Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures.

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard-of-care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long-term morbidity, including the risk of LCH-associated neurodegeneration. Historically, the nature of LCH-whether a reactive condition versus a neoplastic/malignant condition-was uncertain. Over the past 15 years, seminal discoveries have broadly defined LCH pathogenesis; specifically, activating mitogen-activated protein kinase pathway mutations (most frequently, BRAFV600E) in myeloid precursors drive lesion formation. LCH therefore is a clonal neoplastic disorder, although secondary inflammatory features contribute to the disease. These paradigm-changing insights offer a promise of rational cures for patients based on individual mutations, clonal reservoirs, and extent of disease. However, the pace of clinical trial development behind lags the kinetics of translational discovery. In this review, the authors discuss the current understanding of LCH biology, clinical characteristics, therapeutic strategies, and opportunities to improve outcomes for every patient through coordinated agent prioritization and clinical trial efforts.

A phase II trial of nifurtimox combined with topotecan and cyclophosphamide for refractory or relapsed neuroblastoma and medulloblastoma.

Children with relapsed/refractory (R/R) neuroblastoma (NB) and medulloblastoma (MB) have poor outcomes. We evaluated the efficacy of nifurtimox (Nfx) in a clinical trial for children with R/R NB and MB. Subjects were divided into three strata: first relapse NB, multiply R/R NB, and R/R MB. All patients received Nfx (30 mg/kg/day divided TID daily), Topotecan (0.75 mg/m2 /dose, days 1-5) and Cyclophosphamide (250 mg/m2 /dose, days 1-5) every 3 weeks. Response was assessed after every two courses using International Neuroblastoma Response Criteria and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. One hundred and twelve eligible patients were enrolled with 110 evaluable for safety and 76 evaluable for response. In stratum 1, there was a 53.9% response rate (CR + PR), and a 69.3% total benefit rate (CR + PR + SD), with an average time on therapy of 165.2 days. In stratum 2, there was a 16.3% response rate, and a 72.1% total benefit rate, and an average time on study of 158.4 days. In stratum 3, there was a 20% response rate and a 65% total benefit rate, an average time on therapy of 105.0 days. The most common side effects included bone marrow suppression and reversible neurologic complications. The combination of Nfx, topotecan and cyclophosphamide was tolerated, and the objective response rate plus SD of 69.8% in these heavily pretreated populations suggests that this combination is an effective option for patients with R/R NB and MB. Although few objective responses were observed, the high percentage of stabilization of disease and prolonged response rate in patients with multiply relapsed disease shows this combination therapy warrants further testing.

Variation of Diagnostic Approaches and Treatment Practices for Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome Among Pediatric Subspecialists.

OBJECTIVE: To assess the diagnostic and treatment practices among a variety of subspecialists at pediatric institutions in the US. STUDY DESIGN: Using a web-based survey, we assessed the consultation, diagnostic, and treatment preferences of providers from the different pediatric subspecialties who care for pediatric patients with hemophagocytic lymphohistiocytosis (HLH)/macrophage activating syndrome (MAS). Domains included demographics, provider training level and specialty, experience and comfort level with the diagnosis and treatment of HLH/MAS, and institutional approaches toward the diagnosis and management of HLH/MAS. Participants also were given 2 case scenarios: one describing Epstein-Barr virus-associated HLH and another describing an underlying rheumatologic condition with MAS. RESULTS: Of 263 respondents, 23%, 29%, 39%, and 7% identified as hematology/oncology, rheumatology, general pediatrics/critical care/hospitalist, and allergy/immunology, respectively. For Epstein-Barr virus/HLH, hematology/oncology was the preferred first consultant by most respondents other than rheumatologists, of whom only 47% agreed. For MAS, 92% of respondents from all specialties favored a rheumatology consultation. Preferred diagnostic tests varied by subspecialty, with hematology/oncology more likely than rheumatology to order an infectious workup, natural killer cell function, soluble interleukin-2 receptor, bone marrow biopsy, and genetic testing. First-line therapy also varied, with hematology/oncology preferring dexamethasone and etoposide and rheumatology more often preferring methylprednisolone and anakinra. One-half of respondents were unaware of institutional algorithms for diagnosis and treatment of HLH/MAS. Most (85.6%) favored the development of treatment algorithms for HLH/MAS, and 90% supported a multidisciplinary approach. CONCLUSIONS: Current consulting patterns, diagnostic workup, and treatment approaches of HLH/MAS vary by specialty, highlighting the need for standardized management algorithms and institutional multidisciplinary HLH/MAS teams.

Children's Oncology Group's 2023 blueprint for research: Non-Hodgkin lymphoma.

Pediatric non-Hodgkin lymphoma (NHL) includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the United States. Improvements in survival in NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes. As an example, survival for advanced Burkitt lymphoma is now >95%. Major remaining challenges include survival for relapsed and refractory disease and long-term morbidity in NHL survivors. Langerhans cell histiocytosis (LCH) was added to the NHL Committee portfolio in recognition of LCH as a neoplastic disorder and the tremendous unmet need for improved outcomes. The goal of the Children' Oncology Group NHL Committee is to identify optimal cures for every child and young adult with NHL (and LCH). Further advances will require creative solutions, including engineering study groups to combine rare populations, biology-based eligibility, alternative endpoints, facilitating international collaborations, and coordinated correlative biology.

Vaccination practices of pediatric oncologists from eight states.

BACKGROUND: Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors. METHODS: We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2. RESULTS: Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists. CONCLUSIONS: Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment.

Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.

Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found this disease to be highly diverse in presentation and overall outcome. Moreover, we discovered somatically-acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish somatic CBL patients from germline CBL patients, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among germline CBL patients. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.

Two Clonally Distinct B-Cell Lymphomas Reveal the Diagnosis of XLP1 in a Male Child and His Asymptomatic Male Relatives: Case Report and Review of the Literature.

X-linked lymphoproliferative disease type 1 (XLP1) is a primary immunodeficiency disorder caused by pathogenic variants in the SH2D1A gene (SH2 domain containing protein 1A). Patients with XLP1 may present acutely with fulminant infectious mononucleosis, hemophagocytic lymphohistiocytosis, and/or B-cell non-Hodgkin lymphoma (B-NHL). We report a boy who developed 2 clonally distinct B-NHL 4 years apart and was found to have previously unrecognized XLP1. The report highlights the importance of clonal analysis and XLP1 testing in males with presumed late recurrences of B-NHL, and the role of allogeneic stem cell transplant (allo-SCT) in XLP1 patients and their affected male relatives.

Respiratory emergency department use from diagnosis through survivorship in children, adolescents, and young adults with cancer.

BACKGROUND: Children and adolescents and young adults (AYAs) with cancer often experience severe respiratory morbidity and mortality from the therapies used to treat their cancers. Few studies have examined respiratory outcomes among this population using emergency department (ED) visits as an objective measure of respiratory health. METHODS: ED visits for respiratory conditions were identified for children and AYAs diagnosed with cancer, 0-25 years of age, from 1997 through 2012 (2535 cases) and compared with a birthdate-matched and sex-matched cohort without cancer drawn from the general population (7605 controls). Negative binomial regression with robust standard errors was used to estimate incidence rates, rate ratios (RRs), and 95% confidence intervals for primary respiratory ED visits, combined and by diagnosis (asthma, respiratory disease, and respiratory infection) from 1997 through 2015. Analyses were performed for new cases (0 to <5 years from diagnosis) and survivors (5-18 years from diagnosis). RESULTS: Subjects were followed for an average of 8 years (range, 0-18 years). Relative to the comparison cohort, cancer cases had higher incidence rates for all types of respiratory ED visits over both follow-up times. New cases had significantly higher RRs for any respiratory condition (RR, 4.14), respiratory disease (RR, 4.62), and respiratory infection (RR, 4.74). Among survivors, the RRs for any respiratory condition (RR, 2.00) and respiratory infection (RR, 2.10) were significantly elevated, although the magnitude tended to decline in survivorship. Demographic and clinical risk factors found to be associated with respiratory ED visits included Hispanic/other race/ethnicity, male sex, exposure to chemotherapy, diagnosis at a younger age, and a diagnosis of leukemia. CONCLUSIONS: The results of the current study demonstrated that children and AYAs with cancer face an increased burden of respiratory complications compared with a comparison cohort without cancer from diagnosis through survivorship.

Infection-related mortality in Hispanic and non-Hispanic children with cancer.

BACKGROUND: Hispanic children with cancer experience poorer survival than their White counterparts. Infection is a known cause of cancer-related mortality; however, little is known about the risk of infection-related death among Hispanic children with cancer. We examine the association of Hispanic ethnicity with infection-related mortality and life-threatening events among children with cancer. PROCEDURE: For a cohort of all pediatric cancer patients diagnosed from 1986 to 2012 and treated at a single tertiary care center, we obtained national death records to determine all-cause mortality and infection-related mortality, as well as intensive care unit (ICU) admissions as a surrogate for life-threatening events. Cox proportional hazard models assessed all-cause mortality and infection-related mortality using ethnicity as the main independent variable. ICU admission rates were modeled using a zero-inflated Poisson regression model. Models were adjusted for gender, diagnosis year, age, residential location, and diagnosis. RESULTS: Of 6,198 patients, 741 (12%) were Hispanic. Mean follow-up was 11 years (SD = 8.04). There were 1,205 deaths, with 193 attributable to infection. Differences in all-cause mortality between Hispanic and non-Hispanic patients did not reach significance (hazard ratio [HR] = 1.14, 95% confidence interval [CI]: 0.96-1.36). However, Hispanic patients were 68% (HR = 1.68, 95% CI: 1.16-2.43) more likely to have an infection-related cause of death. Hispanic ethnicity was statistically associated with a higher rate of ICU admissions (rate ratio = 1.32, 95% CI: 1.12-1.56). CONCLUSION: Hispanic pediatric cancer patients were more likely to have an infection-related death and higher rates of ICU admissions than non-Hispanic patients. Infection may be an overlooked contributor to poorer outcomes among Hispanic patients.

The impact of language barriers and immigration status on the care experience for Spanish-speaking caregivers of patients with pediatric cancer.

BACKGROUND: An increasing proportion of pediatric cancer patients in the United States are Latino and many have Spanish-speaking immigrant parents with limited English proficiency (LEP). Little is known about how language or undocumented immigration status impacts their care experience. PROCEDURE: A cross-sectional survey was administered to English (N = 310) and Spanish-speaking LEP (N = 56) caregivers of pediatric cancer patients. To assess differences in healthcare experiences between the language groups, t-tests and chi-square statistics were used. Multivariable logistic regression evaluated associations between primary language and knowledge of clinical trial status. RESULTS: Spanish-speaking caregivers were more likely to report higher rates of quitting or changing jobs as a direct result of their child's cancer, and their children were more likely to experience a delay in education. Although Spanish-speaking caregivers reported higher satisfaction with care, 32% reported feeling that their child would have received better care if English was their primary language. Spanish-speaking caregivers were more likely to incorrectly identify whether their child was on a clinical trial compared with English-speaking caregivers. The majority of Spanish-speaking caregivers reported at least one undocumented caregiver in the household and 11% of them avoided or delayed medical care for their child due to concerns over their undocumented immigration status. CONCLUSIONS: Language barriers and undocumented immigration status may negatively impact the quality of informed decision-making and the care experience for Spanish-speaking LEP caregivers of pediatric cancer patients. These families may benefit from culturally appropriate Spanish language resources to improve communication and open a dialogue regarding undocumented immigration status.

Health care experiences of long-term survivors of adolescent and young adult cancer.

PURPOSE: Evaluate health care access and experiences with care among long-term survivors of adolescent and young adult (AYA) cancer relative to a comparison group in the USA. METHODS: The 2008 to 2012 Medical Expenditure Panel Surveys identified 1163 survivors of cancer, diagnosed ages 15-39, current ages 20-64, who were at least 5 years after diagnosis. A comparison group without cancer was matched using age, sex, and other characteristics. Primary outcomes included having ≥1 visit to doctor's office/clinic in the previous year and perceived health care quality (0 = worst to 10 = best; categorized as low (0-4), intermediate (5-7), and high (8-10)). Other experience-related outcomes (e.g., having adequate time with providers and providers show respect) were also evaluated. Bivariate analyses compared these outcomes between survivors and the comparison group. Multivariable logistic regressions identified survivor-level factors associated with health care visits and quality. RESULTS: Survivors had ≥1 visit more often (82.1 vs. 75.8 %, p = 0.005) yet rated their health care quality lower (low or intermediate 30.7 vs. 23.6 %, p < 0.001) than the comparison group. Fewer survivors reported always having enough time with providers (41.7 vs. 54.6 %, p < 0.001) and that providers always show respect (57.5 vs. 67.7 %, p = 0.002). Uninsured survivors were less likely to have ≥1 visit (odds ratio (OR) = 0.26, 95 % confidence interval (CI) 0.17-0.40, p < 0.001) and rated their health care quality lower (OR = 0.25, 95 % CI 0.13-0.48, p < 0.001) than privately insured. Many other factors were associated with visits and quality. CONCLUSION: Survivors of AYA cancer reported more health care visits but worse health care experiences than individuals without cancer. Targeted interventions that may improve survivors' experiences with health care should be evaluated.

Understanding psychological distress among pediatric cancer caregivers.

PURPOSE: Few studies have examined distress in caregivers of pediatric cancer patients. We evaluated the association of socioeconomic, demographic, and patient clinical factors on caregivers' self-reported psychological distress associated with having a child with cancer. METHODS: N = 366 pediatric cancer caregivers completed a self-administered questionnaire from July 2010 to July 2012. The Impact of Event Scale (IES), along with two subscales "intrusion" and "avoidance" measured caregiver cancer-specific distress, with higher scores indicating greater distress. Multivariable linear regression models were used to calculate coefficients (ß) and 95 % confidence intervals (95 % CI) of IES by socioeconomic, demographic, and clinical factors. RESULTS: Average caregiver IES score was 31.2 (standard deviation (SD) = 16.9, range 0-75). Mean intrusion score was 18.1 (SD 9.8, range 0-35) and avoidance score was 12.8 (SD 9.0, range 0-40). Caregivers with household incomes <$40,000 reported higher mean distress scores than those with incomes ranging from $40,000 to $79,999 (ß = 4.45, 95 % CI 0.04-8.87, p = 0.05). Infrequently or never attending religious services, younger child age, and a diagnosis of AML were associated with higher intrusion (all p < 0.05). Caregivers with a child currently receiving therapy reported higher overall IES (ß = 5.9, 95 % CI 2.15-9.7, p < 0.01) and intrusion (ß = 4.1, 95 % CI 1.9-6.3, p < 0.001) scores compared to those off therapy (ß = 3.13, 95 % CI 0.93-5.33, p < 0.01). CONCLUSIONS: Our findings identify socioeconomic and clinical factors that influence psychological distress for caregivers of pediatric oncology patients. These findings underscore the importance of developing and testing interventions aimed at evaluating and addressing the psychosocial needs for high-risk caregivers in addition to those of patients.

Geography and the burden of care in pediatric cancers.

BACKGROUND: Childhood cancers typically require rigorous treatment at specialized centers in urban areas, which can create substantial challenges for families residing in remote communities. We evaluated the impact of residence and travel time on the burden of care for families of childhood cancer patients. PROCEDURE: We conducted a cross-sectional, self-administered survey of 354 caregivers of pediatric cancer patients at a children's hospital serving a seven state area. Measures included the impact of cancer treatment on relocation, employment, schooling, and finances. We evaluated these domains by rural/urban residence and travel time (>1 hour and >2 hours) to the hospital in multivariable regression models. RESULTS: Of the 29% of caregivers who reported moving residences as their child was diagnosed, 33% reported that the move was due to their child's cancer. Rural and remote (e.g., >1 hour travel time) caregivers missed more days of work during the first month after diagnosis than did urban and local caregivers, however, these differences did not persist over the first 6 months of therapy. One-third of caregivers reported quitting or changing jobs as a direct result of their child being diagnosed with cancer. Rural respondents had greater out-of-pocket travel expenses and reported a significantly greater perceived financial burden. Rural patients missed more school days and were at an increased risk of having to repeat a grade. CONCLUSIONS: Childhood cancer has an appreciable impact on the lives of patients and caregivers. The burden is greater for those living far from a treatment center.

Childhood cancer survivors' primary care and follow-up experiences.

PURPOSE: Although most childhood cancer survivors see a primary care provider (PCP), little is known about these encounters. We explored themes related to survivors' (1) experiences with primary care, (2) communication with their PCPs about their cancer, and (3) their knowledge and impressions about follow-up care, including their interest in a survivor care plan (SCP). METHODS: From April to July 2012, we conducted in-depth, semi-structured telephone interviews with 53 adult survivors recruited from the Utah Cancer Surveillance, Epidemiology, and End Results (SEER) Registry. Participants were randomly selected from sex, age, and rural/urban strata and were younger than 21 years at the time of diagnosis. Participants were asked if they had a PCP and whether they discussed their cancer history with their provider and their interest in a SCP. Interviews were recorded, transcribed, and content-analyzed. RESULTS: The average age at interview was 39.1 years (SD = 11.2). Most survivors had a current PCP (83.0 %). Almost half were not worried about their health despite having had cancer. Detailed discussions about cancer history with PCPs were generally rare. Few survivors had a follow-up care plan, but over half thought a SCP could empower their medical decision making. However, one-third of the survivors were skeptical about the usefulness of a SCP and some were worried about health-care costs. CONCLUSIONS: Childhood cancer survivors need better care coordination. Of concern is that many do not discuss their cancer history with their current PCPs and most have no SCP.

Endoscopy in the diagnosis of intestinal graft-versus-host disease: is lower endoscopy with biopsy as effective in diagnosis as upper endoscopy combined with lower endoscopy?

BACKGROUND: Graft-versus-host disease (GvHD) causes morbidity and mortality in recipients of hematopoietic stem cell transplantation (SCT). This study assessed the distribution of GvHD in gastrointestinal (GI) biopsies from the upper and lower GI tract in pediatric patients who had undergone SCT and evaluated if there was correlation between biopsy findings and possible extra-intestinal manifestations of GvHD. PROCEDURE: We performed a retrospective chart review for all patients diagnosed with GvHD, who underwent both upper and lower endoscopy. We also reviewed pathology and clinical reports to determine which biopsy sites were diagnostic of GvHD and to evaluate for the possible presence of extra-intestinal manifestations GvHD at the time of biopsy. RESULTS: Twenty patients were identified who had undergone both upper and lower endoscopy for evaluation of GvHD. Patients with GvHD diagnosed on upper endoscopy also had GvHD identified in the sigmoid colon region 100% of the time (positive predictive value [PPV] = 1). In patients that were found to have underlying liver disease, GvHD was diagnosed in the sigmoid colon region 90% of the time (PPV = 0.9). CONCLUSION: Use of sigmoid biopsy for GvHD diagnosis is effective, safe, and less expensive compared to other endoscopic interventions.

A comparison of central lines in pediatric oncology patients: Early removal and patient centered outcomes.

BACKGROUND: While there is increasing evidence supporting the choice of subcutaneous ports (SPs) over external venous catheters (EVCs) in pediatric oncology patients, prior conflicting studies exist and little data have been gathered as to which type of central line is preferred from the patient/family perspective. PROCEDURE: We performed a single institution, 10 years, retrospective analysis of central lines in pediatric oncology patients (n = 878) to evaluate unplanned early removal and cause of removal while simultaneously obtaining a cross sectional survey of 143 of the primary caretakers/parents of these patients to evaluate their overall satisfaction with the line. RESULTS: EVCs have significantly higher odds of unplanned early removal in comparison to SPs (6.7% of SPs vs. 27.3% of EVCs, odds ratio (OR) = 6.3, P < 0.0001 when controlling for age and diagnosis) secondary to increased infection, malfunction and patient preference. Patients with SPs felt like their central line was easier to care for, had less daily impact in their life, and were overall more satisfied with their central line compared to patients with EVCs, even when controlling for early removal (P < 0.0001 for all). SP patients were much more likely to state that they would choose the same type of line again (OR = 15, P < 0.0001) than EVC patients. CONCLUSION: SPs demonstrated lower removal rates and greater patient satisfaction than EVCs. These data should be considered when choosing a central line for pediatric cancer patients.

Macrophage activation syndrome in children with systemic lupus erythematosus and children with juvenile idiopathic arthritis.

OBJECTIVE: To describe patient demographics, interventions, and outcomes in hospitalized children with macrophage activation syndrome (MAS) complicating systemic lupus erythematosus (SLE) or juvenile idiopathic arthritis (JIA). METHODS: We performed a retrospective cohort study using data recorded in the Pediatric Health Information System (PHIS) database from October 1, 2006 to September 30, 2010. Participants had International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for MAS and either SLE or JIA. The primary outcome was hospital mortality (for the index admission). Secondary outcomes included intensive care unit (ICU) admission, critical care interventions, and medication use. RESULTS: A total of 121 children at 28 children's hospitals met the inclusion criteria, including 19 children with SLE and 102 children with JIA. The index admission mortality rate was 7% (8 of 121 patients). ICU admission (33%), mechanical ventilation (26%), and inotrope/vasopressor therapy (26%) were common. Compared to children with JIA, those with SLE had a similar mortality rate (6% versus 11%, respectively; exact P = 0.6). More patients with SLE than those with JIA received ICU care (63% versus 27%; P = 0.002), received mechanical ventilation (53% versus 21%; P = 0.003), and had cardiovascular dysfunction (47% versus 23% received inotrope/vasopressor therapy; P = 0.02). Children with SLE and those with JIA received cyclosporine at similar rates, but more children with SLE received cyclophosphamide and mycophenolate mofetil, and more children with JIA received interleukin-1 antagonists. CONCLUSION: Organ system dysfunction is common in children with rheumatic diseases complicated by MAS, and more organ system support is required in children with underlying SLE than in children with JIA. Current treatment of pediatric MAS varies based on the underlying rheumatic disease.

Geographic Access to Pediatric Cancer Care in the US.

Importance: Although access to pediatric cancer care has implications for use of such care and patient outcomes, little is known about the geographic accessibility of pediatric cancer care and how it may vary by population characteristics across the continental US. Objective: To estimate the travel time to pediatric cancer care settings in the continental US, identify potential disparities among subgroups of children and adolescents and young adults (AYAs), and identify areas needing improved access to pediatric cancer care. Design, Setting, and Participants: This cross-sectional study collected data from August 1 to December 1, 2021. Pediatric oncologists' service locations in 2021 served as the pediatric cancer care settings, data for which were scraped from 2 websites containing information about health professionals. Demographic characteristics for younger children and AYAs aged 0 to 21 years were obtained from the 2015 to 2019 American Community Survey 5-year estimates. Data were analyzed from January 1 to April 31, 2022. Main Outcomes and Measures: The main outcome was the travel time from geographic centroids of zip code tabulation areas to the nearest pediatric oncologist. The median (IQR) travel times for each demographic subgroup were estimated. Per capita pediatric oncologist supply was calculated by dividing the total number of pediatric oncologists for each state or US Census division by its population. Results: Of the 90 498 890 children and AYAs included in the study, 63.6% were estimated to travel less than 30 minutes and 19.7% to travel between 30 and 60 minutes (for a total of 83.3%) to the nearest pediatric oncologist. Median (IQR) travel times were longest for the American Indian or Alaska Native pediatric population (46 [16-104] minutes) and residents of rural areas (95 [68-135] minutes), areas with high deprivation levels (36 [13-72] minutes), and the South (24 [13-47] minutes) and Midwest (22 [11-51] minutes) compared with the general population of children and AYAs. The pediatric oncologist supply was lowest in Wyoming (0 oncologists per 100 000 pediatric population) and highest in Washington, DC (53.3 oncologists per 100 000 pediatric population). Pediatric oncologist supply across Census divisions was lowest in the Mountain division (3.3 oncologists per 100 000 pediatric population) and highest in the New England division (8.1 oncologists per 100 000 pediatric population). Conclusions and Relevance: Results of this study showed that most children and AYAs in the continental US had adequate access to pediatric cancer care, although disparities existed among racial and ethnic groups and residents in rural areas, areas with high deprivation levels, and some Southern and Midwestern states. Reducing these disparities may require innovative approaches, such as expanding the capabilities of local facilities and creating partnerships with adult oncology centers and primary care physicians.

Limitations in health care access and utilization among long-term survivors of adolescent and young adult cancer.

BACKGROUND: Health care outcomes for long-term survivors of adolescent and young adult (AYA) cancer were compared with young adults without a cancer history, using the 2009 Behavioral Risk Factor Surveillance System data. METHODS: Eligible participants were 20 to 39 years of age. There were N = 979 who self-reported a cancer diagnosis between the ages of 15 to 34 years and were at least 5 years from diagnosis (excluding nonmelanoma skin cancer). The remaining 67,216 participants with no cancer history were used as controls. Using multivariable regressions, relative risks and 95% confidence intervals were generated to examine the relationship of survivor status on indicators of poor health care (uninsured, no personal health care provider, no routine care, and avoiding seeing a doctor due to cost). Adjusted proportions were calculated by demographic groups. Results are weighted by Behavioral Risk Factor Surveillance System survey design. RESULTS: Although the proportion uninsured did not differ (21% of survivors vs 23% of controls), AYA survivors reported forgoing care due to cost at higher levels than controls (relative risk = 1.67, 95% CI = 1.44-1.94). Cost barriers were particularly high for survivors aged 20 to 29 years (44% vs 16% of controls; P < .001) and female survivors (35% vs 18% of controls; P < .001). Survivors reporting poorer health had more cost barriers. Moreover, uninsured survivors tended to report lower use of health care than did controls. CONCLUSIONS: AYA cancer survivors may forgo health care due to cost barriers, potentially inhibiting the early detection of late effects. Expanding health insurance coverage for young cancer survivors may be insufficient without adequate strategies to reduce their medical cost burdens.