Can serum markers be used to predict acute and late toxicity in patients with lung cancer? Analysis of RTOG 91-03
Can serum markers be used to predict acute and late toxicity in patients with lung cancer? Analysis of RTOG 91-03
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DOI：
10.1097/01.coc.0000260950.44761.74
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发表时间：
2007-08-01
影响因子：
2.6
通讯作者：
Weigensberg, Irving J.
中科院分区：
文献类型：
--
作者：
Hartsell, William F.;Scott, Charles B.;Weigensberg, Irving J.
目的：确定预测明确放射治疗的满意急性和长期肺耐受的因素，反之，预测肺功能过度损害的因素。通过临床表现、肺功能检查和/或肺炎/纤维化的影像学表现，确定放疗患者血液中生化标志物的早期升高与随后肺部异常之间是否存在相关性。材料和方法：这是一项由放射治疗肿瘤小组赞助的多机构前瞻性试验。符合条件的患者为手术不能切除或医学上不能手术的II期或III期非小细胞肺癌。预处理评估包括基线呼吸困难指数（BDI）和肺功能测试（PFT）。放射治疗包括每日一次治疗，剂量为2gy至总剂量为60至66 Gy。定量核医学灌注研究与放射治疗入口相关，评估肺部受照比例。在放射治疗开始前抽取血清标志物（表面活性剂载脂蛋白、III型前胶原、白细胞介素[IL]-1、白细胞介素-6和肿瘤坏死因子-a），然后在治疗期间每周（在10、20、30、40、50和60 Gy时）抽取血液。治疗后随访包括PFT，每3个月随访1年，然后每年随访一次。在相同的时间间隔内重新评估BDl。结果：可分析患者127例。鳞状细胞癌是主要的组织学，93%的患者为AJCC III期。中位生存时间为10.9个月，43%的患者生存1年，10%的患者生存3年。18%的患者出现>= 2级急性肺毒性；最不可能发生肺毒性的患者是那些IL-6水平在10 Gy时检测不到且肺一氧化碳弥散能力为100% （DLCO%）的患者。最有可能发生急性毒性的患者是那些IL-6升高和年龄在60岁以下的患者。30%的患者出现>= 2级晚期肺毒性。Karnofsky性能状态是预测晚期肺毒性的唯一预处理因素。放射场内肺的比例、BDI指数、医生评估的基线呼吸困难和基线PFT不能预测肺毒性。以>= 2级毒性为事件，年龄>60岁，性别和表面活性剂水平= 2急性肺毒性，20 Gy时高血清表面活性剂载脂蛋白水平与>= 2级晚期肺毒性相关。这些发现有待证实，但可能有助于建立模型，预测高剂量辐射造成肺损伤的风险。在未来的研究中，有必要在治疗过程中多个时间点评估血清标志物，在这些血清标志物的收集、储存和分析过程中，质量控制是至关重要的。
Purpose: To identify factors that are predictive of satisfactory acute and long-term pulmonary tolerance of definitive irradiation and, conversely, factors that are predictive of excessive impairment of pulmonary functions. To determine if there is any correlation between early elevation of biochemical markers obtained in blood of irradiated patients and subsequent pulmonary abnormalities as detected by clinical findings, pulmonary function tests, and/or radiographic findings of pneumonitis/fibrosis.Materials and Methods: This was a multi-institutional prospective trial sponsored by the Radiation Therapy Oncology Group. Eligible patients had surgically unresectable or medically inoperable stage II or III non-small cell lung cancer. Pretreatment evaluation included baseline dyspnea index (BDI) and pulmonary function tests (PFT). Radiation therapy consisted of once-daily treatment with 2 Gy to a total of 60 to 66 Gy. A quantitative nuclear medicine perfusion study was correlated to the radiation therapy portals to assess the proportion of lung irradiated. Blood for serum markers (surfactant apoprotein, procollagen type III, interleukin [IL]-1, interleukin-6, and tumor necrosis factor-a) was drawn prior to the beginning of radiation therapy and then weekly during treatment (at 10, 20, 30, 40, 50, and 60 Gy). Post-treatment follow-up included PFT every 3 months for 1 year and then annually. The BDl was reevaluated at the same intervals.Results: There were 127 analyzable patients. Squamous cell carcinoma was the predominant histology and 93% of the patients had AJCC stage III disease. The median survival time is 10.9 months with 43% of patients living 1 year and 10% living 3 years. Grade >= 2 acute lung toxicity was seen in 18 % of patients; patients least likely to develop lung toxicity are those with undetectable levels of IL-6 at 10 Gy and diffusing capacity of the lung for carbon monoxide percent (DLCO%) >54. Patients most likely to develop acute toxicity are those with elevated IL-6 and age >60 years. Grade >= 2 late lung toxicity was seen in 30% of patients. Karnofsky performance status was the only pretreatment factor predictive of late lung toxicity. The proportion of lung within the irradiated field, BDI indices, physician-assessed baseline dyspnea, and baseline PFT were not predictive of pulmonary toxicity. Using grade >= 2 toxicity as an event, age >60 years, gender, and a surfactant level = 2 acute lung toxicity, and high serum levels of surfactant apoproteins at 20 Gy correlated with grade >= 2 late pulmonary toxicity. These findings need to be confirmed but could be useful in a model to predict risk of pulmonary injury with high doses of radiation. For future studies, it is necessary to evaluate serum markers at multiple time-points during treatment, and quality control is critical during the collection, storage, and analysis of these serum markers.