Chest CT scan plus x-ray versus chest x-ray for the follow-up of completely resected non-small-cell lung cancer (IFCT-0302): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC. METHODS: In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling. FINDINGS: Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported. INTERPRETATION: The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures. FUNDING: French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Evidence of slight improvement in five-year survival in non-small-cell lung cancer over the last 10 years: Results of the French KBP-CPHG real-world studies.

BACKGROUND: Although improved during the last decades, the prognosis of lung cancer is poor. In 2000, the French College of general hospital respiratory physicians, conducted KBP-2000-CPHG, a prospective multicenter epidemiological study including all volunteer adult patients diagnosed for primary lung cancer; with the five-year survival as primary endpoint. The primary objective of KBP-2010-CPHG was to compare overall five-year survival data with KBP-2000-CPHG ones. MATERIAL AND METHODS: All consecutive patients≥18 years of age with primary lung cancer diagnosed between 1st January and 31st December 2010 were included. The KBP-2010-CPHG protocol was approved by the advisory committee on research information processing in the health field (CCTIRS) on November 19, 2009. RESULTS: Respectively, 5667 and 7051 patients were included in KBP-2000-CPHG and KBP-2010-CPHG. Five-year survival was improved: 12.7% [11.9%-13.5%] in 2010 versus 10.0% [9.2%-10.9%] in 2000 (P<0.001). Non-small-cell lung cancer showed improvement (13.8% [13.0%-14.8%] in 2010 versus 11.4% [10.5%-12.4%] in 2000; P<0.001); but not small-cell lung cancer (5.7% [4.4%-7.4%] in 2010 versus 3.3% [2.3%-4.7%] in 2000; P=0.56). The KBP-2010-CPHG study showed an overall 6% reduction in risk of death (HR=0.94 [0.89-0.98]; P=0.004). CONCLUSIONS: Survival of patients with lung cancer improved over a 10-year period. This improvement was slight and limited to non-small-cell lung cancer, possibly partly because of 2010 advances in diagnosis and targeted therapy.

Prediagnosis weight loss, a stronger factor than BMI, to predict survival in patients with lung cancer.

OBJECTIVES: Recent studies have demonstrated that elevated BMI is associated with improved survival in patients with lung cancer. According to the authors, this "obesity paradox" could be a true benefit or a spurious relationship. In this context, data from the French KBP-2010-CPHG cohort (7,051 patients followed up for primary lung cancer diagnosed in 2010 in the respiratory medicine departments of 104 nonacademic hospitals) were analyzed. METHODS: Patients were stratified according to BMI at diagnosis using the definition of the French-Speaking Society of Clinical Nutrition and Metabolism (Société Francophone de Nutrition Clinique et Métabolisme). Survival was analyzed using log-rank and a univariate Cox model. Prognostic factors were identified using a multivariate Cox model with backward elimination procedure, and with or without inclusion of prediagnosis weight loss in the model. RESULTS: Patients were followed for a median 20.2 months. At diagnosis, respectively 12%, 28%, 45%, and 15% of the 6,595 patients with BMI data were obese, overweight, normal-weight, and underweight; 35%, 43%, 57%, and 75% reported prediagnosis weight loss (i.e., weight loss within the 3 months prior to diagnosis). One-year survival (% [95% CI]) was 53% [50%-57%], 50%, [48%-52%], 43%, [42%-45%], and 32% [29%-35%] in obese, overweight, normal-weight, and underweight patients, respectively (p < 0.001). It was particularly low in underweight patients with prediagnosis weight loss: 27% [24-30%]. BMI did not remain an independent prognostic factor associated with survival when prediagnosis weight loss was introduced in the Cox model. Risk of death was increased by 17%, 23%, and 46% in patients with <5 kg, 5-10 kg, or ≥10 kg prediagnosis weight loss, respectively (p < 0.001). CONCLUSION: BMI is an easy but crude assessment tool. Other variables should be used to improve management of patients, and understanding of how prediagnosis body size and nutritional status are associated with cancer survival.

Impact of distance from surgery department on the outcome of patients followed for non-small-cell lung cancer in the respiratory department of nonacademic hospitals: Results of the KBP-2010-study.

OBJECTIVE: Increased postoperative mortality in low volume centers has contributed to merge and space thoracic surgical centers. Some studies have showed that the likelihood of receiving surgery was lower in lung cancer patients living far from a thoracic surgery center. Our objective was thus to determine whether surgery and survival rates in patients with non-small-cell lung cancer (NSCLC) were influenced by the distance between the respiratory and thoracic surgery departments. METHODS: KBP-2010-CPHG is a prospective multicenter epidemiological study including 6083 patients followed in 104 nonacademic hospitals for primary NSCLC diagnosed in 2010. Distance between respiratory and thoracic surgery departments were obtained retrospectively. Predictive factors for surgery and mortality were identified by logistic regression and Cox hazard model. RESULTS: Twenty-three percent of hospitals had a thoracic surgery department; otherwise, mean distance between the hospital and the surgery center was 65km. Nineteen percent of patients underwent surgery. Distance was neither an independent factor for surgery (odds-ratios [95% CI]: 0.971 [0.74-1.274], 0.883 [0.662-1.178], and 1.015 [0.783-1.317] for 1-34, 35-79, and ≥80km vs. 0km) nor for mortality (hazard-ratios [95% CI]: 1.020 [0.935-1.111], 1.003 [0.915-1.099], and 1.006 [0.927-1.091]) (P>0.05). DISCUSSION: This result supports the French national strategy which merges surgery departments and should reassure patients (and physicians) who could be afraid to be lately addressed to surgery or loose chance when being followed far from the thoracic surgical center.

New insights into stage and prognosis in small cell lung cancer: an analysis of 968 cases.

BACKGROUND: The French College of General Hospital Respiratory Physicians conducted two studies that consecutively included all patients followed in participating general hospitals for primary small cell (SCLC) or non-small cell (NSCLC) lung cancer diagnosed in 2000 and 2010. These studies allow descriptive statistics and outcome assessment for SCLC and NSCLC separately and comparison over a 10-year period. METHODS: A standardised form was completed for each patient at inclusion. Then, vital status was collected. RESULTS: In 2000 and 2010, 948 (15.5% female) and 968 (23.3%) SCLC patients, mainly heavy active- or former-smoker seniors, participated in these studies. One-year survival rate was 35.8% for SCLC vs. 44.8% for NSCLC in 2010 and 33.1% for SCLC in 2000. In 2010, in reference to stage 0-IIB (4.1% of SCLCs), the hazard ratio was 0.92 [95% confidence interval (CI): 0.6-1.5; P=0.76], 1.8 (95% CI: 1.1-2.8; P=0.019), and 3.4 (95% CI: 2.2-5.3; P<0.001) for stage IIIA (10.2%), IIIB (14.5%), and IV (71.2%). Positron emission tomography (PET)-scan use, which has increased in 10 years, was frequent in patients with limited disease. CONCLUSIONS: One-year survival in SCLC patients was poor in 2010 and dependent of SCLC stage. TNM classification reintroduction and new diagnostic techniques (e.g., PET-scan) should allow lung oncologists to tailor treatment based on disease stage at diagnosis.

Early mortality in lung cancer: French prospective multicentre observational study.

BACKGROUND: Despite the progress seen in the last decade in diagnosis and treatment, lung cancer has still a bad prognosis and a substantial number of patients died within the weeks following diagnosis. The objective of this study was to quantify early mortality in lung cancer, to identify patients who are at high risk of early decease, and to describe their management in a real world. METHODS: Prospective observational study including consecutively all adult patients managed for primary lung cancer histologically or cytologically diagnosed in 2010 in the respiratory medicine department of one of the participating French general hospitals. Patients and cancer characteristics and first therapeutic strategy were collected at diagnosis. Dates of death were obtained from investigators or town council of the patient's birth place. All fatal cases were considered regardless of the cause of the death. Multivariate logistic regression model was used to determine the factors significantly and independently associated with death at 1 and 3 months. RESULTS: Seven thousand fifty-one patients from 104 centres were included in the study. Vital status was obtained for 6,981 patients. Respectively, 678 (9.7%) and 1,621 (23.2%) of the 6,981 patients with available data died within 1 and 3 months following diagnosis. As compared with the other patients, they were significantly older and frailer (based on performance status [PS] and recent weight loss) and more frequently reported stage IV tumour. Overall, 64.5% (1 month) and 42.8% (3 months) of patients had no cancer therapy and less than 1% were included in a therapeutic trial. CONCLUSION: About one in four patients died within 3 months following lung cancer diagnosis. Early mortality mainly involves frail patients with advanced cancer and is associated with lack of cancer therapy. This supports the need for early diagnosis and clinical trials in this population. Reducing early mortality to give supplementary time to patients to organise the future is a major challenge for 21(st) century physicians.

The new face of non-small-cell lung cancer in men: Results of two French prospective epidemiological studies conducted 10 years apart.

OBJECTIVES: To evaluate the impact of epidemiological changes observed in 10 years in men with NSCLC on 1-year mortality; to compare prognosis factors of 1-year mortality according to gender. MATERIAL AND METHODS: The French College of General Hospital Respiratory Physicians conducted two prospective epidemiological multicentre studies at a 10-year interval (KBP-2000-CPHG and KBP-2010-CPHG). These studies included all adult patients with primary lung cancer histologically or cytologically diagnosed between 1(st) January and 31(st) December for the years 2000 and 2010, managed in the pneumology department of the participating hospitals. A standardised form was completed for each patient. A steering committee checked recruitment exhaustiveness. Vital status 1 year after diagnosis was collected. RESULTS: In 2000 and 2010 respectively, 137 and 104 centres included 3921 and 4597 men and 748 and 1486 women with NSCLC. In 2010 compared to 2000, male patients were older but had better performance status (PS); they were less frequently ever-smokers and heavy smokers; their cancer (usually diagnosed at advanced stage) was more often adenocarcinoma (p<0.0001). In 10 years, 1-year mortality has significantly decreased in men (from 61.2% to 56.6%, p<0.0001) and in women (from 58.1% to 50.9%, p<0.0001), but remained higher in men than in women leading to increased difference between men and women. Decreased 1-year mortality remained statistically significant after adjustment on age, PS, smoking, and histology (men: OR=0.81, 95% CI=0.73-0.90, p<0.0001; women: 0.71, 0.57-0.88, p<0.002). Active smoking was not a prognosis factor in men (OR=1.04, CI=0.79-1.37, p=0.78); age (>75 years) had less impact on mortality in men than in women (men: OR=1.43, CI=1.22-1.67, p ≤ 0.0001; women: OR=2.32, CI=1.71-3.15; p<0.0001). CONCLUSIONS: The improved 1-year survival in 2010 as compared with 2000 was independent of age, smoking, PS, and histology, suggesting that it reflected new treatment and strategy efficacy. One-year mortality remains higher in men than in women.

Major changes in lung cancer over the last ten years in France: the KBP-CPHG studies.

The incidence of lung cancer has dramatically increased in ten years, being now the most commonly diagnosed cancer in males and the fourth most commonly diagnosed cancer in females. Considering social and scientific evolution, the aim of the present study conducted by the French College of General Hospital Respiratory Physicians (CPHG) was to compare patient and lung cancer characteristics at a ten-year interval. Two epidemiological studies, KBP-2000-CPHG and KBP-2010-CPHG, were conducted at a ten-year interval. These prospective multicentre studies included all patients ≥ 18 years of age with primary lung cancer diagnosed between 1st January and 31st December 2000 or 2010, and managed in the respiratory departments of one of the participating general hospitals. A standardised form was completed for each patient. A steering committee checked recruitment exhaustiveness. Respectively, in 2000 and 2010, 137 and 104 centres included 5667 and 7051 patients. Compared to 2000, patients in 2010 were significantly older (65.5 ± 11.3 vs. 64.3 ± 11.5 years, p < 0.0001), more frequently women (24.3% vs. 16.0%, p < 0.0001) and never-smokers (10.9% vs. 7.2%, p < 0.0001). In 2010, adenocarcinoma was the most common tumour (45.4%, vs. 29.0% in 2000, p < 0.0001). The adenocarcinoma rate increased irrespective of sex, age, or smoking status (relative risk [RR] before and after adjustment, RR = 2.07 [1.92-2.24], p < 0.0001 and 2.06 [1.90-2.23], p < 0.0001). In ten years, lung cancer characteristics have therefore changed: more women, more never-smokers, and more adenocarcinomas. The particular high increase in adenocarcinoma rate deserves further analysis.

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.

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.

[Standards, Options and Recommendations for the management of non-small cell lung carcinoma patients]. / Standards, Options et Recommandations 2000 pour la prise en charge des patients atteints d'un cancer bronchopulmonaire non á petites cellules (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of non small cell lung carcinoma patients. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers. This is a short version of the SOR guideline covering diagnosis, treatment and follow-up and includes the algorithms for the management of patients with non-small cell lung cancer.

[2000 Standards, Options and Recommendations for prognostic value of oncogenes and tumor suppressor genes in non small cell lung cancer]. / Standards, Options et Recommandations 2000 pour l'intérêt pronostique des oncogènes et gènes suppresseurs de tumeurs dans les cancers bronchopulmonaires non à petites cellules.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French cancer centers (FNCLCC), the 20 French cancer centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non small cell lung cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers. RESULTS: This article presents the chapter "Prognosis significance of oncogenes and tumor suppressor genes" from the full report "Standards, Options and Recommendation for non small cell lung cancer" validated in August 2000. The main recommendations are: 1) No clear clinical prognostic value of oncogenes and tumor suppressor genes (p53, bcl-2, Ki-ras, c-erbB-2, Rb, p16) in non small cell lung cancer, can be established from the available evidences (standard, level of evidence C). 2) Prospective multicenter studies should be performed to assess prognostic significance of oncogenes and tumor suppressor genes in non small cell lung cancer.