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Abstract Background To study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT) guided hypofractionated radiotherapy with active breathing control (ABC) for patients with non-small cell lung cancer (NSCLC) or metastatic tumors in lung. Methods 32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed. Results The pre-correction systematic and random errors in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20%) grade1-2 acute pneumonitis, 3 (15%) grade1 acute esophagitis, 2 (10%) grade1 late pneumonitis and 1 (5%) grade 1 late esophagitis. Conclusion The positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used.

Background Non-small cell lung cancer ( NSCLC) harboring kinase-domain mutations in epidermal growth factor receptors ( EGFR) has been observed to be sensitive to ionizing radiation ( IR). We explore Rad51-dependent homologous recombination ( HR) DNA repair in regulating radiosensitivity in two NSCLC cell lines with different EGFR mutation status. Methods NSCLC cell lines, wild-type EGFR A549 and mutant EGFR H820 with an in-frame deletion in exon 19 of EGFR (Δ E746- E750), were cultured. Radiosensitivity was estimated by colony forming assay. Rad51 expression was evaluated by quantitative real time-polymerase chain reaction and Western-blot. Lentiviral small hairpin ribonucleic acid- Rad51 and Δ E746- E750 deletion mutant EGFR were constructed and transfected into cells. Flowcytometry assay was used to analyze DNA double strand breaks, cell cycle alterations, and apoptosis. Results A549 had a higher survival factor ( SF)2 (0.66 vs. 0.44) and lower α/β value (4.07 vs. 9.01). Compared with the A549 cell, the H820 cell exhibited defective arrest in the S-phase, a higher rate of G2/M accumulation, early apoptosis, and residual γ- H2AX. Downregulated Rad51 expression decreased SF2 (0.42 vs. 0.31) and increased the α/β ratio (7.51 vs. 10.5), G2/M accumulation, early apoptosis, and γ- H2AX in two cell lines. H820 had a low IR-induced Rad51 expression and nuclear translocation. Exogenous expression of the Δ E746- E750 deletion mutant EGFR caused the A549 cell to become more radiosensitive. Conclusions An EGFR mutated NSCLC cell line is sensitive to IR , which is correlated with reduced IR-induced Rad51 expression and nuclear translocation. The signaling pathway of EGFR maintaining Rad51 protein levels maybe a novel lung cancer therapeutic target to overcome radioresistance. [ABSTRACT FROM AUTHOR]