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Bronchomediastinal Fistula During Durvalumab Therapy After Chemoradiotherapy in Stage III NSCLC

Open ArchivePublished:June 12, 2019DOI:https://doi.org/10.1016/j.jtho.2019.06.003
      A 75-year-old man underwent endobronchial ultrasound-guided transbronchial needle aspiration of station 10L for a left lower lobe mass with associated intrathoracic adenopathy. Histology revealed adenocarcinoma, and subsequent imaging established a diagnosis of stage IIIB NSCLC. Driver mutations were negative, and the tumor proportion score was 55%. The patient underwent chemoradiotherapy. Chemotherapy consisted of carboplatin (area under the curve 2) and paclitaxel (40 mg/m2) on days 1, 8, and 15 every 3 weeks for two cycles. Once-daily thoracic radiotherapy was administered at a total dose of 60 Gy, 5 days a week, in 30 fractions. After chemoradiotherapy, the tumor regressed, and therapy evaluation was partial response. He was then followed-up as an outpatient and continued to receive maintenance chemotherapy with durvalumab (10 mg/kg every 2 weeks). After five cycles of durvalumab, he was admitted to an outside hospital with the chief complaint of hemoptysis. Bronchoscopy revealed blood emanating from the left mainstem bronchus and a mucosal defect (Fig. 1). Computed tomography (CT) scan revealed a bronchomediastinal fistula with an aberrant tract between the left mainstem bronchus and the great vessels (Figs. 2 and 3). The fistula was also confirmed by volume-rendering reconstructions (Fig. 4). Moreover, CT scan revealed a new infiltrate in the left lower lobe, consistent with pneumonitis, which was possibly due to the aspiration of necrotic debris. The patient refused additional therapeutic interventions and opted for palliative care.
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      Figure 1Bronchoscopy shows a fistula entrance (arrow) and a hemorrhagic mucosa in the proximal left main trunk.
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      Figure 2Axial computed tomography shows a fistulous tract of the left main bronchus (arrow) between the aorta (Ao) and left pulmonary artery (LPA). Eso, esophagus.
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      Figure 3Sagittal view of a computed tomography image shows a bronchomediastinal fistula (arrow) between the aorta (Ao) and left main bronchus. LPA, left pulmonary artery; LPV, left pulmonary vein.
      Figure thumbnail gr4
      Figure 4Volume-rendering reconstruction shows a fistula (arrow) at the left mainstem bronchus.
      A bronchomediastinal fistula is a serious and fatal complication of cancer and cancer therapy, and it is very rarely reported. Therefore, the incidence is unknown.
      • Machuzak M.S.
      • Santacruz J.F.
      • Jaber W.
      • Gildea T.R.
      Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation plus bevacizumab: management with a Y-silicone stent inside a metallic covered stent.
      Regarding advanced lung cancer, a tracheal-mediastinal-parenchymal-pleural fistula and tracheoesophageal fistula have been described as rare complications of antiangiogenic drugs, such as bevacizumab, and concurrent mediastinal radiation.
      • Machuzak M.S.
      • Santacruz J.F.
      • Jaber W.
      • Gildea T.R.
      Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation plus bevacizumab: management with a Y-silicone stent inside a metallic covered stent.
      • Goodgame B.
      • Veeramachaneni N.
      • Patterson A.
      • Govindan R.
      Tracheo-esophageal fistula with bevacizumab after mediastinal radiation.
      However, to the best of our knowledge, no data exist on a bronchomediastinal fistula caused by immune checkpoint inhibitor therapy (both anti–programmed death 1 and anti–programmed death ligand 1 inhibitors) in a patient with lung cancer. It has been reported that bronchial necrosis caused by radiation therapy or chemoradiation therapy can occur at 3 to 7 months
      • Machuzak M.S.
      • Santacruz J.F.
      • Jaber W.
      • Gildea T.R.
      Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation plus bevacizumab: management with a Y-silicone stent inside a metallic covered stent.
      • Mehta A.C.
      • Dweik R.A.
      Necrosis of the bronchus. Role of radiation.
      ; however, our patient developed a fistula 2 months after radiation therapy, which is relatively early. CT scan before durvalumab therapy did not reveal an obvious mucosal defect or air density in the mediastinal lymph nodes. The tumor and lymph node sizes after durvalumab therapy indicated maintenance of partial response. Furthermore, no malignant cells were found in a biopsy specimen of the fistula. Therefore, although the possibility of chemoradiation-induced necrosis cannot be completely ruled out, effective durvalumab therapy was more likely associated with the mucosal defect. The treatment of a tracheobronchial fistula is challenging, and various approaches have been reported, including stent placement and autologous stem cell therapy.
      • Machuzak M.S.
      • Santacruz J.F.
      • Jaber W.
      • Gildea T.R.
      Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation plus bevacizumab: management with a Y-silicone stent inside a metallic covered stent.
      • Alvarez P.D.
      • García-Arranz M.
      • Georgiev-Hristov T.
      • García-Olmo D.
      A new bronchoscopic treatment of tracheomediastinal fistula using autologous adipose-derived stem cells.
      Durvalumab is indicated for stage III NSCLC after definitive chemoradiotherapy, and its use is expected to increase. Close monitoring clinically and with imaging is necessary in cases of chemoradiotherapy and durvalumab therapy for lung cancers with mediastinal lymphadenopathy adjacent to the trachea, considering the possibility of a bronchomediastinal fistula.

      Acknowledgments

      The authors thank Editage (www.editage.jp) for English language editing.

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