Objective:Population pharmacokinetics analysis explored the pharmacokinetics of anlotinib in children with soft tissue sarcomas (STS) and identified the optimal dose for children across various age brackets. Method:From 2021 to 2023, a single dose of anlotinib (4.62 mg/m2) was orally administered in 16 children with advanced STS in 8 days. Anlotinib plasma concentration was evaluated by LC-MS/MS. Pharmacokinetic models were developed using nonlinear mixed-effects modelling. The effect of predefined covariates on pharmacokinetic parameters was assessed. Results:Totally 128 samples from 16 children (aged 5-14) were collected for pop-PK analysis. The two-compartment model was most consistent with the data of oral anlotinib in pediatrics with advanced STS, and the relevant parameters were: Ka (h-1) 0.419; Vc/F (L) 760; Q (L∙h-1) 21.2; Vp/F (L) 547. Covariate screening showed that the clearance of anlotinib gradually increased with age in a sigmoidal relationship, the maximum CL/F was 15.7L∙h-1, and age of median clearance (Age50) was 6.84 years; the Vc/F increased linearly with BSA. Dose of 8 mg anlotinib for children aged 5-7, and 10 mg or 12 mg for children aged 8-10 would be expected to lead to a similar exposure of anlotinib compared with an adult patient receiving 12 mg. Conclusion:The population pharmacokinetics of orally administrated anlotinib were evaluated in pediatric advanced STS patients. BSA and age were significant physiologic factors on PK. A simulation of 8 mg anlotinib in children aged 5-7, 10 mg or 12 mg in 8-10 and 12 mg for children over 11 would get similar exposure of adults receiving 12mg.

Background: Retinoblastoma (RB) is the most common intraocular malignancy in infancy and childhood. Bone metastases are common and usually involve the skull and axial bones; limb bone metastases are rare. Herein, we evaluated the clinical features, image manifestations, treatment, and prognosis of patients with recurrent RB with limb bone metastasis and without central neural system involvement. Procedure: Clinical data of 5 patients with retinoblastoma who were diagnosed at the Department of Pediatrics in Beijing Tongren Hospital, between January 2015 and January 2021, were retrospectively analyzed. Results: Three males and two females were included (7 eyes: 4 stage E and 1 each of stage D, C, and B). The interval between symptom onset and bone metastasis was 12-102 months. Three cases were unilateral (2 left and 1 right), and two were bilateral. The most common symptom was pain. Three patients had bone marrow and lymph node metastasis. Three patients had single and two had multiple skeletal lesions. The main limb bones involved were the femur, humerus, talus, and ulna. Serum neuron specific enolase (NSE) was significantly elevated in 4 cases, and slightly elevated in 1 case; primary intravenous chemotherapy resulted in a decrease in NSE and gradual resolution of bone lesions. At the time of follow-up, 2 patients died and 3 were in complete remission. Conclusions: Regular lifelong follow-up of patients with RB is warranted to identify bone metastases. Clinicians should consider examination findings, imaging findings, and laboratory results to identify bone metastases and initiate appropriate treatment.

Purpose: To investigate the clinical characteristics, treatment, and outcomes of metastatic and recurrent retinoblastoma in patients with stable primary tumors. Methods: Clinical data were reviewed for nine patients (two boys and seven girls; median age, 23 months) with stable primary tumors who exhibited metastatic and recurrent retinoblastoma. All patients were treated in the Pediatrics Department of our hospital in the past 5 years. The clinical characteristics, treatment methods, and patient prognoses were recorded. Results: Of the nine patients, three had binocular disease and six had monocular disease (n=12 eyes in this study). The median interval between the end of initial treatment and onset of recurrence was 12 months (range, 3–96 months). Of the nine patients, primary tumors were proved to be stable, seven had bone metastasis, five had lymph node metastasis, two had parotid gland involvement, and three had bone marrow infiltration. At the end of the study period, one patient was lost to follow-up, one patient died, seven patients were alive and three of them were in complete remission and survived disease-free until the end of follow-up. In December 2020, the median overall survival after onset was 32.0 months (range, 18–155 months); the median overall survival after recurrence was 18.0 months (range, 5–34 months). Conclusions: Recurrent and metastatic retinoblastomas are uncommon and easily misdiagnosed at an early stage in patients with stable primary tumors. These cancers can be effectively treated using systemic intravenous chemotherapy combined with surgery, radiotherapy, and hematopoietic stem cell transplantation.

Objectives: To summarize the clinical characteristics and outcome of infantile extracranial germ cell tumors(GCTs) from four different centers in China since the last 10 years. Methods: Fifteen cases of infantile extracranial GCTs diagnosed between January 1st, 2010 to December 31st, 2019 were evaluated. Results: Nine patients were males(60%) and six were females(40%). The median age was 5.2 months(ranges:2.4-11.8months). There were six cases(40%) in retroperitoneum, six cases(40%) in sacrococcygeal, one case(6.6%) in testicular, one case(6.6%) in hip and one case(6.6%) in mediastinum. Histologically, there were 10 cases(66.6%) of immature teratoma, 3(20%) mixed GCTs and 2(13.3%) malignant GCTs. One case was stageII(6.6%), eleven stageIII(73.3%), one stageIV(6.6%) and two cases were unclear(13.3%). Nine cases(60%) had alpha-fetoprotein(AFP) level of higher than 1000ng/ml. All of the cases received adjuvant chemotherapy in which platinum-based chemotherapy regimens were mostly used. The median follow-up time was 31 months(range: 3–81 months). At the end of treatment, 12 patients got CR(80%), 1 PR(6.7%) and 2 NR(13.3%). During the follow-up period, 12 patients alive without disease and 3 patient who did not got CR at the end of treatment died of disease progression. Conclusions: Most of infantile extracranial GCTs located outside the gonads. Sacrococcygeal and retroperitoneal regions were common sites. Histologically, teratoma was more common in infantile GCTs. Early diagnosis is needed and chemotherapy regimen needs to be further standardized in China. An evaluation system is needed to figure out treatment efficacy and prognosis in the future.

Background: Hepatic metastasis from retinoblastoma (RB) is rare. We evaluated clinical features, imaging manifestations, treatment, and prognosis in these patients. Procedure: Clinical data of five patients diagnosed with hepatic metastases of RB at the Department of Pediatrics in Beijing Tongren Hospital between January 2009 and January 2019 were analyzed retrospectively. Results: Two patients had bilateral lesions, while three had unilateral lesions. Among the seven eyes with lesions, six and one were classified as stage E and C, respectively (International Integrated Reporting Council staging). On computed tomography (CT), low-density foci were observed (three, multiple foci and two, single foci). After chemotherapy, tumor regression was observed in four patients, while there was no response in one patient. Three patients who underwent enucleation were at high risk for extensive choroidal invasion. All patients had severe disease with multiple system involvement, including central nervous system (CNS) and bone metastases. Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels were significantly elevated in all patients; after treatment, they decreased in four patients and remained unchanged in one patient with end-stage disease. Two patients died, with survival durations of 1 and 3 months following the diagnosis of hepatic metastasis. Three patients survived and continued treatment. Conclusion: Hepatic metastasis from RB is rare and usually occurs with CNS and bone metastases. On CT, hepatic foci could be indicated by low-density lesions with calcification. Chemotherapy could be effective for hepatic metastases. The prognosis of these patients is poor; however, hepatic metastasis is not a direct cause of death.

Background: Granulocyte colony-stimulating factors (G-CSF) can be used as prophylaxis for febrile neutropenia (FN) in adults. There is no meta-analysis about the effects of pegfilgrastim on the occurrence of FN in pediatric/adolescent cancer patients. Purpose: To determine the effect of pegfilgrastim on FN in pediatric and adolescent cancer patients. Methods: PubMed, Embase, and the Cochrane library were searched for studies published prior to April 7, 2020. The outcome was the occurrence of FN. For analyses showing high heterogeneity (I2>50% and Q-test P<0.10), the random-effect model was used; otherwise, the fixed-effect model was used. Results: Eight studies were included, comprising 167 patients and 550 courses of treatment. Pegfilgrastim decreased the rate of FN compared with controls (ES=0.26, 95%CI: 0.15-0.36, P<0.001); this was observed in prospective and retrospective studies. There was no difference between pegfilgrastim and filgrastim for the rate of FN in children receiving chemotherapy (OR=0.68, 95%CI: 0.20-2.23, P=0.520). Pegfilgrastim decreased the rate of grade 4 FN compared with controls (ES=0.40, 95%CI: 0.16-0.63, P=0.017); this was observed when analyzing the courses of treatment, but not the patients. Pegfilgrastim had no impact on treatment delays due to FN (ES=0.05, 95%CI: -0.00-0.10, P=0.061). Pegfilgrastim decreased the rate of severe neutropenia compared with controls (ES=0.39, 95%CI: 0.04-0.74, P=0.031). Conclusion: Compared with the control, pegfilgrastim significantly decreases the occurrence of FN, grade 4 FN, and severe neutropenia in pediatric patients receiving chemotherapy. Pegfilgrastim had no impact on treatment delays due to FN.