Physical function patient-reported outcomes among adolescent and young adult cancer survivors: A systematic review.

BACKGROUND: The physical challenges faced by adolescents and young adults (AYA) after a cancer diagnosis may be different from those experienced by paediatric and older adult cancer patients. Patient-reported outcome measures (PROMs) are valuable tools that can be useful in exploring the experiences of AYAs and identifying important issues, recurrent themes and areas to potentially improve quality of life. OBJECTIVE: We compared patient-reported physical function outcomes between AYAs diagnosed with cancer and non-cancer controls. METHOD: This paper builds on a scoping review published in early 2023 and focuses on PROMs related to physical function. RESULTS: This systematic review includes 16 studies that measured and reported on physical function PROMs in AYA cancer survivors compared with their cancer-free peers. Of these studies, 14 found that physical function in AYA survivors was significantly worse. This paper also includes a meta-analysis conducted on 5 studies using the EORTC-QLQ-C30 to measure physical function, which found that physical function score was an average of 7.03 (95% CI: -10.21, -3.86) points lower in the AYA cancer group, compared to their cancer free-peers, a difference that is clinically meaningful. CONCLUSIONS: The results overwhelmingly demonstrate that AYAs post a cancer diagnosis have worse health-related quality of life from a physical function perspective than their cancer-free peers, providing a compelling argument for the need to address this issue. All but one of the studies were cross-sectional, which highlights the need for further assessment of this group longitudinally throughout their cancer journey.

Psychiatric disorders in childhood cancer survivors: A retrospective matched cohort study of inpatient hospitalisations and community-based mental health services utilisation in Western Australia.

OBJECTIVE: We examined the impact of long-term mental health outcomes on healthcare services utilisation among childhood cancer survivors in Western Australia using linked hospitalisations and community-based mental healthcare records from 1987 to 2019. METHOD: The study cohort included 2977 childhood cancer survivors diagnosed with cancer at age < 18 years in Western Australia from 1982 to 2014 and a matched non-cancer control group of 24,994 individuals. Adjusted hazard ratios of recurrent events were estimated using the Andersen-Gill model. The cumulative burden of events over time was assessed using the method of mean cumulative count. The annual percentage change in events was estimated using the negative binomial regression model. RESULTS: The results showed higher community-based service contacts (rate/100 person-years: 30.2, 95% confidence interval = [29.7-30.7] vs 22.8, 95% confidence interval = [22.6-22.9]) and hospitalisations (rate/1000 person-years: 14.8, 95% confidence interval = [13.6-16.0] vs 12.7, 95% confidence interval = [12.3-13.1]) in childhood cancer survivors compared to the control group. Childhood cancer survivors had a significantly higher risk of any event (adjusted hazard ratio = 1.5, 95% confidence interval = [1.1-2.0]). The cumulative burden of events increased with time since diagnosis and across age groups. The annual percentage change for hospitalisations and service contacts significantly increased over time (p < 0.05). Substance abuse was the leading cause of hospitalisations, while mood/affective and anxiety disorders were common causes of service contacts. Risk factors associated with increased service events included cancer diagnosis at age < 5 years, leukaemia diagnosis, high socioeconomic deprivation, and an attained age of < 18 years. CONCLUSIONS: The elevated utilisation of healthcare services observed among childhood cancer survivors emphasises the need for periodic assessment of psychiatric disorders, particularly in high-risk survivors, to facilitate early management and optimise healthcare resources.

Development and validation of thromboembolism diagnostic algorithms in children with cancer from real-world data.

OBJECTIVE: To evaluate the accuracy of diagnostic algorithms developed using the International Classification of Diseases (ICD-9-CM and ICD-10-CA) diagnostic codes and physician billing codes for thromboembolism (TE) from health administrative data compared to chart review diagnoses of TE in children with cancer. METHODS: Using data linkage between the Pediatric Oncology Group of Ontario Network Information System (Ontario pediatric cancer registry) and various administrative data housed at ICES, eight algorithms were developed including a single reference to one of the billing codes, multiple references with varying time intervals, and combinations of various billing codes during primary cancer therapy for the whole cohort and, for early (<04/2002) and later (≥04/2002, solely ICD-10 codes) periods. Reference standard was chart review data from prior studies (from 1990 to 2016) among children (≤19 years) with cancer and radiologically confirmed TE. RESULTS: Records of 2056 patients diagnosed with cancer at two participating sites during study period were reviewed; 112 had radiologically confirmed TE. The algorithm with addition of anticoagulation utilization codes was the best performing algorithm (sensitivity = 0.76;specificity = 0.85). With use of ICD-10 only codes, sensitivity of the same algorithm improved to 0.84 with specificity of 0.80. CONCLUSION: This study provides a valid approach for ascertaining pediatric TE using real-world data. IMPACT: Research in pediatric thrombosis, especially cancer-related thrombosis, is limited mainly due to small-sized studies. Real-world data provide ready access to large and diverse populations. However, there are no validated algorithms for identifying thrombosis in real-world data for children. An algorithm based on combination of thrombosis and anticoagulation utilization codes had 76% sensitivity and 85% specificity to identify diagnosis of thrombosis in children in administrative data. This study provides a valid approach for ascertaining pediatric thrombosis using real-world data and offers a good avenue to advance pediatric thrombosis research.

Patient Reported Fatigue Among Adolescent and Young Adult Cancer Patients Compared to Non-Cancer Patients: A Systematic Review and Meta-Analysis.

Adolescent and young adult (AYA) cancer patients and survivors are a growing population due to more frequent diagnoses and improved survival. Fatigue is a common symptom experienced by cancer patients and it is often missed by health care professionals. Patient reported outcome measures (PROMs) can assist in evaluating patient reported fatigue. This systematic review aims to determine if AYA cancer patients report more fatigue than AYAs who have not been diagnosed with cancer. We used a subset of articles from a larger review that searched PubMed, EMBASE, CINAHL, and PsycINFO to determine which PROMs and domains are currently being used to evaluate AYA cancer. This study identified 175 articles related to PROMs in the AYA cancer population. Articles with PROMs reporting on fatigue/vitality were used in this review. From the original 175 articles, we identified 8 fatigue/vitality articles for this review. All eight articles found an increase in fatigue/decrease in vitality in the AYA cancer population compared to healthy controls. A meta-analysis was performed on four articles that used the same PROM tool (EORTC QLQ-C30). This found a statistically significant and clinically meaningful increase in mean fatigue of 12.5 95% confidence interval: 3.3-21.8 points (scale 0-100, higher number indicates more fatigue) in the AYA cancer group compared to healthy noncancer controls. Fatigue in the AYA cancer population is a significant issue, it is often undetected and underreported, and early interventions are needed to prevent the negative subsequent sequelae.

Medical imaging utilization and associated radiation exposure in children with down syndrome.

OBJECTIVE: To evaluate the frequency of medical imaging or estimated associated radiation exposure in children with Down syndrome. METHODS: This retrospective cohort study included 4,348,226 children enrolled in six U.S. integrated healthcare systems from 1996-2016, 3,095 of whom were diagnosed with Down syndrome. We calculated imaging rates per 100 person years and associated red bone marrow dose (mGy). Relative rates (RR) of imaging in children with versus without Down syndrome were estimated using overdispersed Poisson regression. RESULTS: Compared to other children, children with Down syndrome received imaging using ionizing radiation at 9.5 times (95% confidence interval[CI] = 8.2-10.9) the rate when age <1 year and 2.3 times (95% CI = 2.0-2.5) between ages 1-18 years. Imaging rates by modality in children <1 year with Down syndrome compared with other children were: computed tomography (6.6 vs. 2.0, RR = 3.1[95%CI = 1.8-5.1]), fluoroscopy (37.1 vs. 3.1, RR 11.9[95%CI 9.5-14.8]), angiography (7.6 vs. 0.2, RR = 35.8[95%CI = 20.6-62.2]), nuclear medicine (6.0 vs. 0.6, RR = 8.2[95% CI = 5.3-12.7]), radiography (419.7 vs. 36.9, RR = 11.3[95%CI = 10.0-12.9], magnetic resonance imaging(7.3 vs. 1.5, RR = 4.2[95% CI = 3.1-5.8]), and ultrasound (231.2 vs. 16.4, RR = 12.6[95% CI = 9.9-15.9]). Mean cumulative red bone marrow dose from imaging over a mean of 4.2 years was 2-fold higher in children with Down syndrome compared with other children (4.7 vs. 1.9mGy). CONCLUSIONS: Children with Down syndrome experienced more medical imaging and higher radiation exposure than other children, especially at young ages when they are more vulnerable to radiation. Clinicians should consider incorporating strategic management decisions when imaging this high-risk population.

Rates and predictors of visits to primary care physicians during and after treatment of childhood acute lymphoblastic leukemia: A population-based cohort study.

INTRODUCTION: Patient re-engagement with primary care physicians (PCPs) after cancer treatment is essential to facilitate survivorship care and to meet non-oncology primary care needs. We identified rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with acute lymphoblastic leukemia (ALL). METHODS: Children of age less than 18 years at ALL diagnosis in Ontario between 2002 and 2012 were linked to administrative data and matched to controls without cancer. PCPs at diagnosis were identified and PCP visit rates during treatment compared between patients and controls. Post-treatment PCP visit rates were also calculated. Predictors included demographic-, disease-, and PCP-related variables. RESULTS: A total of 743/793 (94%) patients and 3112/3947 (79%) controls had a PCP at diagnosis. Almost half of patients (361/743, 45%) did not visit their PCP during treatment. Visit rate during treatment was 0.64 per person per year (PPPY) versus 1.4 PPPY among controls (adjusted rate ratio [aRR] 0.47, 95th confidence interval [95CI]: 0.40-0.54; p < .0001). No disease- or PCP-related factors were associated with visit rates. Total 711 patients completed frontline therapy; 287 (40.4%) did not have a PCP visit after treatment. Nonetheless, survivors overall visited PCPs post treatment more often than controls (aRR 1.4, 95CI: 1.2-1.6; p < .0001). Survivors who saw their PCP during treatment had post-treatment visit rates twice that of other survivors (aRR 2.0, 95CI: 1.6-2.5; p < .0001). CONCLUSIONS: Only a portion of children with ALL see their PCPs during treatment and return to PCP care following treatment completion. Post-treatment engagement with PCPs may be improved by PCP involvement during ALL treatment.

Mental health patient-reported outcomes among adolescents and young adult cancer survivors: A systematic review.

BACKGROUND: Adolescent and young adult (AYA) cancer patients and survivors face significant mental health challenges throughout their cancer journey that are different to those faced by children and older adults. Patient-reported outcome measures (PROMs) can be used to explore the experiences of AYAs, and to identify important issues and areas for potential improvement in quality of life. OBJECTIVE: We aimed to compare patient reported mental health outcomes between AYAs diagnosed with cancer and non-cancer controls. METHOD: We built on a larger systematic review of AYA cancer PROMs which searched PubMed, EMBASE, CINAHL and PsychINFO. This review identified 175 articles, which were filtered to those reporting on mental health and including a non-cancer control group. RESULTS: We identified 12 eligible studies. Seven studies (58%) found those diagnosed with cancer reported poorer mental health than the non-cancer controls. The remaining five (42%) studies found no significant difference in severity or prevalence of mental health between the AYA cancer cohort and the healthy control group. Most (83%) were cross-sectional studies, highlighting the need for further longitudinal assessment of this group throughout their journey. CONCLUSIONS: The mental health outcomes feature conflicting results and illustrate the need for larger studies to characterise discrepancies.

Treatment patterns and outcomes in adolescents and young adults with nodular lymphocyte-predominant Hodgkin lymphoma: an IMPACT cohort study.

We leveraged population-based clinical and healthcare data to identify treatment patterns and long-term outcomes among adolescents and young adults (AYA) with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). All Ontario, Canada, AYA aged 15-21 years at diagnosis with NLPHL between 1992 and 2012 were identified, and their detailed clinical data were collected. Linkage to healthcare databases identified additional events (subsequent malignant neoplasms [SMN], relapses and deaths). Event-free survival (EFS) and overall survival (OS) were compared by locus of care (adult vs. paediatric) and predictors of outcomes determined. Of 1014 AYA with Hodgkin lymphoma, 54 (5.3%) had NLPHL; 15 (27.8%) were treated at a paediatric centre. No paediatric centre patient received radiation only versus 16 (41.0%) of adult centre patients. Excision only was more common in paediatric centres (p < 0.001). The 20-year EFS and OS rates were 82.9% ± 5.2% and 100% respectively. Advanced stage (hazard ratio: 4.9, 95% CI: 1.3-18.4; p = 0.02) was associated with inferior EFS. Although the 25-year cumulative incidence of SMN was 19.3% ± 9.6% for the entire cohort, there were no SMN among the patients treated with excision only. AYA with NLPHL have outstanding long-term survival. Resection alone was rare outside of paediatric institutions but associated with excellent outcomes. Given substantial SMN risks, chemotherapy-sparing and radiation-sparing strategies for appropriate subsets of patients are warranted.

Measuring what gets done: Using goal attainment scaling in a vocational counseling program for survivors of childhood cancer.

BACKGROUND: Childhood cancer survivors face education and employment challenges due to physical, cognitive, and psychosocial effects of the disease and treatments, with few established programs to assist them. The objectives of this study were to describe the implementation of Goal Attainment Scaling (GAS) to evaluate an educational and vocational counseling program established for survivors of childhood cancer, and analyze patterns of program engagement and client outcomes, stratified by demographic and diagnostic characteristics. METHODS: A population-based retrospective cohort study of childhood cancer survivors who were engaged with the Pediatric Oncology Group of Ontario's School and Work Transitions Program (SWTP) between January 2015 and December 2018 was utilized. Survivors were followed from SWTP engagement until May 30, 2019 to capture goal attainment. Individual goals were summarized across various demographic, disease, and treatment strata. RESULTS: In total, 470 childhood cancer survivors (median age = 17.9, 58% male) set 4,208 goals in the SWTP during the study period. The mean length of observation was 130.8 weeks (SD = 56.9). Overall, 68% of the goals were achieved. Eighty-three percent of the goals related to further education. Clients diagnosed with a solid tumor set the most goals on average, followed by those with central nervous system tumors and leukemia/lymphoma. CONCLUSIONS: The SWTP assists childhood cancer survivors in realizing their academic and vocational goals. Application of GAS in this setting is a feasible way to evaluate program outcomes. From the volume and breadth of the GAS goals set and achieved, the overall success of the SWTP appears strong.

Financial toxicity among adolescent and young adult cancer survivors: A systematic review of educational attainment, employment, and income.

PURPOSE: To identify, evaluate and summarize the evidence on educational attainment, employment status and income of AYAs surviving cancer. METHODS: A search of six databases for articles published between 01/01/2010 and 03/31/2022 was performed. Articles with an AYA survivorship population, quantitative design and a cancer-free comparator group were included. Data extraction was conducted, and quality appraisal was completed using ROBINS-I. Results were summarized using a narrative synthesis. RESULTS: A total of 2801 articles were identified, of which 12 were included. Among the limited evidence, educational attainment did not differ from cancer-free peers. Survivors were more likely to be unemployed, have lower incomes and require social security for income supplementation. Evidence suggested that females, diagnosis of brain cancer and the presence of late-effects were among the risk factors for severe outcomes. CONCLUSIONS: Limited socioeconomic evidence exists for AYAs surviving cancer. Long-lasting financial toxicities occur and highlights a need for further investigation.

Patient reported outcome measure domains and tools used among adolescents and young adults with cancer: A scoping review.

Adolescent and young adult (AYA) cancer patients and survivors are growing and face with distinct issues from paediatric and older cancer survivors. Hence it is important the issues they encounter are measured using appropriate Patient Reported Outcome Measures (PROMs). We searched PubMed, EMBASE, CINAHL, and PsycINFO for articles including: (1) AYAs (ages 15-39), (2) Malignant neoplasms, and (3) PROMs. This resulted in 3566 unique articles, 523 were included for full text review, of which 175 were included. These studies included 203 distinct tools to measure PROMs across 31 domains. Physical function was most frequently measured domain, followed by social, emotional and mental health. The most commonly used tools were the EORTC QLQ-C30, HADS and SF-36. PROMs used in AYA cancer patients is a complex topic, this comprehensive review serves as a useful reference for researchers, clinicians and health services who want to better understand, and improve, outcomes among their patients.

Childhood cancer survival and avoided deaths in Australia, 1983-2016.

BACKGROUND: Large improvements in childhood cancer survival have been reported over recent decades. Data from cancer registries have the advantage of providing a 'whole of population' approach to gauge the success of cancer control efforts. OBJECTIVES: The aim of this study was to investigate recent survival estimates for children diagnosed with cancer Australia and to examine the extent of changes in survival over the last 35 years. For the first time, we also estimated the number of deaths among Australian children that were potentially avoided due to improvements in survival. METHODS: A retrospective, population-based cohort study design was used. Case information was extracted from the Australian Childhood Cancer Registry for 1983-2016, with follow-up to 31 December 2017. Eligible children were aged 0-14 with a basis of diagnosis other than autopsy or death certificate only. Five-year relative survival was calculated using the semi-complete cohort method for three diagnosis periods (1983-1994, 1995-2006 and 2007-2016), and changes in survival over time were assessed via flexible parametric models. Avoided deaths within 5 years for those diagnosed between 1995 and 2016 were estimated under the assumption that survival rates remained the same as for 1983-1994. RESULTS: Overall 5-year survival within the study cohort (n = 20,871) increased from 72.8% between 1983 and1994 to 86.1% between 2007 and 2016, equating to an adjusted excess mortality hazard ratio of 1.82 (95% confidence interval 1.67, 1.97). Most cancers showed improvements in survival; other gliomas, hepatoblastoma and osteosarcoma were exceptions. Among children diagnosed between 1995 and 2016, 38.7% of expected deaths within 5 years of diagnosis (n = 1537 of 3970) were avoided due to temporal improvements in survival. CONCLUSIONS: Survival for childhood cancer has continued to improve over recent years, thanks mainly to ongoing progress in treatment development combined with improved supportive care. Providing innovative measures of survival, such as avoided deaths, may assist with understanding outcome data produced by cancer registries.

Publicly subsidised smoking cessation medicines in times of COVID-19 in Australia: An interrupted time series analysis.

INTRODUCTION: In Australia, the available published literature demonstrated a spike in dispensed prescription medicines after the onset of the COVID-19 pandemic that subsequently returned to expected levels. Smoking cessation medicines may not follow this pattern because quit attempts are influenced by a range of factors. Knowledge of whether dispensing of these medicines has changed since the pandemic is lacking. We explored the change in dispensing of publicly subsidised smoking cessation medicines since the pandemic. METHODS: Australia's universal health-care system provides access to government-subsidised medicines via the Pharmaceutical Benefits Scheme and records of dispensed medicines are publicly available on a nationally aggregated level. We retrieved Pharmaceutical Benefits Scheme data from January 2016 to January 2021. We used interrupted time series modelling to quantify the impact of COVID-19 on dispensing of nicotine replacement therapy (NRT) patches, varenicline and all smoking cessation treatments combined separately. RESULTS: After an initial spike in medicines at the onset of the pandemic, the monthly rate of prescriptions dispensed for varenicline was predominantly within predicted ranges, while that of NRT patches was predominantly below predicted ranges. DISCUSSION AND CONCLUSIONS: There has been a differential change in the number of subsidised smoking cessation medicines supplied in Australia since the COVID-19 pandemic, with varenicline prescriptions largely within, and NRT patches largely lower than, expected ranges. The reasons for the apparent change in dispensing of subsidised smoking cessation medicines are unclear.

Healthcare utilization and costs associated with acute lymphoblastic leukemia in children with and without Down syndrome.

BACKGROUND: Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are at increased risk of treatment-related morbidity and mortality compared to non-DS-ALL, requiring increased supportive care. We examined the healthcare utilization and costs in DS-ALL patients to inform future evaluations of novel therapies. METHODS: A provincial registry identified all children (1-17 years) diagnosed with B-lineage ALL in Ontario, Canada between 2002 and 2012. Detailed demographic, disease, treatment, and outcome data were abstracted. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization costs were available for patients diagnosed during 2006-2012 using validated algorithms (2018 Canadian dollars). Healthcare utilization rates and costs were compared between DS and non-DS patients using regression models, adjusting for all covariates. RESULTS: Of 711 patients, 28 (3.9%) had DS. Adjusting for all covariates, children with DS-ALL experienced substantially higher rates of ED visits (rate ratio [RR] 1.5, 95% confidence interval [95% CI]: 1.2-2.0; p = .001) and inpatient days (RR 2.5, 95% CI: 1.4-4.5; p = .002) compared to non-DS children. Outpatient visit rates were similar (RR 1.1, 95% CI: 0.9-1.3; p = .41). Among patients with available cost data (N = 533, DS = 19), median 5-year healthcare utilization cost was $247,700 among DS patients (interquartile range [IQR]: 200,900-354,500) and $196,200 among non-DS patients (IQR: 148,900-280,300; p = .02). In adjusted analyses, DS-associated costs were 50% higher (RR 1.5, 95% CI: 1.2-1.9; p < .002). CONCLUSIONS: Healthcare utilization and treatment costs of DS-ALL patients are substantially higher than those of non-DS-ALL. Our data provide a baseline for future DS-specific cost-effectiveness studies.

Temporal clustering of neuroblastic tumours in children and young adults from Ontario, Canada.

BACKGROUND: The aetiology of neuroblastic tumours is likely to involve both genetic and environmental factors. A number of possible environmental risk factors have been suggested, including infection. If an irregular temporal pattern in incidence is found, this might suggest that a transient agent, such as an infection, is implicated. Previous work has found evidence for temporal clustering in children and young adults living in northern England. METHODS: We examined data from a second population-based registry from Ontario, Canada to determine whether there was evidence of temporal clustering of neuroblastic tumours. Cases diagnosed in children and young adults aged 0-19 years between 1985 and 2016 were extracted from the population-based Pediatric Oncology Group of Ontario Networked Information System (POGONIS). A modified version of the Potthoff-Whittinghill method was used to test for temporal clustering. Estimates of extra-Poisson variation (EPV) and standard errors (SE) were obtained. RESULTS: Eight hundred seventy-six cases of neuroblastic tumours were diagnosed during the study period. Overall, no evidence of temporal clustering was found between fortnights, between months or between quarters within years. However, significant EPV was found between years within the full study period (EPV = 1.05, SE = 0.25; P = 0.005). CONCLUSIONS: The findings are consistent with the possibility that a transient agent, such as an infection that is characterised by 'peaks and troughs' in its occurrence, might be implicated in the aetiology of neuroblastic tumours. However, this pattern may also reflect a long-term increase in the numbers of cases, rather than peaks and troughs.

The Impact of Hospital Surgical Volume on Healthcare Utilization Outcomes After Pediatric Thyroidectomy.

BACKGROUND: A positive relationship between an individual surgeon's operative volume and clinical outcomes after pediatric and adult thyroidectomy is well-established. The impact of a hospital's pediatric operative volume on surgical outcomes and healthcare utilization, however, are infrequently reported. We investigated associations between hospital volume and healthcare utilization outcomes following pediatric thyroidectomy in Canada's largest province, Ontario. METHODS: Retrospective analysis of administrative and health-related population-level data from 1993 to 2017. A cohort of 1908 pediatric (<18 years) index thyroidectomies was established. Hospital volume was defined per-case as thyroidectomies performed in the preceding year. Healthcare utilization outcomes: length of stay (LOS), same day surgery (SDS), readmission, and emergency department (ED) visits were measured. Multivariate analysis adjusted for patient-level, disease and hospital-level co-variates. RESULTS: Hospitals with the lowest volume of pediatric thyroidectomies, accounted for 30% of thyroidectomies province-wide and performed 0-1 thyroidectomies/year. The highest-volume hospitals performed 19-60 cases/year. LOS was 0.64 days longer in the highest, versus the lowest quartile. SDS was 83% less likely at the highest, versus the lowest quartile. Hospital volume was not associated with rate of readmission or ED visits. Increased ED visits were, however, associated with male sex, increased material deprivation, and rurality. CONCLUSIONS: Increased hospital pediatric surgical volume was associated with increased LOS and lower likelihood of SDS. This may reflect patient complexity at such centers. In this cohort, low-volume hospitals were not associated with poorer healthcare utilization outcomes. Further study of groups disproportionately accessing the ED post-operatively may help direct resources to these populations.

Quantifying cancer risk from exposures to medical imaging in the Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study: research methods and cohort profile.

PURPOSE: The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods. METHODS: The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages. RESULTS: The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine. CONCLUSION: The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.

Locus-of-care disparities in end-of-life care intensity among adolescents and young adults with cancer: A population-based study using the IMPACT cohort.

BACKGROUND: Adolescents and young adults (AYAs) with cancer may experience elevated rates of high-intensity end-of-life (HI-EOL) care. Locus-of-care (LOC) disparities (pediatric vs adult) in AYA end-of-life (EOL) care are unstudied. METHODS: A decedent population-based cohort of Ontario AYAs diagnosed between 1992 and 2012 at the ages of 15 to 21 years was linked to administrative data. The authors determined the prevalence and associations of a composite outcome of HI-EOL care that included any of the following: intravenous chemotherapy within 14 days of death, more than 1 emergency department visit, more than 1 hospitalization, or an intensive care unit (ICU) admission within 30 days of death. Secondary outcomes included measures of the most invasive EOL care (ventilation within 14 days of death and ICU death) and in-hospital death. RESULTS: There were 483 decedents: 60.5% experienced HI-EOL care, 20.3% were ventilated, and 22.8% died in the ICU. Compared with patients with solid tumors, patients with hematological malignancies had the greatest odds of HI-EOL care (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.5-3.4), ventilation (OR, 4.7; 95% CI, 2.7-8.3), and ICU death (OR, 4.4; 95% CI, 2.6-4.4). Subjects treated in pediatric centers versus adult centers near death (OR, 2.4; 95% CI, 1.2-4.8) and those living in rural areas (OR, 2.1; 95% CI, 1.1-3.9) were more likely to experience ICU death. CONCLUSIONS: AYAs with cancer experience high rates of HI-EOL care, with patients in pediatric centers and those living in rural areas having the highest odds of ICU death. This study is the first to identify LOC-based disparities in EOL care for AYAs, and it highlights the need to explore the mechanisms underlying these disparities.

Positive predictive value and sensitivity of ICD-9-CM codes for identifying pediatric leukemia.

BACKGROUND: To facilitate community-based epidemiologic studies of pediatric leukemia, we validated use of ICD-9-CM diagnosis codes to identify pediatric leukemia cases in electronic medical records of six U.S. integrated health plans from 1996-2015 and evaluated the additional contributions of procedure codes for diagnosis/treatment. PROCEDURES: Subjects (N = 408) were children and adolescents born in the health systems and enrolled for at least 120 days after the date of the first leukemia ICD-9-CM code or tumor registry diagnosis. The gold standard was the health system tumor registry and/or medical record review. We calculated positive predictive value (PPV) and sensitivity by number of ICD-9-CM codes received in the 120-day period following and including the first code. We evaluated whether adding chemotherapy and/or bone marrow biopsy/aspiration procedure codes improved PPV and/or sensitivity. RESULTS: Requiring receipt of one or more codes resulted in 99% sensitivity (95% confidence interval [CI]: 98-100%) but poor PPV (70%; 95% CI: 66-75%). Receipt of two or more codes improved PPV to 90% (95% CI: 86-93%) with 96% sensitivity (95% CI: 93-98%). Requiring at least four codes maximized PPV (95%; 95% CI: 92-98%) without sacrificing sensitivity (93%; 95% CI: 89-95%). Across health plans, PPV for four codes ranged from 84-100% and sensitivity ranged from 83-95%. Including at least one code for a bone marrow procedure or chemotherapy treatment had minimal impact on PPV or sensitivity. CONCLUSIONS: The use of diagnosis codes from the electronic health record has high PPV and sensitivity for identifying leukemia in children and adolescents if more than one code is required.