Margarita Kirienko

Clinical use of PET-CT data for radiotherapy planning : what are we looking for?

Personalized medicine is the new driving force in the modern era of medicine. In oncology, personalized management of a patient’s disease means the application of specific therapeutic strategies that are best suited for an individual patient and for the particular type of tumour, which the therapy is aiming to target. Molecular diagnostics influences cancer management in several ways that aid personalisation and this is why research has now focused on individualizing treatment strategies by incorporating a combination of physiological variables, genetic characteristics and environmental factors together with the traditional tumour characteristics that currently drive clinical decision making. Imaging is playing a major role in individualizing treatment strategies and the approach differs depending on whether the target is a single disease control point or a general disease control point applicable to a number of treatment paradigms (e.g. proliferation, angiogenesis, inflammation, etc.). Among the many different imaging tools that are available nowadays, Positron emission tomography (PET) can be used to visualize molecular alterations in the living subject, thus facilitating early diagnosis and treatment of disease. The state of art of molecular imaging with PET requires the use of integrated PET and computed tomography (CT) scanners, which are able to offer combined information on molecular and morphological characteristics of tumours. PET-CT using fluoro-deoxy-glucose as a molecular probe of glucose metabolism in cancer cells has been demonstrated to have high accuracy for detection of many tumour types [1]. Along with diagnosis, staging, detection of relapse, restaging and follow-up, one of the main applications of PET-CT is the assessment of therapy response and treatment planning. In routine practice, structural and tumour volume changes are used to guide therapeutic strategies and to measure the disease-free and overall survival. However, tissue metabolism changes more rapidly than morphology, and changes in tumour FDG uptake may therefore predict alterations in volume [2]. The use of FDG-PET as a surrogate tool for monitoring therapy response offers better patient care by individualizing treatment and avoiding ineffective chemotherapy. The use of PET, not only with FDG, to identify patients who can benefit from targeted therapies with monoclonal antibodies has also been demonstrated to be useful, as well as to evaluate the response to therapy in those patients selected for treatment [3,4].

PET Radiomics in NSCLC: state of the art and a proposal for harmonization of methodology

Imaging with positron emission tomography (PET)/computed tomography (CT) is crucial in the management of cancer because of its value in tumor staging, response assessment, restaging, prognosis and treatment responsiveness prediction. In the last years, interest has grown in texture analysis which provides an “in-vivo” lesion characterization, and predictive information in several malignances including NSCLC; however several drawbacks and limitations affect these studies, especially because of lack of standardization in features calculation, definitions and methodology reporting. The present paper provides a comprehensive review of literature describing the state-of-the-art of FDG-PET/CT texture analysis in NSCLC, suggesting a proposal for harmonization of methodology.

Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery

PurposeRadiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery.MethodsA cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built.ResultsThe Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65–0.85), 0.68 (95%CI: 0.57–0.80), and 0.68 (95%CI: 0.58–0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51–0.69), 0.64 (95%CI: 0.53–0.75), and 0.65 (95%CI: 0.50–0.72) for the CT, the PET, and the PET+CT images, respectively.ConclusionsA radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery.

PET/MRI in Infection and Inflammation

Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) systems are now more and more available for clinical use. PET/MR combines the unique features of MR including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most of the evidence of the potential clinical utility of PET/MRI is available for neuroimaging. Other areas, where PET/MR can play a larger role include head and neck, upper abdominal, and pelvic tumours. Although the role of PET/MR in infection and inflammation of the cardiovascular system and in musculoskeletal applications are promising, these areas of clinical investigation are still in the early phase and it may be a little longer before these areas reach their full potential in clinical practice. In this review, we outline the potential of hybrid PET/MR for imaging infection and inflammation. A background to the main radiopharmaceuticals and some technical considerations are also included.

[18F]FDG PET/CT features for the molecular characterization of primary breast tumors

PurposeThe aim of this study was to evaluate the role of imaging features derived from [18F]FDG-PET/CT to provide in vivo characterization of breast cancer (BC).MethodsImages from 43 patients with a first diagnosis of BC were reviewed. Images were acquired before any treatment. Histological data were derived from pretreatment biopsy or surgical histological specimen; these included tumor type, grade, ER and PgR receptor status, lymphovascular invasion, Ki67 index, HER2 status, and molecular subtype. Standard parameters (SUVmean, TLG, MTV) and advanced imaging features (histogram-based and shape and size features) were evaluated. Univariate analysis, hierarchical clustering analysis, and exact Fisher’s test were used for statistical analysis of data. Imaging-derived metrics were reduced evaluating the mutual correlation within group of features as well as the mutual correlation between groups of features to form a signature.ResultsA significant correlation was found between some advanced imaging features and the histological type. Different molecular subtypes were characterized by different values of two histogram-based features (median and energy). A significant association was observed between the imaging signature and luminal A and luminal B HER2 negative molecular subtype and also when considering luminal A, luminal B HER2-negative and HER2-positive groups. Similar results were found between the signature and all five molecular subtypes and also when considering the histological types of BC.ConclusionsOur results suggest a complementary role of standard PET imaging parameters and advanced imaging features for the in vivo biological characterization of BC lesions.

The “3M” Approach to Cardiovascular Infections: Multimodality, Multitracers, and Multidisciplinary

Cardiovascular infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient management, as early treatment improves the prognosis. The diagnosis cannot be made on the basis of a single symptom, sign, or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data, and imaging data. The application of multimodality imaging, including molecular imaging techniques, has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. In this review, we describe data supporting the use of a Multimodality, Multitracer, and Multidisciplinary approach (the 3M approach) to cardiovascular infections. In particular, the role of white blood cell SPECT/CT and [18F]FDG PET/CT in most prevalent and clinically relevant cardiovascular infections will be discussed. In addition, the needs of advanced hybrid equipment, dedicated imaging acquisition protocols, specific expertise for image reading, and interpretation in this field are discussed, emphasizing the need for a specific reference framework within a Cardiovascular Multidisciplinary Team Approach to select the best test or combination of tests for each specific clinical situation.

Ability of FDG PET and CT radiomics features to differentiate between primary and metastatic lung lesions

PurposeTo evaluate the ability of CT and PET radiomics features to classify lung lesions as primary or metastatic, and secondly to differentiate histological subtypes of primary lung cancers.MethodsA cohort of 534 patients with lung lesions were retrospectively studied. Radiomics texture features were extracted using the LIFEx package from semiautomatically segmented PET and CT images. Histology data were recorded in all patients. The patient cohort was divided into a training and a validation group and linear discriminant analysis (LDA) was performed to classify the lesions using both direct and backward stepwise methods. The robustness of the procedure was tested by repeating the entire process 100 times with different assignments to the training and validation groups. Scoring metrics included analysis of the receiver operating characteristic curves in terms of area under the curve (AUC), sensitivity, specificity and accuracy.ResultsRadiomics features extracted from CT and PET datasets were able to differentiate primary tumours from metastases in both the training and the validation group (AUCs 0.79 ± 0.03 and 0.70 ± 0.04, respectively, from the CT dataset; AUCs 0.92 ± 0.01 and 0.91 ± 0.03, respectively, from the PET dataset). The AUC cut-off thresholds identified by LDA using direct and backward elimination strategies were −0.79 ± 0.06 and −0.81 ± 0.08, respectively (CT dataset) and −0.69 ± 0.05 and −0.68 ± 0.04, respectively (PET dataset). For differentiation between primary subgroups based on CT features, the AUCs in the training and validation groups were 0.81 ± 0.02 and 0.69 ± 0.04 for adenocarcinoma (Adc) vs. squamous cell carcinoma (Sqc) or “Other”, 0.85 ± 0.02 and 0.70 ± 0.05 for Sqc vs. Adc or Other, and 0.77 ± 0.03 and 0.57 ± 0.05 for Other vs. Adc or Sqc. The same analyses for the PET data revealed AUCs of 0.90 ± 0.10 and 0.80 ± 0.04, 0.80 ± 0.02 and 0.61 ± 0.06, and 0.97 ± 0.01 and 0.88 ± 0.04, respectively.ConclusionPET radiomics features were able to differentiate between primary and metastatic lung lesions and showed the potential to identify primary lung cancer subtypes.

The Role of Nuclear Cardiac Imaging in Infective Endocarditis

Purpose of ReviewInfective endocarditis (IE) remains a deadly disease despite improvements in its management. Echocardiography is crucial for the diagnosis of IE; however, its value is operator-dependent and its sensitivity can decrease in the presence of valvular prosthesis. This review aims to provide an overview on the role of nuclear cardiac imaging in the diagnosis of IE.Recent FindingsAmong all nuclear cardiac imaging modalities, both radiolabeled leukocyte scintigraphy and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) have been recently introduced in the guidelines of European Society of Cardiology (ESC) for the management of IE. The ESC guidelines included some minor criteria (mainly clinical), and two different sets of major criteria based on blood culture and imaging, respectively. The positivity of either radiolabeled leukocyte scintigraphy or [18F]FDG-PET/CT images is considered itself a major criterion to diagnose IE. However, nuclear cardiac imaging analysis may be tricky and methodological and technical aspects should be carefully considered.SummaryAvailable evidence supports the role of nuclear cardiac imaging in the diagnosis and management of IE. However, all practitioners who act within the “Endocarditis Team” should present a very high level of expertise.

Hodgkin lymphoma and imaging in the era of anti-PD-1/PD-L1 therapy

The assessment of treatment response is crucial for patient management since it guides further treatment or surveillance program. For the purpose of response evaluation in Hodgkin Lymphoma patients, contrast-enhanced CT (CECT) and fluorodeoxyglucose (FDG)–positron emission tomography (PET) were demonstrated to be the most reliable imaging modalities. Response criteria based on tumor size variations on CT and/or modification of tumor glycolytic metabolism on FDG PET have been designed for the assessment of response to chemotherapy and targeted molecular agents. The recent introduction of biological agents with immunological activity revealed the need for criteria revision and for novel biomarkers. The treatment response assessment using the standard criteria for defining anatomical or metabolic remission has been shown to be poorly fit for the immune checkpoint inhibitors since they may determine the “tumor flares”, a phenomenon that has not the same prognostic implications as progressive disease. Accordingly, the response evaluation criteria have been reviewed introducing as main novelty the concept of “pseudo-progression”. Furthermore, PD-1 blockade is not effective in all patients, and delayed or mixed tumor regression can be seen. Therefore, some biomarkers including the detection of PD-L1 on tumor cells, the identification of specific genetic signatures, the longitudinal track of the circulating cell-free DNA, and the imaged-derived parameters have been evaluated to predict response to anti-PD-1/PD-L1 therapy. The present paper reports the available evidence on the role of imaging in patients with HL and future directions for the investigations in the field, with the special focus on the treatment with immune checkpoint inhibitors.