局部晚期非小细胞肺癌三维放疗后放射性肺损伤风险因素分析

目的 探讨局部晚期非小细胞肺癌(NSCLC)三维放疗后放射性肺损伤(RILT)与临床和剂量学因素的关系,以寻找RILT的可能风险因素。方法 回顾分析2001-2007年间接受三维放疗的未手术Ⅲ期NSCLC患者 253例临床和剂量学资料,采用NCI-CTC 3.0标准评估RILT级别,以放疗结束后3个月内发生的≥2级RILT作为终点事件,用Logistic回归模型分析影响RILT发生的相关因素。结果 253例中≥ 2级RILT的发生率为26.5%。单因素分析显示年龄、放疗前1 s用力呼吸体积占预测值百分比(FEV1%)、一氧化碳弥散量占预测值百分比(DLCO%)、健肺 V₅~V₁₅、患肺 V₅~V₄₀、全肺 V₅~V₅₀、患肺及全肺的平均肺剂量(MLD)与RILT的发生相关(χ²=4.46~23.99,P=0.000~0.035)。多因素分析显示全肺MLD>17.5 Gy、FEV1%≥72%是≥2级RILT的独立危险因素(χ²=17.49、9.30,P=0.000、0.002)。根据MLD和FEV1%将患者分为低危、中危、中高危和高危组,RILT的发生率分别为9.3%、24.7%、38.5%和63.6%(χ²=25.27,P=0.000)。结论 全肺MLD及放疗前FEV1%与放疗后≥2级RILT发生密切相关。基线较差的肺功能并未增加RILT风险,甚至可能具有相对较低的风险,该趋势尚需在大样本人群中进行验证。

Risk factors for radiation induced lung toxicity in locally advanced non-small cell lung cancer treated with three-dimensional radiotherapy

Objective To investigate the patient and treatment related predictors for the development of radiation induced lung toxicity (RILT) in patients with locally advanced non-small cell lung cancer (NSCLC) receiving definitive three-dimensional radiotherapy. Methods Data were retrospectively collected from inoperable or unresectable 253 patients with stage Ⅲ NSCLC treated with definitive three-dimensional radiotherapy between January 2001 and April 2007. National cancer institute common toxicity criteria version 3.0 was employed to evaluate the classification of RILT and grade ≥2 toxicity served as the endpoint. The correlation between RILT and aforementioned factors was analyzed. Results The grade ≥ 2 RILT was 26.5%. Univariate analysis showed age, FEV1%, DLCO%, contralateral lung (CL) V₅-V₁₅,ipsilateral lung (IL) V₅-V₄₀, total lung (TL) V₅-V₅₀, IL and TL mean lung dose (MLD) were significantly correlated with the development of RILT (χ²=4.46－23.99,P=0.000－0.035). Mmultivariate analysis showed TL MLD>17.5 Gy and FEV1%≥72% were significantly correlated with the development of RILT (χ²=17.49,9.30,P=0.000,0.002). Patients were stratified into four groups according to MLD and FEV1%, corresponding to the RILT incidence of 9.3%, 24.7%, 38.5% and 63.6%, respectively (χ²=25.27,P=0.000). Conclusions TL MLD and baseline FEV1% are significant factors correlated with the development of RILT in NSCLC patients treated with three-dimensional radiation therapy. The combination of TL MLD and FEV1% may help classify NSCLC patients per risk of RILT and subsequently direct risk-adaptive radiation therapy. Poor baseline pulmonary function does not increase the risk of RILT and may even be associated with lower RILT probability, whichhas yet to be validated in larger patient cohorts.