In vitro and in vivo evaluation of the safety and efficacy of a novel liquid fiducial marker for image-guided radiotherapy.

The true extent of a tumor is difficult to visualize, during radiotherapy, using current modalities. In the present study, the safety and feasibility of a mixture of N-butyl cyanoacrylate and lipiodol (NBCA/Lip) was evaluated in order to investigate the optimal combination for application as a fiducial marker for radiotherapy. Four combinations of NBCA/Lip injection (1:1-0.1, 1:1-0.15, 1:3-0.1 and 1:3-0.15 ml) were injected into the subcutaneous tissue of BALB/c mice. The changes in gross histopathology, body weight, skin score, marker volume, neutrophil and macrophage counts were observed to analyze the effects of the different mixing ratios and injection volumes, in order to identify the best combination. Evaluation according to the International Organization for Standardization criteria was further conducted in order to test the biocompatibility of the mixture, including an acute systematic assay with mice, cytotoxicity with L929 fibroblasts and delayed-type hypersensitivity tests with guinea pigs and an intradermal test with rabbits. The results revealed that at the seventh week, 42 markers (42/48; 87.5%) were still visible using computed tomography (CT) imaging. No serious adverse effects were observed throughout the study period; however, the combination of 1:1-0.1 ml had the lowest body weight and worst skin score. A review of the histopathological reaction to NBCA/Lip revealed a combination of acute inflammation, chronic inflammation, granulation tissue, foreign-body reaction and fibrous capsule formation. The 1:1 NBCA combination ratio resulted in the most intense tissue repair reaction and a slower degradation rate of markers. In general, the combination of 1:3-0.15 ml had a better fusion with local tissue, maintained a stable imaging nodule on CT images for 7 weeks and the final biocompatibility test demonstrated its safety. Overall, the findings of the present study demonstrated NBCA/Lip as a safe and feasible fiducial marker, when using the 1:3-0.15 ml combination.

[A comparative study on radiology and pathology target volume in non-small-cell lung cancer].

OBJECTIVE: Defining the margin of clinical target volume (CTV) is very important for three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT). In this study, according to the comparison between gross tumor volume (GTV) silhouetted by radiology and pathology in non-small-cell lung cancer (NSCLC), we tried to define the correlation of GTV by radiology and pathology, and assess the degree of correlation to local microscopic extension (ME) among different pathologic types of NSCLC, so as to define the margin of CTV precisely. METHODS: From February 2001 to February 2002, forty-three NSCLC patients after surgical resection were studied. All patients had had CT scans of the chest before surgery and routine pathology examination after surgery. The tumor size at X (lateral direction), Y (ventrodorsal direction) and Z (craniocaudal direction) axes were measured on CT. Also by pathology examination, the tumor size at X, Y, Z axes and the degree of ME at X, Y, Z axes were measured, respectively. RESULTS: Without taking into account the value of ME, there was almost total agreement on the GTV by radiology and pathology in three dimensions. The mean value of ME was 2.18 mm for adenocarcinoma (ADC) and 1.33 mm for squamous cell carcinoma (SCC) (P = 0.001). But, taking into account 95% of the ME, a margin of 7 mm and 5 mm must be allowed for ADC and SCC, respectively. CONCLUSION: There exists a correlation of GTV by radiology and pathology. In the target volume defining for 3DCRT and IMRT, we could use the GTV by radiology instead of the GTV by pathology, with the ME being different for ADC and SCC. To cover 95% of the ME, the margin from GTV to CTV must be extended to 7 mm and 5 mm for ADC and SCC, respectively.