| Part I Prognostic factors of Stereotactic body radiotherapy for lung metastatsesObjective To analyze the clinical outcome and toxicity of patients with lung metastases.Methods and Materials From January 2000 to December 2006,71 lung metastases patients with total 172 lesions treated with fractionated stereotactic body radiotherapy (SBRT) were retrospectively reviewed. All patients were unfit for surgery and/or resisted to chemotherapy. The most primary diagnosis was lung cancer in 13 patients and colorectal cancer in 11. Twenty-four patients had lung metastases in the lung alone and 47 metastases in other sites. Fifty-nine patients received one course of SBRT,9 two courses and 1 three,four and six courses respectively. The median total dose was 48 (range,30-60) Gy in 4 (range,2-12) fractions. Results All patients except two were followed up. The median follow up was 24.0 months (range,3-84.5 months). The median size of irradiated lesion was 2.1 cm (range,0.9-7.9 cm) and the target volume 1.8 cm3 (range,0.18-35.3 cm3). The 1-,3-and 5-year local control,overall survival and progression-free survival were 96.6%,89.2% and 89.2%,77.5%,42.0% and 21.1%, 53.5%,13.7% and 6.3%, respectively. In the univariate analysis, lesions small than 1.5 cm had better control than large lesions (100% vs.90.6%, P=0.048). Patients younger than 35 and older than 65 (P=0.04), good KPS (P=0.023), disease free interval more than 12 months (P=0.028), without extrapulmonary metastases (P=0.035) and primary soft tissue tumor (P=0.159) were good prognostic factors. Multivariate analysis showed patients younger than 35 and older than 65 was independent prognosis factor (P=0.044). No grade 3 or more SBRT treatment related toxicity occurred. Conclusions SBRT is an effective and safe treatment for lung metastases, with high long term survival and tolerable complications. Part II Initial microarray analysis on different fractionated radiation regimens in xenografts with human lung adenocarcinomaObjective To identify the tumor growth inhibition and the gene expression on different fractionated radiation regimens with the same total radiation dose in xenografts with human lung adenocarcinoma. Methods Forty-eight BALB/c-nu mice, implanted with human lung adenocarcinoma (Anip973), were randomized into 4 groups:normal control group,60 Gy in 30 fractions conventional radiation group (2 Gy group),60 Gy in 10 fractions successive hypofractionated radiation group within 2 weeks (6 Gy group),60 Gy in 6 fractions intermittent hypofractionaed radiation group within 2 weeks (10 Gy group). The size of the xenografts was measured as the longest diameter. Gene alterations were investigated with the microchip analytical procedures covering the entire genome. Genes with significantly different expression were further measured by the quantitative real-time polymerase chain reaction (RT-PCR). Results The tumor inhibition rate in 2 Gy,6 Gy and 10 Gy group is 12.4%,60.3% and 56.2%. Compared to the 2 Gy group, the expression of the genes related with the cell growth inhibition and apoptosis increased, while the genes related with the cell proliferation, anti-apoptosis and DNA damage repair decreased in the 6 Gy and 10 Gy groups. Confirmed by RT-PCR, c-myc gene was distinctly suppressed in the 6 Gy group (2.9%) than 2 Gy (5.6%) group and 10 Gy (4.8%) group (P=0.000, P=0.002), and was slightly suppressed in the 10 Gy group than 2 Gy group (P=0.069). Conclusions In the BALB/c-nu mice implanted with human lung adenocarcinoma, the hypofractionated radiation regimens clearly inhibit the tumor growth more than conventional fractionation group, though with the same total dose. The 6 Gy group seem to be more effective than 10 Gy group in the inhibition of tumor growth.
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