Search

Background: Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer.Methods: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15-20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs.Findings: Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34-50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5-6·2) and among 5804 childhood cancer survivors (median age 34 years; 27-42), it was 6·2 (5·8-6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 [95% CI 4·4-5·1] vs 6·8 [6·2-7·4]), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3-5) health conditions than siblings of the same age (HR 4·2 [95% CI 3·7-4·8] for early adolescent and young adult cancer survivors and 5·6 [4·9-6·3] for childhood cancer survivors), and at increased risk of developing grade 3-5 cardiac (4·3 [3·5-5·4] and 5·6 [4·5-7·1]), endocrine (3·9 [2·9-5·1] and 6·4 [5·1-8·0]), and musculoskeletal conditions (6·5 [3·9-11·1] and 8·0 [4·6-14·0]) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors.Interpretation: Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3-5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors.Funding: National Cancer Institute and American Lebanese-Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Purpose: Little evidence exists regarding the emetogenicity of chemotherapy in pediatric patients. This study describes the prevalence of chemotherapy-induced nausea and vomiting (CINV) in pediatric patients receiving etoposide plus ifosfamide over 5 days, a common pediatric regimen.Methods: English-speaking, non-chemotherapy-naïve patients aged 4 to 18 years about to receive etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day over 5 days participated. Antiemetic prophylaxis was determined by each patient's care team. Emetic episodes were recorded and nausea severity was assessed by patients beginning with the first chemotherapy dose, continuing until 24 h after the last chemotherapy dose (acute phase) and ending 7 days later (delayed phase). The proportion of patients experiencing complete acute CINV control (no nausea, no vomiting, and no retching), the primary study endpoint, was described. The prevalence of complete chemotherapy-induced vomiting (CIV) and chemotherapy-induced nausea (CIN) during the acute, delayed, and overall (acute plus delayed) phases; complete delayed and overall CINV control; and anticipatory CINV were also determined.Results: Twenty-four patients participated; acute CINV was evaluable in 22. Most (75%; 18/24) received a 5-HT3 antagonist plus dexamethasone for antiemetic prophylaxis. Few (23%; 5/22) experienced complete acute CINV control. Complete acute CIV and CIN control were experienced by 57% (13/23) and 27% (6/22) of patients, respectively. Complete delayed CINV, CIV, and CIN control rates were 42% (8/19), 70% (14/20), and 42% (8/19), respectively.Conclusions: Our findings support the classification of etoposide 100 mg/m2/day plus ifosfamide 1800 mg/m2/day IV over 5 days as highly emetogenic. This information will optimize antiemetic prophylaxis selection and CINV control in pediatric patients. [ABSTRACT FROM AUTHOR]

Although a cancer diagnosis during the adolescent and young adult (AYA) years is a traumatic event, and psychiatric disorders generally manifest during the AYA period, the impact of a cancer diagnosis on long-term mental health outcomes in this population is not well characterized. We conducted a systematic review and meta-analysis to determine if survivors of AYA cancers are more likely to develop psychiatric disorders. A systematic literature search of five databases, MEDLINE, CINAHL, Web of Science, EMBASE, and PsycINFO, was conducted from their inception to November 2018. The outcome measures were psychiatric disorders as per the Diagnostic Statistical Manual criteria, or psychiatric medication use. Study eligibility, appraisal, and data abstraction were independently conducted by two reviewers. Of 7934 total studies, four met eligibility criteria for the systematic review, three of which were included in the meta-analysis. Compared to cancer-free controls, survivors were at an elevated risk of mood disorders (odds ratio [OR] 1.36; 95% CI 1.19–1.55) and anxiety disorders (OR 1.16; 95% CI 1.05–1.28), but not substance-related disorders, (OR 0.88; 95% CI 0.63–1.22). The most commonly identified risk factors were the female sex and older age at diagnosis. We found higher odds of anxiety and mood disorders in AYA-onset cancer survivors. However, few AYA-specific studies currently exist that analyze psychiatric disorders using consistent and standardized methods. Additional studies confirming these findings are warranted. [ABSTRACT FROM AUTHOR]

Background: Adolescent women treated for Hodgkin lymphoma (HL) are at increased risk of breast cancer (BC). We evaluate the cost-utility of eight high-risk BC surveillance strategies for this population, including the Children's Oncology Group guideline of same-day annual mammography and magnetic resonance imaging (MRI) beginning at age 25 years.Methods: A discrete event simulation model was used to simulate the life histories of a cohort of 500 000 25-year-old women treated for HL at age 15 years. We estimated BC incidence and mortality, life expectancy, quality-adjusted life-years (QALYs), health-care costs, and the relative cost-utility (incremental cost-utility ratio [ICUR]) under the eight assessed surveillance strategies. One-way sensitivity analysis enabled modeling of uncertainty evaluation. A publicly funded health-care payer perspective was adopted.Results: Costs across the eight screening strategies ranged from $32 643 to $43 739, whereas QALYs ranged from 24.419 to 24.480. In an incremental cost-effectiveness analysis, annual mammography beginning at age 25 years was associated with an ICUR of $43 000/QALY gained, annual MRI beginning at age 25 years with a switch to annual mammography at age 50 years had an ICUR of $148 000/QALY, and annual MRI beginning at age 25 years had an ICUR of $227 222/QALY. Among all assessed surveillance strategies, the differences in life expectancy were small.Conclusions: Current high-risk BC surveillance guidelines do not reflect the most cost-effective strategy in survivors of adolescent HL. The results suggest that groups at high risk of BC may require high-risk surveillance guidelines that reflect their specific risk profile. [ABSTRACT FROM AUTHOR]

Infections are a common complication of treatment for pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Less is known about infections occurring after treatment. We performed a systematic review of the literature to assess the incidence of infections after therapy completion in children and young adults with ALL or AML. Twenty-eight studies, with 4138 patients, were included. Four studies reported infections in patients who did not undergo hematopoietic stem cell transplant (HSCT). Respiratory tract and urinary tract infections affected 9.9–72.5% and 2.9–19.8% of patients, respectively. Twelve studies reported infections in patients treated with HSCT. Late bacterial, viral and fungal infections affected 3.9–38.5%, 16.1–66.7%, and 0.2–41.7% of patients, respectively. Viral hepatitis affected 0.8–75.4% of patients from 12 studies. Our review suggests that infections are a frequent complication after treatment for leukemia in children, especially after HSCT and identifies several knowledge gaps in the current literature. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors are at risk for adverse psychological outcomes. Whether exercise can attenuate this risk is unknown.Methods: In total, 6199 participants in the Childhood Cancer Survivor Study (median age, 34.3 years [range, 22.0-54.0 years]; median age at diagnosis, 10.0 years [range, 0-21.0 years]) completed a questionnaire assessing vigorous exercise and medical/psychological conditions. Outcomes were evaluated a median of 7.8 years (range, 0.1-10.0 years) later and were defined as: symptom level above the 90th percentile of population norms for depression, anxiety, or somatization on the Brief Symptom Inventory-18; cancer-related pain; cognitive impairment using a validated self-report neurocognitive questionnaire; or poor health-related quality of life. Log-binomial regression estimated associations between exercise (metabolic equivalent [MET]-hours per week-1 ) and outcomes adjusting for cancer diagnosis, treatment, demographics, and baseline conditions.Results: The prevalence of depression at follow-up was 11.4% (95% CI, 10.6%-12.3%), anxiety 7.4% (95% CI, 6.7%-8.2%) and somatization 13.9% (95% CI, 13.0%-14.9%). Vigorous exercise was associated with lower prevalence of depression and somatization. The adjusted prevalence ratio for depression was 0.87 (95% CI, 0.72-1.05) for 3 to 6 MET hours per week-1 , 0.76 (95% CI, 0.62-0.94) for 9 to 12 MET-hours per week-1 , and 0.74 (95% CI, 0.58-0.95) for 15 to 21 MET-hours per week-1 . Compared with 0 MET hours per week-1 , 15 to 21 MET-hours per week-1 were associated with an adjusted prevalence ratio of 0.79 (95% CI, 0.62-1.00) for somatization. Vigorous exercise also was associated with less impairment in the physical functioning, general health and vitality (Ptrend  < .001), emotional role limitations (Ptrend  = .02), and mental health (Ptrend  = .02) domains as well as higher cognitive function in the domains of task completion, organization, and working memory (P < .05 for all), but not in the domain of cancer pain.Conclusions: Vigorous exercise is associated with less psychological burden and cognitive impairment in childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Retrospective studies have shown adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have superior survival when treated in pediatric versus adult centers (locus of care; LOC). Several adult centers recently adopted pediatric protocols. Whether this has narrowed LOC disparities in real–world settings is unknown. Methods: The IMPACT Cohort is an Ontario population–based cohort that captured demographic, disease and treatment (treatment protocol, chemotherapy doses) data for all 15‐21 year olds diagnosed with ALL 1992‐2011. Cancer outcomes were determined by chart abstraction and linkage to provincial healthcare databases. Treatment protocols were classified as pediatric‐ or adult‐based. We examined predictors of outcome, including LOC, protocol, disease biology, and time period. Results: Of 271 patients, 152 (56%) received therapy at adult centers. 5‐year event‐free survival (EFS ± SE) among AYA at pediatric vs adult centers was 72% ± 4% vs 56% ± 4% (P = 0.03); 5‐year overall survival (OS) was 82% ± 4% vs 64% ± 4% (P < 0.001). After adjustment, OS remained inferior at adult centers (hazard ratio 2.5; 95% confidence interval 1.1‐6.1; P = 0.04). In the most recent period (2006‐2011), 39/59 (66%) AYA treated at adult centers received pediatric protocols. These AYA had outcomes superior to the 20 AYA treated on adult protocols, but inferior to the 44 AYA treated at pediatric centers (EFS 72% ± 5% vs 60% ± 9% vs 81% ± 6%; P = 0.02; OS 77% ± 7% vs 65% ± 11% vs 91% ± 4%; P = 0.004). Induction deaths and treatment–related mortality did not vary by LOC. Conclusions: Survival disparities between AYA with ALL treated in pediatric vs adult centers have persisted over time, partially attributable to incomplete adoption of pediatric protocols by adult centers. Although pediatric protocol use has improved survival, residual disparities remain, perhaps due to other differences in care between adult and pediatric centers.Previous studies demonstrated that pediatric–based acute lymphoblastic leukemia (ALL) protocols were associated with superior adolescent and young adult (AYA) outcomes than cohorts treated with adult–based protocols. Using a population–based AYA database, we found that though pediatric–based protocols were adopted for many AYA in adult centers and that these patients experienced superior outcomes to AYA treated with adult–based protocols, their outcomes were still inferior to AYA treated at pediatric institutions. [ABSTRACT FROM AUTHOR]

Background: Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow-up of a previously reported Late Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk-based screening recommendations.Methods: The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow-up was 26.6 years.Results: In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14-fold increased risk of developing an sSMN (95% confidence interval, 12.0-fold to 16.3-fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age <10 years were found to be at highest risk of developing lung cancer. Survivors of HL who were treated with abdominal/pelvic radiotherapy and high-dose alkylating agents were found to be at highest risk of developing colorectal cancer and females exposed to neck radiotherapy at age <10 years were at highest risk of thyroid cancer. By age 50 years, the cumulative incidence of breast, lung, colorectal, and thyroid cancer was 45.3%, 4.2%, 9.5%, and 17.3%, respectively, among those at highest risk.Conclusions: Survivors of childhood HL remain at an increased risk of developing sSMNs. In the current study, subgroups of survivors of HL at highest risk of specific sSMNs were identified, and evidence for screening provided. [ABSTRACT FROM AUTHOR]

Aims: To estimate the level of alcohol consumption behaviors in adult survivors of childhood cancer and to test associations between alcohol consumption behaviors and symptoms of neurocognitive impairment and emotional distress. Design Retrospective cohort study with longitudinal follow‐up of self‐reported health outcomes. Setting: Childhood Cancer Survivor Study (CCSS), a 26‐center study of ≥ 5‐year survivors of childhood cancer diagnosed ≤ 21 years of age between 1970 and 1986 in the United States and Canada. Participants: A total of 4484 adult survivors of childhood cancer [mean (standard deviation) age at evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651 sibling controls who completed surveys reporting on alcohol use, neurocognitive impairment and emotional distress. Measurements Survivor report of alcohol use included age at drinking initiation and quantity and frequency of alcohol consumption. Neurocognition was assessed using the CCSS Neurocognitive Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms Inventory–18 and the Posttraumatic Stress Diagnostic Scale. Findings After adjustment for childhood cancer treatment exposures, including cranial radiation therapy, drinking initiation prior to 18 years of age was associated with 30% increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95% confidence interval (CI) = 1.1–1.5]. Younger age at drinking initiation was associated with future risk of depression (RR = 1.3; 95% CI = 1.1–1.5), anxiety (RR = 1.6; 95% CI = 1.3–2.1), and somatization (RR = 1.2; 95% CI = 1.1–1.4). Persistent heavy/risky drinking was associated with 80% increased risk of persistent psychological distress (RR = 1.8, 95% CI = 1.4–2.3). Conclusions: Drinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Although paediatric astrocytoma has an excellent 5-year survival rate, survivors remain at risk for morbidity and late mortality. This study aimed to estimate the risk of late mortality, chronic conditions, poor health status and social impairment in ageing paediatric astrocytoma survivors. Methods We longitudinally evaluated 1182 5-year astrocytoma survivors diagnosed between 1970 and 1986 and 4023 siblings enrolled in a retrospective cohort study. Kaplan–Meier estimates of late mortality and cumulative incidence of serious chronic conditions were estimated. Cox regression models provided hazard ratios (HRs) with 95% confidence intervals (CIs) for development of chronic conditions, and generalised linear models provided relative risks (RRs) of the poor health status and social outcomes. Results At 30 years from diagnosis, cumulative late mortality was 22.1% (CI 20.0–24.3%), primarily due to disease progression or recurrence. Compared with siblings, survivors were at increased risk of serious chronic conditions (HR 4.6, CI 3.8–5.5). Survivors reported higher rates of poor general health (RR 3.3, CI 2.8–3.8), poor mental health (RR 1.9, CI 1.7–2.1), functional impairment (RR 9.0, CI 7.7–10.5) and activity limitation (RR 3.6, CI 3.1–4.2) and lower rates of college graduation (RR 0.75, CI 0.69–0.82), marriage (RR 0.62, CI 0.58–0.66), employment (RR 0.75, CI 0.72–0.79) and household income ≥$40,000 (RR 0.68, CI 0.64–0.73). Even survivors without radiation exposure had elevated risk of chronic conditions, poor health status and social impairment compared with siblings. Conclusions Survivors of paediatric astrocytoma are at high risk for long-term complications of their disease and its treatment. They require lifelong monitoring for late effects. Highlights • At 30 years after diagnosis of astrocytoma, cumulative late mortality was 22.1%. • By 30 years after diagnosis, 56.7% of survivors had a serious chronic condition. • Survivors reported more functional impairment and activity limitations than siblings. • Survivors were less likely than siblings to be college educated, working or married. • Survivors treated without radiation had increased medical and psychosocial conditions. [ABSTRACT FROM AUTHOR]

Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk.Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15-25), the 20-year cumulative incidence of at least one grade 3-5 chronic condition decreased significantly from 33·2% (95% CI 32·0-34·3) in those diagnosed 1970-79 to 29·3% (28·4-30·2; p<0·0001) in 1980-89, and 27·5% (26·4-28·6; p=0·012 vs 1980-89) in 1990-99. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition in 5051 siblings was 4·6% (95% CI 3·9-5·2). The 15-year cumulative incidence of at least one grade 3-5 condition was lower for survivors diagnosed 1990-99 compared with those diagnosed 1970-79 for Hodgkin lymphoma (17·7% [95% CI 15·0-20·5] vs 26·4% [23·8-29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0-19·7] vs 23·8% [19·9-27·7]; p=0.0053), astrocytoma (30·5% [27·8-33·2] vs 47·3% [42·9-51·7]; p<0·0001), Wilms tumour (11·9% [9·5-14·3] vs 17·6% [14·3-20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5-33·1] vs 36·5% [31·5-41·4]; p=0·021), and osteosarcoma (65·6% [60·6-70·6] vs 87·5% [84·1-91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-99 vs 1970-79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4-63·3] vs 42·9% [34·9-50·9]; p=0·00060), and neuroblastoma (25·0% [21·8-28·2] vs 18·0% [14·5-21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64-0·92; HR with treatment in the model=0·89, 95% CI 0·72-1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65-0·85; HR with treatment=0·91, 95% CI 0·73-1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970-79 to survivors diagnosed 1990-99 were noted for endocrinopathies (5·9% [5·3-6·4] vs 2·8% [2·5-3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3-3·1] vs 1·9% [1·6-2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2-6·4] vs 3·3% [2·9-3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0-2·7] vs 1·5% [1·3-1·8]; p=0·00037), while hearing loss increased (3·0% [2·6-3·5] vs 5·7% [5·2-6·1]; p<0·0001).Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population.Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer are at significant risk for serious chronic health conditions and subsequent cancers because of their prior treatment exposures. However, little is known about survivors' perceptions of their future health risks.Methods: This study examined self-reported levels of concern about future health and subsequent cancer in 15,620 adult survivors of childhood cancer (median age, 26 years; median time since diagnosis, 17 years) and 3991 siblings in the Childhood Cancer Survivor Study. The prevalence of concerns was compared between survivors and siblings, and the impact of participant characteristics and treatment exposures on concerns was examined with multivariable modified Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results: A substantial proportion of survivors were not concerned about their future health (31%) or developing cancer (40%). The prevalence of concern in survivors was modestly higher (RR for future health, 1.12; 95% CI, 1.09-1.15) or similar (RR for subsequent cancer, 1.02; 95% CI, 0.99-1.05) in comparison with siblings. Survivors exposed to high doses of radiation (≥20 Gy) were more likely to report concern (RR for future health, 1.13; 95% CI, 1.09-1.16; RR for subsequent cancer, 1.14; 95% CI, 1.10-1.18), but 35% of these high-risk survivors were not concerned about developing cancer, and 24% were not concerned about their future health.Conclusions: A substantial subgroup of survivors were unconcerned about their future health and subsequent cancer risks, even after exposure to treatments associated with increased risk. These survivors may be less likely to engage in beneficial screening and risk-reduction activities. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors are at risk for a range of cardiovascular diseases (CVD) as a consequence of their cancer therapy.[1] However, most studies have focused on anthracycline-related heart failure (HF) only. Because the prevalence of CVD is expected to increase with age, this study reinforces the need for periodic CVD surveillance, and consideration of all CVD types, in childhood cancer survivors. 1 Mulrooney DA Yeazel MW Kawashima T Mertens AC Mitby P Stovall M Donaldson SS Green DM Sklar CA Robison LL Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. [Extracted from the article]

Objective: This study assessed the effects of a group intervention-Siblings Coping Together (SibCT)-on siblings' and caregivers' anxiety symptoms compared to controls, and potential moderators.Methods: Seventy healthy siblings of children on or off treatment (7-16 y old, 41 males) participated in a randomized controlled trial (RCT) with 2 arms/groups: SibCT (n = 41) and an attention control (CG) (n = 34). Both groups had eight 2-hour weekly sessions. EG followed SibCT's educational, social, and problem-solving activities. CG had planned games and crafts. Siblings and caregivers self-reported on anxiety symptoms at baseline, intervention end, and 3 months later. Multivariable mixed model analyses examined the intervention effect over time, and potential moderators (gender, on/off ill child's treatment).Results: No main effects of group or time were found in sibling scores. A group × gender interaction (P < .05) indicated that in the intervention group female siblings reported less total anxiety symptoms than male siblings, with no significant gender differences in the control group. Caregivers' total anxiety symptoms declined over time (P < .02). A group × on/off treatment interaction in physiological/panic subscale (P < .03) indicated that when ill child was on treatment, caregivers of siblings in SibCT reported less anxiety compared with caregivers of CG.Conclusions: There was no clear SibCT intervention effect. SibCT may benefit female siblings, and caregivers whose ill child is on active treatment. Contextual factors (gender) seem to influence psychosocial intervention in this population. [ABSTRACT FROM AUTHOR]

Background: Anthracycline-induced cardiac toxicity is a cause of significant morbidity and early mortality in survivors of childhood cancer. Current strategies for predicting which children are at greatest risk for toxicity are imperfect and diagnosis of cardiac injury is usually made relatively late in the natural history of the disease. This study aims to identify genomic, biomarker and imaging parameters that can be used as predictors of risk or aid in the early diagnosis of cardiotoxicity.Methods: This is a prospective longitudinal cohort study that recruited two cohorts of pediatric cancer patients at six participating centres: (1) an Acute Cohort of children newly diagnosed with cancer prior to starting anthracycline therapy (n = 307); and (2) a Survivor Cohort of long-term survivors of childhood cancer with past exposure to anthracycline (n = 818). The study team consists of three collaborative cores. The Genomics Core is identifying genomic variations in anthracycline metabolism and in myocardial response to injury that predispose children to treatment-related cardiac toxicity. The Biomarker Core is identifying existing and novel biomarkers that allow for early diagnosis and prognosis of anthracycline-induced cardiac toxicity. The Imaging Core is identifying echocardiographic and cardiac magnetic resonance (CMR) imaging parameters that correspond to early signs of cardiac dysfunction and remodeling and precede global dysfunction and clinical symptoms. The data generated by the cores will be combined to create an integrated risk-prediction model aimed at more accurate identification of children who are most susceptible to anthracycline toxicity.Discussion: We aim to identify genomic risk factors that predict risk for anthracycline cardiotoxicity pre-exposure and imaging and biomarkers that facilitate early diagnosis of cardiac injury. This will facilitate a personalized approach to identifying at-risk children with cancer who may benefit from cardio- protective strategies during therapy, and closer surveillance and earlier initiation of medications to preserve heart function after cancer therapy.Trial Registration: NCT01805778 . Registered 28 February 2013; retrospectively registered. [ABSTRACT FROM AUTHOR]

Background Childhood and adolescent cancers are uncommon, but they have important economic and health impacts on patients, families, and health care systems. Few studies have measured the economic burden of care for childhood and adolescent cancers. Objectives To estimate costs of cancer care in population-based cohorts of children and adolescents from the public payer perspective. Methods We identified patients with cancer, aged 91 days to 19 years, diagnosed from 1995 to 2009 using cancer registry data, and matched each to three noncancer controls. Using linked administrative health care records, we estimated total and net resource-specific costs (in 2012 Canadian dollars) during 90 days prediagnosis and 1 year postdiagnosis. Results Children (≤14 years old) numbered 4,396: 36% had leukemia, 21% central nervous system tumors, 10% lymphoma, and 33% other cancers. Adolescents (15–19 years old) numbered 2,329: 28.9% had lymphoma. Bone and soft tissue sarcoma, germ cell tumor, and thyroid carcinoma each comprised 12% to 13%. Mean net prediagnosis costs were $5,810 and $1,127 and mean net postdiagnosis costs were $136,413 and $62,326 for children and adolescents, respectively; the highest were for leukemia ($157,764 for children and $172,034 for adolescents). In both cohorts, costs were much higher for patients who died within 1 year of diagnosis. Inpatient hospitalization represented 69% to 74% of postdiagnosis costs. Conclusions Treating children with cancer is costly, more costly than treating adolescents or adults. Substantial survival gains in children mean that treatment may still be very cost-effective. Comprehensive age-specific population-based cost estimates are essential to reliably assess the cost-effectiveness of cancer care for children and adolescents, and measure health system performance. [ABSTRACT FROM AUTHOR]

The article discusses a meeting to produce international partnerships for the promotion of the Adolescent and Young Adults (AYA) activities sponsored by the Canadian Institutes of Health Research American Health Association that was held in Melbourne, Australia on December 7-8, 2015.

The article focuses on the socioeconomic and health system factors of the population on childhood cancer medical care and screening including enrollment in the Childhood Cancer Survivor Study (CCSS) and individual-level factors from U.S. Area Health Resource File was reported.

Background: The effect of temporal changes in cancer therapy on health status among childhood cancer survivors has not been evaluated.Objective: To compare proportions of self-reported adverse health status outcomes among childhood cancer survivors across 3 decades.Design: Cross-sectional. (ClinicalTrials.gov: NCT01120353).Setting: 27 North American institutions.Participants: 14 566 adults, who survived for 5 or more years after initial diagnosis (median age, 27 years; range, 18 to 48 years), treated from 1970 to 1999.Measurements: Patient report of poor general or mental health, functional impairment, activity limitation, or cancer-related anxiety or pain was evaluated as a function of treatment decade, cancer treatment exposure, chronic health conditions, demographic characteristics, and health habits.Results: Despite reductions in late mortality and the proportions of survivors with severe, disabling, or life-threatening chronic health conditions (33.4% among those treated from 1970 to 1979 and 21.0% among those treated from 1990 to 1999), those reporting adverse health status did not decrease by treatment decade. Compared with survivors diagnosed in 1970 to 1979, those diagnosed in 1990 to 1999 were more likely to report poor general health (11.2% vs. 13.7%; P < 0.001) and cancer-related anxiety (13.3% vs. 15.0%; P < 0.001). From 1970 to 1979 and 1990 to 1999, the proportions of survivors reporting adverse outcomes were higher (P < 0.001) among those with leukemia (poor general health, 9.5% and 13.9%) and osteosarcoma (pain, 23.9% and 36.6%). Temporal changes in treatment exposures were not associated with changes in the proportions of survivors reporting adverse health status. Smoking, not meeting physical activity guidelines, and being either underweight or obese were associated with poor health status.Limitation: Considerable improvement in survival among children diagnosed with cancer in the 1990s compared with those diagnosed in the 1970s makes it difficult to definitively determine the effect of risk factors on later self-reported health status without considering their effect on mortality.Conclusion: Because survival rates after a diagnosis of childhood cancer have improved substantially over the past 30 years, the population of survivors now includes those who would have died in earlier decades. Self-reported health status among survivors has not improved despite evolution of treatment designed to reduce toxicities.Primary Funding Source: The National Cancer Institute. [ABSTRACT FROM AUTHOR]

Background: Health complications related to childhood cancer may be influenced by risky health behaviors (RHBs), particularly when RHBs co-occur. To the authors' knowledge, only limited information is available describing how RHBs cluster among survivors of childhood cancer and their siblings and the risk factors for co-occurring RHBs.Methods: Latent class analysis was used to identify RHB clusters using longitudinal survey data regarding smoking, alcohol use, and physical activity from adult survivors (4184 survivors) and siblings (1598 siblings) in the Childhood Cancer Survivor Study. Generalized logistic regression was used to evaluate associations between demographic characteristics, treatment exposures, psychological distress, health conditions, and cluster membership.Results: Three RHB clusters were identified: a low-risk cluster, an insufficiently active cluster, and a high-risk cluster (tobacco and risky alcohol use and insufficient activity). Compared with siblings, survivors were more likely to be in the insufficiently active cluster (adjusted odds ratio [ORadj ], 1.17; 95% confidence interval [95% CI], 1.06-1.27) and were less likely to be in the high-risk cluster (ORadj , 0.79; 95% CI, 0.69-0.88). Risk factors for membership in the high-risk cluster included psychological distress (ORadj , 2.76; 95% CI, 1.98-3.86), low educational attainment (ORadj , 7.49; 95% CI, 5.15-10.88), income <$20,000 (ORadj , 2.62; 95% CI, 1.93-3.57), being divorced/separated or widowed (ORadj , 1.36; 95% CI, 1.03-1.79), and limb amputation (ORadj , 1.52; 95% CI, 1.03-2.24). Risk factors for the insufficiently active cluster included chronic health conditions, psychological distress, low education or income, being obese or overweight, female sex, nonwhite race/ethnicity, single marital status, cranial radiation, and cisplatin exposure.Conclusions: RHBs co-occur in survivors of childhood cancer and their siblings. Economic and educational disadvantages and psychological distress should be considered in screening and interventions to reduce RHBs. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2747-2756. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

By the middle of this century, racial/ethnic minority populations will collectively constitute 50% of the US population. This temporal shift in the racial/ethnic composition of the US population demands a close look at the race/ethnicity-specific burden of morbidity and premature mortality among survivors of childhood cancer. To optimize targeted long-term follow-up care, it is essential to understand whether the burden of morbidity borne by survivors of childhood cancer differs by race/ethnicity. This is challenging because the number of minority participants is often limited in current childhood cancer survivorship research, resulting in a paucity of race/ethnicity-specific recommendations and/or interventions. Although the overall childhood cancer incidence increased between 1973 and 2003, the mortality rate declined; however, these changes did not differ appreciably by race/ethnicity. The authors speculated that any racial/ethnic differences in outcome are likely to be multifactorial, and drew on data from the Childhood Cancer Survivor Study to illustrate the various contributors (socioeconomic characteristics, health behaviors, and comorbidities) that could explain any observed differences in key treatment-related complications. Finally, the authors outlined challenges in conducting race/ethnicity-specific childhood cancer survivorship research, demonstrating that there are limited absolute numbers of children who are diagnosed and survive cancer in any one racial/ethnic minority population, thereby precluding a rigorous evaluation of adverse events among specific primary cancer diagnoses and treatment exposure groups. Cancer 2016;122:2426-2439. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Female survivors treated with thoracic radiation therapy (RT) for childhood cancer experience increased risks of breast cancer (BC). There are currently no data quantifying the potential mortality gains of early BC screening among such survivors.Methods: A mathematical model of BC development was used to evaluate the marginal benefit of early-initiated screening of female survivors of adolescent Hodgkin's lymphoma (HL) starting at age 25 years on BC mortality compared with screening initiated at age 40 years. Sensitivity analyses were performed to evaluate the robustness of the estimates over a plausible range of conditions.Results: For survivors treated at age 15 years, the absolute risk of BC mortality by age 75 years was predicted to decrease from 16.65% with no early screening to 16.28% (annual mammography), 15.40% (annual MRI), 15.38% (same-day annual mammography and MRI), and 15.37% (alternating mammography and MRI every six months). Approximately 80 patients would need to be invited to MRI-based screening to prevent one BC death. In sensitivity analyses, the number needed to invite to MRI-based screening to prevent one BC death ranged from 71 to 333. Combinations of MRI plus mammography were predicted to produce 99.52 false positives per 1000 screenings done between age 25 to 39 years.Conclusions: These findings are the first to indicate that early MRI-based screening should reduce BC mortality among women treated with RT for adolescent HL. The magnitude of this benefit is superior to that described for other accepted screening indications although MRI can produce a substantial rate of false-positive results. [ABSTRACT FROM AUTHOR]

Background: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown.Methods: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database.Results: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes.Conclusions: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients. [ABSTRACT FROM AUTHOR]

Background: Several randomized controlled trials (RCTs) have demonstrated that dexrazoxane reduces anthracycline cardiotoxicity in adults, but use in children has been hindered by lack of direct evidence of cardioprotection and concerns regarding second malignant neoplasms (SMNs). This study aimed to systematically review the evidence regarding dexrazoxane in children.Methods: We searched Medline, Embase, the Cochrane Library, and abstracts for RCTs and nonrandomized studies (NRSs) that compared dexrazoxane to no cardioprotection among children. We combined findings using random-effects models. All statistical tests were two-sided.Results: Eleven eligible publications reported results from five RCTs (1254 patients), and 15 publications reported results from 12 NRSs (3385 patients). Dexrazoxane did not impact clinical cardiotoxicity in RCTs because of a low cardiotoxic event rate (three events among all patients) but was associated with a reduction in subclinical cardiotoxicity. Among NRSs, dexrazoxane was associated with a reduction in clinical cardiotoxicity (relative risk (RR) = 0.29, P = .001) and clinical+subclinical cardiotoxicity (RR = 0.43, P < .001). Among RCTs, 17 of 635 (2.7%) patients treated with dexrazoxane developed an SMN compared with seven of 619 (1.1%) who did not receive dexrazoxane (RR = 2.37, P = .06). Two RCTs that used concurrent etoposide reported an increased risk of acute myeloid leukemia, while one that used cranial radiation reported an increased risk of brain tumors. Event-free survival did not differ (P = .91).Conclusion: Dexrazoxane is associated with a statistically significant risk reduction for most cardiotoxic outcomes. Dexrazoxane is associated with a statistically borderline increase in SMNs, possibly because of an interaction with concurrent cancer therapies. The decision to use dexrazoxane in children should balance the risks of cardiotoxicity and SMNs specific to each treatment protocol. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy emetogenicity is the most important known determinant of chemotherapy-induced vomiting (CIV) in children. However, direct evidence regarding the emetogenic potential of chemotherapeutic agents in children is limited. This study describes the prevalence of complete control of acute and delayed phase chemotherapy-induced nausea and vomiting (CINV) in children receiving methotrexate. The prevalence of anticipatory CINV is described, and risk factors for CINV are explored.Methods: English-speaking children (4 to 18 years) receiving intermediate-dose (ID-MTX: >1 to <12 g/m(2)/dose) or high-dose methotrexate (HD-MTX: ≥12 g/m(2)/dose) participated in this prospective study. Emetic episodes, nausea severity, and antiemetic administration were documented for 24 h from the start of the methotrexate infusion (acute phase) and for up to a further 168 h (delayed phase). CINV prophylaxis was provided at the discretion of the treating physician. Anticipatory CINV was assessed in the 24 h preceding chemotherapy. Complete CINV control was defined as no emetic episodes and no nausea.Results: Thirty children (mean age, 11.8 ± 4 years; ID-MTX, 20; HD-MTX, 10) completed the study. CINV prophylaxis included the following: ondansetron/granisetron plus dexamethasone or nabilone. Few patients experienced complete CINV control (ID-MTX: acute phase 20%, delayed phase 5%; HD-MTX: acute phase 0%, delayed phase 30%). Complete emesis control was higher (ID-MTX: acute phase 70%, delayed phase 50%; HD-MTX: acute phase 70%, delayed phase 60%). Anticipatory CINV was reported by 6/28 patients (21%). Patient age, sex, and history of motion sickness were not significant predictors of CINV.Conclusions: The poor complete CINV control rate in children receiving methotrexate confirms the classification of HD-MTX as highly emetogenic chemotherapy (HEC) and suggests that ID-MTX be reclassified as HEC. [ABSTRACT FROM AUTHOR]

Background: Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects.Methods: We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals.Results: Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor.Conclusions: The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer. (Funded by the National Cancer Institute and the American Lebanese-Syrian Associated Charities.). [ABSTRACT FROM AUTHOR]

Effective cancer therapies have resulted in significant improvement in survival. However, treatment-related acute and subacute complications are a cause of significant morbidity and mortality. Effects of cancer therapy in children can be seen early in the survival period or later in life in almost all organ systems of the body. Many of these conditions are evaluated by imaging and some are diagnosed based on characteristic imaging features. This article aims to discuss acute and subacute toxicities of cancer therapy in children involving multiple organ systems, pulmonary, gastrointestinal, hepatobiliary, genitourinary and musculoskeletal systems with emphasis on those in which imaging plays a role in diagnosis or management. We also discuss the role of imaging and choice of imaging modalities in these conditions. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer are at considerable risk of experiencing treatment-related adverse health outcomes. To provide survivors with specialized care focused on these risks during adulthood, the government of Ontario funded a provincial network of specialized survivor clinics in 1999. The aim of this study was to determine whether prior attendance at survivor clinics by adult survivors of childhood cancer was associated with rates of emergency department (ED) visits.Methods: This was a population-based, retrospective cohort study using multiple linked administrative health databases. The cohort consisted of all adult survivors of childhood cancer diagnosed between January 1, 1986 and December 31, 2005 in Ontario, Canada. A recurrent event regression model was used to evaluate the association between prior attendance at survivor clinics and the rate of ED visits; adjustments were made for individual, demographic, treatment, and provider characteristics.Results: The study consisted of 3912 adult survivors of childhood cancer. Individuals who had at least 1 prior visit to a survivor clinic had a 19% decreased rate of ED visits in comparison with individuals who had not visited a survivor clinic (adjusted relative rate, 0.81; 95% confidence interval, 0.78-0.85). Each additional prior visit to a survivor clinic was associated with a 5% decrease in the rate of ED visits (adjusted relative rate, 0.95; 95% confidence interval, 0.93-0.96). These results were independent of whether or not survivors received care from a primary care physician.Conclusions: Attendance at a specialized survivor clinic was significantly associated with decreased ED visits among adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

We evaluated the construct validity (including responsiveness), reliability, and feasibility of the Pain Squad multidimensional smartphone-based pain assessment application (app) in children and adolescents with cancer, using 2 descriptive studies with repeated measures. Participants (8-18 years) undergoing cancer treatment were drawn from 4 pediatric cancer centers. In study 1, 92 participants self-reported their level of pain twice daily for 2 weeks using the Pain Squad app to assess app construct validity and reliability. In study 2, 14 participants recorded their level of pain twice a day for 1 week before and 2 weeks after cancer-related surgery to determine app responsiveness. Participants in both studies completed multiple measures to determine the construct validity and feasibility of the Pain Squad app. Correlations between average weekly pain ratings on the Pain Squad app and recalled least, average, and worst weekly pain were moderate to high (0.43-0.68). Correlations with health-related quality of life and pain coping (measured with PedsQL Inventory 4.0, PedsQL Cancer Module, and Pain Coping Questionnaire) were -0.46 to 0.29. The app showed excellent internal consistency (α = 0.96). Pain ratings changed because of surgery with large effect sizes between baseline and the first week postsurgery (>0.85) and small effect sizes between baseline and the second week postsurgery (0.13-0.32). These findings provide evidence of the construct validity, reliability, and feasibility of the Pain Squad app in children and adolescents with cancer. Use of real-time data capture approaches should be considered in future studies of childhood cancer pain. A video accompanying this abstract is available online as Supplemental Digital Content at http://links.lww.com/PAIN/A169. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate scales to measure constructs that survivors of childhood cancer report as barriers and/or facilitators to the process of transitioning from paediatric to adult‐oriented long‐term follow‐up (LTFU) care. Methods: Qualitative interviews provided a dataset that were used to develop items for three new scales that measure cancer worry, self‐management skills and expectations about adult care. These scales were field‐tested in a sample of 250 survivors aged 15–26 years recruited from three Canadian hospitals between July 2011 and January 2012. Rasch Measurement Theory (RMT) analysis was used to identify the items that represent the best indicators of each scale using tests of validity (i.e. thresholds for item response options, item fit statistics, item locations, differential item function) and reliability (Person Separation Index). Traditional psychometric tests of measurement performance were also conducted. Results: RMT led to the refinement of a 6‐item Cancer Worry scale (focused on worry about cancer‐related issues such as late effects), a 15‐item Self‐Management Skills scale (focused on skills an adolescent needs to acquire to manage their own health care), and a 12‐item Expectations scale (about the nature of adult LTFU care). Our study provides preliminary evidence about the reliability and validity of these new scales (e.g. Person Separation Index ≥ 0.81; Cronbach's α ≥ 0.81; test–retest reliability ≥ 0.85). Conclusion: There is limited knowledge about the transition experience of childhood cancer survivors. These scales can be used to investigate barriers survivors face in the process of transition from paediatric to adult care. [ABSTRACT FROM AUTHOR]

Background: Survivors of pediatric cancer have elevated risks of mortality and morbidity. Many late adverse effects associated with cancer treatment (eg, second cancers and cardiac and pulmonary disease) are also associated with cigarette smoking, and this suggests that survivors who smoke may be at high risk for these conditions.Methods: This study examined the self-reported smoking status for 9397 adult survivors of childhood cancer across 3 questionnaires (median time interval, 13 years). The smoking prevalence among survivors was compared with the smoking prevalence among siblings and the prevalence expected on the basis of age-, sex-, race-, and calendar time-specific rates in the US population. Multivariable regression models examined characteristics associated with longitudinal smoking patterns across all 3 questionnaires.Results: At the baseline, 19% of survivors were current smokers, whereas 24% of siblings were current smokers, and 29% were expected to be current smokers on the basis of US rates. Current smoking among survivors dropped to 16% and 14% on follow-up questionnaires, with similar decreases in the sibling prevalence and the expected prevalence. Characteristics associated with consistent never-smoking included a higher household income (relative risk [RR], 1.16; 95% confidence interval [CI], 1.08-1.25), higher education (RR, 1.32; 95% CI, 1.22-1.43), and receipt of cranial radiation therapy (RR, 1.08; 95% CI, 1.03-1.14). Psychological distress (RR, 0.86; 95% CI, 0.80-0.92) and heavy alcohol drinking (RR, 0.64; 95% CI, 0.58-0.71) were inversely associated. Among ever-smokers, a higher income (RR, 1.17; 95% CI, 1.04-1.32) and education (RR, 1.23; 95% CI, 1.10-1.38) were associated with quitting, whereas cranial radiation (RR, 0.86; 95% CI, 0.76-0.97) and psychological distress (RR, 0.80; 95% CI, 0.72-0.90) were associated with not having quit. The development of adverse health conditions was not associated with smoking patterns.Conclusions: Despite modest declines in smoking prevalence, the substantial number of consistent current smokers reinforces the need for continued development of effective smoking interventions for survivors. [ABSTRACT FROM AUTHOR]

Background: Survivors of young adult malignancies are at risk of accumulated exposures to radiation from repetitive diagnostic imaging. We designed a population-based cohort study to describe patterns of diagnostic imaging and cumulative diagnostic radiation exposure among survivors of young adult cancer during a survivorship time period where surveillance imaging is not typically warranted. Methods: Young adults aged 20-44 diagnosed with invasive malignancy in Ontario from 1992-1999 who lived at least 5 years from diagnosis were identified using the Ontario Cancer Registry and matched 5 to 1 to randomly selected cancer-free persons. We determined receipt of 5 modalities of diagnostic imaging and associated radiation dose received by survivors and controls from years 5-15 after diagnosis or matched referent date through administrative data. Matched pairs were censored six months prior to evidence of recurrence. Results: 20,911 survivors and 104,524 controls had a median of 13.5 years observation. Survivors received all modalities of diagnostic imaging at significantly higher rates than controls. Survivors received CT at a 3.49-fold higher rate (95 % Confidence Interval [CI]:3.37, 3.62) than controls in years 5 to 15 after diagnosis. Survivors received a mean radiation dose of 26 miliSieverts solely from diagnostic imaging in the same time period, a 4.57-fold higher dose than matched controls (95 % CI: 4.39, 4.81). Conclusions: Long-term survivors of young adult cancer have a markedly higher rate of diagnostic imaging over time than matched controls, imaging associated with substantial radiation exposure, during a time period when surveillance is not routinely recommended. [ABSTRACT FROM AUTHOR]

Objectives Characterize longitudinal changes in the use of medical care in adult survivors of childhood cancer. Data Sources The Childhood Cancer Survivor Study, a retrospective cohort study of 5+ year survivors of childhood cancer. Study Design Medical care was assessed at entry into the cohort (baseline) and at most recent questionnaire completion. Care at each time point was classified as no care, general care, or survivor-focused care. Data Collection There were 6,176 eligible survivors. Multivariable models evaluated risk factors for reporting survivor-focused care or general medical care at baseline and no care at follow-up; and survivor-focused care at baseline and general care at follow-up. Principal Findings Males ( RR, 2.3; 95 percent CI 1.8-2.9), earning <$20,000/year ( RR, 1.6; 95 percent CI 1.2-2.3) or ≤high school education ( RR, 2.5; 95 percent CI 1.6-3.8 and RR 2.0; 95 percent CI 1.5-2.7 for

BACKGROUND Childhood cancer survivors treated with radiotherapy to a field including the colon or rectum have an elevated risk of developing radiation-induced colorectal cancer (CRC). The Children's Oncology Group recommends colonoscopy every 5 years beginning at age 35 years for at-risk survivors. METHODS Analyses included 702 five-year survivors (Childhood Cancer Survivor Study) aged ≥36 years who received ≥30 gray of abdominal, pelvic, or spinal radiotherapy. Multivariate generalized linear models were used to calculate relative risks (RR) with 95% confidence intervals (95% CI) for adherence to the Children's Oncology Group's CRC surveillance recommendations. RESULTS With a median age of 43 years (range, 36-58 years), 29.5% of the survivors (207 of 702 survivors) met surveillance recommendations. In multivariate analyses, age ≥50 years versus age 36 to 49 years (RR, 2.6; 95% CI, 2.0-3.4), reporting a routine cancer follow-up visit within 1 year before the study (RR, 1.5; 95% CI, 1.0-2.2), reporting ≥10 physician visits within the past year versus 0 to 9 visits (RR, 1.4; 95% CI, 1.1-1.7), and discussing future cancer risk with a physician at the time of the most recent follow-up visit (RR, 1.4; 95% CI, 1.1-1.7) were found to be associated with adherence to CRC surveillance recommendations. CONCLUSIONS Greater than 70% of survivors at an increased risk of CRC were not screened as recommended. Regular physician contact and discussion of screening were associated with a 60% increase in CRC surveillance. Educational interventions targeted at survivors and their primary care physicians are needed to heighten knowledge of CRC risk after radiotherapy and the importance of appropriate surveillance. Cancer 2015;121:1856-1863. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

This study describes skeletal, neuromuscular and fitness impairments among 109 children (median age 10 [range 4-18] years, 65.1% male, 63.3% white) with acute lymphoblastic leukemia (ALL). Outcomes were measured 7-10 days after diagnosisand compared to age-and sex-specific expected values. Associations between function and health-related quality of life (HRQL) were evaluated with logistic regression. Children with ALL had sub-optimal bone mineral density (BMD) Z-score/height (mean ± standard error: - 0.53 ± 0.16 vs. 0.00 ± 0.14, p < 0.01), body mass index percentile (57.6 + 3.15 vs. 50.0 ±3.27%, p = 0.02), quadriceps strength (201.9 ± 8.3 vs. 236.1 ±5.4 N, p<0.01), 6 min walk distance (385.0 ±13.1 vs. 628.2 ±7.1 m, p< 0.001) and Bruininks-Oseretsky Test of Motor Proficiency scores (23 ± 2.5 vs. 50 ± 3.4%, p < 0.01). Quadriceps weakness was associated with a 20.9-fold (95% confidence interval 2.5-173.3) increase in poor physical HRQL. Children with newly diagnosed ALL have weakness and poor endurance and may benefit from early rehabilitation that includes strengthening and aerobic conditioning. [ABSTRACT FROM AUTHOR]

Medication-induced diabetes ( MID) is seen in children treated for acute lymphoblastic leukemia ( ALL) mostly during induction, due to the use of l-asparaginase and glucocorticoids. Our objective was to assess whether MID during induction, is a risk factor for future impaired glucose tolerance ( IGT), diabetes, or metabolic syndrome. Ninety survivors of pediatric ALL, ages 10 yr and older were recruited, 30 with history of MID and 60 controls. Waist/height ratio >0.5 was considered as an increased risk for central adiposity and insulin resistance. Lipid profile and an oral glucose tolerance test ( OGTT) were performed. Study patients were older than controls (17.2 vs. 14.9, p < 0.05). The groups had similar sex distribution, body mass index ( BMI) z-score, and Tanner staging. A waist/height ratio of >0.5 was seen in 60 and 31.7% of the study and control groups, respectively (p = 0.01). Increased frequency of IGT in the study group compared with the control group was seen (13.3 and 1%, respectively) (p = 0.07). We observed a trend toward higher proportion of patients with multiple features of metabolic syndrome in the study compared with control group (16.7 vs. 5%, p = 0.09). In conclusion, MID during induction may be an early marker for metabolic disturbances later in life. The higher rates of increased waist/height ratio, and subjects with multiple metabolic syndrome features, may predict a metabolic risk in children with history of MID. Rates of IGT were four fold higher in the study group although not statistically significant. MID may be a 'red flag' indicating the need for ongoing metabolic screening and lifestyle modifications to prevent future metabolic disease. [ABSTRACT FROM AUTHOR]

DNA replication−associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutation consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (>250/Mb), which was greater than all childhood and most cancers (>7,000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerase ɛ or δ. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germ-line bMMRD (P < 10−13). Sequential tumor biopsy analysis revealed that bMMRD/polymerase-mutant cancers rapidly amass an excess of simultaneous mutations (∼600 mutations/cell division), reaching but not exceeding ∼20,000 exonic mutations in <6 months. This implies a threshold compatible with cancer-cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair. [ABSTRACT FROM AUTHOR]

Background: Cancer is the leading cause of disease-related death in adolescents and young adults (AYA). Annual improvements in AYA cancer survival have been inferior to those observed in children and older adults. Prior studies of AYA with cancer have been limited by their focus on patients from select treatment centres, reducing generalizability, or by being population-based but lacking diagnostic and treatment details. There is a critical need to conduct population-based studies that capture detailed patient, disease, treatment and system-level data on all AYA regardless of treatment location. Methods/Design: We will create a cohort of all AYA (aged 15-21 years) at the time of diagnosis with any malignancy between 1992 and 2011 in Ontario, Canada (n = 5,394). Subjects will be identified through the Ontario Cancer Registry and the final cohort will be expanded to include 2012 diagnoses, as these data become available. Detailed diagnostic, treatment and outcome data for those patients treated at a pediatric cancer centre will be provided by a population-based pediatric cancer registry (n = 1,030). For 15-18 year olds treated at adult centres (n = 923) and all 19-21 year olds (n = 3396), trained abstractors will collect the comparable data elements from medical records. We will link these data to population-based administrative health data that include physician billings, hospitalizations and emergency room visits. This will allow descriptions of health care access and use prior to cancer diagnosis, and during and after treatment. Discussion: The IMPACT cohort will serve as a platform for addressing questions that span the AYA cancer journey. These will include determining which factors influence where AYA receive care, the impact of locus of care on the types and intensity of cancer therapy, appropriateness of surveillance for disease recurrence, access to clinical trials, and receipt of palliative and survivor care. Findings using the IMPACT cohort have the potential to lead to changes in practice and cancer policy, reduce mortality, and improve quality of life for AYA with cancer. The IMPACT data platform will be a permanent resource, accessible to researchers across Canada. [ABSTRACT FROM AUTHOR]

Background: Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. Methods: We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. Findings: We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. Interpretation: The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted. Funding: National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research. [ABSTRACT FROM AUTHOR]

This study asks which siblings of children with cancer (SCC) benefit most from a group intervention specifically designed for them. One hundred and eleven SCC (aged 8–17) participated in eight weekly, two-hour, manualized group sessions. Changes in anxiety and depression symptoms were used as outcome measures. Anxiety and depression scores improved more for siblings who were initially most depressed and, thus, considered “less resilient” (p< 0.0001). Within this group, males improved more than females, and siblings of children with brain tumors improved less than SCC with other cancers,(p =0.05), with female siblings of children with brain tumors improving the least (p= 0.0397). [ABSTRACT FROM PUBLISHER]

Background: Adult childhood cancer survivors (CCSs) are at high risk for illness and premature death. Little is known about the physicians who provide their routine medical care.Objective: To determine general internists' self-reported attitudes and knowledge about the care of CCSs.Design: Cross-sectional survey.Setting: Mailed survey delivered between September 2011 and August 2012.Participants: Random sample of 2000 U.S. general internists.Measurements: Care preferences, comfort levels with caring for CCSs (7-point Likert scale: 1 = very uncomfortable, 7 = very comfortable), familiarity with available surveillance guidelines (7-point Likert scale: 1 = very unfamiliar, 7 = very familiar), and concordance with Children's Oncology Group Long-Term Follow-Up Guidelines in response to a clinical vignette.Results: The response rate was 61.6% (1110 of 1801). More than half the internists (51.1%) reported caring for at least 1 CCS; 72.0% of these internists never received a treatment summary. On average, internists were "somewhat uncomfortable" caring for survivors of Hodgkin lymphoma, acute lymphoblastic leukemia, and osteosarcoma. Internists reported being "somewhat unfamiliar" with available surveillance guidelines. In response to a clinical vignette about a young adult survivor of Hodgkin lymphoma, 90.6% of respondents did not appropriately recommend yearly breast cancer surveillance, 85.1% did not appropriately recommended cardiac surveillance, and 23.6% did not appropriately recommend yearly thyroid surveillance. Access to surveillance guidelines and treatment summaries were identified as the most useful resources for caring for CCSs.Limitation: Findings, based on self-report, may not reflect actual clinical practice.Conclusion: Although most general internists report involvement in the care of CCSs, many seem unfamiliar with available surveillance guidelines and would prefer to follow patients in collaboration with a cancer center.Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Background: Adult childhood cancer survivors (CCSs) are at high risk for illness and premature death. Little is known about the physicians who provide their routine medical care. Objective: To determine general internists' self-reported attitudes and knowledge about the care of CCSs. Design: Cross-sectional survey. Setting: Mailed survey delivered between September 2011 and August 2012. Participants: Random sample of 2000 U.S. general internists. Measurements: Care preferences, comfort levels with caring for CCSs (7-point Likert scale: 1 = very uncomfortable, 7 = very comfortable), familiarity with available surveillance guidelines (7- point Likert scale: 1 = very unfamiliar, 7 = very familiar), and concordance with Children's Oncology Group Long-Term Follow-Up Guidelines in response to a clinical vignette. Results: The response rate was 61.6% (1110 of 1801). More than half the internists (51.1%) reported caring for at least 1 CCS; 72.0% of these internists never received a treatment summary. On average, internists were "somewhat uncomfortable" caring for survivors of Hodgkin lymphoma, acute lymphoblastic leukemia, and osteosarcoma. Internists reported being "somewhat unfamiliar" with available surveillance guidelines. In response to a clinical vignette about a young adult survivor of Hodgkin lymphoma, 90.6% of respondents did not appropriately recommend yearly breast cancer surveillance, 85.1% did not appropriately recommended cardiac surveillance, and 23.6% did not appropriately recommend yearly thyroid surveillance. Access to surveillance guidelines and treatment summaries were identified as the most useful resources for caring for CCSs. Limitation: Findings, based on self-report, may not reflect actual clinical practice. Conclusion: Although most general internists report involvement in the care of CCSs, many seem unfamiliar with available surveillance guidelines and would prefer to follow patients in collaboration with a cancer center. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. Design: Retrospective cohort study. Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Abstract: Background: Positive health-related behaviours are essential for the future wellbeing of childhood cancer survivors, though relatively few maintain healthy behaviours into adulthood. Methods: Neurocognitive function and emotional distress were examined in 6,440 adult survivors from the Childhood Cancer Survivor Study, and used to predict rates of expected health-related behaviours. Covariates included cancer diagnosis, age, sex, body mass index, insurance status, income and antidepressant medication use, and multivariable models were constructed adjusting for these factors. Findings: In multivariable regression models, survivors with neurocognitive problems in task efficiency (RR=0.77, 95% CI=0.72–0.84) were less likely to meet the Centers for Disease Control guidelines for weekly physical activity. Survivors with neurocognitive impairment were more likely to engage in general survivor care (RR=1.20, 95% CI=1.10–1.30), and less likely to engage in dental care (RR=0.92, 95% CI=0.88–0.97). Obese survivors were less likely to report receiving a bone density exam (RR=0.67, 95% CI=0.54–0.82), a mammogram (RR=0.71, 95% CI=0.57–0.89), and a skin exam (RR=0.78, 95% CI=0.68–0.89). Survivors reporting somatisation, i.e. vague physical symptoms associated with anxiety, were more likely to report receiving echocardiograms (RR=1.53, 95% CI=1.32–1.77). Interpretation: These results support the link between neurocognitive and emotional problems and health-related behaviours in adult survivors of childhood cancer. Monitoring neurocognitive and emotional outcomes may help to identify survivors at risk for poor adherence to prescribed health behaviours and health screening exams. [Copyright &y& Elsevier]

Background: The 5-year survival rate for individuals with neuroblastoma is approaching 70%. Few data exist, however, on the long-term outcomes of these patients, who are often treated at a very young age. Methods: Outcome data were obtained for 954 5-year neuroblastoma survivors who were diagnosed in 1970-1986 and enrolled in the Childhood Cancer Survivor Study (CCSS). Late mortality, second malignant neo-plasms, and chronic health conditions were analyzed in relation to treatment factors using Poisson regression models and their modification with generalized estimating equations. Neuroblastoma survivors were compared with a cohort of 3899 siblings of CCSS participants for risk of chronic health conditions and selected sociodemographic outcomes. All statistical tests were two-sided. Results: Six percent of patients died more than 5 years after their diagnosis (standardized mortality ratio = 5.6; 95% confidence interval [l] = 4.4 to 6.9). The most common causes of death were disease recurrence (n = 43) and second malignant neoplasms (n = 13). The cumulative incidence of second malignant neoplasms was 3.5% at 25 years and 7.0% at 30 years after diagnosis. Compared with the sibling cohort, survivors had an increased risk of selected chronic health conditions (risk ratio ERR) = 8.3; 95% Cl = 7.1 to 9.7) with a 20-year cumulative incidence of 41.1%. The most prevalent outcomes involved the neurological, sensory, endocrine, and musculoskeletal systems, with 20-year cumulative incidences of 29.8%, 8.6%, 8.3%, and 7.8%, respectively. Neuroblastoma survivors who were treated with multimodality therapy were more likely to develop a chronic health condition than survivors treated with surgery alone (RR = 2.2; 95% Cl = 1.6 to 3.0). Neuroblastoma survivors were less likely than siblings to have ever been employed (P= .04) or to be married (P< .001) and had a lower-personal income (P= .009). Conclusions: Neuroblastoma survivors have an increased rate of mortality and second malignant neoplasms, relative to the age- and sex-comparable US population, and of chronic health conditions, relative to their siblings, which underscores the need for long-term medical surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: It is unclear what the risk of negative health outcomes is after cancer during adolescence and young adulthood. We conducted a review to understand the risk of second cancers, chronic conditions, and death in adolescent and young adult (AYA) cancer survivors and found factors that increase the risk. In total, 652 studies were identified, of which 106 were included in the review: 23 for second cancers, 34 for chronic conditions, and 54 for deaths. The number of included studies increased over time, from four studies in 2010 to 17 in 2020. The studies found that AYA cancer survivors are at an increased risk of second cancers, chronic conditions, and deaths. In particular, the following factors increased risk: radiation exposure for second cancers; younger attained age and earlier calendar period of diagnosis for chronic conditions; and non-Hispanic Black or Hispanic, low socioeconomic status, and earlier calendar period of diagnosis for deaths. Risk factors associated with late effects in survivors of adolescent and young adult (AYA) cancer are poorly understood. We conducted a systematic scoping review to identify cohort studies published in English from 2010–2020 that included: (1) cancer survivors who were AYAs (age 15–39 years) at diagnosis and (2) outcomes of subsequent malignant neoplasms (SMNs), chronic conditions, and/or late mortality (>5 years postdiagnosis). There were 652 abstracts identified and, ultimately, 106 unique studies were included, of which 23, 34, and 54 studies related to the risk of SMNs, chronic conditions, and mortality, respectively. Studies investigating late effects among survivors of any primary cancer reported that AYA cancer survivors were at higher risk of SMN, chronic conditions, and all-cause mortality compared to controls. There was an indication that the following factors increased risk: radiation exposure (n = 3) for SMNs; younger attained age (n = 4) and earlier calendar period of diagnosis (n = 3) for chronic conditions; and non-Hispanic Black or Hispanic (n = 5), low socioeconomic status (n = 3), and earlier calendar period of diagnosis (n = 4) for late mortality. More studies including the full AYA age spectrum, treatment data, and results stratified by age, sex, and cancer type are needed to advance knowledge about late effects in AYA cancer survivors. [ABSTRACT FROM AUTHOR]

Simple Summary: There are many commonalities between children with cancer and other populations that experience early-life stress. Thus, it is important to review the existing research surrounding the stress response in the pediatric cancer population. In this review, we describe the psychoneuroimmunology behind stress regulation and the differences observed in stress regulatory pathways in childhood cancer patients. Our objective is to provide a clinically relevant summary of the stress pathways contributing to, and exacerbating, childhood illness and outline some potential interventions. Stress is a ubiquitous experience that can be adaptive or maladaptive. Physiological stress regulation, or allostasis, can be disrupted at any point along the regulatory pathway resulting in adverse effects for the individual. Children with cancer exhibit significant changes to these pathways in line with stress dysregulation and long-term effects similar to those observed in other early-life stress populations, which are thought to be, in part, a result of cytotoxic cancer treatments. Children with cancer may have disruption to several steps in the stress-regulatory pathway including cognitive-affective function, neurological disruption to stress regulatory brain regions, altered adrenal and endocrine function, and disrupted tissue integrity, as well as lower engagement in positive coping behaviours such as physical activity and pro-social habits. To date, there has been minimal study of stress reactivity patterns in childhood illness populations. Nor has the role of stress regulation in long-term health and function been elucidated. We conclude that consideration of stress regulation in childhood cancer may be crucial in understanding and treating the disease. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Long-term survival after childhood cancer has improved dramatically over recent decades but survivors face lifelong risks of adverse health effects. Many of these chronic conditions are a direct result of previous therapeutic exposures. Compared to their siblings, survivors face a greater than 8-fold increase in relative risk of severe or life-threatening medical conditions; the most significant of these include second malignancies and cardiovascular and pulmonary diseases. Imaging can play a key role in identifying and characterizing such complications, which can be reasonably predicted with knowledge of the child's treatment. This article highlights the varied radiologic presentations and features seen in late cancer-therapy-related conditions. [ABSTRACT FROM AUTHOR]