Multimodal therapy is the standard treatment for pediatric rhabdomyosarcoma, but for adolescents and young adults (AYAs: ages 15–39) and older adults with rhabdomyosarcoma, the use of adjuvant ...therapy is variable, and survival is greatly decreased compared with younger patients.
All patients with rhabdomyosarcoma who had a curative operative were identified from the 1998–2012 National Cancer Database. Regression analyses identified independent factors relating to receipt of multimodal therapy (resection + chemotherapy + radiation) and the influence of multimodal therapy on 5-year overall survival.
Of 2,312 patients, 44% were pediatric (age < 15 years), 22% AYA (ages 15–39), and 34% adult (age ≥ 40 years). Adults received multimodal therapy least often (pediatric: 62%, AYA: 46%, adults: 24%; P < .001), even after controlling for demographic characteristics, tumor features, and stage. In the entire cohort, multimodal therapy was associated with a decreased risk of death within 5 years (hazard ratio HR 0.72, 95% confidence interval CI 0.62–0.84), with similar findings after stratification by age (pediatric: HR 0.64, 95% CI 0.48–0.85; AYA: HR 0.72, 95% CI 0.55–0.95; adult: HR 0.74, 95% CI 0.58–0.93). In AYAs only, black and Hispanic patients had an increased risk of death within 5 years (black patients: HR 1.64, 95% CI 1.14–2.37; Hispanic patients: HR 1.62, 95% CI 1.11–2.36).
This first large national study suggests that multimodal therapy is independently associated with improved survival for both AYAs and adults with rhabdomyosarcoma, similar to pediatric patients, but multimodal therapy is appreciably underused. Implementation of multimodal therapy for all patients could potentially improve overall outcomes of patients with rhabdomyosarcoma.
Purpose
Thalidomide, originally developed as a sedative, was subsequently identified to have antiangiogenic properties. Lenalidomide is an antiangiogenic and immunomodulatory agent that has been ...utilized in the treatment of patients with brain tumors. We studied the pharmacokinetics and cerebrospinal fluid (CSF) penetration of thalidomide and lenalidomide in a nonhuman primate model.
Methods
A dose of 50 mg of thalidomide or 20 mg of lenalidomide was administered once orally to each of three rhesus monkeys. Plasma and CSF samples were obtained at specified intervals, and the thalidomide or lenalidomide concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods. CSF penetration was calculated as area under the concentration–time curve (AUC) CSF/AUC plasma.
Results
For thalidomide, the median apparent clearance (Cl/F) was 2.9 mL/min/kg, the median plasma AUC was 80 μM h, and the median terminal half-life (t
½
) was 13.3 h. For lenalidomide, the median Cl/F was 8.7 mL/min/kg, the median AUC was 9 μM h, and the median t
½
was 5.6 h. Thalidomide was detected in the CSF of all animals, with a median penetration of 42%. Lenalidomide was detected in the CSF of 2 of 3 animals, with a CSF penetration of 11% in each.
Conclusion
Thalidomide and lenalidomide penetrate into the CSF after oral administration of clinically relevant doses. Plasma exposure to lenalidomide was similar in our model to that observed in studies involving children who have brain tumors. These results support further development of lenalidomide for the treatment of central nervous system malignancies.
Neuroblastoma (NB) is the most common solid extracranial malignancy of childhood with an incidence of 1 per 100,000 in the United States compromising approximately 10 % of childhood cancer. ...Unfortunately, patients with high-risk NG continue to have long-term survival less than 50 %. Both Children's Oncology Group and the International Society of Paediatric Oncology have demonstrated the important role of surgery in the treatment of high-risk NB. Herein, we compose the results of an extensive literature review as well as expert opinion from leaders in pediatric surgical oncology, to present the critical elements of effective surgery for high-risk neuroblastoma.
Abstract Background Appendiceal carcinoid tumors, also know as well-differentiated neuroendocrine neoplasms, are rare lesions detected incidentally after appendectomy in children. There are limited ...data about the natural history of these tumors, and guidelines regarding family counseling and need for additional surgery or follow-up imaging are not established in the pediatric age group. The purpose of this study was to review our institutional experience with appendiceal carcinoid tumors to provide data that might improve management. Methods After institutional review board approval, the charts of all patients treated at our institution for an appendiceal carcinoid tumor between 2002 and 2014 were reviewed. Data collected included patient demographics, pathologic details, postoperative management, and follow-up information. Descriptive analyses were performed. Results Twenty-eight patients were identified, which represents an incidence of 0.2% of children undergoing appendectomy during that time interval. The mean age at surgery was 13.8 ± 2.1 y; 54% were females. Two patients had symptoms suspicious for carcinoid syndrome at presentation, though none had evidence of metastatic disease. The mean tumor size was 0.73 ± 0.4 cm. Five patients (18%) underwent subsequent ileocecectomy or right hemicolectomy because of pathologic findings of invasion of the mesoappendix ( n = 4) or lymphovascular invasion and subserosal extension ( n = 1), two of whom had residual disease in the resected specimen (one in a lymph node). No recurrences have been detected at mean follow-up of 1.8 y. Conclusions Appendiceal carcinoid tumors are discovered incidentally in about 0.2% of children undergoing appendectomy. Based on findings from a large contemporary series, we can conclude that these tumors are generally small and demonstrate lymphovascular invasion or mesenteric extension in fewer than 20% of cases. Prospective, multicenter studies are necessary to better define the indication for ileocecectomy and follow-up imaging protocols.
Standardized clinical pathways for simple appendicitis decrease length of stay and result in cost savings. We performed a prospective cohort study to assess a same day discharge (SDD) protocol for ...children with simple appendicitis.
All children undergoing laparoscopic appendectomy for simple appendicitis after protocol implementation (February 2016 to January 2017) were assessed. Length of stay (LOS), 30-day resource utilization (ED visits and hospital readmissions), patient satisfaction, and hospital accounting costs for SDD were compared to non-SDD patients.
Of 602 children treated at our institution, 185 (31%) were successfully discharged per protocol. SDD patients had longer median PACU duration (3.0 vs. 1.0h, p<0.001), but postoperative LOS (4.4 vs. 17.4h, p<0.001) and overall LOS (17.1 vs. 31.2h, p<0.001) were significantly shorter. Complication rates (1.6% vs. 3.1%), ED visits (4.3% vs. 6.0%), and readmissions (0.5% vs. 2.4%) were not significantly different for SDD compared to non-SDD patients. However, SDD decreases total cost of an appendectomy episode ($8073 vs $8424, p=0.002), and patients report high satisfaction with their hospital experience (mean 9.4 out of 10).
Safe and satisfactory outpatient management of pediatric simple appendicitis is achievable with appropriate patient selection. An SDD protocol can lead to significant generation of value to the healthcare system.
Prognosis study, Level II.
To explore the relationships between interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) levels and disease extent and clinical outcome in childhood neuroblastoma.
Pretreatment peripheral blood ...(PB; n=53) and bone marrow (n=18) samples from patients with neuroblastoma were assayed by ELISA for IL-6 and sIL-6R. PB values were compared with healthy pediatric controls (n=28).
PB IL-6 levels were significantly elevated in patients with high-risk disease compared with those with low and intermediate risk disease (23.9 versus 4.3 pg/mL; P<0.001) and the normal control group (23.9 versus 3.3 pg/mL; P<0.001). Similarly, bone marrow IL-6 levels were higher in high-risk patients when compared with low- and intermediate-risk patients (15 versus 0 pg/mL; P<0.02). Other factors correlated with higher IL-6 levels were age of >18 months, bony metastases, and unfavorable histology. sIL-6R levels were not significantly correlated with disease stage. Patients with detectable PB IL-6 at diagnosis had significantly lower event-free survival rates (P<0.008). sIL-6R levels <2.5 x 10(4) pg/mL were also associated with a significantly worse event-free survival (P=0.016).
Elevated PB IL-6 levels correlated with features of high-risk neuroblastoma and poor prognosis in this population. Decreased PB sIL-6R levels correlated with the presence of metastatic disease. Further study of these markers in children with neuroblastoma seems warranted.
Pancreatic islet cell tumors are rare in adolescents, and most studies published to date focus on older patients. We utilized a national database to describe the histology and clinical pattern of ...pancreatic islet cell tumors in adolescent and young adult (AYA) patients, and to compare AYAs to older adults. We hypothesized that AYAs with pancreatic islet cell tumors would have better overall survival.
The National Cancer Data Base (NCDB, 1998–2012) was queried for AYA patients (15–39 years) with a pancreatic islet cell tumor diagnosis. Demographics, tumor characteristics, treatment modalities, and outcomes were abstracted and compared to adults (≥40 years).
383 patients (56.4% female, 65% non-Hispanic Whites) were identified, with a median age of 27 (IQR 16–34) years. Islet cell carcinoma was the most common histology. Of patients with known stage of disease, 49% presented with early stage (I or II). Seventy percent of patients underwent surgical resection, including local excision 44%, Whipple procedure 37.5%, or total pancreatectomy 19%. Chemotherapy was utilized in 27% and radiotherapy in 7%. All-cause mortality was 36%. AYA patients underwent more extensive resections (p = 0.001) and had lower mortality rates (p < 0.001), with no differences in tumor stage or use of adjuvant therapies, when compared to adults.
AYA patients with pancreatic islet cell tumors had comparable utilization of adjuvant therapies but underwent more extensive resections and demonstrated a higher overall survival rate than adult counterparts. Further investigation into approaches to earlier diagnosis and tailoring of multimodality therapy of these neoplasms in the AYA population is needed.
Prognostic Study, Level II — retrospective study.
Background
Children with hepatoblastoma routinely undergo repetitive surveillance imaging, with CT scans for several years after therapy, increasing the risk of radiation-induced cancer.
Objective
...The purpose of this study was to determine the utility of surveillance CT scans compared to serum alpha-fetoprotein (AFP) levels for the detection of hepatoblastoma relapse.
Materials and methods
This was a retrospective study of all children diagnosed with AFP-positive hepatoblastoma from 2001 to 2011 at a single institution.
Results
Twenty-six children with hepatoblastoma were identified, with a mean age at diagnosis of 2 years 4 months (range 3 months to 11 years). Mean AFP level at diagnosis was 132,732 ng/ml (range 172.8–572,613 ng/ml). Five of the 26 children had hepatoblastoma relapse. A total of 105 imaging exams were performed following completion of therapy; 88 (84%) CT, 8 (8%) MRI, 5 (5%) US and 4 (4%) FDG PET/CT exams. A total of 288 alpha-fetoprotein levels were drawn, with a mean of 11 per child. The AFP level was elevated in all recurrences and no relapses were detected by imaging before AFP elevation. Two false-positive AFP levels and 15 false-positive imaging exams were detected. AFP elevation was found to be significantly more specific than PET/CT and CT imaging at detecting relapse.
Conclusion
We recommend using serial serum AFP levels as the preferred method of surveillance in children with AFP-positive hepatoblastoma, reserving imaging for the early postoperative period, for children at high risk of relapse, and for determination of the anatomical site of clinically suspected recurrence. Given the small size of this preliminary study, validation in a larger patient population is warranted.
Abstract Background Focal nodular hyperplasia (FNH) is uncommonly diagnosed in pediatric patients and may be difficult to distinguish from a malignancy. We present a review of all children with a ...tissue diagnosis of FNH at our institution, describe the diagnostic modalities, and provide recommendations for diagnosis and follow-up based on our experience and review of the literature. Methods A retrospective review of children < 18 years of age diagnosed with FNH at a single institution was performed from 2000 to 2013. Results Twelve patients were identified with a tissue diagnosis of FNH. Two patients required surgical resection of their lesion owing to concern for malignancy. Ten patients were managed expectantly with imaging surveillance after biopsy confirmed a diagnosis of FNH. All patients who underwent MRI had very typical findings including hypointensity on T1 weighted sequences, hyperintensity on T2, and homogenous uptake of contrast on the arterial phase. On follow-up all patients had either a stable lesion or reduction in size. Conclusions Focal nodular hyperplasia presents typically in children with liver disease, have undergone chemotherapy, and adolescent females. Young children, particularly < 5 years of age, without underlying liver disease or history of chemotherapy can pose a diagnostic dilemma. In this unique subgroup of children with FNH, MRI and/or needle biopsy should be adequate diagnostic modalities for these lesions.
Elective ambulatory surgical care traditionally involves three independent visits. Single-Visit Surgery (SVS) is an alternative surgical model that consolidates care into one visit. Evaluation of the ...effect of this novel program on hospital operations is limited. The objective of this study was to analyze SVS from an institutional perspective.
We retrospectively reviewed patients scheduled for SVS at a freestanding children’s hospital between January 2016 and August 2017. Data collected included clinic “no show” rates, operating room (OR) utilization, reimbursement rates, and postoperative visits.
There were 89 patients scheduled for SVS, of which 63% (n=56) were male, and the median age was 6 years IQR, 4–9. The SVS clinic “no show” rate was 2% (n=2) compared to the pediatric surgery clinic “no show” rate of 11% (p=0.01). The SVS OR block utilization rate was 90%. Payment was received from third-party payors for 92% of consultations and 100% of operative procedures without securing prior authorization. Postoperatively 25% (n=17) of patients presented to clinic for follow-up, and one child presented to the emergency department for vomiting. There were no hospital admissions.
Single-Visit Surgery is an alternative model of ambulatory surgical care that improves institutional efficiency while also enhancing the patient experience.
Retrospective cohort review
III
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