Cost-effectiveness of a novel AI technology to quantify coronary inflammation and cardiovascular risk in patients undergoing routine Coronary Computed Tomography Angiography.

AIMS: Coronary Computed Tomography Angiography (CCTA) is a first line investigation for chest pain in patients with suspected obstructive coronary artery disease (CAD). However, many acute cardiac events occur in the absence of obstructive CAD. We assessed the lifetime cost-effectiveness of integrating a novel artificial intelligence-enhanced image analysis algorithm (AI-Risk) that stratifies the risk of cardiac events by quantifying coronary inflammation, combined with the extent of coronary artery plaque and clinical risk factors, by analysing images from routine CCTA. METHODS AND RESULTS: A hybrid decision-tree with population cohort Markov model was developed from 3,393 consecutive patients who underwent routine CCTA for suspected obstructive CAD and followed up for major adverse cardiac events over a median(IQR) of 7.7(6.4-9.1) years. In a prospective real-world evaluation survey of 744 consecutive patients undergoing CCTA for chest pain investigation, the availability of AI-Risk assessment led to treatment initiation or intensification in 45% of patients. In a further prospective study of 1,214 consecutive patients with extensive guideline recommended cardiovascular risk profiling, AI-Risk stratification led to treatment initiation or intensification in 39% of patients beyond the current clinical guideline recommendations. Treatment guided by AI-Risk modelled over a lifetime horizon could lead to fewer cardiac events (relative reductions of 4%, 4%, 11%, and 12% for myocardial infarction, ischaemic stroke, heart failure and cardiac death, respectively). Implementing AI-Risk classification in routine interpretation of CCTA is highly likely to be cost-effective (Incremental cost-effectiveness ratio £1,371-3,244), both in scenarios of current guideline compliance or when applied only to patients without obstructive CAD. CONCLUSIONS: Compared with standard care, the addition of AI-Risk assessment in routine CCTA interpretation is cost effective, by refining risk guided medical management.

Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma.

Background and purpose: This study aimed to assess the role of T1 mapping and oxygen-enhanced MRI in patients undergoing radical dose radiotherapy for HPV positive oropharyngeal cancer, which has not yet been examined in an OE-MRI study. Materials and methods: Variable Flip Angle T1 maps were acquired on a 3T MRI scanner while patients (n = 12) breathed air and/or 100 % oxygen, before and after fraction 10 of the planned 30 fractions of chemoradiotherapy ('visit 1' and 'visit 2', respectively). The analysis aimed to assess to what extent (1) native R1 relates to patient outcome; (2) OE-MRI response relates to patient outcome; (3) changes in mean R1 before and after radiotherapy related to clinical outcome in patients with oropharyngeal squamous cell carcinoma. Results: Due to the radiotherapy being largely successful, the sample sizes of non-responder groups were small, and therefore it was not possible to properly assess the predictive nature of OE-MRI. The tumour R1 increased in some patients while decreasing in others, in a pattern that was overall consistent with the underlying OE-MRI theory and previously reported tumour OE-MRI responses. In addition, we discuss some practical challenges faced when integrating this technique into a clinical trial, with the aim that sharing this is helpful to researchers planning to use OE-MRI in future clinical studies. Conclusion: Altogether, these results suggest that further clinical OE-MRI studies to assess hypoxia and radiotherapy response are worth pursuing, and that there is important work to be done to improve the robustness of the OE-MRI technique in human applications in order for it to be useful as a widespread clinical technique.

Using Variable Flip Angle (VFA) and Modified Look-Locker Inversion Recovery (MOLLI) T1 mapping in clinical OE-MRI.

BACKGROUND AND PURPOSE: The imaging technique known as Oxygen-Enhanced MRI is under development as a noninvasive technique for imaging hypoxia in tumours and pulmonary diseases. While promising results have been shown in preclinical experiments, clinical studies have mentioned experiencing difficulties with patient motion, image registration, and the limitations of single-slice images compared to 3D volumes. As clinical studies begin to assess feasibility of using OE-MRI in patients, it is important for researchers to communicate about the practical challenges experienced when using OE-MRI on patients to help the technique advance. MATERIALS AND METHODS: We report on our experience with using two types of T1 mapping (MOLLI and VFA) for a recently completed OE-MRI clinical study on oropharyngeal squamous cell carcinoma. RESULTS: We report: (1) the artefacts and practical difficulties encountered in this study; (2) the difference in estimated T1 from each method used - the VFA T1 estimation was higher than the MOLLI estimation by 27% on average; (3) the standard deviation within the tumour ROIs - there was no significant difference in the standard deviation seen within the tumour ROIs from the VFA versus MOLLI; and (4) the OE-MRI response collected from either method. Lastly, we collated the MRI acquisition details from over 45 relevant manuscripts as a convenient reference for researchers planning future studies. CONCLUSION: We have reported our practical experience from an OE-MRI clinical study, with the aim that sharing this is helpful to researchers planning future studies. In this study, VFA was a more useful technique for using OE-MRI in tumours than MOLLI T1 mapping.

The Impact of Radiobiologically Informed Dose Prescription on the Clinical Benefit of 90Y SIRT in Colorectal Cancer Patients.

The purpose of this study was to establish the dose-response relationship of selective internal radiation therapy (SIRT) in patients with metastatic colorectal cancer (mCRC), when informed by radiobiological sensitivity parameters derived from mCRC cell lines exposed to 90Y. Methods: Twenty-three mCRC patients with liver metastases refractory to chemotherapy were included. 90Y bremsstrahlung SPECT images were transformed into dose maps assuming the local dose deposition method. Baseline and follow-up CT scans were segmented to derive liver and tumor volumes. Mean, median, and D70 (minimum dose to 70% of tumor volume) values determined from dose maps were correlated with change in tumor volume and volumetric RECIST response using linear and logistic regression, respectively. Radiosensitivity parameters determined by clonogenic assays of mCRC cell lines HT-29 and DLD-1 after exposure to 90Y or external beam radiotherapy (EBRT; 6 MV photons) were used in biologically effective dose (BED) calculations. Results: Mean administered radioactivity was 1,469 ± 428 MBq (range, 847-2,185 MBq), achieving a mean absorbed radiation dose to tumor of 35.5 ± 9.4 Gy and mean normal liver dose of 26.4 ± 6.8 Gy. A 1.0 Gy increase in mean, median, and D70 absorbed dose was associated with a reduction in tumor volume of 1.8%, 1.8%, and 1.5%, respectively, and an increased probability of a volumetric RECIST response (odds ratio, 1.09, 1.09, and 1.10, respectively). Threshold mean, median and D70 doses for response were 48.3, 48.8, and 41.8 Gy, respectively. EBRT-equivalent BEDs for 90Y are up to 50% smaller than those calculated by applying protraction-corrected radiobiological parameters derived from EBRT alone. Conclusion: Dosimetric studies have assumed equivalence between 90Y SIRT and EBRT, leading to inflation of BED for SIRT and possible undertreatment. Radiobiological parameters for 90Y were applied to a BED model, providing a calculation method that has the potential to improve assessment of tumor control.

Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.

Purpose: Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes in vivo using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology in vivo Experimental Design: Untreated preclinical tumors with different levels of vascularization were imaged sequentially using DCE-MRI and CT. Relationships between functional parameters from MR (iAUC, K trans, and BATfrac) and structural parameters from CT (vessel volume, radius, and tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2 antibody were then imaged to determine whether antiangiogenic therapy altered these relationships. Finally, functional-structural relationships were measured in 10 patients with liver metastases from colorectal cancer.Results: Functional parameters iAUC and K trans primarily reflected vessel volume in untreated preclinical tumors. The relationships varied spatially and with tumor vascularity, and were altered by antiangiogenic treatment. In human liver metastases, all three structural parameters were linearly correlated with iAUC and K trans For iAUC, structural parameters also modified each other's effect.Conclusions: Our findings suggest that MR imaging biomarkers of vascular function are linked to structural changes in tumor vessels and that antiangiogenic therapy can affect this link. Our work also demonstrates the feasibility of three-dimensional functional-structural validation of MR biomarkers in vivo to improve their biological interpretation and clinical utility. Clin Cancer Res; 24(19); 4694-704. ©2018 AACR.