Each patient was set up under daily stereoscopic x-ray and kv CBCT guidance. A single radiation oncologist retrospectively re-contoured the tumor volume on each sequential kv CBCT image and volumetric variances were recorded both in terms of cubic centimeters (CC) and Hounsfield units (HU). A univariate and Kruskall-Wallis analysis were employed using statistical software. Results: One hundred and twenty-nine NSCLC patients treated with definitive intent SBRT were identified. 72 (55.8%) patients were female and 57 (44.2%) were male. 26 (20.2%) continued to smoke during their treatment, 86 (66.7%) were former smokers, and 17 (13.2%) had never smoked before. 37 (28.7%) received steroids prior to each treatment while 92 (71.3%) did not. 90 (69.8%) were located peripherally while 39 (30.2%) were located centrally (by the RTOG 0813 definition). 59 (45.7%) patients received an SBRT dose of 54 Gy / 3 fractions while 69 (53.5%) received 50-60 Gy / 5 fractions. In the 3 fraction group, there was a median increase in tumor size of +17.64% CC (-52.78% to +225.75%), and +2.46% HU (-271.05% to +215.43%), between the first and third fractions; in the 5 fraction group, a median increase in tumor size of +10.40% CC (-50.00% to +112.62%) and +7.87% HU (-122.09% to +417.49%) was observed between the first and fifth fractions. Nine (7.0%) patients experienced local recurrence, 14 (10.9%) patients experienced locoregional recurrence, and 13 (10.1%) experienced distant recurrence. On Kruskall-Wallis Test, locoregional recurrence correlated with tumor volume change between first and third fractions in 3 fraction patients (HU) (PZ0.0440) and between the first and fifth fractions (CC) in 5 fraction patients (PZ0.0232). Conclusion: In this study, we observed interfraction tumor size changes in patients treated with SBRT. Of the patient, tumor, and dosimetric factors analyzed; locoregional recurrence significantly correlated with interfraction tumor size change between the first and last fraction. Further lung NSCLC SBRT interfraction volumetric studies are needed to further characterize the degree of tumor volume growth and thresholds that may predict recurrence.
Rats chronically exposed to acrylonitrile (ACN) have shown a dose-dependent increase in the incidence of astrocytomas in the brain. The mechanism(s) by which ACN induces cancer in rodents has not been established. ACN does not appear to be directly genotoxic in the brain and thus a nongenotoxic mode of action has been proposed. Inhibition of gap junctional intercellular communication (GJIC) has been shown to be a property of many nongenotoxic carcinogens. The present study examined the effects of ACN on GJIC in a rat astrocyte transformed cell line, DI TNC1 cells (a target cell for ACN carcinogenicity) and primary cultured hepatocytes (a nontarget cell for ACN carcinogenicity). ACN inhibited GJIC in rat astrocytes in a dose-dependent manner. Inhibition of GJIC was observed following 2 h treatment with 0.10 mmol/L and 1.00 mmol/L ACN. However, in primary cultured hepatocytes, ACN exposed did not result in inhibition of GJIC even after 48 h of continued treatment. In the astrocytes, GJIC inhibition plateaued after 4 h of treatment and remained blocked throughout the entire experimental period examined. Inhibition of GJIC in DI TNC1 cells was reversed by removal of ACN from the culture medium after 4 or 24 h of treatment. Cotreatment of astrocytes with vitamin E reduced the effect of ACN-induced inhibition of GJIC. Similarly, inhibition of GJIC was prevented by treatment with 2-oxothiazolidine-4-carboxylic acid (OTC), a precursor of glutathione synthesis. Decreasing cellular glutathione by treatment with buthionine sulfoxamine alone (without ACN) did not affect GJIC in astrocytes. Collectively, these results demonstrate that treatment with ACN caused a selective inhibition of GJIC in rat DI TNC1 astrocytes (the target cell type), but not in rat hepatocytes (a nontarget tissue). Inhibition of GJIC in astrocytes was reversed by treatment with antioxidants and suggests a potential role for oxidative stress in ACN-induced carcinogenesis.
SBRT compared to 20.2 months in the combined group (HR¼1.3; p<0.001; CI: 1.22-1.44). Conclusion: SBRT should be the sole modality treatment for patients with inoperable stage I NSCLC. However, patients with stage II disease appear to benefit from adjuvant chemotherapy. Randomized trials are needed in this area to answer this question conclusively.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.