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Predictors of Radiation Esophagitis in Locally Advanced Non-Small Cell Lung Cancer with Modern Radiation Therapy Planning

      Purpose/Objective(s)

      Radiation esophagitis (RE) is major side effect of concurrent chemoradiation (cCRT) for locally advanced non-small cell lung cancer (NSCLC). Advances in radiation technology allow for better esophageal sparing, potentially affording opportunities to reduce RE without compromising outcomes. Existing studies on RE largely do not include patients treated using intensity modulated radiation therapy (IMRT). In this study, we aimed to determine RE frequency and predictors with modern radiation planning.

      Materials/Methods

      We retrospectively analyzed 594 NSCLC patients treated with definitive intent with cCRT using 3D-conformal RT (3D-CRT) or IMRT at one institution from 2001-2014. A mean esophageal dose constraint of 34 Gy was used in most cases. RE events were graded with the Radiation Therapy Oncology Group (RTOG) system. Predictors of RTOG grade ≥3 RE were analyzed with multivariable logistic regression using backward selection. Overall survival (OS) and progression free survival (PFS) were calculated with the Kaplan-Meier method.

      Results

      Median follow-up was 22.8 months (mo), median OS was 25.2 mo, and median PFS was 10.8 mo. Median age was 65.2 years and 49.8% of patients were male. At presentation, 8.4% were Stage II, 55.9% Stage IIIA, and 35.7% Stage IIIB. Adenocarcinoma made up 46.0% of cases, squamous cell carcinoma 30.0%, and NSCLC-NOS 24.1%. 3D-CRT was used in 75.1% of cases, and IMRT in 24.9%. Median prescribed dose was 66 Gy (range, 36-74 Gy) and median dose per fraction was 2 Gy (range, 1.8-3 Gy). Median maximum and mean esophageal doses were 64.7 Gy (range, 0.9-78.8 Gy) and 24.0 Gy (range, 0.4-56.8 Gy), respectively. Mean esophageal dose was >34 Gy in 95 (16.0%) of patients. Median esophageal V45, V55, and V60 were 28.7% (range, 0-82.7%), 17.0% (range, 0-73.7%), and 8.4% (range, 0-66.8%), respectively, and these values were higher in patients treated with IMRT (Table 1). Grade ≥3 RE was observed in 113 (19%) patients. On multivariable analysis, NSCLC-NOS histology (OR 2.08, 95% CI 1.23-3.53, p=0.006), IMRT (OR 0.36, 95% CI 0.20-0.63, p<0.001), and mean esophageal dose per Gy (OR 1.10, 95% CI 1.07-1.13, p<0.001) were associated with grade ≥3 RE.
      Abstract TU_26_3574; Table 13D-CRT and IMRT dose-volume metrics
      3D-CRT (n=446)IMRT (n=148)p-value
      Prescribed dose, Gy (median, range)66 (36-74)66 (40-72)0.65
      Maximum esophageal dose, Gy63.2 (0.9-78.8)66.9 (7.5-77.5)0.0001
      Mean esophageal dose, Gy22.7 (0.4-56.8)27.5 (1.6-55.4)<0.0001
      Esophageal V45, %28.1 (0-77.8)33.2 (0-82.7)0.0002
      Esophageal V55, %16.0 (0-71.2)21.0 (0-73.7)0.0005
      Esophageal V60, %5.8 (0-66.8)16.0 (0-66.6)0.0003

      Conclusion

      Mean esophageal dose was the strongest dosimetric predictor of grade ≥3 RE. Even after controlling for higher mean esophageal dose, IMRT was associated with lower RE risk. This suggests that different dose-volume constraints may be important in 3D-CRT and IMRT plans.

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