Clinical and dosimetric predictors of radiation-induced esophageal toxicity

Abstract

Purpose: To evaluate the incidence, severity, and clinical/dosimetric predictors of acute and chronic esophageal toxicities in patients with non-small cell lung cancer (NSCLC) treated with high-dose conformal thoracic radiation.

Methods and Materials: Ninety-one patients with localized NSCLC treated definitively with high-dose conformal radiation therapy (RT) at Duke University Medical Center (DUMC) were reviewed. Patient characteristics were as follows: 53 males and 38 females; median age 64 yr (range 46–82); stage I—16, II—3, IIIa—40, IIIb—30, X—2; dysphagia pre-RT—6 (7%). Treatment parameters included: median corrected dose—78.8 Gy (range 64.2–85.6); BID fractionation—58 (64%); chemotherapy—43 (47%). Acute and late esophageal toxicities were graded by RTOG criteria. Using 3D treatment planning tools, the esophagus was contoured in a uniform fashion, the 3D dose distribution calculated (with lung density correction), and the dose–volume (DVH) and dose–surface histograms (DSH) generated. At each axial level, the percentage of the esophageal circumference at each dose level was calculated. The length of circumferential esophagus and the maximum circumference treated to doses >50 Gy were assessed. Patient and treatment factors were correlated with acute and chronic esophageal dysfunction using univariate and multivariate logistic regression analyses.

Results: There were no acute or late grade 4 or 5 esophageal toxicities. Ten of 91 patients (11%) developed grade 3 acute toxicity. On univariate analysis of clinical parameters, both dysphagia pre-RT (p = 0.10) and BID fractionation (p = 0.11) tended toward significantly predicting grade 3 acute esophagitis. None of the dosimetric parameters analyzed significantly predicted for grade 3 acute esophagitis. Twelve of 66 assessable patients (18%) developed late esophageal toxicity. Of the clinical parameters analyzed, only dysphagia pre-RT (p = 0.06) tended toward significantly predicting late esophageal toxicity. On univariate analyses, the effects of percent organ volume treated >50 Gy (p = 0.05), percent surface area treated >50 Gy (p = 0.05), length of 100% circumference treated >50 Gy (p = 0.04), and maximum percent of circumference treated >80 Gy (p = 0.01) significantly predicted for late toxicity of all grades. On multivariate analysis, percent organ volume treated >50 Gy (p = 0.02) and maximum percent of circumference treated >80 Gy (p = 0.02) predicted for late toxicity.

Conclusions: Late esophageal toxicity following aggressive, high-dose conformal radiotherapy is common but rarely severe. Dosimetric variables addressing the longitudinal and circumferential character of the esophagus have biologic rationale and are predictive of late toxicity. Further studies are needed to assess whether these parameters are better predictors than those derived from traditional DVHs.

Introduction

In the radiotherapeutic management of lung cancer, 3D planning tools allow clinicians to minimize irradiation of normal tissues. However, the esophagus often cannot be excluded from the treatment field due to the presence of mediastinal adenopathy or central location of the primary tumor. Thus, acute esophagitis remains a common side effect of treatment, though in most cases it is manageable. Severe late effects are uncommon, but are the source of considerable morbidity. Unfortunately, minimal data are available upon which to base decisions regarding esophageal tolerance. Therefore, the goal of this study was to examine clinical and dosimetric factors that relate to the development of acute and late esophageal toxicities in patients treated with high-dose conformal radiotherapy for non-small cell lung cancer (NSCLC). In addition to the traditional dose–volume histogram (DVH) parameters 1, 2, a novel approach that considers the longitudinal and circumferential character of the 3D esophageal dose distribution is applied (3).