Stereotactic body radiotherapy for centrally located early-stage non-small cell lung cancer or lung metastases from the RSSearch (R) patient registry

Background: The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch (R) Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. Methods: Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. Results: In total, 111 patients with 114 centrally located lung tumors (48 T1-T2, N0, M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1-72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16 - 60 Gy (median 48 Gy) delivered in 1-5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. Conclusion: Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity was low, although low grade toxicities were observed in patients where dose tolerances approached or exceeded published guidelines. Prospective studies are needed to further define the optimal SBRT dose for this cohort of patients

Stereotactic body radiotherapy for centrally located early-stage non-small cell lung cancer or lung metastases from the RSSearch® patient registry

Background: The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch® Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. Methods: Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. Results: In total, 111 patients with 114 centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1–72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16 – 60 Gy (median 48 Gy) delivered in 1–5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. Conclusion: Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity was low, although low grade toxicities were observed in patients where dose tolerances approached or exceeded published guidelines. Prospective studies are needed to further define the optimal SBRT dose for this cohort of patients. Trial registration Clinicaltrials.gov Identifier: NCT0188529

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: clinical outcomes from a National Patient Registry

Objectives: Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates and patients who refuse surgery. The purpose of this study was to assess the impact of SBRT on T1–T2 NSCLC from a national registry, reflecting practices and outcomes in a real-world setting. Methods: The RSSearch® Patient Registry was screened for T1–T2N0M0 NSCLC patients treated from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient, tumor, and treatment characteristics. Overall survival (OS) and local control (LC) were calculated using the Kaplan-Meier method. Results: In total, 723 patients with 517 T1 and 224 T2 lesions were treated with SBRT. Median follow-up was 12 months (1–87 months) with a median age of 76 years. Median SBRT dose was 54 Gy (range 10–80 Gy) delivered in a median of 3 fractions (range 1–5), and median biological equivalent dose (BED10) was 151.2 Gy (range 20–240 Gy). Median OS was 30 and 26 months for T1 and T2 tumors, respectively (p = 0.019). LC was associated with higher BED10 for T2 tumors, but not in T1 tumors at a median follow-up of 17 months. Seventeen-month LC for T2 tumors treated with BED10 105 Gy

Capturing Excited States in the Fast-Intermediate Exchange Limit in Biological Systems Using (HNMR)-H-1 Spectroscopy

Changes in molecular structure are essential for the function of biomolecules. Characterization of these structural fluctuations can illuminate alternative states and help in correlating structure to function. NMR relaxation dispersion (RD) is currently the only method for detecting these alternative, high-energy states. In this study, we present a versatile H-1 R-1 RD experiment that not only extends the exchange timescales at least three times beyond the rate limits of C-13/N-15 R-1 and ten times for CPMG experiments, but also makes use of easily accessible probes, thus allowing a general description of biologically important excited states. This technique can be used to extract chemical shifts for the structural characterization of excited states and to elucidate complex excited states.Funding Agencies|Swedish Research Council [2012-5136]; Tryggers foundation [CTS14-383, CTS15-388]; Karolinska Institutet; Swedish Foundation for Strategic Research [ICA 14-0023]; Ragnar Soderberg foundation [M91/14]; Karolinska Institute; MBB Department</p

Excited States of Nucleic Acids Probed by Proton Relaxation Dispersion NMR Spectroscopy

In this work an improved stable isotope labeling protocol for nucleic acids is introduced. The novel building blocks eliminate/minimize homonuclear 13C and 1H scalar couplings thus allowing proton relaxation dispersion (RD) experiments to report accurately on the chemical exchange of nucleic acids. Using site-specific 2H and 13C labeling, spin topologies are introduced into DNA and RNA that make 1H relaxation dispersion experiments applicable in a straightforward manner. The novel RNA/DNA building blocks were successfully incorporated into two nucleic acids. The A-site RNA was previously shown to undergo a two site exchange process in the micro- to millisecond time regime. Using proton relaxation dispersion experiments the exchange parameters determined earlier could be recapitulated, thus validating the proposed approach. We further investigated the dynamics of the cTAR DNA, a DNA transcript that is involved in the viral replication cycle of HIV-1. Again, an exchange process could be characterized and quantified. This shows the general applicablility of the novel labeling scheme for 1H RD experiments of nucleic acids