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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. 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. 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. 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. National Cancer Institute and American Lebanese-Syrian Associated Charities.

Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1–18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6–43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3–69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13–0·73; p=0·0036). The most common grade 3–4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 178 participant cycles in the sodium thiosulfate group vs 145 [65%] of 224 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 149 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. US National Cancer Institute.

Adolescent and young adult (AYA) enrollment in cancer clinical trials (CCT) is suboptimal. Few studies have explored site level barriers and facilitators to AYA enrollment on CCTs and the efficacy of interventions to enhance enrollment. A cross sectional survey was developed by the COG AYA Oncology Discipline Committee Responsible Investigator (RI) Network to identify perceived barriers and facilitators to enrollment, as well as opportunities to improve enrollment. Associations of barriers and facilitators to enrollment with program demographics were assessed. The survey was sent to all AYA RI Network members (n = 143) and quantitative and thematic analyses were conducted. The overall response rate was 42% (n = 60/143). Participants represented diverse institutions based on size, presence or absence of dedicated AYA programs, and proximity and relationship between pediatric and medical oncology practices within the institution. The most frequently cited barriers to enrolling AYAs in CCTs were administrative logistical issues (45%), disparate enrollment practices (42%) and communication issues (27%) between pediatric and medical oncology and perceived limited trial availability (27%). The most frequently reported facilitators to enrollment included having strong communication between pediatric and medical oncology (48%), having a supportive research infrastructure (35%) and the presence of AYA champions (33%). Many barriers and facilitators were similar across institutions and AYA program types. Shared barriers and facilitators to AYA CCT enrollment exist across the landscape of cancer care settings. Interventions aimed at increasing coordination between pediatric and medical oncology clinical trials offices and providers have high potential to improve site-level AYA enrollment.

Approximately 85,000 adolescent and young adults (AYAs; age 15–39) are diagnosed with cancer in the United States annually. Experiencing a cancer diagnosis as an AYA can substantially impact social connections and social health. This paper describes the design and protocol of an observational study to prospectively assess social health and its association with physical activity and quality of life among AYAs after a cancer diagnosis. The study uses a longitudinal observational design to prospectively explore the relationships between social health and activity behaviors (physical activity and sedentary time) at four clinically significant timepoints over the course of 12 months among AYAs newly diagnosed with cancer. Patients are recruited at three hospitals and surveyed at each time period. Multiple dimensions of social health are assessed including social support, social roles, loneliness, social anxiety, and social networks. A wrist accelerometer is worn for one week at each assessment period. Change in social network structures will be analyzed using egocentric social network analysis. Structural equation models will be fitted to analyze the relationship between social constructs and physical activity. Findings from this study will address gaps in our understanding of the impact of a cancer diagnosis on multiple dimensions of social health for AYAs and the potential role social factors play in physical activity and quality of life. Understanding these processes will inform age-tailored interventions to improve health and quality of life outcomes for this at-risk population.

Objective Previous work in pediatric oncology has found that clinicians and parents tend to under-report the frequency and severity of treatment-related symptoms compared to child self-report. As such, there is a need to identify high-quality self-report instruments to be used in pediatrie oncology research studies. This study's objective was to conduct a systematic literature review of existing English language instruments used to measure self-reported symptoms in children and adolescents undergoing cancer treatment. Methods A comprehensive literature search was conducted in MEDLINE/PubMed, EMBASE, CINAHL, and PsycINFO to identify relevant articles published through November 10, 2016. Using pre-specified inclusion/exclusion criteria, six trained reviewers carefully screened abstracts and full-text articles for eligibility. Results There were 7738 non-duplicate articles identified in the literature search. Forty articles met our eligibility criteria, and within these articles, there were 38 self-report English symptom instruments. Most studies evaluated only cross-sectional psychometric properties, such as reliability or validity. Ten studies assessed an instrument's responsiveness or ability to detect changes in symptoms over time. Eight instruments met our criteria for use in future longitudinal pediatrie oncology studies. Conclusions This systematic review aids pediatrie oncology researchers in identifying and selecting appropriate symptom measures with strong psychometric evidence for their studies. Enhancing the child's voice in pediatrie oncology research studies allows us to better understand the impact of cancer and its treatment on the lives of children.

Background Adolescent and young adult (AYA) childhood cancer survivors (CCS) should be empowered to continue their survivor-focused care as they transition into adult medicine. However, the majority of AYA-aged survivors become lost to follow up around the age of typical transition to adulthood. The purpose of this study was to identify, from the patient’s perspective, key factors that facilitate successful transitions to adult-centered survivorship care. Methods A qualitative study was conducted with AYA CCS ( n  = 29) from the survivorship clinic of a single institution as key informants. Data were collected through a series of structured phone interviews and subjected to thematic content analysis. Results Four major themes with multiple subthemes were identified: (1) transition practices need to be flexible and individually tailored; (2) effective communication is critical to a successful transition; (3) continuity in providers is needed during the transition; and (4) comprehensive care means care that also addresses psycho-social well-being. Conclusions From the perspective of AYA CCS, the ideal model of transitional survivorship care could include a patient navigator who promotes provider flexibility, consistent communication, and pro-active comprehensive care that encompasses both medical and psycho-social well-being. Models of care for CCS should be built to provide, or seamlessly facilitate, continuous survivor-focused care across the age continuum. A longitudinal relationship with a survivor-focused provider can help promote the values that CCS’ report as important in transitioning care from pediatric- to adult-centered care.

IntroductionExcessive sedentary behaviour (SB) is highly prevalent among children and adolescents and young adults (AYAs) treated for cancer. Although SB is associated with adverse health outcomes in adults with cancer, little is known about SB in younger cancer patients and survivors. In this scoping review, we aim to summarise current literature on (1) the association between SB and clinical outcomes and (2) results of intervention trials to reduce SB, specifically in paediatric and AYA cancer patients and survivors.Methods and analysisThe scoping review will follow the five stages described in the Arksey and O’Malley methodology framework. We will conduct a comprehensive search in five varied electronic databases (PubMed, Embase, Web of Science, CINAHL and SportDiscus) for original articles published in peer-reviewed journals since 1 January 2000, and search reference lists of identified articles and previous review articles. All original research article types will be considered (ie, cross-sectional, cohort, interventional trials). Two reviewers will independently screen all articles based on predetermined inclusion and exclusion criteria, including (1) more than half the sample at the time of study must have been children (0–14 years old) and/or adolescent and young adults (AYAs, 15–39-year old) who were being or had been previously treated for cancer and (2) reporting of SB. Data will be extracted as a descriptive and quantitative summary of each study’s key characteristics and results. Study-specific quality assessment will be performed using established tools. Results will be presented in evidence tables with an accompanying narrative summary.Ethics and disseminationEthics approval is not required as only publicly available data will be analysed. Results will be published in a peer-reviewed journal and may be presented at a scientific conference.Registration detailsThe protocol is registered in Open Science Framework (https://osf.io/ua8z9).

Background There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. Methods Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications. Results Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection. Conclusions Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes. Trial registration clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1 .

Although landmark studies in the 1990s demonstrated that adolescents and young adults (AYAs, ages 15-39 years) with cancer had lower survival improvement compared to other ages, therapeutic advances warrant reappraisal of those observations. We utilized more recent data to study site-specific AYA survival trends and disparities and gain a more contemporary understanding of this problem. Using California Cancer Registry data from 1988 to 2014, we calculated 1) 5-year overall survival improvement for AYAs compared to other age groups; 2) hazard ratios (HRs) of death for AYAs comparing 2001-2014 with 1988-2000 stratified by site, stage, sex, age group, race and ethnicity, and socioeconomic status (SES); and 3) site-specific adjusted HRs (aHRs) for AYA risk groups and interaction analyses by time period. For all cancers combined, AYAs demonstrated survival improvement that exceeded all other age groups, largely due to reduced mortality in human immunodeficiency virus and acquired immunodeficiency syndrome-related cancers. The strongest predictor of death was cancer stage (aHR = 6.32 for distant vs localized, 95% confidence interval [CI] = 6.20 to 6.45). The aHR of death was statistically significantly higher for blacks (1.46, 95% CI = 1.42 to 1.50), Asian and Pacific Islanders (1.12, 95% CI = 1.09 to 1.15), and Latino whites (1.06, 95% CI = 1.04 to 1.08) compared to non-Latino whites, and was statistically significantly higher for low SES compared to high (1.31, 95% CI = 1.29 to 1.34). Survival disparities by stage, race and ethnicity, and SES worsened over time. For AYAs in aggregate, the historical cancer survival improvement gap has been closed. However, the growing survival disparities in AYA subsets reported here, including advanced stage disease, racial and ethnic minorities, and low SES, highlight new priorities in need of increased attention, including inequities in cancer care and delivery within this vulnerable population.

Introduction Childhood cancer survivors (CCS) experience many long-term health problems that can be alleviated by receiving guideline-concordant survivorship care. However, many CCS encounter barriers to accessing care and do not receive recommended survivorship care. We reviewed the empirical evidence of barriers to and facilitators of survivorship care for CCS. Methods As part of a larger project on CCS, this systematic review followed a detailed protocol (CRD42021227965) and searched PubMed, CINAHL, and PsycINFO for studies on survivorship care for CCS without date restriction, and abstracted reported barriers and facilitators. Searches identified 8585 citations and 2 independent reviewers screened 2934 publications at full text. We evaluated the risk of bias for individual studies and quality of evidence (QoE) across barriers and facilitators. Results A total of 49 studies reported barriers and facilitators (survivors N = 33, clinicians N = 19, family members N = 8, and health system leaders N = 7) addressing knowledge (beliefs, autonomy, culture), prioritization (active avoidance, trust, communication), and infrastructure (health system resources, transitions). We found high QoE of barriers including lack of knowledge and inaccurate beliefs (survivorship care not needed or redundant), active avoidance and lack of trust (high level of emotional trauma and anxiety, lack of confidence in care team, no local providers with experience in survivorship care), and gaps in infrastructure (financial toxicity/hardship, lack of insurance coverage, difficulty scheduling appointments, and lack of stable housing). Conversely, knowledge (providing a survivorship care plan or treatment summary, supporting patient autonomy) and prioritization (close relationships with clinicians, enhanced care coordination, communication) can also facilitate survivorship care engagement, documented with high QoE. Conclusions We found strong empirical evidence of barriers to and facilitators of survivorship care, including potentially modifiable factors surrounding knowledge, prioritization, and infrastructure survivorship care. Prospective, multilevel approaches are needed to improve the receipt of guideline-concordant survivorship care among CCS. Plain Language Summary Childhood cancer survivors (CCS) experience many long-term health problems that can be alleviated by receiving guideline-concordant survivorship care. However, many CCS encounter barriers to accessing care and do not receive recommended survivorship care. We reviewed the empirical evidence of barriers to and facilitators of survivorship care for CCS. We found strong empirical evidence of barriers to and facilitators of survivorship care, including financial, insurance, scheduling, transportation, local availability of services, and resources needed to deliver survivorship care. Prospective, multilevel approaches are likely needed to improve the receipt of guideline-concordant survivorship care among CCS.