group comparative effectiveness design comparing: (1) Patient Activation and Education (PAE) including text messaging, print and web-based tutorials over 12 months; (2) PAE plus physician activation (PAE + MD) adding physician activation/educational materials about survivors' increased skin cancer risk and conducting full-body skin exams; and (3) PAE plus physician activation, plus teledermoscopy (PAE + MD + TD) adding participant receipt of a dermatoscope intended to empower them to photograph suspect moles or lesions for review by the study dermatologist. DISCUSSION: The current study addresses barriers to screening in this population by providing educational and motivational information for both survivors and physicians regarding the value of periodic skin examinations. It also utilizes innovative mobile health technology to encourage and motivate (that is activate) survivors to conduct skin self-examinations, request physician exams, and obtain treatment when worrisome lesions are found. Finally, as a comparative effectiveness trial, this study isolates the effects of adding specific components to the patient activation intervention to test the most effective intervention for enhancing skin examination vigilance among this high-risk group. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02046811 ; Registration date: 22 January 2014.

Factors associated with recruiting adult survivors of childhood cancer into clinic-based research.

BACKGROUND: A high proportion of pediatric cancer patients are now surviving into adulthood, but are at increased risk for late morbidity and premature mortality related to their diagnosis and therapeutic exposures. Little is known about the potential success of recruiting adult survivors of childhood cancer into research projects that would require a risk-based health evaluation within a clinical setting. PROCEDURES: Pediatric cancer survivors and siblings eligible for the current study were Childhood Cancer Survivor Study participants who lived within 100 miles of one of five Consortium for Pediatric Intervention Research institutions, regardless of where they were initially diagnosed and treated. A short survey was mailed to 829 survivors and 373 siblings to identify factors that predict interest, potential barriers, and motivators, to participation in research including a risk-based clinical evaluation. RESULTS: Overall, 92% of survivors responding to the survey were very interested/interested in participating in a research study requiring a visit to a local hospital clinic. Siblings of survivors were less interested than survivors in participating in such a study, with only 78% indicating that they were very interested/interested. Potential motivators to participation included visiting their treating hospital and receiving health information. The primary barrier to participation was related to taking time off from work. CONCLUSIONS: This study demonstrates that a subgroup of survivors would be willing to return to a long-term follow-up center to participate in intervention-based research. Identified motivating factors and perceived barriers need to be considered in determining the feasibility, design and execution of future research.

Expression of galanin and galanin receptor-1 in normal bone and during fracture repair in the rat.

The neuropeptide galanin (GAL) has recognized physiological actions in the nervous system and other tissues, but there is no documented evidence of GAL influencing normal or pathological bone metabolism. GAL expression, however, is upregulated in central and peripheral nerves following axotomy and is known to influence neural regeneration. Thus, severance of skeletal-associated nerves during fracture could similarly increase local GAL concentrations and thereby influence fracture healing. The initial aim of this study was therefore to identify the presence of GAL in normal bone and/or fracture callus by assessing the concentration and cellular localization of GAL in intact and/or fractured rat rib, using radioimmunoassay and immunohistochemistry, respectively. Groups of Sprague-Dawley rats (13 weeks old) had their left sixth ribs surgically fractured or underwent sham surgery and then calluses and nonfractured rib samples were analyzed at 1 and 2 weeks postsurgery (n = 5-6 per group). Low (basal) concentrations of GAL were detected in control ribs, whereas at 1 and 2 weeks postfracture, callus samples contained markedly increased levels of peptide ( approximately 32- and 18-fold increase, respectively, relative to controls; P < 0.01), revealing a strong upregulation during bone healing. Plasma GAL concentrations were also increased at 2 weeks postfracture (P < 0.005). In normal (nonfractured) rib, minimal levels of GAL-like immunoreactivity (LI) were present in cortical bone, periosteum, endosteum, and surrounding skeletal muscle. In costal cartilage plates, intense GAL-LI was present in all chondrocytes of the hypertrophic zone and in a population of chondrocytes in the reserve zone. GAL-LI was not present, however, in chondrocytes in the proliferative zone of costal cartilage or skeletal muscle fibers. In fracture callus, levels of GAL-LI were moderate to intense in osteoprogenitor cells and osteoblasts, in some chondrocytes, and in cartilaginous, osseous, and periosteal matrices. Subsequent studies revealed the presence of galanin receptor-1-like immunoreactivity (GALR1-LI) in most cell types shown to contain GAL-LI, although the distribution of GALR1-LI was more extensive in reserve zone chondrocytes than that of GAL-LI; and GALR1-LI also appeared in late proliferative zone chondrocytes of costal cartilage. In summary, GAL concentrations were significantly increased in fracture callus and plasma of rats that underwent rib fracture. In addition, GAL- and GALR1-LI was also detected in specific cells and structures within costal cartilage, bone, and fracture callus. These results strongly implicate GAL in aspects of cartilage growth plate physiology and fracture repair, possibly acting in an autocrine/paracrine fashion via GALR1.