4-year mortality in patients with non-small-cell lung cancer: development and validation of a prognostic index.

BACKGROUND: Lung cancer is the commonest cause of death due to cancer in the world. Non-small-cell lung carcinoma (NSCLC) represents about 80% of overall lung cancer cases worldwide. An accurate predictive model of mortality in patients with NSCLC could be useful to clinicians, policy makers, and researchers involved in risk stratification. The objective of this study was to develop and validate a simple prognostic index for 4-year mortality in patients with NSCLC by use of information obtained at the time of lung cancer diagnosis. METHODS: In 2000, 4669 patients with histologically or cytologically proven NSCLC were enrolled prospectively from 137 pneumology departments in French general hospitals. Patients not lost to follow-up (n=4479) were randomly assigned to the development cohort (n=2979) or the validation cohort (n=1500). Every patient's physician completed a standard and anonymous questionnaire. We used a Cox model to identify variables independently associated with mortality and weighted the variables to create a prognostic index. FINDINGS: Median follow-up for survivors was 49 months (IQR 46-51). There were 2585 deaths (87%) in the development cohort and 1310 deaths (87%) in the validation cohort. Five independent predictors of mortality were identified: age (>70 years, 1 point); sex (male, 1 point); performance status at diagnosis (reduced activity, 3 points; active >50%, 5 points; inactive >50%, 8 points; and total incapacity, 10 points); histological type (large-cell carcinoma, 2 points); and tumour-node-metastasis (TNM) staging system (IIA or IIB, 3 points; IIIA or IIIB, 6 points; and IV, 8 points). The minimum and maximum possible point scores were 0 and 22, respectively. Scores of the prognostic index were strongly associated with 4-year mortality in the development cohort: 0-1 points predicted a 35% (95% CI 28-43) risk, 2-4 points a 59% (52-66) risk, 5-7 points a 77% (72-81) risk, 8-10 points an 88% (85-90) risk, 11-14 points a 97% (96-98) risk, and 15-22 points a 99% (97-100) risk. The corresponding percentages in the validation cohort were 36% (24-47), 60% (50-70), 77% (71-83), 89% (86-93), 96% (95-98), and 99% (98-100), respectively. The prognostic index showed good discrimination, with mean bootstrap c statistics of 0.85 (95% CI 0.84-0.86) in the development cohort and 0.86 (95% CI 0.85-0.87) in the validation cohort. INTERPRETATION: This prognostic index, incorporating personal, tumour, and functional information would be helpful in guiding patient management, resource use, and the design of clinical trials.

Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer.

BACKGROUND: Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC). METHODS: Patients with stage IIIB NSCLC were treated with two monthly MIC cycles followed by radiotherapy; those with "wet" stage IIIB (pleural or pericardial involvement), with stage IIIB with supraclavicular node involvement, or stage IV (i.e., metastatic) NSCLC were treated with four monthly MIC cycles. Patients who responded to induction treatment were randomly assigned to receive intravenous vinorelbine at a dose of 25 mg x m(-2) x wk(-1) for 6 months or no further treatment. Survival comparisons used the log-rank test and the Cox regression adjusted for stage. All statistical tests were two-sided. RESULTS: A total of 573 patients were registered, of whom 227 responded to induction treatment and 181 were randomly assigned (91 to maintenance vinorelbine and 90 to observation) between January 1994 and March 2000. One- and 2-year survival rates were 42.2% and 20.1% in the vinorelbine arm and 50.6% and 20.2% in the observation arm, respectively (log-rank P = .48). The hazard ratio of survival after adjustment on stage, in the vinorelbine arm relative to the observation arm, was 1.08 (95% confidence interval = 0.79 to 1.47; P = .65). There was also no difference between arms in progression-free survival (log-rank P = .32). CONCLUSION: Maintenance vinorelbine did not improve survival of patients with advanced NSCLC who responded to induction MIC treatment. Nevertheless, other agents, including docetaxel and targeted agents, should be evaluated as maintenance agents before the concept is abandoned.

Lung cancer among women in France. Analysis of the 904 French women with lung cancer included in the KBP-2000-CPHG study of the French College of General Hospital-based Pneumologists (CPHG).

As the incidence of primary lung cancer in women seems to be increasing in parallel with that of smoking, we conducted an exhaustive epidemiological study in 137 hospitals in 2000. We identified 904 women with proven primary lung cancer (mean age 63.9 years), many of whom have never smoked (32.3%), particularly in cases of adenocarcinoma (43.4%). Small cell cancer accounted for 16.1% of cases. Adenocarcinomas were the most frequent (45.3%) of the non-small cell lung cancer (NSCLC), followed by squamous cell (23.4%), large cell (11.6%) and bronchoalveolar (1.9%) carcinomas. About one third (32.2%) of NSCLC were stage III and 48.1% were stage IV. Over half of all adenocarcinomas were stage IV. According to multivariate analysis, adenocarcinoma is related to less smoking and younger age. In conclusion, many women affected by lung cancer have never smoked. Adenocarcinoma appears to be the most frequent form and more often at a metastatic stage.

Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer.

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m(2), day 1), ifosfamide (1.5 g/m(2), days 1 to 3) and cisplatin (30 mg/m(2), days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P =.38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P =.15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P =.027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P =.044). Disease-free survival time was significantly longer in the PCT arm (P =.033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.