RESUMO
PURPOSE: Memantine is standard in certain adults receiving brain radiation therapy (RT) to decrease cognitive impacts, but it is unknown whether pediatric patients can take, tolerate, and/or benefit from memantine. In this prospective single-arm feasibility study, we hypothesized that pediatric patients receiving central nervous system (CNS) RT would tolerate memantine with good adherence. METHODS AND MATERIALS: Patients aged 4 to 18 years with a primary CNS malignancy (excluding World Health Organization grade 4 astrocytoma, glioblastoma) receiving intracranial RT were eligible. A 6-month memantine course was given during and after RT, with dose titration in 5 mg increments over 4 weeks targeting a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg twice a day. The primary endpoint was to achieve 80% drug adherence rate in 80% of patients measured 1 month after RT. Secondary objectives included memantine feasibility at 3 and 6 months. RESULTS: Eighteen patients enrolled from 2020 to 2022 and were prescribed memantine with RT. The study closed early to avoid competing with the phase 3 randomized Children's Oncology Group study AACL2031. No predefined stopping rules were met. One patient withdrew for cognition-altering substance use, leaving 17 patients available for analysis. One patient discontinued memantine after one dose due to nausea. For the remaining 16 patients, there was a median of 100% pill completion rate (range, 74%-100%; n = 9/17 with 100% adherence) at 1 month after RT, with 15/16 (94%) with adherence rates >80%. At the 3- and 6-month post-RT time points for secondary endpoints, the median adherence rates were 100% (range, 55%-100%) and 96% (range, 33%-100%), respectively. Grade 1 to 2 fatigue, headache, and nausea were the most common toxicity events, at least possibly related to the study drug (n = 27), without attributable grade 3+ events. CONCLUSIONS: Memantine is a feasible, safe, and well-tolerated addition to multimodality treatment for pediatric CNS malignancies. Results of "Anonymized for Review" are awaited to define the value of memantine in this population.
RESUMO
Purpose: Myxofibrosarcoma (MFS) is a subtype of soft tissue sarcoma with a highly infiltrative growth pattern that leads to a higher risk of inadvertent positive surgical margins and local relapse. Poorly defined tumor margins also pose a challenge for radiation therapy (RT) planning, in terms of treatment volumes and administration of pre- versus postoperative RT. This study aims to evaluate local control and patterns of recurrence in patients with MFS treated with neoadjuvant RT followed by definitive surgical excision. Methods and Materials: Multiple institutional databases were retrospectively searched for patients diagnosed with MFS between 2013 and 2021 who were exclusively treated with preoperative RT followed by definitive surgery at our institution. The endpoints of the study were defined as local tumor recurrence, distant metastasis, and death after the date of definitive surgery. Results: Forty-nine patients met the inclusion criteria and were included in the final study. The median age at diagnosis was 67 years, and 71% of patients were male. The tumor was superficially located in 63% of patients, and the mean tumor size at presentation was 7.8 cm. All patients received neoadjuvant RT and completed their planned course of treatment. Neoadjuvant chemotherapy was administered in 22% of patients. Inadvertent excision (IE) before definitive treatment was performed in 25 patients (51%), 84% of which had superficially located tumors. All margins were assessed using frozen section analysis at the time of definitive surgery, and 100% of patients had negative surgical margins, with 25% having no residual tumor. With a median follow-up of 4.7 years, the 5-year local control rate was 87%, and 5-year overall survival was 98%. Tumor depth was associated with distant metastasis (P < .01). Conclusions: Despite the infiltrative nature of MFS, preoperative RT followed by definitive surgical excision, especially in the setting of a reliable frozen section margin analysis, was associated with excellent local control.
