Risk of increased mortality in underweight survivors: A brief report from the Childhood Cancer Survivor Study.

BACKGROUND: Approximately 1 in 10 adult survivors of childhood cancer is underweight. Although the consequences of being overweight or obese have been well described, outcomes among childhood cancer survivors who are underweight are unknown. OBJECTIVE: To determine whether underweight status increases the risk of mortality. PROCEDURE: Cohort study: Marginal models with generalized estimating equations to evaluate the associations between body mass index (BMI), serious or life-threatening chronic conditions, and death in the setting of long-term follow-up questionnaires and National Death Index search. PARTICIPANTS: C. EXPOSURE: Underweight status, defined as body mass index (BMI) < 18.5 kg/m2 compared with ideal body weight. Based on available literature on body weight and mortality from the general population, ideal body weight was defined as BMI 22.0-24.9 kg/m2. MAIN OUTCOMES: Overall mortality and cancer-specific mortality. RESULTS: Of 9454 survivors (median age 35 years old (range, 17-58), an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline or follow-up questionnaire. Of 184 deaths, 29 were among underweight survivors. Underweight status was more common among females (9.1% vs. 4.5%, p < .01) and participants with younger age at diagnosis (8.2% for < 5 years vs. 6.1% for ≥5 years, p < .01), lower household income (8.9% for < $20,000 vs. 6.0% for ≥ $20,000, p < .01), or a history of serious chronic condition (p = .05). After adjustment for these factors, in addition to prior smoking and a history of radiation therapy, the risk of all-cause mortality within two years of BMI report was increased (OR 2.85; 95% CI: 1.63-4.97; p < .01) for underweight survivors, compared with ideal-weight survivors. CONCLUSIONS: Childhood cancer survivors who are underweight are at increased risk for late mortality that appears unrelated to smoking status, recognized chronic disease, or subsequent malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.

Fertility preservation in pediatric solid tumors: A report from the Children's Oncology Group.

Treatment for childhood solid tumors may lead to an increased risk for gonadal dysfunction/infertility. Discussion of risk should occur at diagnosis, any changes in therapy, and during survivorship. Gonadotoxic therapies were abstracted from 32 Children's Oncology Group (COG) phase III, frontline solid tumor protocols, in use from 2000 to 2022. Risk for gonadal dysfunction/infertility was assessed based on gonadotoxic therapies, sex, and pubertal status and assigned as minimal, significant, and high following the Oncofertility Consortium Pediatric Initiative Network (PIN) risk stratification. Most protocols (65.6%, 21/32) contained at least one therapeutic arm with a high level of increased risk. Solid tumor therapies present challenges in risk stratification due to response-adjusted therapy and the need to account for radiation field in the risk assessment. This guide hopes to serve as a tool to assist in standardizing gonadotoxic risk assessments across disciplines and improve referral for fertility services and reproductive health counseling for patients receiving COG-based solid tumor therapy. Internationally, many solid tumor therapies follow similar paradigms to COG studies, and risk stratifications may be generalizable to similar styles of therapy. In addition, this model may be applied to other international groups with the goal of standardizing fertility assessments.

Utility of apical four-chamber longitudinal strain in the assessment of childhood cancer survivors: A multicenter study.

BACKGROUND: A previous multicenter study showed that longitudinal changes in standard cardiac functional parameters were associated with the development of cardiomyopathy in childhood cancer survivors (CCS). Evaluation of the relationship between global longitudinal strain (GLS) changes and cardiomyopathy risk was limited, largely due to lack of quality apical 2- and 3-chamber views in addition to 4-chamber view. We sought to determine whether apical 4-chamber longitudinal strain (A4LS) alone can serve as a suitable surrogate for GLS in this population. METHODS: A4LS and GLS were measured in echocardiograms with acceptable apical 2-, 3-, and 4-chamber views. Correlation was evaluated using Pearson and Spearman coefficients, and agreement was evaluated with Bland-Altman plots. The ability of A4LS to identify normal and abnormal values compared to GLS as the reference was evaluated. RESULTS: Among a total of 632 reviewed echocardiograms, we identified 130 echocardiograms from 56 patients with adequate views (38% female; mean age at cancer diagnosis 8.3 years; mean follow-up 9.4 years). Correlation coefficients between A4LS and GLS were .89 (Pearson) and .85 (Spearman), with Bland-Altman plot of GLS-A4LS showing a mean difference of -.71 ± 1.8. Compared with GLS as the gold standard, A4LS had a sensitivity of 86% (95% CI 79%-93%) and specificity of 82% (69%-95%) when using normal range cutoffs and 90% (82%-97%) and 70% (58%-81%) when using ±2 standard deviations. CONCLUSION: A4LS performs well when compared with GLS in this population. Given the more recent adoption of apical 2- and 3-chamber views in most pediatric echocardiography laboratories, A4LS is a reasonable stand-alone measurement in retrospective analyses of older study cohorts and echocardiogram biorepositories.

Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies.

BACKGROUND: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. METHODS: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m2 ) and obesity (≥30 kg/m2 ) using multinomial regression. RESULTS: We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. CONCLUSIONS: Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials.

Clinic reported facilitators and barriers to pediatric cancer survivor care delivery among survivorship clinics: A fishbone analysis.

BACKGROUND: Childhood cancer survivors need regular, long-term survivor care. The Children's Oncology Group (COG) recommends that pediatric patients receive ongoing, evidence-based surveillance for late effects, beginning 2 years after the completion of cancer therapy. However, at least a third of survivors are not engaging in long-term survivorship care. This study assessed facilitators and barriers to follow-up survivorship care through the perspectives of pediatric cancer survivor clinic representatives. METHODS: As part of a hybrid implementation-effectiveness trial, a representative from 12 participating pediatric cancer survivor clinics completed a survey about site characteristics and a semi-structured interview on facilitators and barriers to survivor care delivery at their institution. Interviews were grounded in the socio-ecological model (SEM) framework and utilized a fishbone diagram to understand what facilitates and impedes survivor care. We ran descriptive statistics and conducted thematic analyses of the interview transcripts to create two meta-fishbone diagrams. RESULTS: All participating clinics (N = 12) have existed for at least 5 years (mean = 15, median = 13, range = 3-31), and half (n = 6, 50%) reported seeing more than 300 survivors annually. In the fishbone diagram, the top facilitators were in the SEM domain of organization, specifically with familiar staff (n = 12, 100%), resource utilization (n = 11, 92%), dedicated survivorship staff (n = 10, 83%), and clinic processes (n = 10, 83%). Common barriers were across the domains of organization, community, and policy, which included distance/transportation to the clinic (n = 12, 100%), technology limits (n = 11, 92%), scheduling issues (n = 11, 92%), and insufficient funding/insurance (n = 11, 92%). CONCLUSION: Clinic staff and provider perceptions are instrumental in understanding multilevel contextual issues related to survivor care delivery for pediatric cancer survivor clinics. Future research can aid in developing education, processes, and services to promote cancer survivor follow-up care.

Fertility assessment and treatment in adolescent and young adult cancer survivors.

In the survivorship setting, adolescent and young adult (AYA) cancer survivors frequently demonstrate little knowledge of infertility risk, are unclear regarding their fertility status, and may under- or overestimate their treatment-related risk for infertility. In female AYA survivors, ovarian function usually parallels fertility, and can be assessed with serum hormone levels and ultrasonography. Posttreatment fertility preservation may be appropriate for survivors at risk for primary ovarian insufficiency. In male AYA survivors, fertility and gonadal function are not always equally affected, and can be assessed with a semen analysis and serum hormones, respectively. As reproductive health issues are commonly cited as an important concern by survivors of AYA cancer, multidisciplinary care teams including oncology, endocrinology, psychology, and reproductive medicine are advocated, with the aim of optimal provision of fertility advice and care for AYA cancer survivors.

Female Reproductive Health Outcomes after Hematopoietic Cell Transplantation for Sickle Cell Disease: Is Reduced Intensity Better Than Myeloablative Conditioning?

Curative therapy for sickle cell disease (SCD) through hematopoietic cell transplantation (HCT) is associated with a high level of risk for treatment-related gonadal dysfunction and future infertility. Both the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens used for SCD HCT are considered to carry a high risk for ovarian damage. Cyclophosphamide equivalent doses (CEDs) are thought to correlate with the degree of gonadal damage in pediatric oncology patients. We aimed to evaluate ovarian outcomes previously reported from our center, characterize the conditioning regimens as MAC or RIC, and calculate the CED for each regimen. The ovarian outcomes diminished ovarian reserve (DOR), as determined by an anti-Müllerian hormone (AMH) below the normal limits for age and assay or <5%, and premature ovarian insufficiency (POI), defined as a follicle-stimulating hormone (FSH) level >40 mIU/ML, are presented by conditioning regimen from 3 clinical studies from our center (2 published and 1 presented as an abstract in 2022). The studies were not mutually exclusive of patients. CEDs were calculated for each regimen. The CED ranged from 3388 to 9705 mg/m2 for MAC regimens and from 5600 to 18,750 mg/m2 for RIC regimens. DOR was observed in all regimens; however, in one study 2 patients had normal AMH levels after a fludarabine/melphalan regimen, and 1 patient had a normal AMH level after a fludarabine/melphalan/thiotepa regimen. Rates of POI were more variable and ranged from 40% to 100% after MAC regimens and from 0 to 100% after RIC regimens. Female patients with SCD who undergo HCT have very high rates of DOR after both MAC HCT and RIC HCT. Two of the 3 RIC regimens evaluated had higher CEDs than were seen in any of the MAC regimens evaluated. Rates of POI were more variable but may increase with time from transplantation. All SCD patients need to be counseled about the risk of infertility and provided information about fertility preservation.

Fertility preservation in pediatric leukemia and lymphoma: A report from the Children's Oncology Group.

Certain chemotherapy agents, radiation, and surgery can all negatively impact future fertility. Consults regarding treatment-related risk for infertility and gonadal late effects of these agents should occur at the time of diagnosis as well as during survivorship. Counseling on fertility risk has traditionally varied significantly across providers and institutions. We aim to provide a guide to standardize the assignment of gonadotoxic risk, which can be used in counseling patients both at the time of diagnosis and in survivorship. Gonadotoxic therapies were abstracted from 26 frontline Children's Oncology Group (COG) phase III protocols for leukemia/lymphoma, in use from 2000-2022. A stratification system based on gonadotoxic therapies, sex, and pubertal status was used to assign treatments into minimal, significant, and high level of increased risk for gonadal dysfunction/infertility. Risk levels were assigned to protocols and different treatment arms to aid oncologists and survivor care providers in counseling patients regarding treatment-related gonadotoxicity. Males were most commonly at high risk, with at least one high-risk arm in 14/26 protocols (54%), followed by pubertal females (23% of protocols) and prepubertal females (15% of protocols). All patients who received direct gonadal radiation or hematopoietic stem cell transplant (HSCT) were considered at high risk. Partnering with patients and their oncology/survivorship team is imperative for effective fertility counseling both prior to and post treatment, and this comprehensive guide can be used as a tool to standardize and improve reproductive health counseling in patients undergoing COG-based leukemia/lymphoma care.

Diminished ovarian reserve in adolescent cancer survivors treated with heavy metal chemotherapy.

The extent to which heavy metal chemotherapy results in treatment-related ovarian damage is controversial. Anti-Mullerian hormone (AMH) levels measured more than 1 year after cancer therapy completion were abstracted from the medical records of 39 female survivors of childhood cancer aged 11 years and older, whose only gonadotoxic exposure was heavy metal chemotherapy. One-fifth of survivors who received cisplatin had AMH levels indicative of diminished ovarian reserve at last measurement. There was an observed clustering of low AMH in patients diagnosed in the peripubertal age range (i.e., 10-12 years). These findings may support a small, but present, risk of gonadal damage after heavy metal chemotherapy.

Parental perspective on the risk of infertility and fertility preservation options for children and adolescents with sickle cell disease considering hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HCT) performed in children from human leukocyte antigen (HLA)-identical related donors is associated with very high survival rates and disease-free survival. Patients are exposed to gonadotoxic alkylating agents or irradiation in the HCT conditioning regimen. Consequently, infertility is a major long-term complication of HCT for sickle cell disease (SCD). We sought to understand how caregivers perceive the risk of infertility from HCT, how they perceive the options for fertility preservation, and how this risk perception impacted their decision-making to pursue HCT. PROCEDURES: We conducted qualitative interviews with primary caregivers after a consultation for HCT for SCD. Data were analyzed using descriptive qualitative analysis. RESULTS: We interviewed 19 primary caregivers who had attended a consultation with an HCT physician (female, age 25-59 [median 39] years). Eleven participants reported that their child had an available HLA-matched donor. Analysis revealed that (i) mothers were worried about death and graft-versus-host disease from HCT, more than about the risk of infertility; (ii) parents have a realistic understanding of the risk of infertility after HCT and take it into consideration in decision-making; (iii) parents report multiple barriers to fertility preservation. CONCLUSION: For parents actively considering HCT for their child with SCD, the risk of infertility while important was not a barrier to pursuing HCT. Inconvenience and invasiveness of fertility preservation procedures are some of the barriers to pursuing fertility preservation for their child. Future research must aim at addressing these barriers to fertility preservation.

Fertility Preservation Practices at Pediatric Oncology Institutions in the United States: A Report From the Children's Oncology Group.

PURPOSE: Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS: A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS: One hundred forty-four programs (65.5%) returned surveys. Of these, 65 (45.1%) reported routine discussions of fertility with all female patients and 55 (38.5%) all male patients (P = .25). Ninety-two (63.8%) reported no specific criteria for offering females fertility preservation (FP), compared with 40 (27.7%) for males (P < .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION: Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

Expecting more: the case for incorporating fertility services into comprehensive sickle cell disease care.

Assisted reproductive technologies (ART) are not yet systematically available to people with sickle cell disease or their parents. Fertility care for these groups requires addressing sickle cell disease-associated infertility risks, fertility preservation options, pregnancy possibilities and outcomes, and, when needed, infertility treatment. People with a chance of having a child with sickle cell disease can use in-vitro fertilisation with preimplantation genetic testing to conceive a child unaffected by sickle cell disease. Also, parents of children with sickle cell disease can use this technology to identify embryos to become potential future matched sibling donors for stem cell transplant. In the USA, disparities in fertility care for the sickle cell disease community are especially stark. Universal screening of newborn babies' identifies sickle cell disease and sickle cell trait, guidelines direct preconception genetic carrier screening, and standard-of-care fertility preserving options exist. However, potentially transformative treatments and cures for patients with sickle cell disease are not used due to iatrogenic infertility concerns. In diversely resourced care settings, obstacles to providing fertility care to people affected by sickle cell disease persist. In this Viewpoint, we contend that fertility care should be incorporated into the comprehensive care model for sickle cell disease, supporting alignment of treatment goals with reproductive life plans and delivering on the promise of individualised high-quality care for people with sickle cell disease and their families. We consider the obligation to provide fertility care in light of medical evidence, with acknowledgment of formidable obstacles to optimising care, and powerful historical and ethical considerations.

The evolution of fertility preservation care models in a large pediatric cancer and blood disorders center.

BACKGROUND: Children and adolescents who receive gonadotoxic treatments are at risk for future infertility. While there is a growing focus on integrating fertility preservation (FP) within pediatric cancer and blood disorder centers, wide variations in care models and methods exist across institutions. The purpose of this work is to describe the evolution of FP care models within a large pediatric hematology/oncology center. METHODS: Models of care and associated timeframes are described, including a pre-FP program model, establishment of a formal FP program, integration of nurse navigators, and the addition of FP consult stratification based on urgency (urgent/nonurgent). The number of patient consults within each model, patient sex, diagnosis (oncologic/hematologic), and consult timing (pre-gonadotoxic treatment/posttreatment completion) were abstracted from the clinical database. RESULTS: The number of annual consults increased from 24 during the pre-FP program model (2015) to 181 during the current care model (2020). Over time, the proportion of consults for females and patients with nonmalignant hematologic disorders increased. Patient stratification reduced the proportion of consults needing to be completed urgently from 75% at the advent of the FP program to 49% in the current model. CONCLUSIONS: The evolution of care models within our FP program allowed for growth in the number of consults completed, expansion of services to more patients with nonmalignant hematologic disorders, and more consults for female patients. Nurse navigators play a critical role in care facilitating referrals, coordination, and patient education. Urgency stratification has allowed FP team members to manage increasing FP-related encounters.

Optimizing health literacy to facilitate reproductive health decision-making in adolescent and young adults with cancer.

Despite being considered "standard of care" by many organizations, fertility and reproductive health communications and counseling practices remain inconsistent for adolescents and young adults (AYAs) newly diagnosed with cancer and during survivorship. One factor known to affect how information is provided and received in the medical setting is health literacy. Providers should consider health literacy to optimize reproductive health communication with AYAs as they cope with their diagnosis, understand what it means for their future, process information about treatment options, learn about their potential harmful effects on fertility, make quick decisions about fertility preservation, and navigate a future family planning course. Thus, the objectives of this manuscript are to (a) summarize literature on reproductive health literacy; (b) describe health literacy frameworks; (c) examine ways to assess health literacy; and (d) identify ways to enhance clinician-patient communication in the AYA oncofertility setting.

Cancer-Related Barriers to Health Behaviors Among Adolescent and Young Adult Survivors of Pediatric Cancer and Their Families.

Adolescent and young adult (AYA) survivors of pediatric cancer and their caregivers frequently do not meet national guidelines for physical activity (PA), nutrition, or sleep. Respondents from N = 73 AYA-aged (mean [M] = 19.0 years, range = 11-30 years) survivor families completed a survey on cancer-related barriers to health behaviors. Almost all respondents (68/73, 93.2%) endorsed ≥1 cancer-specific barrier(s) to current health behaviors (median = 5, standard deviation = 3.42, range = 0-16) in their family. Cancer-related barriers to PA, nutrition, and sleep were positively correlated (PA-nutrition: r = 0.39, p = 0.001; PA-sleep: r = 0.41, p < 0.001; nutrition-sleep: r = 0.52, p < 0.001). Wellness interventions are needed to address the unique needs of AYA-aged survivors and support multiple health behaviors simultaneously.

Interest in fertility status assessment among young adult survivors of childhood cancer.

BACKGROUND: Cancer survivors who received gonadotoxic treatment are at-risk for future infertility and may desire a fertility status assessment (FSA), defined as semen analysis for males and consultation with a reproductive specialist for females. The purpose of this study was to describe the proportion of, and factors associated with, interest in FSA among young adult survivors of childhood cancer. METHODS: This retrospective single-institution review included patients with prior gonadotoxic treatment, aged 18-25 years and >1 year from cancer treatment completion, who received a fertility-focused discussion during survivorship. Documentation of interest in and completion of FSA, worry about infertility, sociodemographic, and clinical characteristics were abstracted from medical records. Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with interest in FSA. RESULTS: Survivors (N = 259) were on average 19.2 ± 1.2 years at their fertility discussion; 55.6% were male and 57.9% non-Hispanic white. Interest in FSA was reported by 50.7% of males and 46.1% of females. Factors related to interest in FSA for males and females respectively, included worry about infertility (OR 2.40, 95%CI 1.11-5.27, p = 0.026 and OR 4.37, 95%CI 1.71-12.43, p = 0.003) and ≥2 fertility discussions (OR 3.78, 95%CI 1.70-8.75, p = 0.001 and 2.45, 95%CI 1.08-5.67, p = 0.033). Among males, fertility preservation consult/procedure at diagnosis (OR 3.02, 95%CI 1.09-9.04, p = 0.039) and high-risk for infertility (OR 2.47, 95%CI 1.07-5.87, p = 0.036) were also associated with interest in FSA. CONCLUSIONS: Cancer survivors are interested in FSA, particularly those who have had repeated fertility-focused discussions during survivorship care and who report worry about infertility.

Feasibility of Fitbit Use in Adolescent Survivors of Pediatric Cancer: Who Consistently Uses It and for How Long?

Purpose: Wearable activity trackers with real-time feedback and goal-setting features are being incorporated into programs to increase physical activity among childhood cancer survivors. This analysis describes the adoption and use of a Fitbit® Flex™ among adolescent-aged survivors of childhood cancer without incentives, reminders, or interventions to encourage use. Procedures: Cancer survivors aged 13-18 and ≥2 years from therapy received a Fitbit Flex with instructions to wear it daily. Researchers downloaded participants' daily total steps and active minutes for 1 year. Participants were classified as consistent (≥5 days/week for >4 weeks during the first 12 weeks) or inconsistent users, and comparisons between user types were made. Longitudinal use of the Fitbit and participants' 1-year acceptability evaluations are described. Results: Overall, 67.1% (47/70) of survivors enrolled, and Fitbit data were available for 36 participants. Initially, 30.6% (11/36) were consistent users. Consistent users had lower body mass index z-scores at enrollment (0.4 ± 0.7 vs. 1.2 ± 0.9; p = 0.01), but were otherwise comparable with inconsistent users. Over time survivors' use declined; at 12 months, only one participant was using his or her Fitbit. Survivors who completed a survey (n = 22) reported their Fitbit helped them self-monitor their exercise (72.7%, 16/22) and lead a more active lifestyle (63.6%, 14/22), but found it challenging to charge and not lose, forget about, or break the device. Conclusions: In the real-world setting, only a small subset of adolescent-aged survivors will initially consistently use a Fitbit and their interest diminishes over time. To maximize engagement, interventions incorporating wearable activity trackers likely need to include additional behavior change strategies.

Incorporating gonadal health counseling into pediatric care of sickle cell patients.

Discussions regarding gonadal function and possible disease or treatment-related ovarian or testicular dysfunction, sexual dysfunction, and possible future infertility can be challenging in the sickle cell disease (SCD) pediatric care setting. A construct that stratifies topics into those that are time sensitive and those that require reproductive care expertise vs address gonadal health as a part of normal SCD care may be helpful. Pediatric health care discussions of gonadal function/dysfunction for patients with SCD can include (1) time-sensitive fertility consults preceding the start of gonadotoxic therapy and (2) targeted discussions at key time points during normally scheduled hematology clinic visits. The former conversations are best led by individuals with expertise in the risk for treatment-related infertility and fertility preservation. The latter discussions can be incorporated into targeted regularly scheduled visits with hematologists. These topics can be addressed as a part of planned education in pediatric care for adolescents and incorporated into transition plans as young adults transfer care to adult providers. Although the topics of puberty and gonadal health can be uncomfortable and many complex interdisciplinary and ethical issues arise in this process, these discussions can be aided by the collaterals and teaching handouts presented in this article.

Germline Genetic and Treatment-Related Risk Factors for Diabetes Mellitus in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study and St Jude Lifetime Cohorts.

PURPOSE: To characterize germline genetic risk factors of diabetes mellitus among long-term survivors of childhood cancer. METHODS: Adult survivors of childhood cancer from the Childhood Cancer Survivor Study (CCSS) Original Cohort (n = 5,083; 383 with diabetes) were used to conduct a discovery genome-wide association study. Replication was performed using the CCSS Expansion (n = 2,588; 40 with diabetes) and the St Jude Lifetime (SJLIFE; n = 3,351; 208 with diabetes) cohorts. Risk prediction models, stratified on exposure to abdominal radiation, were calculated using logistic regression including attained age, sex and body mass index, diagnosis, alkylating chemotherapy, age at cancer diagnosis, and a polygenic risk score (PRS) on the basis of 395 diabetes variants from the general population. Area under the receiver operating characteristic curve (AUC) was calculated for models on the basis of traditional risk factors, clinical risk factors, and PRS. RESULTS: There was a genome-wide significant association of rs55849673-A with diabetes among survivors (odds ratio, 2.9; 95% CI, 2.0 to 4.2; P = 3.7 × 10-8), which is related to expression of ERCC6L2 in the Genotype-Tissue Expression project. The association of rs55849673-A was observed largely among survivors not exposed to abdominal radiation (odds ratio = 3.5, P = 1.1 × 10-7) and the frequency of rs55849673-A was consistently higher among diabetic survivors in the CCSS Expansion and SJLIFE cohorts. Risk prediction models including traditional diabetes risk factors, clinical risk factors and PRS had an optimism-corrected AUC of 0.801, with an AUC of 0.751 in survivors treated with abdominal radiation versus 0.813 in survivors who did not receive abdominal radiation. CONCLUSION: There is evidence for a novel locus of diabetes among survivors not exposed to abdominal radiation. Further refinement and validation of clinic-based risk prediction models for diabetes among long-term survivors of childhood cancer is warranted.

Fertility-related worry among emerging adult cancer survivors.

PURPOSE: Cancer survivors with a history of gonadotoxic treatment are at risk for future infertility and reproductive concerns, including worry about infertility. The purpose of this study was to describe factors associated with fertility-related worry among emerging adult survivors of childhood cancer. METHODS: This chart review included patients aged 18.00-25.99 years and > 1 year from cancer treatment completion with a history of gonadotoxic treatment. Survivors were offered structured fertility-focused discussions at age ≥ 18 years, which assessed worry about future infertility. Data from this discussion (i.e., reported fertility-related worry (yes/no), sociodemographic, and clinical characteristics were abstracted from the medical record. Multivariable logistic regression with backwards elimination was used to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with fertility-related worry. RESULTS: Survivors (N = 249) were a mean age of 19.1 ± 1.2 years at initial fertility discussion; 55.8% were male, 58.2% non-Hispanic White, and 27.3% were at high risk for future treatment-related infertility. Fertility-related worry was reported by 66.3% of survivors. Factors related to worry on multivariable analysis included female sex (OR: 2.64, 95%CI: 1.44-4.96, p = .002), solid tumor diagnosis (OR: 2.31, 95%CI: 1.15-4.71, p = .019), moderate and high risk of infertility (OR: 2.94, 95%CI: 1.23-7.64, p = .02; OR: 3.25, 95%CI: 1.55-7.17, p = .002), and ≥ 2 fertility discussions during survivorship care OR: 2.71, 95%CI: 1.46-5.20, p = .002). CONCLUSIONS: Two-thirds of emerging adult cancer survivors expressed worry about future infertility, which has been linked to a variety of adverse quality of life outcomes. Survivors who are worried about infertility may benefit from psychological interventions.