Programme Overview Session: FS 04

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Learning points
1.The overall role of FDG-PET/CT in Oncology
2.Introducing examples of key-indications
3.Thoughts on cost-effectiveness and implementation of PET/CT
4.Future perspectives

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PSMA-targeted PET imaging allows for therapy guidance in prostate cancer with significantly higher diagnostic accuracy than conventional staging. The current clinical scenario focuses on high-risk patients with a Gleason score >7, PSA>20 or a clinical stadium T2c to T3a, that have a high probability for metastasis, predominantly in lymph nodes and bone. These metastases are diagnosed with significantly higher sensitivity and specificity than with conventional imaging. Consequently, patient tumor stadium is determined at higher accuracy with significant influence on therapeutic management and potentially patient outcome. However, despite rapid clinical translation of PSMA ligands from the lab bench to clinical application and overwhelming data from clinical studies, PSMA imaging is still far away from broad clinical coverage. On the one hand, too few hybrid imaging scanners are available also in highly developed healthcare systems to enable extensive coverage; on the other hand more radiochemical centers are needed to cater for the PSMA-targeting radiopharmaceuticals. Because of longer half-life, the growing availability of 18F-labelled PSMA-ligands allows for the logistical distribution over longer distances. The three major indications for PSMA-targeted hybrid imaging in prostate carcinoma include primary staging, therapy monitoring and biochemical recurrence. Currently, the main indication with the most supporting data available is the clinical situation of biochemical recurrence, where a rising post-therapeutic blood prostate-specific antigen defines tumor recurrence. The precise determination of metastatic localization by conventional staging, however, is frequently a challenge. Main reason is the comparably low sensitivity of standard-of-care imaging with CT and MRI particularly for small lymph node and CT-occult bone metastases. In fact, in this case early biochemical recurrence in prostate carcinoma should be interpreted as a failure-of-staging more than a true recurrence. The implementation and broad availability of PSMA-targeted hybrid imaging could proof as a highly effective and efficient diagnostic method, carrying the potential as a diagnostic disruptor that enables a significant reduction of morbidity and mortality by optimized therapy guidance in prostate carcinoma. The integration of effective and efficient diagnostic tools such as PSMA-targeted hybrid imaging into comprehensive clinical algorithms in prostate cancer has the potential to significantly lower therapeutic costs. Integrated diagnostics with multi-source quantitative data from imaging, liquid biopsy, pathology and genetics will allow for evidence-based personalized clinical decisions with more effective and efficient therapeutic interventions. The anticipated socio-economic impact of powerful diagnostic data on our healthcare systems promotes the forthcoming of integrated diagnostics by healthcare providers that will demand this concept as a prerequisite in line with the implementation of population-based pay-4-performance reimbursement systems.

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Positron emission tomography (PET) was developed in the 1970s as an in-vivo method to measure regional physiological processes. Although absolute quantification of physiological measures (such as metabolic rate of glucose or blood flow) is the defining characteristics of PET imaging, it has not been embraced in clinical routine due to the increased protocol complexity. As a result, simpler and more robust semiquantitative analysis approaches have been adopted in the clinic (such as visual analysis of SUV measures) and were deemed to be sufficient for an accurate diagnosis. In recent years, there has been a renewed interest in absolute quantification, as it has been recognized that semiquantitative methods may lead to sub-optimal or misleading results. Apart from dynamic imaging, absolute quantification requires the measurement of the arterial input function, which represents the amount of non-metabolized radiotracer in the bloodstream as a function of time. However, for absolute quantification to be viable in clinical routine, it needs to be based on a non-invasive protocol. Therefore, a robust method for the non-invasive determination of an accurate arterial input function (AIF) is required. 
Calculating an accurate Image-Derived Input Function (IDIF) for brain studies is challenging. The accuracy of a brain IDIF is challenged by partial volume effects (PVEs) that are highly sensitive to subject motion. In general, the calculation of an IDIF typically involves three main steps: (1) definition of a volume-of-interest (VOI) that represents blood tracer concentration, (2) accounting for involuntary patient motion and (3) recovering the apparent activity in the VOI by performing partial volume correction (PVC). With the advent of fully-integrated PET/MR systems, the above-described challenges can be addressed straightforwardly.  
Our recent work demonstrated that an accurate IDIF could be derived from a fully-integrated PET/MR, which could effectively replace an invasive AIF. A fully-automated, [18F]-FDG PET/MR pipeline that harnesses the synergistic ‘anato-metabolic’ information of the integrated PET/MR was established, allowing the calculation of the metabolic rate of glucose maps for non-lesional epilepsy (NLE) patients. 
We share our initial experience of how building a software pipeline has facilitated our clinicians in adopting our research tools for improving their confidence in routine patient management.

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Cost-effectiveness methods and example use case in the topic of colorectal cancer imaging. Overview of how cost-effectiveness research can help increase reembursement and acceptability of hybrid imaging methods.