Maguire P D, Sibley G S, Zhou S M, Jamieson T A, Light K L, Antoine P A, Herndon J E, Anscher M S, Marks L B
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Int J Radiat Oncol Biol Phys. 1999 Aug 1;45(1):97-103. doi: 10.1016/s0360-3016(99)00163-7.
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.
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.
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.
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.
评估接受高剂量适形胸部放疗的非小细胞肺癌（NSCLC）患者急性和慢性食管毒性的发生率、严重程度以及临床/剂量学预测因素。
回顾了在杜克大学医学中心（DUMC）接受高剂量适形放射治疗（RT）的91例局限性NSCLC患者。患者特征如下：男性53例，女性38例；中位年龄64岁（范围46 - 82岁）；I期16例，II期3例，IIIa期40例，IIIb期30例，X期2例；放疗前吞咽困难6例（7%）。治疗参数包括：中位校正剂量78.8 Gy（范围64.2 - 85.6）；每日两次分割58例（64%）；化疗43例（47%）。急性和晚期食管毒性按RTOG标准分级。使用三维治疗计划工具，以统一方式勾勒食管轮廓，计算三维剂量分布（进行肺密度校正），并生成剂量体积直方图（DVH）和剂量表面直方图（DSH）。在每个轴位层面，计算每个剂量水平下食管周长的百分比。评估接受剂量>50 Gy的食管圆周长度和最大圆周。使用单因素和多因素逻辑回归分析将患者和治疗因素与急性和慢性食管功能障碍相关联。
无急性或晚期4级或5级食管毒性。91例患者中有10例（11%）发生3级急性毒性。在临床参数的单因素分析中，放疗前吞咽困难（p = 0.10）和每日两次分割（p = 0.11）均倾向于显著预测3级急性食管炎。分析的剂量学参数均未显著预测3级急性食管炎。66例可评估患者中有12例（18%）发生晚期食管毒性。在分析的临床参数中，仅放疗前吞咽困难（p = 0.06）倾向于显著预测晚期食管毒性。在单因素分析中，接受剂量>50 Gy的器官体积百分比（p = 0.05）、接受剂量>50 Gy的表面积百分比（p = 0.05）、接受剂量>50 Gy的100%圆周长度（p = 0.04）以及接受剂量>80 Gy的最大圆周百分比（p = 0.01）均显著预测所有级别的晚期毒性。在多因素分析中，接受剂量>50 Gy的器官体积百分比（p = 0.02）和接受剂量>80 Gy的最大圆周百分比（p = 0.02）预测晚期毒性。
积极的高剂量适形放疗后晚期食管毒性常见但很少严重。考虑食管纵向和圆周特征的剂量学变量具有生物学依据，并可预测晚期毒性。需要进一步研究以评估这些参数是否比传统DVH衍生的参数更具预测性。
