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.

[Endobronchial ultrasound and PET positive mediastinal lymph nodes]. / Echographie endobronchique et ganglions TEP positifs dans le cancer broncho-pulmonaire.

INTRODUCTION: In bronchial carcinoma when positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) shows increased emission in the mediastinal lymph nodes, confirmation by tissue biopsy is necessary. In this particular situation we have evaluated the use of real time lymph node aspiration under endobronchial ultrasound control. METHODS: Consecutive patients referred for staging and/or diagnosis of PET positive mediastinal nodes in the setting of suspected or confirmed bronchial carcinoma were included. The results of lymph node aspiration, performed under local anaesthesia in out-patients, were collected and if non-diagnostic surgical exploration was performed. RESULTS: 20 patients were studied between December 2004 and September 2005. The average number of ultrasound guided needle aspirations per patient was 4.8 +/- 1.2. Cytological or histological confirmation of malignancy was obtained by needle biopsy in 12 patients. The 8 negative cases were confirmed by surgical biopsy. In this preliminary series the sensitivity, specificity and negative predictive value of ultrasound guided aspiration of PET positive nodes was 100%. CONCLUSION: Endobronchial ultrasound with needle aspiration should be considered a primary method of investigation of PET positive mediastinal lymph nodes.

Endobronchial ultrasound and positron emission tomography positive mediastinal lymph nodes.

Positron emission tomography with 18F-fluoro-2-deoxy-d-glucose (FDG-PET) is more accurate than computed tomography for staging of mediastinal (hilar) lymph nodes. In the case of positive findings, tissue sampling of lymph nodes is required. The diagnostic/staging yield of transbronchial needle aspiration (TBNA) following endobronchial ultrasound (EBUS) localisation was assessed in this particular clinical setting. The number of avoided surgical procedures was evaluated. All consecutive patients referred for staging and/or diagnosis of mediastinal FDG-PET positive lesions were included. Data were prospectively collected. TBNA sampling of lymph nodes was performed after EBUS localisation. If no diagnosis was reached, further surgical sampling or adequate follow-up was performed. From January 2003 to June 2004, 33 patients were included. The average number of TBNA samples per patient was 4.2+/-1.5. Cytological or histological diagnoses were obtained in 27 (82%) of the patients, of which 78% were obtained after previous EBUS localisation. In 25 (76%) of the 33 patients, surgical staging procedures were suppressed. In conclusion, transbronchial needle aspiration after endobronchial ultrasound localisation should be considered as a primary method of evaluation of lymph nodes positive by positron emission tomography with 18F-fluoro-2-deoxy-d-glucose, and may replace the majority of surgical mediastinal staging/diagnostic procedures.

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.

[Imaging of cancer using positron emission tomography]. / Imagerie des cancers en tomographie par émission de positons.

Positron emission tomography (PET) is a method making use of short half-life radioactive compounds which allow imaging and quantification of functional and metabolic data at the level of multiple organs. This method has been initially oriented towards neurological and cardiological applications but gets now a more widespread use in oncology. This recent development has been made possible thanks to methodological progresses allowing "whole body" imaging and thanks to the use of a practical tracer, the 2-[18 F]fluoro-2-deoxy-D-glucose (FDG). The uptake of this tracer is enhanced in diverse cancer tissues. Recent studies has clarified the biological processes which lead to this enhanced uptake of FDG in cancers. This new insight allows a rational and helpful usage of PET in diverse aspects of clinical oncology: diagnosis of lesion, staging, follow-up of patients and treatment evaluation.