Background: Proton therapy (PT) has potential advantages in pediatric Hodgkin lymphoma (pHL). However, there is limited data on PT, specifically to infradiaphragmatic targets. We report on PT planning details, doses achieved to organs at risk (OARs), and clinical and toxicity outcomes for patients with pHL who received PT to infradiaphragmatic regions. Methods: This is a retrospective study including patients treated between 2011-2022. Demographic and clinical factors were collected, and toxicity was reported using CTCAE version 5.0. Dosimetric and clinical factors associated with key outcomes were assessed via Cox regression. Photon plans were generated for all patients, and the paired t-test or Wilcoxon signed rank sum test were used for dosimetric comparisons. Results: Twenty-one patients comprising 22 PT courses were included. Median follow-up was 5.0 years and mean age was 14.2 years. Median dose was 21 Gray equivalent (GyE) over 14 fractions. Top acute grade 1 (G1) toxicities included fatigue (59%) and anorexia (36%). Rates of acute G2 and G3+ toxicity were 18% and 0%, respectively. After PT, no local or marginal failures occurred. 5% experienced disease progression which were all successfully salvaged, and all patients were alive and disease-free at last follow-up. No secondary malignancies developed. Compared to photon radiation, PT achieved significantly lower doses to the bowels, stomach, spleen, pancreatic tail, liver, and kidneys. Conclusions: PT is well-tolerated and leads to excellent oncologic and toxicity outcomes with long-term follow-up. PT confers dosimetric advantages when compared to photons.

Memantine is used for neurocognitive protection in patients undergoing cranial radiotherapy for central nervous system tumors and is assumed to be well-tolerated. We present a case of memantine-induced altered mental status requiring intensive care unit admission. An adolescent male with relapsed, progressive medulloblastoma presented with severe altered mental status shortly after the first fraction of palliative whole brain radiotherapy. After extensive evaluation, his profound confusion was attributed to memantine, which had been initiated one week prior. Clinicians should be aware of the risk of altered mental status with memantine, given the increased utilization and upcoming clinical trials in pediatric patients.

Background: Characterize indications for pediatric palliative-intent proton radiation therapy (PIPRT). Procedure: We retrospectively reviewed patients ≤21 years who received PIPRT. We defined PIPRT as radiotherapy (RT) aimed to improve cancer related symptoms/provide durable local control in the non-curative setting. Mixed proton/photon plans were included. Adjacent reirradiation (reRT) was defined as a reRT volume within the incidental dose cloud of a prior RT target, whereas direct reRT was defined as in-field overlap with prior RT target. Acute toxicity during RT until first inspection visit was graded according to the Common Terminology Criteria for Adverse Events. The Kaplan-Meier method, measured from last PIPRT fraction, was used to assess progression free survival (PFS) and overall survival (OS). Results: 18 patients underwent PIPRT between 2014-2020. Median age at treatment start was 10 years (2-21). Median follow up was 8.2 months (0-48). Treatment sites included: brain/spine (10), abdomen/pelvis (3), thorax (3) and head/neck (2). Indications for palliation included: durable tumor control (18), neurologic symptoms (4), pain (3), airway compromise (2), and great vessel compression (1). Indications for protons included: reRT (15) (4 adjacent, 11 direct), craniospinal irradiation (4), reduction of dose to normal tissues (3). 16 experienced grade (G) 1-2 toxicity; 2 G3. There were no reports of radionecrosis. Median PFS was 5.3 months (95% CI 2.7-16.3). Median OS was 8.3 months (95% CI 5.5-26.3). Conclusions: The most common indication for PIPRT was reRT to provide durable tumor control. PIPRT appears to be safe, with no cases of high grade toxicity.