A pediatric trial of radiation/cetuximab followed by irinotecan/cetuximab in newly diagnosed diffuse pontine gliomas and high-grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study.

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) and high-grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan. METHODS: Eligible patients of age 3-21 years had newly diagnosed DIPG or HGA. Patients received radiation therapy (5,940 cGy) with concurrent cetuximab. Following radiation, patients received cetuximab weekly and irinotecan daily for 5 days per week for 2 weeks every 21 days for 30 weeks. Correlative studies were performed. The regimen was considered to be promising if the number of patients with 1-year progression-free survival (PFS) for DIPG and HGA was at least six of 25 and 14 of 26, respectively. RESULTS: Forty-five evaluable patients were enrolled (25 DIPG and 20 HGA). Six patients with DIPG and five with HGA were progression free at 1 year from the start of therapy with 1-year PFS of 29.6% and 18%, respectively. Fatigue, gastrointestinal complaints, electrolyte abnormalities, and rash were the most common adverse events and generally of grade 1 and 2. Increased epidermal growth factor receptor copy number but no K-ras mutations were identified in available samples. CONCLUSIONS: The trial did not meet the predetermined endpoint to deem this regimen successful for HGA. While the trial met the predetermined endpoint for DIPG, overall survival was not markedly improved from historical controls, therefore does not merit further study in this population.

The value of positron emission tomography and proliferation index in predicting progression in low-grade astrocytomas of childhood.

Astrocytomas are the most common brain tumors of childhood and adolescence. Low-grade astrocytomas (LGAs), in general, have favorable prognosis, but recurrence or progressive disease with dissemination, malignant transformation, and death occur in some cases. Current clinical and pathological measures including age, sex, imaging characteristics, location and size of the tumor, histopathology, and degree of resection cannot predict with certainty which tumors will demonstrate aggressive behavior. The objective of the study is to determine the predictive value of positron emission tomography (PET) and a proliferation index (PI) in identifying high risk LGAs. We reviewed 46 cases ages 5 months to 17 years with low-grade (WHO I-II) astrocytomas. All patients had PET scans utilizing [(18)F] fluorodeoxyglucose (FDG) and 24 cases had measurements with Ki-67/MIB-1 immunohistochemistry. Review of our data confirmed progressive disease (PD) in 18/46 (39%) of cases with 9/21 (42%) occurring after subtotal resection and 9/25 (36%) after gross total resection. The mortality rate was 5/46 (10.8%). Tumors with FDG hypermetabolism were significantly more likely to demonstrate aggressive behavior and PD. Increased PI values also suggested PD. Progression-free survival and time to progression were significantly longer for patients with hypometabolic scans. Time to progression was significantly longer with lower PI values. Results demonstrate that PET and PI are useful measures in the identification and stratification of high risk LGAs. The ability to identify a subset of progressive LGAs earlier may suggest the need for second-look neurosurgical procedures or more intensified adjuvant treatment that may ultimately improve outcome and survival.

Eltrombopag in long-term management of pediatric thrombocytopenia.

Eltrombopag is a thrombopoietin receptor agonist that may be effective in a broad range of thrombocytopenias of distinct etiology. We have observed rapid, robust, and sustained responses to eltrombopag in two young patients with refractory thrombocytopenia, one with primary immune thrombocytopenia and the other with Evans syndrome.

Positron emission tomography in three children with pleomorphic xanthoastrocytoma.

The pleomorphic xanthoastrocytoma is generally considered a low-grade neoplasm with favorable prognosis. These tumors, however, can demonstrate primary anaplastic features, undergo malignant transformation, disseminate, or progress with poor outcome. Currently, there are no histologic or clinical features that reliably predict recurrent tumor or tumor progression. We report three children with confirmed pleomorphic xanthoastrocytoma who were studied with positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) coregistered with magnetic resonance imaging. One patient had decreased FDG metabolism and, despite a gross total resection and benign pathology, had early local recurrence. Subsequent to a second surgical resection and radiation therapy, he has remained stable for 8 years. One patient with significant FDG uptake had gross total resection of an anaplastic pleomorphic xanthoastrocytoma. Follow-up FDG studies showed no abnormal metabolic activity, and he has been stable without adjuvant treatment for 5 years. The last patient had intermediate FDG uptake and a moderate-grade pleomorphic xanthoastrocytoma by histopathology. She showed early tumor progression with spinal metastases. Following a near-total resection of the recurrent intracranial lesion and neuroaxis radiation, she has been stable for 4 years. Although there are still no reliable prognostic indicators for pleomorphic xanthoastrocytoma, PET with FDG correlates with histopathology, and increased uptake may be a marker for more malignant or aggressive tumors. The extent of surgical resection in regard to prognosis in our limited study is unclear but appears helpful in the anaplastic pleomorphic xanthoastrocytoma case. Adjuvant radiation therapy also may benefit certain patients. Further PET studies are warranted in this group of tumors.

Students with brain tumors: their post-treatment perceptions of teachers, peers, and academics and retrospective views on school during treatment.

The purpose of this pilot study was: (1) to determine how students surviving brain tumors (BTs) perceive their teachers' responses to them, their own academic performance, and their interactions with peers at school using a new measure; and (2) to describe students' retrospective perceptions of schooling while undergoing treatment. Using a sample of 22 students treated for a BT (ages 9-18) and 22 comparison (ages 8-19), no significant BT-control group differences regarding perceptions of teacher response, academic performance, and interactions with peers at school were found. Generally, students with BTs reported positive school experiences during treatment including favorable perceptions of their teachers' effectiveness, enjoyment of schoolwork, and the quality of their schooling. Additionally, they felt that completing schoolwork during treatment was important. The results of this study may provide insight into the perceived psychosocial adjustment and academic performance of students with BTs during and after treatment.