Risk factors for radiation induced lung toxicity in locally advanced non-small cell lung cancer treated with three-dimensional radiotherapy
WANG Jing-bo, CAO Jian-zhong, JI Wei, DAI Jian-rong, Lv Ji-ma, LIANG Jun, FENG Qin-fu, CHEN Dong-fu, ZHOU Zong-mei, ZHNAG Hong-xing, XIAO Ze-fern, YIN Wei-bo, WANG L-hua
Department s of Radiation Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021,China
Corresponding authors:WANG Lv-hua
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.
WANG Jing-bo,CAO Jian-zhong,JI Wei et al. Risk factors for radiation induced lung toxicity in locally advanced non-small cell lung cancer treated with three-dimensional radiotherapy[J]. Chinese Journal of Radiation Oncology, 2012, 21(2): 114-119.
[1] Tyldesley S, Boyd C, Schulze K, et al. Estimating the need for radiotherapy for lung cancer:an evidence-based, epidemiologic approach. Int J Radiat Oncol Biol Phys,2001,49:973-985. [2] Kong FM, Ten Haken RK, Schipper MJ, et al. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer:long-term results of a radiation dose escalation study. Int J Radiat Oncol Biol Phys,2005,63:324-333. [3] Bradley JD, Graham MV, Winter K, et al. Toxicity and outcome results of RTOG 9311:a phase Ⅰ-Ⅱ dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys,2005,61:318-328. [4] Rosenzweig KE, Fox JL, Yorke E, et al. Results of a phase I dose-escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma. Cancer,2005,103:2118-2127. [5] Rodrigues G, Lock M, D′souza D, et al. Prediction of radiation pneumonitis by dose-volume histogram parameters in lung cancer-a systematic review. Radiother Oncol,2004,71:127-138. [6] Lind PA, Marks LB, Hollis D, et al. Receiver operating characteristic curves to assess predictors of radiation-induced symptomatic lung injury. Int J Radiat Oncol Biol Phys,2002,54:340-347. [7] Kong FM, Haken RT, Eisbruch A, et al. Non-small cell lung cancer therapy-related pulmonary toxicity:an update on radiation pneumonitis and fibrosis. Semin Oncol,2005,32:42-54. [8] 朱向帜,王绿化,王颖杰,等.三维适形放疗局部晚期非小细胞肺癌的放射性肺炎风险因素研究.中华放射肿瘤学杂志,2007,16:421-426. [9] 王澜,李晓宁,吕冬婕,等.肺低剂量区体积预测急性放射性肺炎价值探讨.中华放射肿瘤学杂志,2010,19:296-300. [10] 庄婷婷,柳青,张黎,等.非小细胞肺癌三维适形放疗同期化疗后急性放射性肺炎发生因素分析.中华放射肿瘤学杂志,2009,18:443-447. [11] 韩蕾,卢冰,付和谊,等.Ⅲ+Ⅳ期非小细胞肺癌三维适形或调强放疗中复合指标预测放射性肺炎前瞻性临床研究.中华放射肿瘤学杂志,2010,19:420-424. [12] Chavaudra J, Bridier A. Definition of volumes in external radiotherapy:ICRU reports 50 and 62. Cancer Radiother,2001,5:472-478. [13] Spierer MM, Hong LX, Wagman RT, et al. Postmastectomy ct-based electron beam radiotherapy:dosimetry, efficacy, and toxicity in 118 patients. Int J Radiat Oncol Biol Phys,2004,60:1182-1189. [14] Jin HK, Tucker SL, Liu HH, et al. Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy. Radiother Oncol,2009,91:427-432. [15] Oh D, Ahn YC, Park HC, et al. Prediction of radiation pneumonitis following high-dose thoracic radiation therapy by 3 Gy/fraction for non-small cell lung cancer:analysis of clinical and dosimetric factors. Jpn J Clin Oncol,2009,39:151-157. [16] Yorke ED, Jackson A, Rosenzweig KE, et al. Dose-volume factors contributing to the incidence of radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys,2002,54:329-339. [17] Zhao L, Wang L, Ji W, et al. Elevation of plasma TGF-beta1 during radiation therapy predicts radiation-induced lung toxicity in patients with non-small-cell lung cancer:a combined analysis from Beijing and Michigan. Int J Radiat Oncol Biol Phys,2009,74:1385-1390. [18] Claude L, Pérol D, Ginestet C, et al. A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer:clinical and dosimetric factors analysis. Radiother Oncol,2004,71:175-181. [19] Gagliardi G, Bjohle J, Lax I, et al. Radiation pneumonitis after breast cancer irradiation:analysis of the complication probability using the relative seriality model. Int J Radiat Oncol Biol Phys,2000,46:373-381. [20] Robnett TJ, Machtay M, Vines EF, et al. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys,2000,48:89-94. [21] Dehing-Oberije C, De Ruysscher D, Van Baardwijk A, et al. The importance of patient characteristics for the prediction of radiation-induced lung toxicity. Radiother Oncol,2009,91:421-426. [22] Tsujino K, Hirota S, Endo M, et al. Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys,2003,55:110-115. [23] Inoue A, Kunitoh H, Sekine I, et al. Radiation pneumonitis in lung cancer patients:a retrospective study of risk factors and the long-term prognosis. Int J Radiat Oncol Biol Phys,2001,49:649-655. [24] Fay M, Tan A, Fisher R, et al. Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys,2005,61:1355-1363. [25] Kong FM, Yuan S, Ten Haken RK, et al. Poorly and well functional lung regions change differently after radiation in lungcancer. ITART 2010,Imagning for Treatment Assessment in
Radiation Therapy[2011-05-30]. http://www.aapm.org/meetings/2010ITART/. [26] Bradley JD, Hope A, El Naqa I, et al. A nomogram to predict radiation pneumonitis, derived from a combined analysis of rtog 9311 and institutional data. Int J Radiat Oncol Biol Phys,2007,69:985-992. [27] Seppenwoolde Y, Lebesque JV, De Jaeger K, et al. Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability. Int J Radiat Oncol Biol Phys,2003,55:724-735.