Patterns of Physical Therapy Referral and Subsequent Attendance Among Childhood Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy at a Regional Childhood Cancer Survivorship Clinic.

OBJECTIVES: Childhood cancer survivors are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Physical therapy (PT) improves CIPN symptoms, but little is known about survivors' PT utilization. We described characteristics of survivors with ≥ grade 2 CIPN, investigated PT referral and attendance, and described characteristics of survivors who attended and did not attend PT. METHODS: Childhood cancer survivors <21 years old at cancer diagnosis and ≥2 years posttherapy, living in the United States, evaluated at a regional survivorship clinic were included in this retrospective analysis if they had motor CIPN. Symptomatic CIPN (≥grade 2 by Common Terminology Criteria for Adverse Events) and PT referral/attendance were tabulated. Patient characteristics from the medical record, and neighborhood characteristics (retrieved using survivors' zip code from the National Neighborhood Data Archive) were described by group. RESULTS: Among 91 survivors with CIPN (median 17.5 years old, 8.1 years postcancer diagnosis, 45.1% female), 35 (38.5%) had ≥ grade 2 CIPN. Survivors with ≥ grade 2 CIPN were 28.6% female, and 45.7% were <13 years old. Twenty-four (68.6%) survivors with ≥ grade 2 CIPN agreed to PT referral, and 15 (42.9%) attended PT. Among survivors who attended PT, 73.3% were <13 years old. Neighborhood characteristics of survivors included median percentage of adults without a high school diploma (6.7% PT attendees, 12.5% nonattendees), median percentage of adults who are foreign-born (11.5% PT attendees, 16.4% nonattendees), and median percentage of households with an annual income of <$15,000 (3.2% PT attendees, 6.5% nonattendees). CONCLUSIONS: While 68.6% of survivors with ≥ grade 2 CIPN were referred to PT, only 42.9% attended. Studies to better understand barriers to PT attendance and interventions to improve attendance are needed, especially in older survivors. IMPLICATIONS FOR NURSING PRACTICE: Nurses can play a key role in survivor education and care coordination to help optimize PT attendance.

Motor and sensory impairment in survivors of childhood central nervous system (CNS) tumors in the St. Jude Lifetime Cohort (SJLIFE).

BACKGROUND: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. METHODS: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0-53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0-70.0] years, 55.7% female) completed in-person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form-36 physical/mental summary scores, social attainment). RESULTS: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%-29.4%) than controls (2.9%, CI 1.4-4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06-18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19-72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01-1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68-11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10-0.84, Sensory: OR 0.35, CI 0.13-0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22-5.72). CONCLUSIONS: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL.

Design and methods of the StepByStep randomized trial of a mobile health and social media physical activity intervention among adolescent and young adult survivors of childhood cancer: A report from the Children's Oncology Group.

BACKGROUND: Interventions to increase physical activity are needed in adolescent and young adult survivors of childhood cancer who are largely inactive but at lifelong elevated risk of multiple chronic conditions improved by physical activity. The goals of the StepByStep study are to evaluate the effects of a 48-week distance-based, multi-component mobile health and social media behavioral intervention on physical activity, biomarkers of cardiometabolic health, and health-related quality of life. METHODS: This ongoing study is a two-arm, prospective, multi-site randomized controlled trial. 384 childhood cancer survivors age ≥ 15 years and < 21 years who were 3-36 months off therapy and not meeting physical activity guidelines were enrolled. The trial will test the efficacy of a 24-week intensive multi-component physical activity intervention combining a wearable physical activity tracker, social media peer support group, and individualized goal setting followed by a 24-week maintenance phase of the intervention to improve outcomes. The control group receives the wearable physical activity tracker only. CONCLUSION: There is a growing need for novel, developmentally appropriate interventions to increase physical activity and improve the health trajectory of adolescent and young adult survivors of childhood cancer. If efficacious, this portable and scalable intervention would be a much-needed tool to reduce the morbidity from cancer treatment and improve quality of life among survivors after treatment ends. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04089358; COG Identifier: ALTE2031.

Trends in physical functioning in acute lymphoblastic leukemia and non-Hodgkin lymphoma survivors across three decades.

PURPOSE: The impact of changes in therapy for childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on the prevalence of physical performance limitations and participation restrictions among survivors is unknown. We aimed to describe the prevalence of reduced function among ALL and NHL survivors by treatment era. METHODS: Participants included survivors of childhood ALL and NHL, and a cohort of their siblings, participating in the Childhood Cancer Survivor Study (CCSS). Physical function was measured using questionnaire. The prevalence of reduced function was compared to siblings using generalized estimating equations, overall and stratified by treatment decade. Associations between organ system-specific chronic conditions (CTCAE v4.03) and function were also evaluated. RESULTS: Among 6511 survivors (mean age 25.9 years (standard deviation 6.5)) and 4127 siblings, risk of performance limitations (15.2% vs. 12.5%, prevalence ratio [PR] = 1.5, 95%CI = 1.3-1.6), restrictions in personal care (2.0% vs. 0.6%, PR = 3.1, 95% CI = 2.0-4.8), routine activities (5.5% vs. 1.6%, PR = 3.6, 95% CI = 2.7-4.8), and work/school attendance (8.8% vs. 2.1%, PR = 4.5, 95% CI = 3.6-5.7) was increased in survivors vs. siblings. The prevalence of survivors reporting reduced function did not decrease between the 1970s and 1990s. The presence of neurological and cardiovascular conditions was associated with reduced function regardless of treatment decade. CONCLUSIONS: Despite changes in therapy, the prevalence of poor physical function remained constant between the 1970s and 1990s. The CCSS clinical trial registration number is NCT01120353 (registered May 6, 2010). IMPLICATIONS FOR CANCER SURVIVORS: Our findings support screening for reduced physical function so that early interventions to improve physical performance and mitigate chronic disease can be initiated.

Physical activity and physical fitness assessments in adolescents and young adults diagnosed with cancer: a scoping review.

PURPOSE: This scoping review describes the assessment methodologies for physical activity (PA) and physical fitness assessments used in studies focusing on adolescents and young adults (AYAs) diagnosed with cancer. METHODS: A search of the literature was conducted in PubMed, CINAHL, Web of Science, and Cochrane Library following the PRISMA-ScR statement. A total of 34 studies were included in this review. RESULTS: PA was primarily assessed via self-reported questionnaires (30/34) either completed in-person (n = 17) or online (n = 13) at different time points and different stages along the cancer trajectory (i.e., from diagnosis onward). A total of 9 studies conducted a physical fitness assessment. CONCLUSIONS: PA and physical fitness measurements are key when trying to describe outcomes, assess for associations, track changes, measure intervention adherence, and test intervention efficacy and effectiveness. Considerable heterogeneity across studies was reported limiting the generation of formal recommendations or guidance for researchers, healthcare providers, and policy makers.

Assessment of proxy-reported responses as predictors of motor and sensory peripheral neuropathy in children with B-lymphoblastic leukemia.

Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children's Oncology Group AALL0932 physical function study, we sought to determine if parent/guardian proxy-reported responses from the Pediatric Outcomes Data Collection Instrument could identify children with motor or sensory CIPN diagnosed by physical/occupational therapists (PT/OT). Four variables moderately discriminated between children with and without motor CIPN (c-index 0.76, 95% confidence interval [CI]: 0.64-0.84), but sensory and optimism-corrected models had weak discrimination (c-index sensory models 0.65, 95% CI: 0.54-0.74). New proxy-report measures are needed to identify children with PT/OT diagnosed CIPN.

Patient-reported neurocognitive function in adult survivors of childhood and adolescent osteosarcoma and Ewing sarcoma.

PURPOSE: Little is known regarding long-term neurocognitive outcomes in osteosarcoma and Ewing sarcoma (EWS) survivors despite potential risk factors. We evaluated associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS. METHODS: Five-year survivors of osteosarcoma (N = 604; median age 37.0 years) and EWS (N = 356; median age 35.0 years) diagnosed at < 21 years from 1970 to 1999, and 697 siblings completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire and reported chronic health conditions, education, and employment. Prevalence of reported neurocognitive difficulties were compared between diagnostic groups and siblings. Modified Poisson regression identified factors associated with neurocognitive difficulties. RESULTS: Osteosarcoma and EWS survivors, vs. siblings, reported higher prevalences of difficulties with task efficiency (15.4% [P = 0.03] and 14.0% [P = 0.04] vs. 9.6%, respectively) and emotional regulation (18.0% [P < 0.0001] and 15.2% [P = 0.03] vs. 11.3%, respectively), adjusted for age, sex, and ethnicity/race. Osteosarcoma survivors reported greater memory difficulties vs. siblings (23.5% vs. 16.4% [P = 0.01]). Comorbid impairment (i.e., ≥ 2 neurocognitive domains) was more prevalent in osteosarcoma (20.0% [P < 0.001]) and EWS survivors (16.3% [P = 0.02]) vs. siblings (10.9%). Neurological conditions were associated with worse task efficiency (RR = 2.17; 95% CI = 1.21-3.88) and emotional regulation (RR = 1.88; 95% CI = 1.01-3.52), and respiratory conditions were associated with worse organization (RR = 2.60; 95% CI = 1.05-6.39) for EWS. Hearing impairment was associated with emotional regulation difficulties for osteosarcoma (RR = 1.98; 95% CI = 1.22-3.20). Patient report of cognitive difficulties was associated with employment but not educational attainment. CONCLUSIONS: Survivors of childhood osteosarcoma and EWS are at increased risk for reporting neurocognitive difficulties, which are associated with employment status and appear related to chronic health conditions that develop over time. IMPLICATIONS FOR CANCER SURVIVORS: Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes.

Nutritional assessment and dietary intervention among survivors of childhood cancer: current landscape and a look to the future.

Over 85% of childhood cancer patients become long-term survivors. Still, cancer and its therapies are associated with a myriad of long-term complications such that childhood cancer survivors (CCS) endure excess disease burden, morbidity, and mortality throughout their lifetimes. Existing literature suggests that CCS maintain poor dietary intake and nutritional status. Thus, as childhood cancer cure rates continue to improve, the role of diet and nutrition in mitigating many of the most common adverse long-term health outcomes among CCS has gained significant interest. Herein we present an in-depth review of existing scientific literature evaluating dietary intake and nutrition status among CCS and its impact on treatment-related health complications; as well as contemporary intervention strategies aimed at overcoming distinctive barriers and improving deleterious lifestyle behaviors in this heterogeneous, at-risk population. Patient-specific, clinical, and systemic factors act as barriers to the timely conduct of comprehensive dietary/nutritional assessments and provision of tailored, risk-based recommendations. This Mini Review discusses the current state of the science, persisting research gaps, and opportunities for advancement of assessment and intervention strategies to address the unique needs of CCS. Search Strategy: We searched PubMed for peer-reviewed articles with the search terms "pediatric cancer," "pediatric malignancy," "pediatric oncology," "childhood cancer," "survivorship," "cancer late effects," "long-term follow-up," "body mass index," "nutritional status," "malnutrition," "body weight," "body weight changes," "body composition," "obesity," "overweight ", "Mediterranean diet," "DASH diet," "processed foods," "micronutrients," "antioxidants," "vitamin D," "calcium," "selenium," "zinc," "metabolic syndrome," "heart disease," "cardiovascular disease," "cardiometabolic disease," "hypertension," "hyperlipidemia," "HDL," "LDL," and "small dense LDL" from January 1, 1995, to July 21, 2023. We also selected relevant articles from our personal files and from reference lists of identified papers. We prioritized publications after 2013; however, commonly cited and highly regarded (defined by high citation count and journal impact factor) older publications were also included. Randomized controlled trials, observational studies, retrospective studies, meta-analysis, editorials, and review articles were included, whereas conference abstracts and case reports were excluded. We only searched for articles published in English, or those translated into English.

Design and methods of a randomized web-based physical activity intervention among children with cancer: A report from the Children's Oncology Group.

BACKGROUND: Promoting physical activity soon after treatment for childhood cancer may benefit health because sedentary lifestyle during curative therapy may perpetuate physical and emotional complications. The primary goals of this study are to evaluate the effects of a 6-month web-based, rewards-based physical activity intervention on fitness, biomarkers of cardiometabolic health, inflammation, adipokine status, quality of life and school attendance, and determine if effect of intervention on markers of cardiometabolic health is mediated by changes in fitness. The primary outcome of interest is fitness (physiological cost index, six-minute walk test) measured at end of intervention. METHODS: This ongoing study is a two-arm, prospective, randomized design with accrual goals of 192 children for intervention and control groups. Children ≥8 years and < 16 years of age, not meeting recommended levels of physical activity, who completed therapy within the past 12 months are eligible. Both groups receive: 1) educational materials encouraging physical activity, 2) activity monitor, 3) access to web-based interface designed to motivate physical activity, 4) rewards based on physical activity levels, and 5) access to their activity data on the web-interface. Those randomized to intervention: 1) can view others' activity and interact with other participants, and 2) receive rewards based on physical activity levels throughout the intervention (vs. at the end of the intervention for control group). CONCLUSION: Unique, scalable, and portable physical activity interventions that motivate young survivors are needed. This study will inform future web-based physical activity interventions for children with cancer by demonstrating effects of rewards and social interaction. CLINICAL TRIALS: ClinicalTrials.gov Identifier: NCT03223753; COG Identifier: ALTE1631.

Unconventional Oil and Gas Development Exposure and Risk of Childhood Acute Lymphoblastic Leukemia: A Case-Control Study in Pennsylvania, 2009-2017.

BACKGROUND: Unconventional oil and gas development (UOGD) releases chemicals that have been linked to cancer and childhood leukemia. Studies of UOGD exposure and childhood leukemia are extremely limited. OBJECTIVE: The objective of this study was to evaluate potential associations between residential proximity to UOGD and risk of acute lymphoblastic leukemia (ALL), the most common form of childhood leukemia, in a large regional sample using UOGD-specific metrics, including a novel metric to represent the water pathway. METHODS: We conducted a registry-based case-control study of 405 children ages 2-7 y diagnosed with ALL in Pennsylvania between 2009-2017, and 2,080 controls matched on birth year. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between residential proximity to UOGD (including a new water pathway-specific proximity metric) and ALL in two exposure windows: a primary window (3 months preconception to 1 y prior to diagnosis/reference date) and a perinatal window (preconception to birth). RESULTS: Children with at least one UOG well within 2km of their birth residence during the primary window had 1.98 times the odds of developing ALL in comparison with those with no UOG wells [95% confidence interval (CI): 1.06, 3.69]. Children with at least one vs. no UOG wells within 2km during the perinatal window had 2.80 times the odds of developing ALL (95% CI: 1.11, 7.05). These relationships were slightly attenuated after adjusting for maternal race and socio-economic status [odds ratio (OR) =1.74 (95% CI: 0.93, 3.27) and OR=2.35 (95% CI: 0.93, 5.95)], respectively). The ORs produced by models using the water pathway-specific metric were similar in magnitude to the aggregate metric. DISCUSSION: Our study including a novel UOGD metric found UOGD to be a risk factor for childhood ALL. This work adds to mounting evidence of UOGD's impacts on children's health, providing additional support for limiting UOGD near residences. https://doi.org/10.1289/EHP11092.

Leveraging Clinical Trial Populations and Data from the Children's Oncology Group for Cancer Survivorship Research.

Children and adolescents diagnosed with cancer can now expect an average 85% 5-year overall survival, with significant improvements in longer-term morbidity and mortality reported over the past several decades. However, the long-term impact of therapeutic agents and modalities introduced in recent years remains unclear and will require dedicated follow-up in the years ahead. The Children's Oncology Group (COG), a part of the NCI's National Clinical Trials Network, with over 200 sites across North America and beyond, enrolls more than 10,000 patients onto research protocols annually, inclusive of first-line clinical trials and nontherapeutic studies. COG provides a platform to conduct survivorship research with several unique strengths: (i) a huge catchment to ascertain relatively rare but important adverse events, (ii) study populations that are otherwise too rare to study in smaller consortia, including access to highly diverse patient populations, (iii) long-term follow-up of clinical trial populations linked to the original trial data, and (iv) a natural platform for intervention research. Enhancements in COG infrastructure facilitate survivorship research, including a COG patient registry (Project:EveryChild), availability of a long-term follow-up tracking resource, and successful deployment of various remote-based study procedures to reduce the burden on participants and participating institutions.

Hispanic Ethnicity Differences in Birth Characteristics, Maternal Birthplace, and Risk of Early-Onset Hodgkin Lymphoma: A Population-Based Case-Control Study.

BACKGROUND: Hispanic ethnicity differences in the risk of early-onset Hodgkin lymphoma diagnosed at <40 years are understudied. We conducted a population-based case-control study to evaluate associations between birth characteristics and early-onset Hodgkin lymphoma with a focus on potential ethnic differences. METHODS: This study included 1,651 non-Hispanic White and 1,168 Hispanic cases with Hodgkin lymphoma endorsing a range of races diagnosed at the age of 0 to 37 years during 1988-2015 and 140,950 controls without cancer matched on race/ethnicity and year of birth from the California Linkage Study of Early-Onset Cancers. OR and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. RESULTS: Having a foreign-born mother versus a United States-born mother (i.e., the reference group) was associated with an increased risk of early-onset Hodgkin lymphoma among non-Hispanic Whites (OR = 1.52; 95% CI, 1.31-1.76; P < 0.01) and a decreased risk among Hispanics (OR = 0.78; 95% CI, 0.69-0.88; P < 0.01). Among both race groups, risk of early-onset Hodgkin lymphoma increased with birthweight and maternal age (all Ptrends < 0.01). Among non-Hispanic Whites, each 5-year increase in maternal age (OR = 1.11; 95% CI, 1.04-1.18; Ptrend < 0.01) and paternal age (OR = 1.07; 95% CI, 1.02-1.13; Ptrend < 0.01) was associated with increased risk of early-onset Hodgkin lymphoma. Compared with female Hispanics, male Hispanics had an increased risk of early-onset Hodgkin lymphoma (OR = 1.26; 95% CI, 1.12-1.42; P < 0.01). CONCLUSIONS: Maternal birthplace may play a role in risk of early-onset Hodgkin lymphoma that differs by ethnicity. IMPACT: The ethnic differences observed between certain birth characteristics, maternal birthplace, and early-onset Hodgkin lymphoma raise questions about the underlying biological, generational, lifestyle, residential, and genetic contributions to the disease.

Persistence of Chemotherapy-Induced Peripheral Neuropathy Despite Vincristine Reduction in Childhood B-Acute Lymphoblastic Leukemia.

BACKGROUND: Children with B-acute lymphoblastic leukemia (B-ALL) are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Children's Oncology Group AALL0932 randomized reduction in vincristine and dexamethasone (every 4 weeks vs 12 weeks during maintenance in the average-risk subset of National Cancer Institute standard-B-ALL (SR AR B-ALL). We longitudinally measured CIPN, overall and by treatment group. METHODS: AALL0932 standard-B-ALL patients aged 3 years and older were evaluated at T1-T4 (end consolidation, maintenance month 1, maintenance month 18, 12 months posttherapy). Physical and occupational therapists (PT/OT) measured motor CIPN (hand and ankle strength, dorsiflexion and plantarflexion range of motion), sensory CIPN (finger and toe vibration and touch), function (dexterity [Purdue Pegboard], and walking efficiency [Six-Minute Walk]). Proxy-reported function (Pediatric Outcome Data Collection Instrument) and quality of life (Pediatric Quality of Life Inventory) were assessed. Age- and sex-matched z scores and proportion impaired were measured longitudinally and compared between groups. RESULTS: Consent and data were obtained from 150 participants (mean age = 5.1 years [SD = 1.7], 48.7% female). Among participants with completed evaluations, 81.8% had CIPN at T1 (74.5% motor, 34.1% sensory). When examining severity of PT/OT outcomes, only handgrip strength (P < .001) and walking efficiency (P = .02) improved from T1-T4, and only dorsiflexion range of motion (46.7% vs 14.7%; P = .008) and handgrip strength (22.2% vs 37.1%; P = .03) differed in vincristine and dexamethasone every 4 weeks vs vincristine and dexamethasone 12 weeks at T4. Proxy-reported outcomes improved from T1 to T4 (P < .001), and most did not differ between groups. CONCLUSIONS: CIPN is prevalent early in B-ALL therapy and persists at least 12 months posttherapy. Most outcomes did not differ between treatment groups despite reduction in vincristine frequency. Children with B-ALL should be monitored for CIPN, even with reduced vincristine frequency.

Physical Therapy Utilization Among Hospitalized Patients With Pediatric Acute Lymphoblastic Leukemia.

PURPOSE: Patients with pediatric acute lymphoblastic leukemia (ALL) are at risk for impaired physical function from treatment. Early physical therapy (PT) may improve physical function and health in children with ALL, yet little is known about PT utilization in this population. METHODS: Leveraging the Premier Healthcare Database, we conducted a cohort study including participants hospitalized with ALL at age 0-21 years from January 1, 2010, through March 31, 2017. A generalized mixed linear model assessed sociodemographic and clinical variables associated with receiving PT within 1 year of first hospitalization. RESULTS: Among 5,488 pediatric ALL patients from 330 hospitals (median age 7 years, interquartile range = 4-14 years), only 27.2% overall and 58.9% with neuromuscular conditions received PT within a year of first ALL admission. In multivariable analysis, patients more likely to receive PT were age 10-14 years (odds ratio [OR] = 1.46; 95% CI, 1.20 to 1.76) or 15-21 years (OR = 1.66; 95% CI, 1.36 to 2.02) versus 0-4 years and Hispanic (OR = 1.27; 95% CI, 1.04 to 1.56) versus White. Patients less likely to receive PT were treated by a nonhematology/oncology pediatric (OR = 0.56; 95% CI, 0.46 to 0.70) or adult (OR = 0.50; 95% CI, 0.38 to 0.65) specialist versus a pediatric hematologist/oncologist and treated at a nonteaching hospital (OR = 0.53; 95% CI, 0.36 to 0.79) versus a teaching hospital. CONCLUSION: Only 27.2% of pediatric ALL patients overall and 58.9% with neuromuscular conditions receive inpatient PT within a year of first ALL admission. Interventions to increase inpatient PT services to pediatric ALL patients and address disparities in PT utilization may improve the physical function and long-term health of survivors.

Recommendations for the surveillance of mental health problems in childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Survivors of childhood, adolescent, and young adult (diagnosed when <25 years of age) cancer are at risk of mental health problems. The aim of this clinical practice guideline is to harmonise international recommendations for mental health surveillance in survivors of childhood, adolescent, and young adult cancer. This guideline was developed by a multidisciplinary panel of experts under the sponsorship of the International Guideline Harmonization Group. We evaluated concordance among existing survivorship clinical practice guidelines and conducted a systematic review following evidence-based methods. Of 7249 studies identified, 76 articles from 12 countries met the inclusion criteria. Recommendations were formulated on the basis of identified evidence in combination with clinical considerations. This international clinical practice guideline strongly recommends mental health surveillance for all survivors of childhood, adolescent, and young adult cancers at every follow-up visit and prompt referral to mental health specialists when problems are identified. Overall, the recommendations reflect the necessity of mental health surveillance as part of comprehensive survivor-focused health care.

A Case of Pheochromocytoma as a Subsequent Neoplasm in a Survivor of Childhood Embryonal Rhabdomyosarcoma.

Childhood cancer survivors are at risk for subsequent neoplasms. We describe the clinical presentation and genetic testing of a 29-year-old woman diagnosed with a pheochromocytoma 22 years post-treatment for childhood embryonal rhabdomyosarcoma of the bladder. Genetic testing for cancer predisposition revealed a pathogenic variant in BRCA2 and a variant of uncertain significance in MSH2. Pathogenic variants associated with deafness were also identified in GJB2. This article reports a novel subsequent neoplasm following childhood embryonal rhabdomyosarcoma, and discusses the potential contribution of genetic cancer predisposition to this case as well as the clinical implications of genetic testing.

Impact of Risk-Stratified Therapy on Health Status in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study.

BACKGROUND: Prior studies have identified that survivors of childhood acute lymphoblastic leukemia (ALL) report poor health status. It is unknown how risk-stratified therapy impacts the health status of ALL survivors. METHODS: We estimated and compared the prevalence of self-reported poor health status among adult (≥18 years) survivors of childhood ALL diagnosed at age <21 years from 1970 to 1999 and sibling controls, excluding proxy reports. Therapy combinations defined treatment groups representative of 1970s therapy (70s), standard- and high-risk 1980s and 1990s therapy (80sSR, 80sHR, 90sSR, 90sHR), and relapse/bone marrow transplant (R/BMT). Log-binomial models, adjusted for clinical and demographic factors, compared outcomes between groups using prevalence ratios (PR) with 95% confidence intervals (CI). RESULTS: Among 5,119 survivors and 4,693 siblings, survivors were more likely to report poor health status in each domain including poor general health (13.5% vs. 7.4%; PR = 1.92; 95% CI, 1.69-2.19). Compared with 70s, 90sSR and 90sHR were less likely to report poor general health (90sSR: PR = 0.75; 95% CI, 0.57-0.98; 90sHR: PR = 0.58; 95% CI, 0.39-0.87), functional impairment (90sSR: PR = 0.56; 95% CI, 0.42-0.76; 90sHR: PR = 0.63; 95% CI, 0.42-0.95), and activity limitations (90sSR: 0.61; 95% CI, 0.45-0.83; 90sHR: PR = 0.59; 95% CI, 0.38-0.91). An added adjustment for chronic conditions in multivariable models partially attenuated 90sSR risk estimates. CONCLUSIONS: Risk-stratified ALL therapy has succeeded in reducing risk for poor general health, functional impairment, and activity limitations among more recent survivors of standard- and high-risk therapy. IMPACT: Future research into the relationship between risk-stratified therapy, health status, and late health outcomes may provide new opportunities to further improve late morbidity among survivors.

Long-term neurocognitive and quality of life outcomes in survivors of pediatric hematopoietic cell transplant.

PURPOSE: Pediatric patients who undergo hematopoietic cell transplant (HCT) are at risk for neurocognitive impairments, which can impact quality of life. Given limited long-term studies, we aimed to characterize the late neurocognitive outcomes in a cohort of pediatric HCT survivors. METHODS: Eligible survivors (HCT at age < 21 year and ≥ 1 year post-HCT) completed a 60-question survey of neurocognitive function and quality of life, which included the Childhood Cancer Survivor Study Neurocognitive Questionnaire (CCSS-NCQ) and the Neuro-Quality of Life Cognitive Function Short Form (Neuro-QoL). Analyses of risk factors included univariate comparisons and multivariable logistic regression. RESULTS: Participants (n = 199, 50.3% female, 53.3% acute leukemia, 87.9% allogeneic transplants) were surveyed at median age of 37.8 years (interquartile range [IQR] 28.5-48.8) at survey and median 27.6 years (IQR 17.0-34.0) from transplant. On the CCSS-NCQ, 18.9-32.5% of survivors reported impairments (Z score > 1.28) in task efficiency, memory, emotional regulation, or organization, compared with expected 10% in the general population (all p < 0.01). In contrast, survivors reported average Neuro-QoL (T score 49.6±0.7) compared with population normative value of 50 (p = 0.52). In multivariable regression, impaired Neuro-QoL (T score < 40) was independently associated with hearing issues (OR 4.97, 95% CI 1.96-12.6), history of stroke or seizure (OR 4.46, 95% CI 1.44-13.8), and sleep disturbances (OR 6.95, 95% CI 2.53-19.1). CONCLUSIONS: Although long-term survivors of pediatric HCT reported higher rates of impairment in specific neurocognitive domains, cognitive quality of life was perceived as similar to the general population. Subsets of survivors with certain co-morbidities had substantially worse neurocognitive outcomes. IMPLICATIONS FOR CANCER SURVIVORS: While the long-term impact of pediatric HCT can include neurocognitive deficits, survivors report average cognitive quality of life.