Febrile neutropenia is the most common reason for admission from the emergency department for pediatric oncology patients. We identified pediatric inpatients age 1 to 21 years with an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code of malignancy and either fever with neutropenia or fever alone over a 6-year period (2007-2012) using the PHIS+ database. We evaluated factors associated with readmission within 7 days after index hospitalization. There were 4029 index hospitalizations among 2349 patients in 6 hospitals, 294 encounters (7.3%) were followed by readmission within 7 days. Factors associated with increased odds of readmission included being in the lowest quartile for median household income (odds ratio [OR]=1.64, P=0.009), diagnosis of acute lymphoblastic leukemia (OR=1.37, P=0.016), lack of anerobic coverage during index hospitalization (OR=1.48, P=0.026), and absolute neutrophil count <200 cells/μL at discharge from index hospitalizations (OR=1.55, P=0.008). Patients who required readmission had a longer median length of stay and greater hospitalization costs during the index hospitalization. There was a trend towards increasing hospitalization rates for febrile neutropenia over time. While absolute neutrophil count is incorporated into many risk stratification strategies for fever management, further work should focus on addressing socioeconomic factors which may impact readmission rates.

Pleuropulmonary blastoma (PPB) is a rare pediatric tumor of the pleura and pulmonary mesenchyme, associated with pathogenic germline DICER1 mutations. Although the most common site of metastasis is the central nervous system (CNS), patients with CNS metastasis have dismal outcome. We report a case of a patient presenting with type II PPB and intracranial and bone metastases. We describe a multimodal therapy approach and highlight the use of intraventricular topotecan for isolated CNS recurrence. In addition, a new pathogenic germline mutation heterozygous for the c.1234delT of DICER1 was identified. Patient remains in remission 3 years after recurrence.

Isolated endobronchial inflammatory myofibroblastic tumors (IMT) are rare, accounting for about 1% of primary endobronchial tumors in children. The mainstay of treatment for this tumor has been surgical resection. Recently, the identification of anaplastic lymphoma kinase (ALK) gene mutations in half of IMTs and promising results of treatment with ALK inhibitors in other ALK-positive tumors have opened the possibility of alternative approaches. We present a 4-year-old child with an ALK-positive endobronchial IMT, treated with endoscopic resection and neoadjuvant therapy with crizotinib, without evidence of tumor recurrence 2 years after the initial resection.

Unresectable hepatocellular carcinoma (HCC) was first removed successfully with total hepatectomy and liver transplantation (LT) in a child over five decades ago. Since then, children with unresectable liver cancer have benefitted greatly from LT and a confluence of several equally important endeavors. Regional and trans-continental collaborations have accelerated the development and standardization of chemotherapy regimens, which provide disease control to enable LT, and also serve as a test of unresectability. In the process, tumor histology, imaging protocols, and tumor staging have also matured to better assess response and LT candidacy. Significant trends include a steady increase in the incidence of and use of LT for hepatoblastoma, and a significant improvement in survival after LT for HCC with each decade. Although LT is curative for most unresectable primary liver sarcomas, such as embryonal sarcoma, the malignant rhabdoid tumor appears relapse-prone despite chemotherapy and LT. Pediatric liver tumors remain rare, and diagnostic uncertainty in some settings can potentially delay treatment or lead to the selection of less effective chemotherapy. We review the current knowledge relevant to diagnosis, LT candidacy, and post-transplant outcomes for these tumors, emphasizing recent observations made from large registries or larger series.

There are nearly 70,000 new cancer diagnoses made annually in adolescents and young adults (AYAs) in the United States. Historically, AYA patients with cancer, aged 15 to 39 years, have not shown the same improved survival as older or younger cohorts. This article reviews the contemporary cancer incidence and survival data through 2015 for the AYA patient population based on the National Cancer Institute's Surveillance, Epidemiology, and End Results registry program and the North American Association of Central Cancer Registries. Mortality data through 2016 from the Centers for Disease Control and Prevention's National Center for Health Statistics are also described. Encouragingly, absolute and relative increases in 5-year survival for AYA cancers have paralleled those of childhood cancers since the year 2000. There has been increasing attention to these vulnerable patients and improved partnerships and collaboration between adult and pediatric oncology; however, obstacles to the care of this population still occur at multiple levels. These vulnerabilities fall into 3 significant categories: research efforts and trial enrollment directed toward AYA malignancies, access to care and insurance coverage, and AYA-specific psychosocial support. It is critical for providers and health care delivery systems to recognize that the AYA population remains vulnerable to provider and societal complacency.

1570 Background: Adolescents and young adults (AYA) aged 15-39 years make up approximately 70,000 new oncology cases in the USA. Historically, mortality from cancer has smaller incremental improvements in AYA patients when compared to children and older adults, and not much is known about current sex-specific trends. We assessed overall and sex specific AYA mortality for the last 10 years (2007-2016). Methods: Trends in age-adjusted mortality rates per 100,000 (1972-2016) were obtained from the CDC’s National Center for Health Statistics (NCHS). Average annual percent changes (AAPCs) in relative survival were analyzed using NCI’s JPSurv webtool and mortality AAPCs were quantified using Joinpoint regression analysis. Results: Overall declines in mortality are similar in AYA men and women from 1972-2016, with 54% and 51% decline, respectively. In the most recent 10 years of data (2007 to 2016), combined sex AYA mortality AAPC’s declined by about 0.8% per year, slightly slower than declines in children <15 years (1.3% per year) and adults ages >40 years (1.5% per year). Among AYA males there have been 10 year AAPC mortality declines in leukemia (-1.8%), Hodgkin lymphoma (HL) (-5.1%), Non-Hodgkin lymphoma (NHL) (-4.1%) and melanoma of the skin (-3.4%). For AYA females, 10 year AAPC mortality declines occurred in leukemia (-1.9%), ovarian (-1.5%), HL (-10%), NHL (-4.9%) and melanoma (-2.8%). These declines have been offset by stable or increasing mortality rates for several common AYA cancers, including colorectal cancer (CRC) (1.1%) and bone and joint cancer (0.6%) in AYA males. AYA females have experienced mortality increases for CRC (0.6%), bone and joint cancer (0.5%) and uterine corpus cancer (2.8%). Conclusions: In general, mortality rates for both AYA men and women have declined over the past 10 years due to decreased mortality in hematologic malignancies and melanoma. Despite overall improvement, tumor categories in both AYA males and female such as CRC, bone and joint cancer, and uterine corpus cancers show increasing mortality. These diseases require specific investigations by both pediatric and adult researchers.

Background: Renal medullary carcinoma (RMC) is a rare, aggressive form of renal cell carcinoma almost exclusively (>90%) diagnosed in individuals with sickle cell trait (SCT), and 2/3 of those affected are male. Based on population-surveillance data, only 246 patients were diagnosed with RMC between 2005-2014 (Carden etal. J Sickle Cell Disease and Hemoglobinopathies, 2018) and many patients have metastatic disease at diagnosis (Msaeoul et al., Clin Genitourin Cancer, 2019). Median overall survival (OS) in patients with metastatic RMC (mRMC) at diagnosis is less than 12 months and predictors of survival are largely unknown, although case reports suggest novel chemotherapeutic strategies are important (Carden et al., Ped Blood Cancer, 2017&2018). The role SCT plays in RMC pathobiology, however, is largely unknown, as many patients do not have a complete hemoglobin subtype profile completed at diagnosis. Studies evaluating sickle hemoglobin concentrations (%HbS) in relation to survival for patients with RMC are needed, as SCT is associated with renal dysfunction and researchers have hypothesized that HbS polymerization within red cells traversing the kidney disrupts blood perfusion, which leads to kidney injury and an increased possibility for cancer formation (Msaeoul et al, Clin Cancer Res, 2018). Patients with %HbS≤36%, such as patients with SCT and concomitant alpha-globin gene deletion(s) might be protected against HbS polymerization and renal concentrating defects (Gupta etal., J Clin Invest, 1991). We hypothesize that lower %HbS is associated with higher survival. In this preliminary multi-institutional study, we retrospectively reviewed available charts from patients diagnosed with mRMC and SCT to evaluate for an association between %HbS and OS. Methods: We found nine patients (3 adults, 6 children) who were diagnosed with mRMC and SCT at our various institutions between 2002-2017 who had survival data. Eight patients had %HbS levels by hemoglobin quantification at diagnosis. In a post-hoc analysis, patients were separated into two groups (%HbS>36% and %HbS≤36%), levels similar to that found in patients with alpha-globin gene deletions described by Gupta et al. Fit-curves were determined for OS vs. %HbS. Three-year OS was determined using Kaplan-Meier analysis and the log-rank method. P<0.05 was considered statistically significant. Results: Clinical characteristics of patients are shown in Table 1. Average age (standard deviation) at diagnosis was 15.2 years (4.9) and most patients were male (87.5%). Six patients had %HbS >36% and 2 patients had %HbS ≤36%. Median OS was 17.8 months. Using fit-function testing, analysis of survival vs. %HbS yielded an exponential relationship (R2=0.69), suggesting higher survival when %HbS≤36% (p=0.05). OS of the two patients with %HbS≤36% was greater than those with %HbS>36%, though results were not statistically significant (p = 0.09). Conclusion: While there are limitations to this small, retrospective analysis, these data suggest that lower intracellular red cell %HbS concentrations could be protective in patients with mRMC and SCT. Chemotherapy and other treatment regimens may also play a role in survival and need to be studied. Further investigation is needed to determine the role SCT plays in RMC pathobiology and to determine if %HbS concentrations, as well as alpha-thalassemia deletion(s), may be protective in patients with RMC. Disclosures Carden: GBT: Honoraria; NIH: Research Funding.

10062 Background: Despite significant advances in diagnosing and treating hemophagocytic lymphohistiocytosis (HLH) in the pediatric population, survival remains low and the extent of disease morbidity and health care utilization is poorly characterized. Thus, we sought to investigate morbidity, mortality, and the health care burden of HLH in a pediatric population. Methods: We queried the Pediatric Health Information System (PHIS) for children admitted with HLH and treated with etoposide and dexamethasone between 1/1/2004 – 9/30/2018. Collected data included demographics and clinical variables associated with morbidity and mortality. Results: A total of 493 patients (10.5 per 100,000 patients admitted) met inclusion criteria during the study period. The majority of patients (n = 284, 58%) were less than 5 years of age. A total of 331 patients were readmitted after the initial hospitalization, with 29% of readmissions complicated by infections. Median cost for initial hospitalization was $101,906 (IQR: $47,552 – $271,822). A significant number of patients required ICU care during both the initial admission (60%) and readmission (57%). Hematopoietic stem cell transplant (HSCT) was performed in 136 patients (28%) with a median time to HSCT of 126 days (IQR: 75-193 days). Overall mortality was 32% (n = 158), half occurring during the initial admission. There was a trend towards increased mortality in younger age groups. Median time to death during and after the initial admission was 45 days (IQR: 20-84 days) and 198 days (IQR: 108-368 days), respectively. Post-HSCT mortality rate was 35%. Conclusions: This represents the largest cohort of pediatric patients treated for HLH. Overall and post-HSCT mortality was consistent with prior publications. We observed significant morbidity and increased health care resource utilization in our cohort. These findings emphasize the need for novel therapeutic approaches to improve not only patient survival but also long-term quality of life. Planned future analysis of the PHIS data will be aimed at assessing treatment variability, morbidity and mortality depending on treatment, and risk factors associated with mortality in pediatric patients with HLH.

Background Hemophagocytic lymphohistiocytosis (HLH) is a severe life threatening hyper-inflammatory syndrome of abnormal immune activation and dysregulation if untreated. The 5-year probability of survival (pSu) obtained from HLH registries and treatment protocols HLH-94 and HLH-2004 ranges from 21%-64%, with improved 5-year pSu of up to 70% following hematopoietic stem cell transplant (HSCT) (Arico et al., Trottestam et al., Bergsten et al.). Despite significant advances in the management of HLH over time, survival remains low and the extent of disease morbidity and healthcare utilization is poorly characterized. In this study, we sought to investigate morbidity, mortality, and the healthcare burden in children and adolescents with HLH who underwent HSCT. Methods Using the Pediatric Health Information System (PHIS) database, we identified patients under the age of 21 years admitted between 01/01/2004 and 09/30/2018 with a primary or secondary ICD-9 or ICD-10 diagnosis codes for HLH, as well as concurrent medication charges for both dexamethasone and etoposide in the same encounter. We then identified the patients who underwent HSCT to further analyze them. We abstracted data on demographics, hospitalizations, HSCT related complications, mortality, resource utilization and costs. Results were summarized using descriptive statistics. Time to HSCT was calculated as elapsed time from the admission date of the initial encounter to the date of the encounter in which there was a procedure code for HSCT. Time to mortality event was calculated as elapsed time from the admission date of the initial encounter to the discharge date of the encounter in which mortality occurred. The PHIS database provides an encrypted patient medical record number; thus, we were able to follow patients over time. This allowed for a better visualization of the patient's hospitalizations trend over 14 years. Results A total of 493 patients met inclusion criteria for HLH during the study period from 52 children's hospitals. The majority of patients (n = 284, 58%) were less than 5 years of age. Of these, 136 patients (28%) underwent HSCT with 155 hospital encounters, including readmissions. The median age at the time HSCT was 2 years (IQR; 0-9 years) and there were 82 males (60%). The median time to HSCT was 126 days (IQR: 75-193 days) and the average length of stay for the initial HSCT hospitalization was 61.1 days. Median initial HSCT hospitalization cost was $463,630 (IQR; 230,795 - 558,533). ICU care was required for 71 (46%) of patients. Overall, 91 (67%) patients developed transplant-related complications, which included infections, sinusoidal obstruction syndrome or graft versus host disease (Table 1). Mortality after HSCT was 22% (n=30) with an increased mortality observed with advanced age at the time of HSCT (Figure 1). The median time to death after the initial HSCT admission was 65 days (IQR; 56-94 days). Conclusion This is a large in-patient cohort of pediatric patients with HLH who underwent HSCT in the US. We observed an improved overall mortality after HSCT in this population compared to previous studies. However, morbidity (particularly from infections) and heath care resource utilization remain high. This stresses the importance of novel therapeutic approaches to improve not only patient survival but also long-term quality of life. Planned future analysis of this database will be aimed at assessing treatment variability; morbidity and mortality by treatment regimen, time to HSCT, and HSCT preparative regimen; and risk factors associated with mortality in pediatric patients with HLH who do and do not undergo HSCT. Disclosures No relevant conflicts of interest to declare.

There is no established salvage regimen for pediatric patients with relapsed nasopharyngeal carcinoma (NPC) and outcomes are dismal. We performed a multicenter retrospective review to determine outcomes after first salvage therapy for pediatric patients with relapsed NPC. Fourteen patients were treated with varied regimens. Two of the 14 patients received oxaliplatin‐containing regimens and achieved a long‐term complete response. Although definitive recommendations cannot be made based on outcomes for 14 patients who received varied regimens, we discuss justification for an oxaliplatin‐containing regimen in combination with gemcitabine as a reasonable choice for first‐line salvage therapy for pediatric patients with relapsed NPC.

Renal medullary carcinoma (RMC) was first described over two decades ago as the seventh sickle nephropathy. Survival after diagnosis with metastatic disease still rarely extends beyond 1 year, with recent reports of median overall survival in patients treated with platinum therapy being just 10 months. We describe our experience using platinum-based chemotherapy plus the proteasome inhibitor bortezomib to treat metastatic RMC in two pediatric patients who had complete responses. One patient passed away 7 years after diagnosis, while another remains disease free nearly 2 years from diagnosis.

Desmoplastic spindle cell tumors of liver are rare tumors of low malignant potential characterized by well-demarcated nests of spindle and epithelioid cells in a dense desmoplastic stroma. While surgery remains the definitive treatment, there have been reports of tumor recurrence locally and metastasis which respond poorly to chemotherapy. Hepatic transplant has been attempted in cases of recurrence or large size of primary tumor. Long-term follow-up and imaging surveillance are required as these tumors have shown a tendency for recurrence many years after initial therapy.

Primary hepatic neoplasms are rare and account for only - of all childhood cancers. Hepatoblastoma accounts for approximately two-thirds of liver tumors in children. Hepatoblastoma and hepatocellular carcinoma (HCC) are the two most common malignancies that arise de novo in the liver. Table 30.1 lists the most prevalent malignant and benign liver tumors in children.

Background The type of treatment center where 15–21‐year‐old adolescent and young adult (AYA) patients with rare pediatric tumors achieve their best clinical outcome is unknown. Procedure We performed a retrospective analysis using the Georgia Cancer Registry (GCR) of 15–21‐year old patients with a malignant, rare pediatric tumor diagnosed during the period from 2000–2009. Patients were identified as being treated at one of five Georgia pediatric cancer centers or at an adult center. Data were analyzed for 10 year overall survival, patient characteristics associated with death, and patient characteristics present at diagnosis associated with choice of treatment center. Results There was a total of 479 patients in our final study population, of which 379 (79.1%) were treated at an adult center and 100 (20.9%) were treated at a pediatric center. Patients treated at an adult center had a 10 year overall survival of 86% compared to 85% for patients treated at a pediatric center ( P = 0.31). Race and poverty were not significantly associated with death. Patients with nasopharyngeal carcinoma (OR = 7.38; 95% CI = 2.30–23.75) and ‘other carcinomas' (OR = 2.64; 95% CI = 1.25–5.60) were more likely to be treated at a pediatric center. Patients with higher‐stage disease (OR = 4.24; 95% CI = 1.71–10.52) and higher poverty (OR = 2.32; 95% CI = 1.23–4.37) were also more likely to be treated at a pediatric center. Conclusion Our data suggest that there is no difference in survival for 15–21‐year old patients with rare pediatric tumors when treated at an adult or pediatric center. Pediatr Blood Cancer 2015;62:456–462. © 2014 Wiley Periodicals, Inc.

BACKGROUND/AIMS:To report a case of subretinal bone formation after the treatment with denosumab for a giant cell tumor of the sphenoid, which had recurred after surgical resection.METHODS:The clinical history and fundus findings including imaging, histologic and immunohistochemical features of the primary tumor and subretinal lesion were reviewed.RESULTS:A 14-year-old boy was evaluated for a suprasellar mass. Resection of the lesion showed giant cell tumor of bone (GCT). An MRI study at the 1-month follow-up appointment showed tumor progression, and denosumab was initiated. Two months after the initial presentation, the patient developed a worsening scotoma of the right eye. Dilated fundus examination showed a yellow-tan-colored subretinal mass temporal to the fovea. The subretinal lesion was removed and showed lamellar bone with associated fibrocellular tissue.CONCLUSION:Denosumab therapy for GCT of the sphenoid may be associated with subretinal bone formation.

Atypical teratoid rhabdoid tumors (AT‐RT) are pediatric tumors of the central nervous system with limited treatment options and poor survival rate. We investigated whether enhancing chemotherapy toxicity by depleting intracellular glutathione (GSH; a key molecule in cisplatin resistance) with high dose acetaminophen (AAP), may improve therapeutic efficacy in AT‐RT in vitro.

Background Patients with relapsed pediatric sarcomas have a poor outcome and are in need of novel effective therapies. Methods We retrospectively reviewed the records of patients at Children's Healthcare of Atlanta who were treated with gemcitabine (675?mg/m2) intravenously (IV) on Day 1 and Day 8, and docetaxel (75?mg/m2) IV on Day 8, repeated every 3 weeks. Results Nineteen patients with a median age of 11 years were treated from 2006-2010 and received 123 total courses. Two patients (11%), both with rhabdomyosarcoma, demonstrated objectives responses [one complete response (CR) and one partial response (PR)]. Seven other patients (39%) had stable disease (SD). The 1-year progression-free survival (PFS) of the entire cohort was 24%+/- 10% with a median time to progression of 2 months (range: 0.514 months). The 1-year overall survival (OS) was 43%+/- 11%. Grade 3 or 4 toxicities occurred in 14 patients (74%) and 52 courses (42%), and were most commonly hematologic (neutropenia?=?37, anemia?=?17, and thrombocytopenia?=?23 courses). Conclusions The dismal outcomes for patients with relapsed and refractory sarcomas and the lack of effective sarcoma salvage regimens highlight the need for new approaches. This report of the therapeutic activity of gemcitabine and docetaxel (GEMDOX) in rhabdomyosarcoma and other pediatric reports describing activity in osteosarcoma and Ewing sarcoma suggest that this combination should be considered for formal evaluation in a pediatric specific clinical trial. At a minimum, it appears to offer a reasonable, tolerable, palliative option. Pediatr Blood Cancer 2012; 59: 854858. (C) 2012 Wiley Periodicals, Inc.

Abstract Acetaminophen (AAP) has been shown to enhance cisplatin (CDDP) cytotoxicity in hepatoblastoma cell lines. Further, one published case report demonstrated clinical efficacy of administering acetaminophen in conjunction with cisplatin and followed 6 hours later with n-acetylcysteine (NAC) rescue. In this study, atypical rhabdoid tumor (ATRT) and germinoma cells were treated with CDDP and AAP with or without NAC rescue. We then evaluated the cells with western blots for cleaved PARP and caspase 3 to demonstrate effects on apoptosis. Further, MTS assays were performed to evaluate cell viability of treated cells. To evaluate the effects of the various treatments on oxidative stress, dihydroethidium (DHE) and 2′,7′-dichlorofluorescin (DCFH) assays were performed to test for superoxide and hydrogen peroxide levels, respectively. It was demonstrated that AAP enhances CDDP cell kill and apoptosis in germinoma and ATRT cell lines. Further, both AAP and CDDP, independently and together, cause increased oxidative stress as measured by DHE and DCFE, but this oxidative stress is only reversed by NAC in the DCFE assay. This makes sense because NAC, a glutathione precursor, detoxifies peroxide but not superoxide. Further, our group has learned of five previously unpublished patients with recurrent liver tumors (hepatocellular carcinoma and hepatoblastoma) treated with AAP and CDDP with delayed NAC rescue. All patients tolerated the treatment well. Two of the five patients responded to the treatment, suggesting the potential of this approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2491. doi:1538-7445.AM2012-2491