Tracheal fistula associated with bevacizumab 20 months after mediastinal radiation

Abstract

Correspondence to Hideto Yamada, otedih@belle.shiga-med.ac.jp DESCRIPTIONWe report a case of a 60-year-old woman who developed a tracheal fistula 20 months after mediastinal radiation while being treated with bevacizumab. She presented with a large right-sided mediastinal mass given a diagnosis of stage IIIB adenocarcinoma. She was treated with definitive thoracic radiation (figure 1) and a concurrent chemotherapy, including both cisplatin and docetaxel. Eleven months after chemoradiotherapy she developed progressive disease with enlargement of the mass and pleural effusion ipsilateral to the site of the mass. She was treated with pemetrexed as a second-line chemotherapy. Seven months later, she developed progressive disease with bilateral pleural effusion. She received a third-line systemic chemotherapy with carboplatin, paclitaxel and bevacizumab (15 mg/kg) every 3 weeks. After three cycles, she developed dry cough and fever. Three weeks after her third cycle, she was obtunded with respiratory failure associated with hypercapnia. CT scan showed destruction of the right tracheal wall (figure 2).Non-invasive positive pressure ventilation was used to improve respiratory failure but she and her family would not agree to further attempts, including intubation, stent placement nor surgical repair. She died of respiratory failure several days later.When administered in combination with thoracic radiation, bevacizumab has been associated with tracheo- Figure 1 Portal radiograph used for irradiation of adenocarcinoma of the lung, adjacent to the mediastinum, in the right upper lobe with a total dose of 60 Gy.

Simulations on the efficacy of radiotherapy with different time schemes of antiangiogenic therapy

“…It has been documented before that bevacizumab, a commonly used antiangiogenic agent, given together with dose-intensive radiotherapy carries a risk of severe and unusual toxicity once irradiating the mucosal organs such as bronchi, intestines, and urethra [38][39][40][41] . The detrimental effect on the mucosa, mostly with hypofractionated high dose regimens, seemed to be true notwithstanding the order and time between the radiotherapy and bevacizumab.…”

Severe esophageal stenosis in a patient with metastatic colon cancer following palliative radiotherapy, ramucirumab, and chemotherapy

“…Findings from these studies indicate that the addition of an antiangiogenic agent to the chemoradiotherapy regimen may cause more adverse effects compared with that caused by chemoradiotherapy alone. Adverse events induced by bevacizumab, such as tracheoesophageal fistulae, were even reported 20‐21 months after chemoradiotherapy in patients with lung cancer, making long‐term follow‐up periods in these patients necessary . The authors indicated that even a history of mediastinal RT using high‐dose radiation may be a risk factor for the development of life‐threatening fistulae upon receiving bevacizumab.…”