This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.
7574 Background: 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) /computed tomography (CT) has a potential improvement for staging and radiation treatment (RT) planning of various tumor sites. But from a clinical standpoint, the open questions are essentially the following: to what extent does PET/CT change the target volume? Can PET/CT reduce inter-observer variability in target volume delineation? We analyzed the use of FDG-PET/ CT images for staging and evaluated the impact of FDG- PET/CT on the radiotherapy volume delineation compared with CT in patients with non-small cell lung cancer (NSCLC) candidates for radiotherapy. Intraobserver variation in delineating tumor volumes was also observed. Methods: Twenty-three patients with stage I-III NSCLC were enrolled in this pilot study and were treated with fractionated RT based therapy with or without chemotherapy. FDG-PET/CT scans were acquired within 2 weeks prior to RT. PET and CT data sets were sent to the treatment planning system Pinnacle through compact disc. The CT and PET images were subsequently fused by means of a dedicated radiation treatment planning system. Gross Tumor Volume (GTV) was contoured by four radiation oncologists respectively on CT (CT-GTV) and PET/CT images (PET/CT-GTV). The resulting volumes were analyzed and compared. Results: For the first phase, two radiation oncologists outlined together the contours achieving a final consensus. Based on PET/CT, changes in TNM categories occurred in 8/23 cases (35%). Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in 12/20 patients (60%) by comparison with CT targeting. The most prominent changes in GTV have been observed in cases with atelectasis. For the second phase was four intraobserver variation in delineating tumor volumes. The mean ratio of largest to smallest CT-based GTV was 2.31 (range 1.01–5.96). The addition of the PET data reduced the mean ratio to 1.46 (range 1.12–2.27). Conclusions: PET/CT fusion images could have a potential impact on both tumor staging and treatment planning. Implementing matched PET/CT reduced observer variation in delineating tumor volumes significantly with respect to CT only. [Table: see text]
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