Characterization of lung tumors motion baseline using cone-beam computed tomography.

PURPOSE: To characterize the interfractional variability in lung tumor volume, position, and tumor boundaries. METHODS: Cone-beam computed tomography (CBCT) scans were acquired weekly during the course of treatment for 34 lung cancer patients (1-20 scans) with large tumors. Spatial registration based on bones was performed between contoured planning CT and CBCT. Gross tumor volume (GTV) on each CBCT was then contoured. Tumor volume, centroid, and boundaries variability were quantified. A commercial deformable registration software was tested and results were compared to manual contours. RESULTS: Mean volume reduction was 41 ± 32% (p < 0.001) after an average time of 51 days. Tumor centroid drifts were 0.03, 0.14, and -0.13 cm in right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions with standard deviations of 0.55, 0.50, and 0.51 cm. GTV boundaries displacements were -0.27, -0.14, and -0.16 cm with standard deviations of 0.64, 0.57, and 0.59 cm in RL, AP, and SI directions. Relative error between deformed and manual contours with the commercial deformable registration software rose up exponentially with the GTV decrease. CONCLUSIONS: GTV size changes for large lung tumors are similar to those for standard tumors. Magnitude absolute values of displacement vector for centroid and boundaries shifts show that there is not a preferred direction for the drifts but shrinkage.

Differential contribution of bacterial N-formyl-methionyl-leucyl- phenylalanine and host-derived CXC chemokines to neutrophil infiltration into pulmonary alveoli during murine pneumococcal pneumonia.

Despite the development of new potent antibiotics, Streptococcus pneumoniae remains the leading cause of death from bacterial pneumonia. Polymorphonuclear neutrophil (PMN) recruitment into the lungs is a primordial step towards host survival. Bacterium-derived N-formyl peptides (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) and host-derived chemokines (KC and macrophage inflammatory protein 2 [MIP-2]) are likely candidates among chemoattractants to coordinate PMN infiltration into alveolar spaces. To investigate the contribution of each in the context of pneumococcal pneumonia, CD1, BALB/c, CBA/ca, C57BL/6, and formyl peptide receptor (FPR)-knockout C57BL/6 mice were infected with 10(6) or 10(7) CFU of penicillin/erythromycin-susceptible or -resistant serotype 3 or 14 S. pneumoniae strains. Antagonists to the FPR, such as cyclosporine H (CsH) and chenodeoxycholic acid, or neutralizing antibodies to KC and MIP-2 were injected either 1 h before or 30 min after infection, and then bronchoalveolar lavage fluids were obtained for quantification of bacteria, leukocytes, and chemokines. CsH was effective over a short period after infection with a high inoculum, while anti-CXC chemokine antibodies were effective after challenge with a low inoculum. CsH prevented PMN infiltration in CD1 mice infected with either serotype 3 or 14, whereas antichemokine antibodies showed better efficacy against the serotype 3 strain. When different mouse strains were challenged with serotype 3 bacteria, CsH prevented PMN migration in the CD1 mice only, whereas the antibodies were effective against CD1 and C57BL/6 mice. Our results suggest that fMLP and chemokines play important roles in pneumococcal pneumonia and that these roles vary according to bacterial and host genetic backgrounds, implying redundancy among chemoattractant molecules.