Biomedical subjects

C Mascaux

Publications and source records attributed to C Mascaux.

At least 19 recordsLinked to original sources

PubMed2006

Thyroid transcription factor 1--a new prognostic factor in lung cancer: a meta-analysis.

BACKGROUND: The aim of this study was to determine the prognostic role for survival of thyroid transcription factor 1 (TTF-1) in lung cancer. METHODS: Studies evaluating survival and TTF-1 in lung cancer patients, published until August 2005, were assessed with a methodological scoring system. The required data for estimation of individual hazard ratios (HRs) for survival were extracted from the publications and a combined HR was calculated. RESULTS: We identified 10 eligible papers, all dealing with non-small-cell lung cancer (NSCLC). Eight were meta-analysed (evaluable studies). Seven studies included patients with local and/or locoregional diseases and three dealt only with adenocarcinoma. Median methodological quality score was 65.9% (range = 31.8%-70.5%). TTF-1 positivity was associated with statistically significant reduced or improved survival in one and four studies, respectively. Combined HR for the eight evaluable studies was 0.64 [95% confidence interval (CI) = 0.41-1.00]. In the subgroup of adenocarcinoma, the combined HR was 0.53 (95% CI = 0.29-0.95). CONCLUSION: TTF-1 is a good prognostic factor for survival in NSCLC. Its effect appears also significant when the analysis is restricted to patients with adenocarcinoma. This study supports the fact that TTF-1 could be included in further prospective trials studying prognostic factors in NSCLC.

Humans↗

PubMed2006

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results.

Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.

Humans↗

PubMed2006

Prognostic role of thyroid transcription factor-1 in stage III non-small cell lung cancer.

UNLABELLED: Stage III NSCLC represents a heterogeneous group and the ISS remains unsatisfactory in term of prognosis prediction. The aim of the present study was to determine the role of TTF-1 as prognostic factor in stage III NSCLC in addition to other known clinical factors. All stage III NSCLC patients treated in our hospital were retrieved and searched for biopsy specimens. TTF-1 was assessed by immunohistochemistry (Novocastra SPT24). Between 01/1987 and 07/2003, 108 assessable stage III NSCLC patients were included in the study. Their principal characteristics were: median age 64 years (range 37-83), male/female 81/27, squamous/non squamous 52/56, IIIA/IIIB 44/64, median Karnofsky PS 80 (range 20-100). Forty-four patients were positive for TTF-1 (squamous 25.0% versus non-squamous 55.4%). In multivariate analysis, only three factors were statistically significantly associated with better survival: good PS, surgery and creatinine level. CONCLUSION: In stage III NSCLC patients, good PS, resectability and low creatinine level but not TTF-1 are prognostic factors for survival.

Adult↗

PubMed2005

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis.

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16-1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26-2.02) and in studies using PCR (HR 1.40; 95% CI 1.18-1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86-1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Survival improvement in resectable non-small cell lung cancer with (neo)adjuvant chemotherapy: results of a meta-analysis of the literature.

The recent publication of many randomised trials about (neo)adjuvant chemotherapy in resectable non-small cell lung cancer (NSCLC) has prompted our group to update a prior meta-analysis of the literature. Randomised studies published in French and English between 1965 and June 2004 were included in this analysis. A qualitative assessment of each trial was first performed using the European lung cancer working party (ELCWP) and the Chalmers' scales. In absence of statistically significant quality difference between positive and negative trials, a quantitative aggregation (meta-analysis) of the individual results was performed. Two trials for which data were available on ASCO virtual meeting website were also included in the meta-analysis. Twenty-five studies eligible for this analysis assessed chemotherapy as induction (n = 6) or adjuvant to surgery (n = 19). No quality difference was detected between positive and negative trials according to the two scores, whatever all trials were combined or only adjuvant chemotherapy studies were considered. The overall meta-analysis showed that the hazard ratio (HR) of the combined results was 0.66 (95% CI 0.48-0.93) in favour of the addition of induction chemotherapy to a standard surgical procedure and 0.84 (95% CI 0.78-0.89) in favour of adjuvant chemotherapy. The effect was significant for adjuvant chemotherapy in stages I and II with a HR of 0.88 (95% CI 0.83-0.94). It was not statistically significant in stage III although the trend was in favour of chemotherapy whatever adjuvant (HR = 0.85; 95% CI 0.69-1.04) or (neo)adjuvant (HR = 0.65; 95% CI 0.41-1.04) chemotherapy was tested. In conclusion, our meta-analysis shows the efficacy of adjuvant chemotherapy in stages I and II resected NSCLC. More data are needed to confirm such a role for induction chemotherapy. Further trials should separate stage III disease from earlier stages.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

COX-2 expression during early lung squamous cell carcinoma oncogenesis.

Cyclooxygenase (COX)-2 is implicated in the oncogenesis of many cancers, and COX-2 inhibitors are effective in preventing the development of tumours, such as in colon cancer. Its expression is increased in nonsmall cell lung cancer and is associated with poor prognosis. The present study assessed COX-2 expression in normal bronchial epithelium, as well as in all the putative precursors of squamous cell carcinomas. COX-2 expression was studied by immunohistochemistry in 106 biopsies collected during autofluorescence bronchoscopy in consecutive patients at high-risk for lung cancer. All biopsies corresponding to normal epithelium or low-grade lesions (lesions up to moderate dysplasia) did not show increased COX-2 expression. Lesions were positive for COX-2 in eight out of 14 severe dysplasia patients, eight out of 14 in situ carcinomas and five out of eight invasive carcinomas. A strong statistically significant difference in COX-2 expression was found between normal epithelium or low-grade lesions and high-grade lesions (severe dysplasia or worse). The positive and negative predictive values of COX-2 expression for high-grade lesion were 100% and 82.35%, respectively. In conclusion, bronchial precursors of squamous cell carcinoma showed increased cyclooxygenase-2 expression and were segregated into low- versus high-grade with a high positive predictive value. Thus, cyclooxygenase-2 appears as a potential early marker of squamous cell carcinoma.

Adult↗

PubMed2004

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis.

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.

Biomarkers, Tumor↗

PubMed2004

Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined according to the new 1999 WHO/IASLC criteria: a preliminary study.

AIMS: The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy. METHODS AND RESULTS: The percentage of Ki67+ lesional nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters (defined as a group of at least two strongly Ki67+ nuclei located in the upper third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended on the proportion of the stained nuclei and on the intensity of staining. MiD, MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and 40% median values of positive cells). Thirty-one percent MiD, 77% MoD, 91% SD and 100% CIS showed one or more positive clusters. When only multiple clusters were considered the difference between high- and low-grade lesions was accentuated. Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD (15%) and MoD (22%). This difference was statistically significant (P < 0.01). Evaluation of the Ki67 score was in line with the above results: high grade lesions (SD and CIS) more often showed scores >4 (P = 0.05 between MiD plus MoD versus SD plus CIS). CONCLUSIONS: Ki67 expression increases from MiD to CIS with a statistically significant difference between MiD plus MoD and SD plus CIS. These results suggest that, in terms of Ki67 positivity, SD behaves like CIS rather than like MiD or MoD.

Biopsy↗

PubMed2003

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature.

C-erbB-2 prognostic value for survival in patients with lung cancer remains controversial. We performed a systematic review of the literature to clarify its impact. Studies were identified by an electronic search in order to aggregate the survival results, after a methodological assessment using the scale of the European Lung Cancer Working Party. To be eligible, a study had to deal with c-erbB-2 assessment in lung cancer patients and to analyse survival according to c-erbB-2 expression. In total, 30 studies were eligible: 24 studies dealt with non-small-cell lung carcinoma (NSCLC), five with adenocarcinoma and one study dealt with small-cell carcinoma. In all, 31% of the patients were positive for c-erbB-2. According to c-erbB-2 expression, 13 studies were 'negative' (significant detrimental effect on survival), one 'positive' (significant survival improvement) and 16 not significant. Significant studies had a better subscore relative to analysis and results report than nonsignificant studies. In total, 86% of the significant studies and only 56% of the nonsignificant studies were evaluable for the meta-analysis. This suggests a possible bias in our aggregated results. For NSCLC, the hazard ratio was 1.55 (95% CI: 1.29-1.86) in favour of tumours that do not express c-erbB-2. In conclusion, the overexpression of c-erbB-2 might be a factor of poor prognosis for survival in NSCLC, but there is a potential bias in favour of the significant studies with an overestimation risk of the magnitude of the true effect of c-erbB-2 overexpression.

Adenocarcinoma↗

PubMed2003

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis.

The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer (NSCLC), we performed a systematic review of the literature. Trials were selected for further analysis if they provided an independent assessment of Bcl-2 in lung cancer and reported analysis of survival data according to Bcl-2 status. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a quality scale designed by the European Lung Cancer Working Party (including study design, laboratory methods and analysis). Of 28 studies, 11 identified Bcl-2 expression as a favourable prognostic factor and three linked it with poor prognosis; 14 trials were not significant. No differences in scoring measurement were detected between the studies, except that significantly higher scores were found in the trials with the largest sample sizes. Assessments of methodology and of laboratory technique were made independently of the conclusion of the trials. A total of 25 trials, comprising 3370 patients, provided sufficient information for the meta-analysis. The studies were categorised according to histology, disease stage and laboratory technique. The combined hazard ratio (HR) suggested that a positive Bcl-2 status has a favourable impact on survival: 0.70 (95% confidence interval 0.57-0.86) in seven studies on stages I-II NSCLC; 0.50 (0.39-0.65) in eight studies on surgically resected NSCLC; 0.91 (0.76-1.10) in six studies on any stage NSCLC; 0.57 (0.41-0.78) in five studies on squamous cell cancer; 0.75 (0.61-0.93) and 0.71 (0.61-0.83) respectively for five studies detecting Bcl-2 by immunohistochemistry with Ab clone 100 and for 13 studies assessing Bcl-2 with Ab clone 124; 0.92 (0.73-1.16) for four studies on small cell lung cancer; 1.26 (0.58-2.72) for three studies on neuroendocrine tumours. In NSCLC, Bcl-2 expression was associated with a better prognosis. The data on Bcl-2 expression in small cell lung cancer were insufficient to assess its prognostic value.

Clinical Trials as Topic↗

PubMed2003

Citation indexes do not reflect methodological quality in lung cancer randomised trials.

BACKGROUND: Citation factors are applied to assess scientific work despite the fact that they were developed commercially in order to compare competing journals. The aim of the present study was to determine whether there is a relationship between citation factors and a trial's methodological quality using published randomised trials in lung cancer clinical research. Material and methods All of the randomised trials included in nine systematic reviews performed by the European Lung Cancer Working Party (ELCWP) were assessed using two quality scales (Chalmers and ELCWP). RESULTS: One hundred and eighty-one articles were eligible. The median overall ELCWP and Chalmers quality scores were 61.8% and 49.0%, respectively, with a correlation coefficient (r(s)) of 0.74 (P <0.001). A weak association was observed between citation factors and quality scores with the respective correlation coefficients ranging from 0.18 to 0.40 (ELCWP scale) and from 0.21 to 0.38 (Chalmers scale). American authors published trials significantly more often in journals with high citation factors than European or non-American authors (P <0.0001), despite no better methodological quality. Positive trials, which were significantly more likely to be published in journals with higher citation factors, were of no better quality than negative ones. CONCLUSION: Journals with higher citation factors do not appear to publish clinical trials with higher levels of methodological quality, at least for trials in the field of lung cancer research.

Chi-Square Distribution↗

PubMed2003

Fragile histidine triad protein expression in nonsmall cell lung cancer and correlation with Ki-67 and with p53.

Fragile histidine triad (FHIT) is a tumour suppressor gene, which is altered in a variety of epithelial tumours, including lung cancer. Biochemical and functional pathways of its tumourigenicity are not yet understood. Its role in tumour proliferation is particularly controversial. The purpose of this study was to correlate the expression of FHIT protein in nonsmall cell lung cancer (NSCLC) with tumour proliferation as estimated by Ki-67 antigen and with p53, a suppressor gene. FHIT, Ki-67 and p53 expression were evaluated by immunohistochemistry in 119 resected NSCLC. Altogether, 58 tumours were negative (expression <10%) for FHIT. The median expression in tumours was 15% positive cells, in comparison with 100% in normal matched lung tissue. The expression was as strong as in normal tissue in only 19 cases. FHIT expression was significantly lower in squamous cell carcinoma (SCC) (5%) than in adenocarcinoma (ADC) (64%). The median expression of Ki-67 was 20% and 69% of tumours were positives (expression >10%). Ki-67 expression was significantly higher in SCC (33.3%) than in ADC (10%). The loss of FHIT protein was not correlated with the expression of p53 (median: 7.5%, 58% of positive tumours for a cut-off of 10% of positive cells) or Ki-67. But percentage of labelled cells for p53 and Ki-67 were significantly correlated. The results suggest that for fragile histidine triad, the pathway of tumourigenesis is independent of p53 and of tumoural proliferation, as reported previously in vitro.

Acid Anhydride Hydrolases↗

PubMed2003

[Immune responses in broncho-pulmonary cancer].

INTRODUCTION: The anti-tumoral immune response is essentially cellular and numerous studies have been conducted with the aim of augmenting it from the therapeutic aspect. STATE OF ART: Activation of the immune system has been reported in the early stages of bronchial carcinoma. On the other hand numerous studies have demonstrated a degree of immuno-suppression in patients with advanced cancer prior to any immuno-suppressant treatment, particularly an alteration of cell mediated immunity. The presence of white cells, infiltrating the tumour is an indication of an active host response to the tumour. Several para-neoplastic syndromes associated with the presence of auto-antibodies have been described, particularly in small cell bronchial carcinoma. Other antibodies not associated with para-neoplastic syndromes have also been found, principally directed against the tumour suppressant gene P53. Non-specific active immuno-therapy (BCG, interferons, interleukins.), passive immuno-therapy (monoclonal antibodies) and adoptive immuno-therapy have been studied for many years without encouraging results. Specific active immuno-therapy (anti-tumour vaccines and gene therapy) is the route being most actively explored at present. PERSPECTIVES: Correct targeting of patients likely to benefit from immuno-therapy, specificity and effectiveness of the agents, the expression of transfected genes and the risk of infection and dissemination during clinical trials are all problems currently under investigation. CONCLUSIONS: Manipulations of the immune response have been and are being undertaken with the aim of improving its effectiveness. Anti-tumour vaccines and gene therapy are the routes most studied.

Autoantibodies↗

PubMed2002

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis.

In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a meta-analysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16-2.84), CD34 (HR: 1.99; 95% CI: 1.53-2.58) or CD31 (HR: 1.80; 95% CI: 1.10-2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

Humans↗

PubMed2002

Role of granulocyte and granulocyte-macrophage colony-stimulating factors in the treatment of small-cell lung cancer: a systematic review of the literature with methodological assessment and meta-analysis.

In order to clarify the role of haematological colony-stimulating factors (CSF) in the treatment of small-cell lung cancer, we performed a systematic review of the randomised trials published on this topic. Since 1991, 12 studies were eligible, including a total of 2107 randomised patients. They were divided into three groups: (1) maintenance of dose-intensity when chemotherapy was given at conventional doses and time intervals (seven trials); (2) accelerated chemotherapy with increased dose-intensity by reducing the delay between chemotherapy cycles (five trials); (3) concentration of chemotherapy on an overall shorter duration time with a lower number of cycles (one trial). Before quantitative aggregation, we performed a methodological assessment using two previously published quality scales (Chalmers and ELCWP). The median quality scores for the pooled 12 trials was 59.9% (range: 42.2-82.0%) for the ELCWP scale and 55.8% (range: 38.0-76.8%) for the Chalmers scale. No statistically significant difference was observed between positive (significant) and negative (non-significant) studies allowing us to perform a meta-analysis. A detrimental effect on response rate was associated with CSF administration in the maintenance group (RR 0.92; 95% confidence interval [CI] 0.87-0.97) without significant effect on survival (HR 1.004; 95% CI, 0.89-1.13). In the accelerated group, no significant impact on response rate (RR 1.02; 95% CI, 0.94-1.09) or survival (HR 0.82; 95% CI, 0.67-1.00) was found. Although no difference in response rate was observed, a reduced survival was associated with concentrated chemotherapy. In conclusion, the published data do not support the routine use of haematological colony-stimulating factors in the treatment of small-cell lung cancer (SCLC).

Carcinoma, Small Cell↗

PubMed2002

Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis.

The role of chemotherapy for unresectable malignant mesothelioma is unclear. The aims of the present study were to evaluate the methodological quality of published papers relative to chemotherapy or immunotherapy in malignant mesothelioma and to aggregate, for trials having a similar methodology, the response rates in order to identify the most active chemotherapeutic drugs and regimens. The literature relative to this topic, published between 1965 and June 2001 was reviewed. A methodological qualitative evaluation was performed according to the European Lung Cancer Working Party scale, specifically designed for phase II trials. A study was considered as potentially positive if the upper limit of the 95% confidence interval (CI) of the response rate was greater than 20% and positive if the lower limit of the 95% CI was > 20%. Eighty-three studies (88 treatment arms) were eligible for the systematic review. Fifty-three arms were considered as positive or potentially positive. No statistically significant difference in the methodological quality was observed between negative and positive studies. Studies were aggregated in four groups according to the presence of cisplatin and/or doxorubicin in the treatment regimen. The combination of cisplatin and doxorubicin had the highest response rate (28.5%; P < 0.001). Cisplatin was the most active single-agent regimen. Our systematic qualitative and quantitative overview of the literature suggests that the most active chemotherapeutic regimen, in term of objective response rate, is the combination of cisplatin and doxorubicin and the best single-agent is cisplatin. The combination of these two drugs can be recommended as control arm for future randomised phase III trials.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis.

The prognostic value of epidermal growth factor receptor (EGF-R) for survival of patients with lung cancer remains controversial. The authors performed a systematic review of the literature in order to clarify its impact. Published studies were identified using an electronic search in order to aggregate the available survival results, after a methodological assessment using a scale specifically designed by the European Lung Cancer Working Party (ELCWP). To be eligible, a study had to have dealt with EGF-R assessment in lung cancer patients on the primary site and to have analysed survival according to EGF-R expression. Among the 16 eligible studies, 14 assessed any nonsmall-cell lung cancer (NSCLC) subtype, one adenocarcinoma only and one squamous-cell carcinoma only. The overall median quality score was 56.3%, with no significant difference either between studies assessable or not assessable for meta-analysis or between studies with significant and nonsignificant results. One individual trial reported a survival benefit for patients with EGF-R expression, three a survival disadvantage and 12 no statistically significant difference. Eleven studies (2,185 patients) provided sufficient data to allow a meta-analysis of the survival results. EGF-R expression positivity was determined according to the cut-off as determined by the authors. The meta-analysis showed that EGF-R expression was not a statistically significant prognostic factor for survival in NSCLC. In the subgroup of studies using immunohistochemistry, statistical tests reached a significant level against EGF-R. Epidermal growth factor receptor might be a poor prognostic factor for survival in nonsmall-cell lung cancer. The amplitude of the impact is small, however, and may be subject to publication bias.

Adenocarcinoma↗

PubMed2002

[VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis].

The process of angiogenesis is an important factor in tumour development. One of the principal factors implicated in this process is vascular endothelial growth factor (VEGF) which induces, among other things, an increase in vascular permeability. We have undertaken a systematic review of the English and French literature in order to clarify its effect on the survival of patients with small cell (SCLC) and non-small cell (NSCLC) lung cancer. To be eligible studies had to deal with the the evaluation of VEGF or its receptors in lung cancer and describe the relationship of their expression to survival. The survival figures were subject to meta-analysis after a methodological evaluation by means of a specific numerical scale evaluating the design of the study, the methodology (including laboratory techniques), and the analysis of results. Among the 20 studies selected 15 identified VEGF expression, using univariate analysis, as a statistically significant indicator of poor prognosis. 17 reported sufficient data to allow aggregation of the survival figures, of which 15 were devoted to NSCLC (1,549 patients). The median overall methodological score was 48.3% (range 21.8-72.4%), without significant difference (p=0.63) between studies eligible or non-eligible for meta-analysis. The meta-analysis, using the authors' threshold of positivity for VEGF, showed that VEGF is an unfavourable prognostic factor in NSCLC (HR=1.48; 95% confidence interval 1.27-1.72). The data were insufficient to determine the prognostic value of VEGF in SCLC and that of its two receptors Flt-1 and KDR, with 1, 2 and 1 published studies respectively. In conclusion the expression of VEGF in MSCLC is a factor indicating a poor prognosis.

Carcinoma, Non-Small-Cell Lung↗