Received: 13 October 2017 Revised: 5 January 2018 Accepted: 18 January 2018 DOI: 10.1002/pbc.27006 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology RESEARCH ARTICLE Esophagitis associated with multimodality management of pediatric Ewing sarcoma of thorax Vibhuti Agarwal 1 Natalie Logie 2 Christopher G. Morris 2 Julie A. Bradley 2 Ronny L. Rotondo 2 Scott M. Bradfield 1 Daniel J. Indelicato 2 1 Division of Hematology/Oncology, Nemours Children's Specialty Care, Jacksonville, Florida 2 Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida Correspondence Daniel J. Indelicato, Department of Radia- tion Oncology, University of Florida College of Medicine, 2015 North Jefferson Street, Jacksonville, FL 32206. Email: dindelicato@floridaproton.org Abstract Background: Ewing sarcoma of the thoracic spine and chest wall is frequently treated with con- current chemotherapy and radiation therapy (RT). Treatment-related acute esophagitis can lead to hospitalization and treatment delays. The aim of this study was to analyze the incidence, risk factors, and management of esophagitis in pediatric patients with Ewing sarcoma of the thoracic region. Methods: We conducted a single-institution retrospective review of patients treated over a 10- year period. Medical records were reviewed for patient and treatment characteristics associated with Common Terminology Criteria for Adverse Events grade 2 or higher esophagitis. RT plans were also reviewed and various esophageal dose metrics were analyzed. Results: Twelve of 37 patients (32%) developed acute esophagitis. Neutropenia was associated with an increased risk of esophagitis (60% vs. 14%; P < 0.01). RT significantly contributed to its incidence when maximum esophageal dose was >47 Gy (69% vs. 5%; P < 0.0001) and esophageal D5cm 3 was >15 Gy (67% vs. 9%; P < 0.001). All 12 patients with esophagitis were managed with oral opioid analgesics. Nine patients with persistent symptoms received subsequent fluconazole for empiric fungal treatment and each had a decreased need for opioid analgesics within 2–5 days. Conclusion: Approximately one-third of patients with Ewing sarcoma of the thoracic region will develop acute esophagitis. An esophageal D5cm 3 dose < 15 Gy and maximal esophageal dose < 47 Gy may keep the rate of acute esophagitis under 5%. However, the association with neu- tropenia and consistent response to antifungal therapy suggest chemotherapy-associated toxicity and an infectious component as part of the process. KEYWORDS disease management, esophagitis, Ewing sarcoma, radiation therapy, thorax 1 INTRODUCTION Ewing sarcoma is the second most common primary bone tumor in chil- dren with an incidence of 2.93 per 1 million children in the US. Improve- ments in systemic agents and multimodality therapy over the last 30 years have helped increase survival rates in patients with localized dis- ease from 10% to 60–70%. 1 Typically, treatment consists of induction chemotherapy followed by local therapy and consolidation chemother- apy. When feasible, surgery is the preferred local therapy; however, in Abbreviations: COG, Children's Oncology Group; CTCAE, Common Terminology Criteria for Adverse Events; EE, EuroEwing; IE, ifosfamide and etoposide; IMRT, intensity-modulated radiation therapy; RT, radiation therapy; VC, vincristine and cyclophosphamide patients for whom surgery would be exceptionally morbid or unlikely to result in gross total resection, radiation therapy (RT) is used for local control. In general, RT plays an important role in the management of patients with Ewing sarcoma of the thoracic spine and chest wall because of the difficulty of achieving negative margins with surgery. RT with con- current chemotherapy, however, may increase toxicity to organs within the radiotherapy field. For these patients, one possible kind of toxicity is acute esophagitis, an adverse event that can lead to hospitalization and affect patient quality of life. Additionally, it can cause treatment interruptions and RT dose reductions, potentially influencing treat- ment outcomes. Over time, acute toxicity and related mucosal damage can result in esophageal stricture formation. 2 Pediatr Blood Cancer. 2018;e27006. c  2018 Wiley Periodicals, Inc. 1 of 6 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.27006