Patterns of nodal spread in stage III NSCLC: importance of EBUS-TBNA and 18F-FDG PET/CT for radiotherapy target volume definition

Purpose!#!The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by !##!Methods!#!This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011-06/2018). Inclusion criteria were curative treatment intent, !##!Results!#!In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (p < 0.0001, exact symmetry test). In a multivariable logistic model for EBUS-positivity at echelon-3, prognostic factors were PET-positivity at echelon-3 (Hazard ratio (HR) = 12.1; 95%-CI: 3.2-46.5), EBUS-TBNA positivity at echelon-2 (HR = 6.7; 95%-CI: 1.31-31.2) and left-sided tumor location (HR = 4.0; 95%-CI: 1.24-13.2). There were significantly less combined ipsilateral upper (LN-stations 2 and 4) and lower (LN-station 7) mediastinal involvements (16.8% of patients) with EBUS-TBNA than with PET (38.9%, p < 0.0001, exact symmetry test). EBUS-TBNA detected a lobe specific heterogeneity between the odds ratios of LN-positivity in the upper versus lower mediastinum (p = 0.0021, Breslow-Day test), while PET did not (p = 0.19).!##!Conclusion!#!Frequent patterns of LN-metastatic spread could be defined by EBUS-TBNA and PET and discrepancies in the pattern were seen between both methods. EBUS-TBNA showed more lobe and tumor laterality specific patterns of LN-metastases than PET and skipped lymph node stations were rare. These systematic relations offer the opportunity to further refine multi-parameter risk of LN-involvement models for target volume delineation based on pattern of spread by EBUS-TBNA and PET

Supramolecular Linear‑<i>g</i>‑Hyperbranched Graft Polymers: Topology and Binding Strength of Hyperbranched Side Chains

Complex, reversible hyperbranched graft polymer topologies have been obtained by spontaneous self-assembly. Well-defined adamantyl- and β-cyclodextrin-functionalized polymers were employed to generate linear-<i>g</i>-(linear–hyperbranched) supramolecular graft terpolymers. For this purpose the synthesis of monoadamantyl-functionalized linear polyglycerols (Ada-<i>lin</i>PG) and hyperbranched polyglycerols (Ada-<i>hb</i>PG) as well as poly­(ethylene glycol)-<i>block</i>-linear polyglycerol (Ada-PEG-<i>b</i>-<i>lin</i>PG) and poly­(ethylene glycol)-<i>block</i>-hyperbranched poly­(glycerol) (Ada-PEG-<i>b</i>-<i>hb</i>PG) block copolymers was established. Isothermal titration calorimetry (ITC) with β-cyclodextrin revealed a shielding effect of hyperbranched polyglycerol for the adamantyl functionality, which was significantly less pronounced when using a linear spacer chain between the adamantyl residue and the hyperbranched polyglycerol block. Additionally, well-defined poly­(2-hydroxypropylamide) (PHPMA) with pendant β-cyclodextrin moieties was synthesized via RAFT polymerization and sequential postpolymerization modification. Upon mixing of the β-cyclodextrin-functionalized PHPMA with Ada-PEG-<i>b</i>-<i>hb</i>PG, a supramolecular linear-<i>g</i>-(linear–hyperbranched) graft terpolymer was formed. The self-assembly was proven by ITC, diffusion-ordered NMR spectroscopy (DOSY), and fluorescence correlation spectroscopy (FCS)

Body composition impacts outcome of bronchoscopic lung volume reduction in patients with severe emphysema: a fully automated CT-based analysis

Abstract Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s [FEV1], r = 0.440; ΔInspiratory vital capacity [IVC], r = 0.397; Δ6Minute walking distance [6MWD], r = 0.509 and ΔCOPD assessment test [CAT], r = −0.324; all p  10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV1) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% −5 vs. 3.4 and ΔIMAT, BAR% −0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients