Shengjie Wu

Background: Reirradiation is used for children and adolescents with recurrent ependymoma after prior surgery and focal irradiation. This study assessed the long-term benefits and risks of a second course of fractionated radiotherapy, patient selection, factors associated with progression-free survival (PFS) and overall survival (OS), and the role of craniospinal irradiation (CSI) at first recurrence. Methods: From July 1994 to January 2024, 150 pediatric ependymoma patients at St. Jude Children’s Research Hospital received a second course of fractionated radiotherapy. Sixty-four were enrolled in a prospective trial. Inclusion required conventional fractionation (≥50.4 Gy) for both courses, with CSI for metastatic disease. Kaplan-Meier estimates measured PFS and OS, Cox models assessed associations with covariates, and competing risks analysis evaluated necrosis and death from complications. Results: At 10 and 20 years, PFS/OS for the cohort were 19.5%/34.3% and 9.0%/13.1%, respectively. Females had significantly better outcomes, and survival varied by initial failure pattern. No significant difference in PFS (P = .1351) or OS (P = .2705) was found between focal irradiation and CSI for patients with local failure (LF). Necrosis was higher with proton therapy vs photons; grade 3 necrosis after reirradiation occurred in 19.9%. The 10-year cumulative incidence of death from complications or secondary tumors was 8.5%. Conclusions: A second course of conventionally fractionated radiotherapy can extend survival in recurrent pediatric ependymoma, but prognosis remains poor, especially for those with combined LF and distant failure or adverse features. Craniospinal irradiation did not improve outcomes for LFs. Proton therapy increased necrosis risk, emphasizing the need for careful selection and follow-up.

BACKGROUND AND PURPOSE: Selumetinib is a promising MAP (mitogen-activated protein) kinase (MEK) 1/2 inhibitor treatment for pediatric low-grade gliomas. We hypothesized that MR imaging–derived ADC histogram metrics would be associated with survival and response to treatment with selumetinib. MATERIALS AND METHODS: Children with recurrent, refractory, or progressive pediatric low-grade gliomas who had World Health Organization grade I pilocytic astrocytoma with KIAA1549–BRAF fusion or the BRAF V600E mutation (stratum 1), neurofibromatosis type 1–associated pediatric low-grade gliomas (stratum 3), or sporadic non-neurofibromatosis type 1 optic pathway and hypothalamic glioma (OPHG) (stratum 4) were treated with selumetinib for up to 2 years. Quantitative ADC histogram metrics were analyzed for total and enhancing tumor volumes at baseline and during treatment. RESULTS: Each stratum comprised 25 patients. Stratum 1 responders showed lower values of SD of baseline ADC_total as well as a larger decrease with time on treatment in ADC_total mean, mode, and median compared with nonresponders. Stratum 3 responders showed a greater longitudinal decrease in ADC_total. In stratum 4, higher baseline ADC_total skewness and kurtosis were associated with shorter progression-free survival. When all 3 strata were combined, responders showed a greater decrease with time in ADC_total mode and median. Compared with sporadic OPHG, neurofibromatosis type 1–associated OPHG had lower values of ADC_total mean, mode, and median as well as ADC_enhancement mean and median and higher values of ADC_total skewness and kurtosis at baseline. The longitudinal decrease in ADC_total median during treatment was significantly greater in sporadic OPHG compared with neurofibromatosis type 1–associated OPHG. CONCLUSIONS: ADC histogram metrics are associated with progression-free survival and response to treatment with selumetinib in pediatric low-grade gliomas.

Background: Left bundle branch pacing (LBBP) is a novel physiological pacing and previous studies have confirmed the feasibility and safety of it. The incidence of complications in LBBP is relatively low as reported. Here we present a case of interventricular septal hematoma complicating LBBP lead implantation.Case summary: LBBP was achieved for treatment of high-grade atrioventricular block in a 67-year-old female. Chest pain began 1 h after implantation when the electrocardiogram showed ST-T changes. Then bedside echocardiography confirmed the formation of interventricular septal hematoma. Urgent coronary angiography showed the contrast agent retention and overflow in the interventricular septum. The symptom was relieved half an hour later. Echocardiogram performed 2 h later revealed the size of the hematoma was the same as before. The electrocardiography, coronary angiography and CTA confirmed the resolution of the hematoma at 1-month follow-up. Pacing parameters and cardiac function remained stable during 6-month follow-up.Conclusion: This is the first reported case describing the clinic features and management of interventricular septum hematoma complicating LBBP. The importance of routine echocardiograms after implantation for identifying the hematoma should be highlighted.

Background: Higher serum gamma-glutamyltransferase (GGT) is associated with high risk of hypertension. We aimed to examine the association between sex-specific serum GGT levels and incident of hypertension in a Chinese population without metabolic syndrome.Methods: Participants who were free of hypertension and metabolic syndrome from the First Affiliated Hospital of Wenzhou Medical University between 2009 and 2014 were included. Participants were grouped into sex-specific quartiles of GGT levels (Q1–Q4) defined as: ≤19, 20–26, 27–38, and ≥39 U/L for male; ≤12, 13–15, 16–19, and ≥20 U/L for female. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of hypertension according to sex-specific quartiles of GGT levels. Kaplan–Meier analysis and interaction analysis were conducted.Results: Among 38,806 participants included (average age 36.0 years, 54.0% men), 4,505 of them developed hypertension. In the overall study population, using Q1 as the reference group, participants in Q2, Q3, and Q4 showed a higher risk of developing hypertension, with HRs (95% CIs) of 1.126 (1.029–1.232), 1.187 (1.083–1.302), and 1.300 (1.182–1.431), respectively (P < 0.001), after adjusting for known confounders. Sex-specific analysis showed that the adjusted HRs for participants in Q4 (reference: Q1) were greater in females [1.321 (1.100–1.586, P < 0.001)] than in males [1.268 (1.133–1.420, P < 0.001)] (P for interaction = 0.047). Moreover, interaction analysis showed that this association was consistently observed when the participants were stratified by age, body mass index, and fatty liver status.Conclusion: Among Chinese adults without metabolic syndrome, serum GGT level was positively associated with incidence of hypertension, and the association was stronger in females than in males.

Low-grade glioma (LGG) diagnosed during infancy is associated with unique clinical profile and challenges in management. Morbidities in long-term survivors are not well described. We retrospectively reviewed patients with LGG diagnosed before 12 months of age managed at St. Jude Children’s Research Hospital from 1986-2013. Altogether, 51 patients were identified, 31 were males, 7 had neurofibromatosis. Primary tumor locations were hypothalamic/optic pathway (n=31), cerebral (n=6), brainstem (n=6), cerebellar (n=4), and spinal (n=4); 12 patients experienced metastasis. At diagnosis, 41 patients required active intervention: surgical resection (n=23; 5 with adjuvant chemotherapy), chemotherapy (n=16), radiation (n=1), or chemotherapy and radiation (n=1). Throughout the course of disease, 39/51 patients required chemotherapy (median number of regimens: 2; range, 1-13); 21 required radiation (focal=19; CSI=2); and 41 received tumor-directed surgeries (median number of operations: 2; range, 1-6). Twenty-nine patients had grade I tumors; 6 had grade II tumors, and 6 had tumors that could not be definitively graded. CSF diversion was performed in 31 patients. The mean duration of follow-up was 11.5y (range, 0.16-29.19y). Thirty-five patients experienced progression (median progressions: 2; range, 1-18), and 9 patients died (progression=3, malignant transformation=3, shunt infection=1, leukemia=1, unknown=1). The respective 5-year, 10-year, and 20-year overall-survival rates were 91.6 ± 4%, 86.4 ± 5.2%, and 71.9 ± 8.8%. Adverse health issues were documented in 49/51 patients; common morbidities included hearing impairment (n=15), visual impairment (n=31), neurocognitive deficit (n=31), hemiplegia/paraplegia (n=19), endocrinopathy (n=31), and cerebrovascular disease (n=15). LGG diagnosed during infancy was almost universally associated with long-term morbidities and survivors should be prioritized for multi-disciplinary surveillance.