中国肺癌杂志
中國肺癌雜誌
중국폐암잡지
CHINESE JOURNAL OF LUNG CANCER
2014年
5期
391-400
,共10页
邵岚%洪卫%郑蕾%何春晓%张贝贝%谢发君%宋正波%娄广媛%张沂平
邵嵐%洪衛%鄭蕾%何春曉%張貝貝%謝髮君%宋正波%婁廣媛%張沂平
소람%홍위%정뢰%하춘효%장패패%사발군%송정파%루엄원%장기평
肺肿瘤%厄洛替尼%血清肿瘤标志物%预后因子%预测模型
肺腫瘤%阨洛替尼%血清腫瘤標誌物%預後因子%預測模型
폐종류%액락체니%혈청종류표지물%예후인자%예측모형
Lung neoplasms%Erlotinib%Serum tumor marker%Prognostic factor%Predictive model
背景与目的分子靶向治疗是肺癌个体化治疗的方向，目前已有学者建立靶向治疗预测模型，为临床个体化治疗提供更多的指导。本研究探讨血清肺表面活性物质相关蛋白（pulmonary surfactant-associated pro-tein D, SP-D）、转化生长因子-α（transforming growthfactorα, TGF-α）、基质金属蛋白-9（matrix metalloproteinase 9, MMP-9）、组织多肽特异性抗原（tissue polypeptide speciifc antigen, TPS）、肺腺癌相关抗原（Krebs von den Lungen-6, KL-6）与晚期复治非小细胞肺癌（non-small cell lung cancer, NSCLC）治疗疗效及生存的关系，并构建生存预测模型。方法采用酶联免疫吸附法（enzyme-linked immuno sorbent assay, ELISA）检测114例晚期复治NSCLC患者治疗前外周血清中SP-D、TGF-α、MMP-9、TPS、KL-6含量，结合临床因素分析与厄洛替尼治疗疗效的关系，采用Kaplan-Meier生存曲线、Cox多因素生存分析模型进行单因素和多因素分析，并构建生存预测模型。结果114例患者厄洛替尼治疗总有效率为22.8%，稳定率为72.8%，中位无疾病进展时间（progression-free survival, PFS）为5.13个月，1年生存率为69.3%。SP-D>110 ng/mL组的有效率及稳定率均高于≤110 ng/mL组（P=0.011, P=0.017），MMP-9≤535 ng/mL的稳定率高于>535 ng/mL组（P=0.009）。TPS<80 U/L组的稳定率要高于≥80 U/L组（P=0.002）。SP-D>110 ng/mL组的mPFS长于≤110 ng/mL组（5.95个月vs 3.25个月，P=0.009），MMP-9≤535 ng/mL的mPFS要长于>535 ng/mL组（5.83个月vs 3.47个月，P=0.046），KL-6中<500 U/mL组要优于≥500 U/mL组（6.03个月vs 3.40个月，P=0.040），TPS<80 U/L组的mPFS要长于≥80 U/L组（6.15个月vs 2.42个月，P=0.014）。多因素分析显示吸烟史、EGFR基因野生型、末次化疗疗效进展、厄洛替尼治疗期间无皮疹、LDH升高和TPS≥80 U/L是PFS不佳的独立影响因素。通过建立预后预测模型，根据患者的预后指数可分成4组：低危组、中低危组、中危组和高危组，中位PFS分别是9.12个月、6.88个月、3.52个月和0.93个月，组间差异具有统计学意义（P<0.001）。结论血清肿瘤标志物TPS水平联合患者临床特征建立预测厄洛替尼治疗晚期复治NSCLC生存模型，在临床上有一定的指导意义。
揹景與目的分子靶嚮治療是肺癌箇體化治療的方嚮，目前已有學者建立靶嚮治療預測模型，為臨床箇體化治療提供更多的指導。本研究探討血清肺錶麵活性物質相關蛋白（pulmonary surfactant-associated pro-tein D, SP-D）、轉化生長因子-α（transforming growthfactorα, TGF-α）、基質金屬蛋白-9（matrix metalloproteinase 9, MMP-9）、組織多肽特異性抗原（tissue polypeptide speciifc antigen, TPS）、肺腺癌相關抗原（Krebs von den Lungen-6, KL-6）與晚期複治非小細胞肺癌（non-small cell lung cancer, NSCLC）治療療效及生存的關繫，併構建生存預測模型。方法採用酶聯免疫吸附法（enzyme-linked immuno sorbent assay, ELISA）檢測114例晚期複治NSCLC患者治療前外週血清中SP-D、TGF-α、MMP-9、TPS、KL-6含量，結閤臨床因素分析與阨洛替尼治療療效的關繫，採用Kaplan-Meier生存麯線、Cox多因素生存分析模型進行單因素和多因素分析，併構建生存預測模型。結果114例患者阨洛替尼治療總有效率為22.8%，穩定率為72.8%，中位無疾病進展時間（progression-free survival, PFS）為5.13箇月，1年生存率為69.3%。SP-D>110 ng/mL組的有效率及穩定率均高于≤110 ng/mL組（P=0.011, P=0.017），MMP-9≤535 ng/mL的穩定率高于>535 ng/mL組（P=0.009）。TPS<80 U/L組的穩定率要高于≥80 U/L組（P=0.002）。SP-D>110 ng/mL組的mPFS長于≤110 ng/mL組（5.95箇月vs 3.25箇月，P=0.009），MMP-9≤535 ng/mL的mPFS要長于>535 ng/mL組（5.83箇月vs 3.47箇月，P=0.046），KL-6中<500 U/mL組要優于≥500 U/mL組（6.03箇月vs 3.40箇月，P=0.040），TPS<80 U/L組的mPFS要長于≥80 U/L組（6.15箇月vs 2.42箇月，P=0.014）。多因素分析顯示吸煙史、EGFR基因野生型、末次化療療效進展、阨洛替尼治療期間無皮疹、LDH升高和TPS≥80 U/L是PFS不佳的獨立影響因素。通過建立預後預測模型，根據患者的預後指數可分成4組：低危組、中低危組、中危組和高危組，中位PFS分彆是9.12箇月、6.88箇月、3.52箇月和0.93箇月，組間差異具有統計學意義（P<0.001）。結論血清腫瘤標誌物TPS水平聯閤患者臨床特徵建立預測阨洛替尼治療晚期複治NSCLC生存模型，在臨床上有一定的指導意義。
배경여목적분자파향치료시폐암개체화치료적방향，목전이유학자건립파향치료예측모형，위림상개체화치료제공경다적지도。본연구탐토혈청폐표면활성물질상관단백（pulmonary surfactant-associated pro-tein D, SP-D）、전화생장인자-α（transforming growthfactorα, TGF-α）、기질금속단백-9（matrix metalloproteinase 9, MMP-9）、조직다태특이성항원（tissue polypeptide speciifc antigen, TPS）、폐선암상관항원（Krebs von den Lungen-6, KL-6）여만기복치비소세포폐암（non-small cell lung cancer, NSCLC）치료료효급생존적관계，병구건생존예측모형。방법채용매련면역흡부법（enzyme-linked immuno sorbent assay, ELISA）검측114례만기복치NSCLC환자치료전외주혈청중SP-D、TGF-α、MMP-9、TPS、KL-6함량，결합림상인소분석여액락체니치료료효적관계，채용Kaplan-Meier생존곡선、Cox다인소생존분석모형진행단인소화다인소분석，병구건생존예측모형。결과114례환자액락체니치료총유효솔위22.8%，은정솔위72.8%，중위무질병진전시간（progression-free survival, PFS）위5.13개월，1년생존솔위69.3%。SP-D>110 ng/mL조적유효솔급은정솔균고우≤110 ng/mL조（P=0.011, P=0.017），MMP-9≤535 ng/mL적은정솔고우>535 ng/mL조（P=0.009）。TPS<80 U/L조적은정솔요고우≥80 U/L조（P=0.002）。SP-D>110 ng/mL조적mPFS장우≤110 ng/mL조（5.95개월vs 3.25개월，P=0.009），MMP-9≤535 ng/mL적mPFS요장우>535 ng/mL조（5.83개월vs 3.47개월，P=0.046），KL-6중<500 U/mL조요우우≥500 U/mL조（6.03개월vs 3.40개월，P=0.040），TPS<80 U/L조적mPFS요장우≥80 U/L조（6.15개월vs 2.42개월，P=0.014）。다인소분석현시흡연사、EGFR기인야생형、말차화료료효진전、액락체니치료기간무피진、LDH승고화TPS≥80 U/L시PFS불가적독립영향인소。통과건립예후예측모형，근거환자적예후지수가분성4조：저위조、중저위조、중위조화고위조，중위PFS분별시9.12개월、6.88개월、3.52개월화0.93개월，조간차이구유통계학의의（P<0.001）。결론혈청종류표지물TPS수평연합환자림상특정건립예측액락체니치료만기복치NSCLC생존모형，재림상상유일정적지도의의。
Background and objective Molecular targeting therapy is the direction of individualized treatment of lung cancer, scholars has been established targeted therapy prediction models which provide more guidance for clinical individual therapy. hTis study investigated the relationship among pulmonary surfactant-associated protein D (SP-D), trans-forming growth factorα(TGF-α), matrix metalloproteinase 9 (MMP-9), tissue polypeptide speciifc antigen (TPS), and Krebs von den Lungen-6 (KL-6) and response as well as survival in the patients with recurrent non-small cell lung cancer, which Erlotinib was as second line treatment atfer failure to chemotherapy. hTis study also established a predictive prognostic model.Methods Serum levels of SP-D, TGF-α, MMP-9, TPS, and KL-6 in 114 patients before erlotinib treatment were detected by ELISA method. Combined with clinical factors, these levels were used to investigate the relationship with effcacy in erlotinib treatment and construct a predicted prognostic model by Kaplan-Meier curve and Cox proportional hazard model multivariate analysis. Results hTe objective response rate (ORR) and disease control rate (DCR) in the 114 patients, were 22.8%(26/114) and 72.8%(83/114), to Erlotinib treatment respectively. hTe median progression-free survival (PFS) and one year survival rate with Erlotinib treatment were 5.13 months and 69.3%, respectively. Patients in the SP-D>110 ng/mL group exhibited more ORR (33.3%vs 13.3%, P=0.011) and DCR (83.3%vs 63.3%, P=0.017) than those in the≤110 ng/mL group. Patients in the MMP-9≤535 ng/mL group showed more DCR (83.9%) than those in the>535 ng/mL group (62.1%) (P=0.009). Patients in the TPS<80 U/L group showed more DCR (82.4%) than those in the≥80 U/L group (55.0%) (P=0.002). hTe SP-D>110 ng/mL (5.95 months vs 3.25 months, P=0.009), MMP-9≤535 ng/mL (5.83 months vs 3.47 months, P=0.046), KL-6<500 U/mL (6.03 months vs 3.40 months, P=0.040), and TPS<80 U/L (6.15 months vs 2.42 months, P=0.014) groups showed better PFS. Multivariate analysis showed that current or ever-smoker, wild style of EGFR status, progression atfer prior chemotherapy, absence of skin rash, elevated serum LDH level, and TPS≥80 U/L were independent adverse prognostic factors for PFS. hTese six factors were used in the prognostic model. Patients were categorized into four prognosis risk groups based on the prog-nostic index from the model, namely, low risk, intermediate low risk, intermediate risk, and high risk groups. hTe median PFS of good, intermediate, poor, and very poor prognosis groups were 9.12, 6.88, 3.52, and 0.93 months (P<0.001), respectively. Conclusion hTe prognostic model based on clinical parameters with TPS will be useful in identifying patients who might be most likely to beneift from Erlotinib therapy in the patients with recurrent non-small cell lung cancer.
