Berghmans T, Lafitte J J, Thiriaux J, VanHoutte P, Lecomte J, Efremidis A, Koumakis G, Giner V, Richez M, Corhay J L, Wackenier P, Lothaire P, Mommen P, Ninane V, Sculier J P
Department of Internal Medicine, Institut Jules Bordet, Rue Héger-Bordet, 1 Bruxelles 1000, Belgium.
Lung Cancer. 2004 Sep;45(3):339-48. doi: 10.1016/j.lungcan.2004.02.016.
The 1997 International staging system (ISS) classification separated stage III non-small cell lung cancer (NSCLC) into stages IIIA and IIIB. In a previous study including unresectable NSCLC initially treated with chemotherapy, we analysed survival according to tumour (T) and node (N) stages and derived a classification into stages IIIbeta (T3-4N3) and IIIalpha (other TN stage III) that had a better discrimination on survival distribution. The aim of this study was to validate these results in a further set of patients. Patients with unresectable stage III NSCLC included in a phase III trial assessing the role of increased dose chemotherapy (SuperMIP: mitomycin 6 mg/m2, ifosfamide 4.5 g/m2, cisplatin 60 mg/m2, carboplatin 200 mg/m2) in comparison to standard chemotherapy MIP (mitomycin 6 mg/m2, ifosfamide 3 g/m2, cisplatin 50 mg/m2), before thoracic irradiation (60 Gy in 30 fractions over 6 weeks) were the subject of this study. Survival distributions were assessed by the method of Kaplan-Meier. Survival comparisons were made by the log-rank test. Multivariate analyses using Cox regression models, included all potential prognostic factors for survival with a P-value <0.2 in univariate analysis. According to the 1997 International staging system classification, 328 eligible patients were included in the study. There was no imbalance between the two arms. Five parameters were significantly associated (P < or = 0.05) with survival in univariate analysis: European lung cancer working party (ELCWP) staging (IIIalpha[n = 294 pts] versus IIIbeta [n = 46]), Karnofsky index, weight loss, platelet count and haemoglobin level. These variables as well as the 1997 ISS staging, white blood cell (WBC) count, LDH and sodium levels were included in a multivariate analysis. Two models were constructed, including either the ELCWP or the 1997 ISS. In model 1 (ISS included), Karnofsky index (HR 0.69; 95% confidence interval (CI) 0.47-1.00; P = 0.05) and haemoglobin (HR 1.49; 95% CI 1.11-1.99; P = 0.007) were found significant. In model 2, including ELCWP staging, two variables were associated with survival: ELCWP staging (HR 1.68; 95% CI 1.20-2.35; P = 0.002) and haemoglobin (HR 1.54; 95% CI 1.15-2.07; P = 0.01).
In initially unresectable stage III NSCLC treated by chemotherapy and radiotherapy, we validated the results of our previous study. The classification into stages IIIbeta (T3-4N3M0) and IIIalpha (other TN stage III) better discriminates the patients in term of survival than the 1997 ISS classification.
1997年国际分期系统（ISS）将Ⅲ期非小细胞肺癌（NSCLC）分为ⅢA期和ⅢB期。在之前一项纳入了最初接受化疗的不可切除NSCLC患者的研究中，我们根据肿瘤（T）和淋巴结（N）分期分析了生存率，并得出了一个分为Ⅲβ期（T3 - 4N3）和Ⅲα期（其他TNⅢ期）的分类，该分类对生存分布的区分度更好。本研究的目的是在另一组患者中验证这些结果。本研究的对象是在Ⅲ期试验中纳入的不可切除Ⅲ期NSCLC患者，该试验评估了与标准化疗MIP（丝裂霉素6mg/m²、异环磷酰胺3g/m²、顺铂50mg/m²）相比，增加剂量化疗（SuperMIP：丝裂霉素6mg/m²、异环磷酰胺4.5g/m²、顺铂60mg/m²、卡铂200mg/m²）的作用，这些患者在胸部放疗（6周内30次分割，共60Gy）之前接受治疗。通过Kaplan - Meier方法评估生存分布。通过对数秩检验进行生存比较。使用Cox回归模型进行多变量分析，纳入了单变量分析中P值<0.2的所有潜在生存预后因素。根据1997年国际分期系统分类，328例符合条件的患者纳入研究。两组之间没有不均衡情况。在单变量分析中，有5个参数与生存显著相关（P≤0.05）：欧洲肺癌工作组（ELCWP）分期（Ⅲα期[n = 294例]与Ⅲβ期[n = 46例]）、卡诺夫斯基指数、体重减轻、血小板计数和血红蛋白水平。这些变量以及1997年ISS分期、白细胞（WBC）计数、乳酸脱氢酶（LDH）和钠水平被纳入多变量分析。构建了两个模型，分别包括ELCWP或1997年ISS。在模型1（包括ISS）中，发现卡诺夫斯基指数（风险比[HR]0.69；95%置信区间[CI]0.47 - 1.00；P = 0.05）和血红蛋白（HR 1.49；95%CI 1.11 - 1.99；P = 0.007）显著。在模型2中，包括ELCWP分期，有两个变量与生存相关：ELCWP分期（HR 1.68；95%CI 1.20 - 2.35；P = 0.002）和血红蛋白（HR 1.54；95%CI 1.15 - 2.07；P = 0.01）。
在最初不可切除的Ⅲ期NSCLC患者接受化疗和放疗的治疗中，我们验证了之前研究的结果。与1997年ISS分类相比，分为Ⅲβ期（T3 - 4N3M0）和Ⅲα期（其他TNⅢ期）的分类在生存方面对患者的区分度更好。
