Jan P. van Meerbeeck

Raman microspectroscopic mapping studies of human bronchial tissue

Characterization of the biochemical composition of normal bronchial tissue is a prerequisite for understanding the biochemical changes that accompany histological changes during lung cancer development. In this study, 12 Raman microspectroscopic mapping experiments are performed on frozen sections of normal bronchial tissue. Pseudocolor Raman images are constructed using principal component analysis and K-means cluster analysis. Subsequent comparison of Raman images with histologic evaluation of stained sections enables the identification of the morphologic origin (e.g., bronchial mucus, epithelium, fibrocollagenous stroma, smooth muscle, glandular tissue, and cartilage) of the spectral features. Raman spectra collected from the basal side of epithelium consistently show higher DNA contributions and lower lipid contributions when compared with superficial epithelium spectra. Spectra of bronchial mucus reveal a strong signal contribution of lipids, predominantly triolein. These spectra are almost identical to the spectra obtained from submucosal glands, which suggests that the bronchial mucus is mainly composed of gland secretions. Different parts of fibrocollagenous tissue are distinguished by differences in spectral contributions from collagen and actin/myosin. Cartilage is identified by spectral contributions of glycosaminoglycans and collagen. As demonstrated here, in situ analysis of the molecular composition of histologic structures by Raman microspectroscopic mapping creates powerful opportunities for increasing our fundamental understanding of tissue organization and function. Moreover, it provides a firm basis for further in vitro and in vivo investigations of the biochemical changes that accompany pathologic transformation of tissue.

Economic evaluation of three two-drug chemotherapy regimens in advanced non-small-cell lung cancer

AbstractBackground: During the 1990s, a number of new cytotoxic agents with clinically relevant activity in non-small-cell lung cancer (NSCLC), and with a more favourable therapeutic index than drugs already in use, became available. Given the high prices of these new drugs and the large number of patients affected, it is important to compare the relative benefits and costs of these treatments with the existing regimens before treatment policy decisions are changed. Purpose: An economic evaluation of three different regimens of chemotherapy in patients with advanced NSCLC was performed from the perspective of the Dutch health insurance system using tariffs valid for 2002. The economic evaluation was integrated into a phase III clinical trial in which the reference regimen cisplatinpaclitaxel was compared with two experimental regimens: cisplatin-gemcitabine and gemcitabine-paclitaxel. Materials and methods: Unit costs were applied to resource use data collected prospectively on case report forms during the trial. The average total (uncensored) cost per patient was determined for each of the treatment groups. The principal outcome measure for the economic evaluation was the estimated mean survival time per treatment group. This outcome was then incorporated into incremental cost-effectiveness ratios based on costs corrected for censoring. The impact of uncertainty was assessed by bootstrap techniques, and the analysis and interpretation of the data focused on the bivariate density of differences in outcomes and costs in the incremental cost-effectiveness plane. The final results were summarised by the derivation of cost-effectiveness acceptability curves. Results: The estimated mean survival time was equivalent in the two cisplatinbased regimens with largely overlapping confidence intervals. There was a 99% probability that cisplatin-gemcitabine is the least costly regimen of the two and a 72% probability that this regimen reduces costs while at the same time improving survival. Compared with cisplatin-paclitaxel, the gemcitabine-paclitaxel regimen engendered a borderline significant reduction in mean survival time combined with an almost 90% probability of an increase in costs. Conclusion: The two cisplatin-based regimens are equivalent in terms of survival, but cisplatin-gemcitabine may reduce costs by approximately €2000 per patient compared with cisplatin-paclitaxel. Gemcitabine-paclitaxel is a dominated option with higher costs and a reduction in mean survival time compared with cisplatinpaclitaxel.