Rising drug cost impacts on cost-effectiveness of 2 chemotherapy regimens for intermediate-risk rhabdomyosarcoma: A report from the Children's Oncology Group.

BACKGROUND: The Children's Oncology Group clinical trial for intermediate risk rhabdomyosarcoma randomized participants to a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) alone or VAC alternating with vincristine plus irinotecan (VAC/VI). Clinical outcomes were similar, but toxicity profiles differed. This study estimates the cost differences between arms from the health care system's perspective. METHODS: A decision-analytic model was used to estimate the incremental cost-effectiveness ratio (ICER) of VAC versus VAC/VI. Protocol-required or recommended medications and laboratory studies were included. Costs were obtained from national databases or supporting literature and inflated to 2019 US dollars. Demographic and outcome data were obtained from the clinical trial and directed chart reviews. Life-years (LY) were estimated from life-expectancy tables and discounted by 3% annually. Probabilistic sensitivity analyses and alternative clinical scenarios identified factors driving costs. RESULTS: Mean direct medical costs of VAC and VAC/VI were $164,757 and $102,303, respectively. VAC was associated with an additional 0.97 LY and an ICER of $64,386/LY compared with VAC/VI. The ICER was sensitive to survival estimations and to alternative clinical scenarios including outpatient cyclophosphamide delivery (ICER $49,037/LY) or substitution of alternative hematopoietic growth factor schedules (ICER $73,191-$91,579/LY). Applying drug prices from 2012 decreased the total costs of VAC by 20% and VAC/VI by 15% because of changes in dactinomycin and pegfilgrastim prices. CONCLUSIONS: Neither arm was clearly more cost-effective. Pharmaceutical pricing and location of treatment drove costs and may inform future treatment decisions. Rising pharmaceutical costs added $30,000 per patient, a finding important for future drug-pricing policy decisions. LAY SUMMARY: Two chemotherapy regimens recently tested side-by-side for rhabdomyosarcoma had similar tumor outcomes, but different side effects. The health care costs of each regimen were compared; neither was clearly more cost-effective. However, the costs of each treatment changed dramatically with choices of supportive medicines and location of treatment. Costs of treatment rose by 15% to 20% because of rising US drug costs not associated with the clinical trial.

US private payers' perspectives on insurance coverage for genome sequencing versus exome sequencing: A study by the Clinical Sequencing Evidence-Generating Research Consortium (CSER).

PURPOSE: There is limited payer coverage for genome sequencing (GS) relative to exome sequencing (ES) in the U.S. Our objective was to assess payers' considerations for coverage of GS versus coverage of ES and requirements payers have for coverage of GS. The study was conducted by the NIH-funded Clinical Sequencing Evidence-Generating Research Consortium (CSER). METHODS: We conducted semi-structured interviews with representatives of private payer organizations (payers, N = 12) on considerations and evidentiary and other needs for coverage of GS and ES. Data were analyzed using thematic analysis. RESULTS: We described four categories of findings and solutions: demonstrated merits of GS versus ES, enhanced methods for evidence generation, consistent laboratory processes/sequencing methods, and enhanced implementation/care delivery. Payers see advantages to GS vs. ES and are open to broader GS coverage but need more proof of these advantages to consider them in coverage decision-making. Next steps include establishing evidence of benefits in specific clinical scenarios, developing quality standards, ensuring transparency of laboratory methods, developing clinical centers of excellence, and incorporating the role of genetic professionals. CONCLUSION: By comparing coverage considerations for GS and ES, we identified a path forward for coverage of GS. Future research should explicitly address payers' conditions for coverage.

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods.

PURPOSE: Methodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES. METHODS: We conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening. RESULTS: Reflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis. CONCLUSION: Our frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.

Using the Delphi method to identify clinicians' perceived importance of pediatric exome sequencing results.

PURPOSE: Information obtained from clinical exome sequencing (ES) may impact clinical care or other aspects of a patient's life. Little is known about clinicians' perceptions regarding either the value of ES results or which among various outcomes are most relevant to determine value. This study aims to assess clinicians' opinions of the importance of ES results for medical decision making and identify a set of outcomes to be measured in future ES evaluations. METHODS: Expert opinion regarding the value of remarkable (diagnostic/positive) and unremarkable (nondiagnostic/negative) ES results was elicited via the Delphi method, consisting of two survey rounds and a teleconference. Participants had expertise in caring for clinically diverse infants and children with suspected underlying genetic etiologies. Descriptive statistics and (dis)agreement were calculated for each survey item. RESULTS: Remarkable ES results were considered important for 17 outcome domains. Unremarkable ES results were also perceived as important in terms of psychological impact and ability to inform follow-up diagnostic test decisions. CONCLUSION: Clinicians regard remarkable ES results as more important in many ways than findings from other diagnostic modalities. Unremarkable ES results were not considered unimportant for decision making, but rather uncertain in most outcome domains.

Exome sequencing compared with standard genetic tests for critically ill infants with suspected genetic conditions.

PURPOSE: As exome sequencing (ES) is increasingly used as a diagnostic tool, we aimed to compare ES with status quo genetic diagnostic workup for infants with suspected genetic disorders in terms of identifying diagnoses, survival, and cost of care. METHODS: We studied newborns and infants admitted to intensive care with a suspected genetic etiology within the first year of life at a US quaternary-referral children's hospital over 5 years. In this propensity-matched cohort study using electronic medical record data, we compared patients who received ES as part of a diagnostic workup (ES cohort, n = 368) with clinically similar patients who did not receive ES (No-ES cohort, n = 368). RESULTS: Diagnostic yield (27.4% ES, 25.8% No-ES; p = 0.62) and 1-year survival (80.2% ES, 84.8% No-ES; p = 0.10) were no different between cohorts. ES cohort patients had higher cost of admission, diagnostic investigation, and genetic testing (all p < 0.01). CONCLUSION: ES did not differ from status quo genetic testing collectively in terms of diagnostic yield or patient survival; however, it had high yield as a single test, led to complementary classes of diagnoses, and was associated with higher costs. Further work is needed to define the most efficient use of diagnostic ES for critically ill newborns and infants.

Is high-risk neuroblastoma induction chemotherapy possible without G-CSF? A pilot study of safety and treatment delays in the absence of primary prophylactic hematopoietic growth factors.

BACKGROUND/OBJECTIVES: Standard supportive care during induction therapy for high-risk neuroblastoma (HR-NBL) includes primary prophylactic granulocyte colony-stimulating factor (G-CSF) aimed at limiting duration of neutropenia, reducing infection risk, and minimizing treatment delays. Preclinical models suggest that G-CSF promotes maintenance of neuroblastoma cancer stem cells and may reduce the efficacy of chemotherapy. This study's objective was to determine the safety and feasibility of administering induction chemotherapy without routine use of prophylactic G-CSF. DESIGN/METHODS: Children with newly diagnosed HR-NBL received six-cycle induction chemotherapy regimen without prophylactic G-CSF in four cycles. G-CSF was administered for stem cell mobilization after cycle 3 and granulocyte-monocyte colony-stimulating factor after cycle 5 prior to surgical resection of primary disease. The primary outcome measure was the incidence of grade 3 or higher infection. We hypothesized that the per patient infection rate would be comparable to our institutional baseline rate of 58% in patients with HR-NBL receiving induction chemotherapy with prophylactic growth factor support. The trial used an A'Hern single-stage design. RESULTS: Twelve patients with HR-NBL received 58 cycles of chemotherapy on study. Three patients completed the entire six-cycle regimen with no infections. Nine patients experienced grade 3 infections (bacteremia four, urinary tract infection two, skin/soft tissue infection three). No patients experienced grade 4 infections or required intensive care treatment for infection. CONCLUSION: A greater than expected number of serious bacterial infections were observed during administration of induction chemotherapy for HR-NBL without primary prophylactic G-CSF. These results support continued prophylactic administration growth factor during induction chemotherapy.

Blood product administration during high risk neuroblastoma therapy.

The increasing intensity of high-risk neuroblastoma (HR NB) treatment over the last decades has resulted in improved survival at the expense of prolonging therapy and exposure to additional potentially toxic agents. Anemia and thrombocytopenia requiring transfusion are common during therapy for HR NB. Risks of cumulative red blood cell and platelet transfusions are incompletely defined in pediatric oncology patients, however, risks of transfusional iron overload are well described in other populations. This study aimed to determine the number of packed red blood cell (pRBC) and platelet transfusions throughout treatment for HR NB and how these numbers have changed with modern therapy. We performed a retrospective review of 92 patients with HR NB from June 2002 until September 2017. Patients received a median of 20 pRBC and 32 platelet transfusions. Our results demonstrated large numbers of transfusions with significantly increased blood product exposures among patients who received intensified therapy, either with additional induction chemotherapy, tandem autologous stem cell transplants, or dinutuximab plus cytokines with isotretinoin. Similar volumes of pRBC transfusions have been associated with iron overload in other populations and warrant further discussion of guidelines for long-term follow up of HR NB patients.

Clinical Application of Genome and Exome Sequencing as a Diagnostic Tool for Pediatric Patients: a Scoping Review of the Literature.

PURPOSE: Availability of clinical genomic sequencing (CGS) has generated questions about the value of genome and exome sequencing as a diagnostic tool. Analysis of reported CGS application can inform uptake and direct further research. This scoping literature review aims to synthesize evidence on the clinical and economic impact of CGS. METHODS: PubMed, Embase, and Cochrane were searched for peer-reviewed articles published between 2009 and 2017 on diagnostic CGS for infant and pediatric patients. Articles were classified according to sample size and whether economic evaluation was a primary research objective. Data on patient characteristics, clinical setting, and outcomes were extracted and narratively synthesized. RESULTS: Of 171 included articles, 131 were case reports, 40 were aggregate analyses, and 4 had a primary economic evaluation aim. Diagnostic yield was the only consistently reported outcome. Median diagnostic yield in aggregate analyses was 33.2% but varied by broad clinical categories and test type. CONCLUSION: Reported CGS use has rapidly increased and spans diverse clinical settings and patient phenotypes. Economic evaluations support the cost-saving potential of diagnostic CGS. Multidisciplinary implementation research, including more robust outcome measurement and economic evaluation, is needed to demonstrate clinical utility and cost-effectiveness of CGS.

Payer and race/ethnicity influence length and cost of childhood cancer hospitalizations.

BACKGROUND: Health disparities related to race, ethnicity, socioeconomic status, and insurance status impact quality, access, and health outcomes for children. Medicaid is a proxy for poverty and restricted access to health care. The goal of this study was to determine if there are discrepancies in the length and cost of hospitalizations between admissions covered by Medicaid or commercial insurance for pediatric patients with cancer. METHODS: Childhood cancer-related admissions were identified from the 2012 Kids Inpatient Database (KID) using the International Classification of Diseases, Ninth revision. Length of hospitalization and cost of hospitalization were compared among hospitalizations paid by Medicaid or commercial insurance. Total admission charges were converted to costs using cost-to-charge ratios, and survey weighting methods were used for all analyses. Linear multiple regression models for both length of hospitalization and cost were developed to include patient-level factors (race, sex, age, diagnosis, reason for admission). RESULTS: In 2012, there were 104 597 childhood cancer-related admissions. Hospitalizations paid by Medicaid were significantly longer than those paid by commercial insurance. Hispanic ethnicity was associated with higher cost of hospitalization regardless of payer, and black race was associated with higher costs within the Medicaid population. CONCLUSIONS: This analysis identifies differences in healthcare utilization for pediatric cancer-related admissions paid for by Medicaid compared with commercial insurance. Prolonged hospitalizations and increased costs create burdens on children and their families, medical delivery systems, and third-party payers. Further exploration into the causes of these disparities is warranted.

Neuroblastoma of the Bone and Bone Marrow Without an Apparent Primary Site: Report of 4 Cases With Long-term Follow-up.

Children with neuroblastoma rarely present with metastatic disease without identifiable primary tumors. We describe the clinical and histopathologic characteristics of 4 patients aged 1, 7, 7, and 11 years with neuroblastoma involving bone or bone marrow without an apparent primary site. One patient presented with a periorbital bone lesion, 1 presented with a distal femoral lesion, and 2 presented with diffuse bone marrow involvement. All tumors were negative for MYCN amplification. All patients were alive without evidence of disease 5 years after completion of multimodality therapy. Patients with neuroblastoma of the bone and bone marrow without an apparent primary site may constitute a unique group characterized by older age at diagnosis, nonamplified MYCN tumors, and good response to treatment.

An overview of disparities in childhood cancer: Report on the Inaugural Symposium on Childhood Cancer Health Disparities, Houston, Texas, 2016.

The Inaugural Symposium on Childhood Cancer Health Disparities was held in Houston, Texas, on November 2, 2016. The symposium was attended by 109 scientists and clinicians from diverse disciplinary backgrounds with interests in pediatric cancer disparities and focused on reviewing our current knowledge of disparities in cancer risk and outcomes for select childhood cancers. Following a full day of topical sessions, everyone participated in a brainstorming session to develop a working strategy for the continued expansion of research in this area. This meeting was designed to serve as a springboard for examination of childhood cancer disparities from a more unified and systematic approach and to enhance awareness of this area of need.

Using decision modeling to guide drug allocation during a shortage.

BACKGROUND: Drug shortages require clinical teams to decide how to allocate drugs in limited supply among their patients. Ethical frameworks are invaluable for promoting rational approaches to drug distribution, but gaps remain between ethical theory and clinical application. The goal of this work was to explore how decision modeling could supplement ethical frameworks to inform drug distribution from the perspective of a clinical team. PROCEDURE: We created a hypothetical pediatric oncology clinic with a limited supply of 50,000 mg of methotrexate (MTX) and 21 patients due for treatment on one of six regimens. We constructed a simple decision analytic model to compare the effectiveness of MTX in milligrams per life year saved for each regimen. The robustness of the model was tested under various conditions including alternative drug effectiveness and time horizons. Effects on outcomes and distribution by substituting alternative dosing were explored for each regimen. RESULTS: Prescribed therapy for this group of patients required 108,791 mg MTX. Two regimens for three patients required ≥20,000 mg/m2 . If distributed in order of arrival, only seven patients could receive full treatment. If distributed in order of efficiency, 19 patients could receive treatment. If less effective regimens were substituted, 20 patients could receive treatment. The primary driver of efficiency was dose per square meter. CONCLUSIONS: In this hypothetical drug shortage, no allocation scenario exists that does not result in a worse outcome for some patients. Evidence of drug efficacy affected the decisions to substitute alternative treatments. First-come-first-served allocation resulted in fewer patients receiving treatment than allocation based on efficiency.

Incidence and risk factors of bacterial and fungal infection during induction chemotherapy for high-risk neuroblastoma.

High-risk neuroblastoma is an aggressive childhood cancer with poor outcomes. Treatment begins with an induction phase comprised of intense multi-agent chemotherapy with the goal of maximally reducing tumor bulk. Given the high intensity of induction chemotherapy, neutropenic fever and infectious complications are common; however, the actual incidence is difficult to determine from clinical trial reports. We performed a retrospective review of infection-related complications in 76 children treated for high-risk neuroblastoma at Texas Children's Hospital. Medical records were reviewed for demographics, febrile neutropenia (FN) episodes, presence, and type of bacterial and fungal infections, and potential risk factors for infection. Fifty-seven percent of patients developed one or more serious bacterial or fungal infections during induction chemotherapy. Additionally, over 75% of patients had at least one admission for FN. Risk factors for developing any infection included female sex, MYCN amplification, and having Medicaid. Patients with external central venous catheters and those requiring parenteral nutrition had higher rates of bacteremia or fungemia. Each cycle, 50% were readmitted for either FN or infection. The overall burden of infectious complications was high, with 70% having two or more unplanned admissions for infection or FN. The incidence of febrile neutropenia and serious bacterial and fungal infections during induction chemotherapy for high-risk neuroblastoma is high. Most patients had at least two additional hospitalizations for infectious complications. Risk factors including female sex, MYCN amplification, payer status, and type of central access were associated with higher rates of infection in this cohort. ABBREVIATIONS: CLABSI Central line associated blood stream infection; CTCAE Common Terminology Criteria for Adverse Events; FN Febrile neutropenia; ANC Absolute neutrophil count; TPN Total parenteral nutrition.

Does Routine Imaging of Patients for Progression or Relapse Improve Survival in Rhabdomyosarcoma?

BACKGROUND: Patients with rhabdomyosarcoma (RMS) who complete therapy typically undergo 4 years of surveillance imaging despite lack of evidence that this improves outcomes. We compared overall survival (OS) between patients in whom progression or relapse was detected by routine clinical evaluation or by imaging. PROCEDURE: Children with progressive or relapsed RMS treated at Texas Children's Hospital between 1992 and 2012 were identified and their records were reviewed. Survival time after progression or relapse was compared between two groups: (1) patients in whom progression or relapse was suspected on the basis of clinical history, symptoms, laboratory evaluation, or physical exam; and (2) patients whose progression or relapse was initially detected by imaging. RESULTS: Of the 43 children with progressive or relapsed RMS, 26 (60%) had metastatic disease at diagnosis and 19 (44%) had alveolar histology. With a median follow up time of 5 years in six survivors, there was no difference in OS between patients in whom progression or relapse was diagnosed based on imaging (n = 15) or by clinical evaluation (n = 28) (3-year OS 20% vs. 11%, respectively, P = 0.38). Disease extent, primary site, and risk group at diagnosis were associated with survival after progression or relapse. CONCLUSIONS: Routine surveillance imaging practice should be critically reviewed for children with RMS. Although our findings must be validated by larger studies, they do have substantive implications. Reduced imaging tailored to the risk and pattern of recurrence, associated risks and cost could improve patient quality of life and decrease health-care expenditure without compromising outcome.

Inpatient versus outpatient vincristine, dactinomycin, and cyclophosphamide for pediatric cancers: Quality and cost implications.

BACKGROUND: Approximately 18% of the United States' gross domestic product is attributed to healthcare expenditures. Several studies have illustrated that shifting healthcare from the inpatient to the outpatient setting is more cost effective, in addition to improving patient satisfaction. Vincristine, dactinomycin, and cyclophosphamide (VAC) are used together to treat children with solid tumors. Our traditional treatment approach included a two day inpatient admission. The purpose of this project was to establish a process for the administration of VAC in the outpatient setting to improve satisfaction, and reduce costs. PROCEDURE: We aimed to benchmark practice standards with other institutions, revised our treatment approach to permit outpatient administration, and implemented the new protocol in a stepwise manner. We collected caregiver satisfaction metrics through the use of surveys. Costs of encounters were obtained from administrative data. Total costs and costs by service type were compared using descriptive and mean comparisons. RESULTS: Seven patients received a total of 31 cycles of VAC in the outpatient setting. The time to achieve an appropriate pre-chemotherapy specific gravity was reduced by a median of 120 min. In addition, time spent in the hospital setting was reduced by a mean of 27.2 hr. Adverse effects were minimal and all caregivers reported greater satisfaction with the outpatient regimen. Outpatient administration of VAC was $3,300 less on average compared to the inpatient administration. CONCLUSION: Outpatient VAC provides a safe alternative for administration that reduces healthcare costs, reduces healthcare utilization, and improves patient satisfaction.

Algorithm for analysis of administrative pediatric cancer hospitalization data according to indication for admission.

BACKGROUND: Childhood cancer relies heavily on inpatient hospital services to deliver tumor-directed therapy and manage toxicities. Hospitalizations have increased over the past decade, though not uniformly across childhood cancer diagnoses. Analysis of the reasons for admission of children with cancer could enhance comparison of resource use between cancers, and allow clinical practice data to be interpreted more readily. Such comparisons using nationwide data sources are difficult because of numerous subdivisions in the International Classification of Diseases Clinical Modification (ICD-9) system and inherent complexities of treatments. This study aimed to develop a systematic approach to classifying cancer-related admissions in administrative data into categories that reflected clinical practice and predicted resource use. METHODS: We developed a multistep algorithm to stratify indications for childhood cancer admissions in the Kids Inpatient Databases from 2003, 2006 and 2009 into clinically meaningful categories. This algorithm assumed that primary discharge diagnoses of cancer or cytopenia were insufficient, and relied on procedure codes and secondary diagnoses in these scenarios. Clinical Classification Software developed by the Healthcare Cost and Utilization Project was first used to sort thousands of ICD-9 codes into 5 mutually exclusive diagnosis categories and 3 mutually exclusive procedure categories, and validation was performed by comparison with the ICD-9 codes in the final admission indication. Mean cost, length of stay, and costs per day were compared between categories of indication for admission. RESULTS: A cohort of 202,995 cancer-related admissions was grouped into four categories of indication for admission: chemotherapy (N=77,791, 38%), to undergo a procedure (N=30,858, 15%), treatment for infection (N=30,380, 15%), or treatment for other toxicities (N=43,408, 21.4%). The positive predictive value for the algorithm was >95% for each category. Admissions for procedures had higher mean hospital costs, longer hospital stays, and higher costs per day compared with other admission reasons (p<0.001). CONCLUSIONS: This is the first description of a method for grouping indications for childhood cancer admission within an administrative dataset into clinically relevant categories. This algorithm provides a framework for more detailed analyses of pediatric hospitalization data by cancer type.

Healthcare Spending and Systemic Bevacizumab for Recurrent Respiratory Papillomatosis.

OBJECTIVES: Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a rare, costly condition linked to human papillomavirus. Standard of care is serial surgical debridement. Many adjunctive therapies have been trialed, with recent success with systemic bevacizumab. This paper examines healthcare spending associated with systemic bevacizumab use for JoRRP and compares it to healthcare spending for surgical care alone to determine whether bevacizumab has a financial benefit. METHODS: Five patients treated with systemic bevacizumab for JoRRP were identified at a single institution. Spending data was derived from the electronic medical record. Sensitivity analysis was performed using variation in spending and frequency of treatments. RESULTS: Patients had an average of 4.2 treatments per year prior to bevacizumab (95% confidence interval [CI] 1.4-7.0) and 1.1 after (0.2-2.0). Patients underwent an average of 9.2 bevacizumab treatments in their first year after initiation, 4.0 in the second, and 4.5 in their third. Mean payment per debridement was $3198 ($2856-3539), with mean total surgical payment per year of $17,966 ($11,673-24,259) prior to initiating bevacizumab. Mean payment on a single bevacizumab infusion visit was $6508 ($6063-6952). Mean total surgical and bevacizumab spending per year after bevacizumab initiation were $83,951 ($12,938-154,964). CONCLUSIONS: Accounting for variations in the number of treatments per year with bevacizumab after initiation, healthcare spending after bevacizumab initiation is similar to spending on surgery alone for JoRRP in patients with severe disease.

Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma.

We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBV-CTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the long-term clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome. We observed persistence for up to 192 weeks for CAR-ATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4(+) cells and central memory cells (CD45RO(+)CD62L(+)) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #NCT00085930.

Parent-Reported Clinical Utility of Pediatric Genomic Sequencing.

BACKGROUND AND OBJECTIVES: Genomic sequencing (GS) is increasingly used for diagnostic evaluation, yet follow-up care is not well understood. We assessed clinicians' recommendations after GS, parent-reported follow-up, and actions parents initiated in response to learning their child's GS results. METHODS: We surveyed parents of children who received GS through the Clinical Sequencing Evidence Generating Research consortium ∼5 to 7 months after return of results. We compared the proportion of parents who reported discussing their child's result with a clinician, clinicians' recommendations, and parents' follow-up actions by GS result type using χ2 tests. RESULTS: A total of 1188 respondents completed survey measures on recommended medical actions (n = 1187) and/or parent-initiated actions (n = 913). Most parents who completed recommended medical actions questions (n = 833, 70.3%) reported having discussed their child's GS results with clinicians. Clinicians made recommendations to change current care for patients with positive GS results (n = 79, 39.1%) more frequently than for those with inconclusive (n = 31, 12.4%) or negative results (n = 44, 11.9%; P < .001). Many parents discussed (n = 152 completed, n = 135 planned) implications of GS results for future pregnancies with a clinician. Aside from clinical recommendations, 13.0% (n = 119) of parents initiated changes to their child's health or lifestyle. CONCLUSIONS: In diverse pediatric clinical contexts, GS results can lead to recommendations for follow-up care, but they likely do not prompt large increases in the quantity of care received.