Background-RTOG 0515 is a Phase II prospective trial designed to quantify the impact of PET/CT compared to CT alone on radiation treatment plans (RTPs) and to determine the rate of elective nodal failure for PET/CT derived volumes.
Escherichia coli endo IV is a bifunctional DNA repair protein, i.e., possessing both apurinic/apyrimidinic (AP) endonuclease and 3'-diesterase activities. The former activity cleaves AP sites, whereas the latter one removes a variety of 3'-blocking groups present at single-strand breaks in damaged DNA. However, the precise reaction mechanism by which endo IV cleaves DNA lesions is unknown. To probe this mechanism, we have identified eight amino acid substitutions that alter endo IV function in vivo. Seven of these mutant proteins are variably expressed in E. coli and, when purified, show a 10-60-fold reduction in both AP endonuclease and 3'-diesterase activities. The most severe defect was observed with the one remaining mutant (E145G) that showed normal protein expression. This mutant has lost the ability to bind double-stranded DNA and showed a dramatic 150-fold reduction in enzymatic activities. We conclude that the AP endonuclease and the 3'-diesterase activities of endo IV are associated with a single active site, that is perhaps remote from the DNA binding domain.
The aim of this study is to report outcomes and prognostic factors for early stage non-small cell lung cancer treated with patient-adapted Cyberknife stereotactic body radiotherapy. A retrospective analysis of 150 patients with T1-2N0 non-small cell lung cancer treated with stereotactic body radiotherapy was conducted. An algorithm based on tumor and patient's characteristics was used to orient patients towards soft tissue (Xsight Lung), fiducials or adjacent bone (Xsight Spine) tracking. Median biological effective dose without correction for tissue inhomogeneities was 180 Gy 10 for peripheral tumors and 113 Gy 10 for central tumors. Median follow-up was 22 months. Actuarial 2 years local control, overall survival and disease-specific survival were respectively 96%, 87% and 95%. Every 1 cm increase in tumor diameter was associated with a relative risk for regional or distant relapse of 2 (95%CI 5 1.2-3.6, p 5 0.009). With doses 132 Gy 10 and 132 Gy 10 , local control was 98% vs. 82% (p 5 0.07), disease-specific survival 97% vs. 78% (p 5 0.02) and overall survival 93% vs. 76% (p 5 0.01), respectively. Better disease-specific survival and a trend for better overall survival was observed for peripheral vs. central tumors (96% vs. 79%, p 5 0.05 and 92% vs. 74%, p 5 0.08, respectively). A higher Charlson comordibity score (4) predicted lower overall survival (79% vs. 98%, p 5 0.01). Toxicities included 3 patients with idiopathic pulmonary fibrosis who developed grade 5 pneumonitis and 2 patients with grade 3 pneumonitis.We therefore report excellent local control and disease-specific survival following patientadapted Cyberknife lung stereotactic body radiotherapy. Although toxicities were in general minimal, patients with pulmonary fibrosis might be at greater risk of severe complications.Small size, peripheral location, dose 132 Gy 10 and a low Charlson co-morbidity score seem to be associated with better outcomes.
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