⁸⁹Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy:A Feasibility Study

Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of −48% and −90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.</p

The hydrodynamic forces and ship motions in waves

Mechanical, Maritime and Materials Engineerin

Reliability-based design methods to determine the extreme response distribution of offshore wind turbines

In this article a reliability-based approach to determine the extreme response distribution of offshore wind turbines is presented. Based on hindcast data, the statistical description of the offshore environment is formulated. The contour lines of different return periods can be determined. Simulations are carried out for a prototype design of a 3 MW offshore wind turbine. Statistical methods are applied to determine the distribution of the extreme responses. Three approaches are used here. In the MAX approach, only the maximum of each simulation is taken into account. The POT (peak over threshold) approach takes also local maxima into consideration. The process model uses the statistical properties of the process to predict the extremes. All three methods show similar results, but POT and the process model require fewer simulations. Comparison is made for the 100 year response between these reliability-based models and a deterministic model. For this specific turbine the deterministic model underestimates the maximum flap moment but overestimates the maximum overturning moment of the support structure compared with the estimates of the reliability-based methods. The application of the reliability-based model can be extended to include other extreme load situations and achieve a more efficient structural design. Copyright © 2003 John Wiley & Sons, Ltd

Extreme responses of non-linear dynamic systems using constrained simulations

The dynamic behavior of structures in the offshore environment is complex, especially in extreme storm conditions. The most accurate methods for estimating structural behavior are based on extensive random time domain simulations of the ocean surface to obtain statistics of the extreme response in (typically) a 3 hour period of a severe storm. However, random time domain simulation is time-consuming and expensive for both the computer and the engineer. In this work the authors use a method to determine the distribution of the extreme structural response in a robust, faster and cheaper way than with full random simulations. This method, which is based on constrained random simulations, has been successfully developed using a grossly simplified model of a jack-up. The aim of this study is now to include more realistic modelling parameters in order to demonstrate that the method can be successfully applied to real problems and that accurate results can be obtained with relatively little effort

Reliability-based design methods to determine the extreme response distribution of offshore wind turbines

In this article a reliability-based approach to determine the extreme response distribution of offshore wind turbines is presented. Based on hindcast data, the statistical description of the offshore environment is formulated. The contour lines of different return periods can be determined. Simulations are carried out for a prototype design of a 3 MW offshore wind turbine. Statistical methods are applied to determine the distribution of the extreme responses. Three approaches are used here. In the MAX approach, only the maximum of each simulation is taken into account. The POT (peak over threshold) approach takes also local maxima into consideration. The process model uses the statistical properties of the process to predict the extremes. All three methods show similar results, but POT and the process model require fewer simulations. Comparison is made for the 100 year response between these reliability-based models and a deterministic model. For this specific turbine the deterministic model underestimates the maximum flap moment but overestimates the maximum overturning moment of the support structure compared with the estimates of the reliability-based methods. The application of the reliability-based model can be extended to include other extreme load situations and achieve a more efficient structural design. Copyright © 2003 John Wiley & Sons, Ltd