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 metaanalysis 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 metaanalytic 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.

Our meta-analysis suggests that the primary tumor SUV measurement has a prognostic value in NSCLC; these results should be confirmed in a meta-analysis on individual patients' data.

We confirmed the results of our previous review showing that SUV is potentially a very interesting factor for predicting patient outcome. We believe that a meta-analysis based on individual patient data would be of great value as allowing to assess the independent prognostic value, to take into account some factors responsible for heterogeneity between studies (SUV assessment method, disease stage, and histology), and to update survival data. We are planning to conduct such a meta-analysis on behalf of the International Association for the Study of Lung Cancer Staging Project.

The clinical added-value of 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (18 FDG PET) in the management of oncology patients is increasingly documented. In the present review, we discuss both the benefits and the limitations of 18 FDG PET in different cancers. Considering the literature data and our own experience, we also indicate the best clinical approach to optimize the use of metabolic imaging in oncology. Contents 1. Introduction 2. Key factors influencing the 18 FDG uptake 3. Indications of 18 FDG PET in oncology 4. Conclusion

SummaryIn the staging of lung cancer with positron emission tomography (PET) positive mediastinal lymph nodes, tissue sampling is required. The performance of transbronchial needle aspiration (TBNA) using linear endobronchial ultrasound (real-time EBUS-TBNA) under local anaesthesia and the value of PET for prediction of pathological results were assessed in that setting. The number of eluded surgical procedures was evaluated. All consecutive patients with suspected/proven lung cancers and FDG-PET positive mediastinal adenopathy were included. If no diagnosis was reached, further surgical sampling was required. Lymph node SUVmax (maximum standardized uptake value) was assessed in patients whose PET was performed in the leading centre. One hundred and six patients were included. The average number of TBNA samples per patient was 4.9 ±1.1. The prevalence of lymph node metastasis was 58%. Sensitivity, accuracy and negative predictive value of EBUS-TBNA in the staging of mediastinal hot spots were 95, 97 and 91%. Patients without malignant lymph node involvement showed lower SUVmax (respective median values of 3.7 and 10.0; p < 0.0001 ). Surgical procedures were eluded in 56% of the patients. Real-time EBUS-TBNA should be preferred over mediastinoscopy as the first step procedure in the staging of PET mediastinal hot spots in lung cancer patients. In case of negative EBUS, surgical staging procedure should be undertaken. The addition of SUVmax cut-off may allow further refinement but needs validation.

FDG-PET/CT is a valuable tool in patients with HIV-associated FUO. FDG-PET/CT was categorized as 'helpful for diagnosis' in nine out of the 10 patients we studied. Adding the CT anatomical landmarks to the PET findings allowed an accurate and easy localization of the sites to be punctured in the six patients in whom histopathological diagnosis was needed.

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.

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.