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Impact of Induction Concurrent Chemoradiotherapy on Pulmonary Function and Postoperative Acute Respiratory Complications in Esophageal Cancer^*

^* From the Departments of Hematology and Medical Oncology (Drs. Abou-Jawde, Mekhail, Adelstein, and Ms. Caroll), Biostatistics (Ms. Rybicki), Pulmonary, Allergy and Critical Care Medicine (Dr. Mazzone), and Thoracic and Cardiovascular Surgery (Dr. Rice), Cleveland Clinic Foundation, Taussig Cancer Center, Cleveland, OH.

Correspondence to: Rony Abou-Jawde, MD, 9500 Euclid Ave, Taussig Cancer Center, R35, Cleveland, OH 44195; e-mail: aboujar{at}cc.ccf.org

Study objective: To evaluate the effects of induction concurrent chemoradiotherapy (cCRT) on pulmonary function and postoperative acute respiratory complications (PARCs).

Design: A retrospective review of our patients treated with induction cCRT to determine the impact on pulmonary function and identify predictors of PARCs. Correlations were sought between patient demographics, clinical characteristics, pre-cCRT and post-cCRT pulmonary function, radiotherapy dose, chemotherapy agents, and the development of PARCs.

Participants: One hundred fifty-five patients treated in three separate clinical trials were identified; 47 patients received 30 Gy (150 cGy bid) of radiation concurrently with a single course of cisplatin/5-fluorouracil (5FU), and 108 patients received 45 Gy (150 cGy bid in a split course) concurrent with two courses of either cisplatin/5FU (n = 69) or cisplatin/paclitaxel (n = 39). Esophagectomy was performed in 141 of these 155 patients following cCRT.

Results: cCRT was only associated with significant worsening of the diffusion capacity of the lung for carbon monoxide (DLCO), which decreased a median of 21.7% in the 45-Gy group (p = 0.007), and 8.6% in the 30-Gy group (p = 0.07). This DLCO decrease was statistically greater in the 45-Gy group than in the 30-Gy group (p = 0.02). PARCs developed in 18 patients. Percentage of predicted FEV₁ and FVC, both before and after cCRT, were both significantly higher in patients without PARCs than in patients with PARCs (p = 0.031 and p = 0.010, respectively). Post-cCRT DLCO was also significantly worse in patients with PARCs (p = 0.002). PARCs occurred significantly more often among those treated with 45 Gy (17 of 102 patients) compared to those treated with 30 Gy (1 of 39 patients) [p = 0.025]. In the 18 patients with PARCs, the median survival was only 2.1 months. This was significantly less than the 16.4-month median survival in the 123 patients who did not have PARCs (p = 0.001).

Conclusions: In patients treated with induction cCRT, higher radiation doses result in increasing impairment of gas exchange. PARCs were more likely in those patients with lower lung volumes, lower post-cCRT DLCO, and in those receiving higher radiation doses. These acute respiratory complications were also associated with a significant reduction in patient survival.

Key Words: diffusion capacity of the lung for carbon monoxide • esophageal cancer • postoperative acute respiratory complication • pulmonary function • radiation therapy