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BACKGROUND: (18)F-fluorodeoxyglucose positron emission tomography integrated with computed tomography ((18)F-FDG PET/CT) is a useful tool for baseline staging in newly diagnosed multiple myeloma (MM) but also for prognostic stratification. This monocentric retrospective study aimed at examining the relation between baseline tumour metabolism assessed by (18)F-FDG PET/CT and linear predictor (LP) score, a new cytogenetic stratification score. METHODS: From March 2012 to March 2019, 57 patients with newly diagnosed MM addressed to our institution for baseline (18)F-FDG PET/CT were included. LP score was determined on systematic iliac crest bone marrow samples. Obtained on CD138-sorted bone marrow plasma cells, this recent composite cytogenetic stratification is a 6-marker based weighted score using fluorescence in situ hybridization (FISH) ± single nucleotide polymorphism (SNP) arrays. We compared quantitative metabolic parameters and LP score using a Kruskal-Wallis test and visual suspicion of diffuse bone marrow involvement (DBI; based on hepatic background as threshold of positivity) and cytogenetic data using a Chi-squared test. RESULTS: The distribution of total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG) values among the three LP score categories was almost stochastic, with no significant association (P=0.70). Additionally, no significant association between TMTV/TLG and any of the six cytogenetic abnormalities included in LP score calculation. A significant association was found between visual high suspicion of DBI and LP score (P=0.036), and between this visual parameter and the presence of 1q gain (P=0.049). CONCLUSIONS: There is no significant association between quantitative metabolic parameters assessed with (18)F-FDG PET/CT and LP score in patients with newly diagnosed MM, suggesting a potential complementarity of these biomarkers for prognostic stratification. A significant association was found between high visual suspicion of DBI and LP score.

Introduction The aim of this study was to evaluate the impact of the contouring methods on dose metrics and their predictive value on tumor control and survival, in both situations of pre-treatment and post-treatment dosimetry, for patients with advanced HCC treated with SIRT. Methods Forty-eight patients who underwent SIRT between 2012 and 2020 were retrospectively included in this study. Target volumes were delineated using two methods: MRI-based contours manually drawn by a radiologist and then registered on SPECT/CT and PET/CT via deformable registration (Pre-CMRI and Post-CMRI), 99mTc-MAA-SPECT and 90Y-microspheres-PET 10% threshold contouring (Pre-CSPECT and Post-CPET). The mean absorbed dose (Dm) and the minimal absorbed dose delivered to 70% of the tumor volume (D70) were evaluated with both contouring methods; the tumor-to-normal liver uptake ratio (TNR) was evaluated with MRI-based contours only. Tumor response was assessed using the mRECIST criteria on the follow-up MRIs. Results No significant differences were found for Dm and TNR between pre- and post-treatment. TNR evaluated with radiologic contours (Pre-CMRI and Post-CMRI) were predictive of tumor control at 6 months on pre- and post-treatment dosimetry (OR 5.9 and 7.1, respectively; p = 0.02 and 0.01). All dose metrics determined with both methods were predictive of overall survival (OS) on pre-treatment dosimetry, but only Dm with MRI-based contours was predictive of OS on post-treatment images with a median of 23 months for patients with a supramedian Dm versus 14 months for the others (p = 0.04). Conclusion In advanced HCC treated with SIRT, Dm and TNR determined with radiologic contours were predictive of tumor control and OS. This study shows that a rigorous clinical workflow (radiologic contours + registration on scintigraphic images) is feasible and should be prospectively considered for improving therapeutic strategy.

Follicular lymphoma (FL) is the most common indolent lymphoma. Despite the clear benefit of CD20-based therapy, a subset of FL patients still progress to aggressive lymphoma. Thus, identifying early biomarkers that incorporate positron emission tomography metrics could be helpful to identify patients with a high risk of treatment failure with rituximab. We retrospectively included a total of 132 untreated FL patients separated into training and validation cohorts. Optimal threshold of baseline whole-body maximum standardized uptake (SUVmax) was first determined in the training cohort (n=48) to predict progression-free survival (PFS). The PET results were investigated along with the tumor and immune microenvironment, which were determined by immunochemistry and transcriptome studies involving gene set enrichment analyses and immune cell deconvolution, together with the tumor mutation profile. We report that baseline SUVmax>14.5 was associated with poorer PFS than baseline SUVmax≤14.5 (hazard ratio =0.28; P=0.00046). Neither immune T-cell infiltration nor immune checkpoint expression were associated with baseline PET metrics. By contrast, FL samples with Ki-67 staining ≥10% showed enrichment of cell cycle/DNA genes (P=0.013) and significantly higher SUVmax values (P=0.007). Despite similar oncogenic pathway alterations in both SUVmax groups of FL samples, four out of five cases harboring the infrequent FOXO1 transcription factor mutation were seen in FL patients with SUVmax>14.5. Thus, high baseline SUVmax reflects FL tumor proliferation and, together with Ki-67 proliferative index, can be used to identify patients at risk of early relapse with rituximab chemotherapy.

Objective: Automated voxel-based analysis methods are used to detect cortical hypometabolism typical of Alzheimer’s Disease (AD) on FDG-PET brain scans. We compared the accuracy of two clinically validated tools for their ability to identify those MCI subjects progressing to AD at followup, to evaluate the impact of the analysis method on FDG-PET diagnostic performance. Methods: SPMGrid and BRASS (Hermes Medical Solutions, Stockholm, Sweden) were tested on 131 MCI and elderly healthy controls from the EADC PET dataset. The concordance between the tools was tested by correlating the quantitative parameters (z- and t-values), calculated by the two software tools, and by measuring the topographical overlap of the abnormal regions (Dice score). Three independent expert readers blindly assigned a diagnosis based on the two map sets. We used conversion to AD dementia as the gold standard. Results: The t-map and z-map calculated with SPMGrid and BRASS, respectively, showed a good correlation (R > .50) for the majority of individual cases (128/131) and for the majority of selected regions of interest (ROIs) (98/116). The overlap of the hypometabolic patterns from the two tools was, however, poor (Dice score .36). The diagnostic performance was comparable, with BRASS showing significantly higher sensitivity (.82 versus .59) and SPMGrid showing higher specificity (.87 versus .52). Conclusion: Despite similar diagnostic performance in predicting conversion to AD in MCI subjects, the two tools showed significant differences, and the maps provided by the tools showed limited overlap. These results underline the urgency for standardization across FDG-PET analysis methods for their use in clinical practice.

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres® or TheraSphere® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments.

Purpose. The use of SPECT/CT in bone scans has been widespread in recent years, but there are no specific guidelines concerning the optimal acquisition protocol. Two strategies have been proposed: targeted SPECT/CT for equivocal lesions detected on planar images or systematic whole-body SPECT/CT. Our aim was to compare the diagnostic accuracy of the two approaches. Methods. 212 consecutive patients with a history of cancer were referred for bone scans to detect bone metastases. Two experienced readers randomly evaluated for each patient either planar images with one-field SPECT/CT targeted on equivocal focal uptakes (targeted SPECT/CT) or a whole-body (two-field) SPECT/CT acquisition from the base of the skull to the proximal femurs (whole-body SPECT/CT). The exams were categorized as “nonmetastatic,” “equivocal,” or “metastatic” on both protocols. The presence or absence of any extra-axial skeletal lesions was also assessed. The sensitivity and specificity of both strategies were measured using the results of subsequent imaging follow-up as the reference standard. Results. Whole-body SPECT/CT had a significantly higher sensitivity than targeted SPECT/CT to detect bone metastases (p=0.0297) and to detect extra-axial metastases (p=0.0266). There was no significant difference in specificity among the two approaches. Conclusion. Whole-body SPECT/CT is the optimal modality of choice for metastatic workup, including detection of extra-axial lesions, with improved sensitivity and similar specificity compared to targeted SPECT/CT.

Breast cancer is the most common cancer in women worldwide, and represented more than 25% of the newly diagnosed cancer cases in women in 2016. PET/CT is recommended in the clinical workup of advanced breast cancers and in cases of breast cancer recurrence and may also be proposed in treatment monitoring. PET/MRI is a new imaging technique which is now being used clinically in different countries, and which may replace PET/CT in some selected breast cancer patients, when available. A detailed description of advantages and indications of, respectively, PET and MRI techniques taken separately in breast cancer patients is beyond the scope of the present work and has already been reviewed elsewhere by our group. We focused on the technical advantages and disadvantages of combined PET/MRI acquisitions in breast cancer patients from diagnosis to follow-up. In this chapter, we cover the specifics of PET/MRI in terms of quantification and provide a summary of the different protocols performed in breast cancer PET/MRI imaging. We will also discuss the clinical advances for patient management, the potential improvements that may occur in the future, as well as the future role that may be given to this technique.

The goal of this study was to determine whether the presence of isolated tumoral cells (ITCs) in sentinel lymph nodes (SLNs) after core needle biopsy (CNB) is related to the time interval between CNB and surgery and to histopathologic features of invasive breast cancer. Data from 633 consecutive patients with no micrometastasis or metastasis on both frozen sections and definitive pathologic examination of SLNs were retrieved from a prospective data base. No association was found between ITCs and the time interval between CNB and SLNB. The association was significant with tumor size, the tumor lymphovascular invasion (LVI) and the histologic type of the tumor. This study adds supplementary data to the association between tumoral LVI and ITCs in SLNs, The time interval between CNB procedure and SLNB was not related to affect presence of ITCs, which might not suggest the iatrogenic origin of these cells.

To evaluate the performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography magnetic resonance imaging (PET/MR) for preoperative breast cancer staging. Preoperative PET/MR exams of 58 consecutive women with breast cancer were retrospectively reviewed. Histology and mean follow-up of 26 months served as gold standard. Four experienced readers evaluated primary lesions, lymph nodes and distant metastases with contrast-enhanced MRI, qualitative/quantitative PET, and combined PET/MR. ROC curves were calculated for all modalities and their combinations. The study included 101 breast lesions (83 malignant, 18 benign) and 198 lymph node groups, (34 malignant, 164 benign). Two patients had distant metastases. Areas under the curve (AUC) for breast cancer were 0.9558, 0.8347 and 0.8855 with MRI, and with qualitative and quantitative PET/MR, respectively (p = 0.066). Sensitivity for primary cancers with MRI and quantitative PET/MR was 100 % and 77 % (p = 0.004), and for lymph nodes 88 % and 79 % (p = 0.25), respectively. Specificity for MRI and PET/MR for primary cancers was 67 % and 100 % (p = 0.03) and for lymph nodes 98 % and 100 % (p = 0.25). In breast cancer patients, MRI alone has the highest sensitivity for primary tumours. For nodal metastases, both MRI and PET/MR are highly specific. • MRI alone and PET/MR have a similar overall diagnostic performance. • MRI alone has a higher sensitivity than PET/MR for local tumour assessment. • Both MRI and PET/MR have a limited sensitivity for nodal metastases. • Positive lymph nodes on MRI or PET/MR do not require presurgical biopsy.

Breast cancer is an international public health concern in which an optimal treatment plan requires a precise staging. Both MRI and PET imaging techniques have made significant progress in the last decades with constant improvements that made both modalities clinically relevant in several stages of breast cancer management and follow-up. On one hand, specific breast MRI permits high diagnostic accuracy for local tumor staging, and whole-body MRI can also be of great use in distant staging, eventually accompanied by organ-specific MRI sequences. Moreover, many different MRI sequences can be performed, including functional MRI, letting us foresee important improvements in breast cancer characterization in the future. On the contrary, 18F-FDG-PET has a high diagnostic performance for the detection of distant metastases, and several other tracers currently under development may profoundly affect breast cancer management in the future with better determination of different types of breast cancers allowing personalized treatments. As a consequence PET/MR is a promising emerging technology, and it is foreseeable that in cases where both PET and MRI data are needed, a hybrid acquisition is justified when available. However, at this stage of deployment of such hybrid scanners in a clinical setting, more data are needed to demonstrate their added value beyond just patient comfort of having to undergo a single examination instead of two, and the higher confidence of diagnostic interpretation of these co-registered images. Optimized imaging protocols are still being developed and are prone to provide more efficient hybrid protocols with a potential improvement in diagnostic accuracy. More convincing studies with larger number of patients as well as cost-effectiveness studies are needed. This article provides insights into the current state-of-the-art of PET/MR in patients with breast cancer and gives an outlook on future developments of both imaging techniques and potential applications in the future. Semin Nucl Med 45:304-321

Purpose: Neuroimaging is increasingly used to support the clinical diagnosis of patients with cognitive impairment. Dopamine transporter (DAT) imaging, such as DaTSCAN SPECT, tests the integrity of the nigrostriatal pathway, whereas FDG-PET identifies typical patterns of cortical and subcortical hypometabolism. The aim of this study was to assess the relative contribution of DAT and regional glucose metabolism imaging to the differential diagnosis.Patients and Methods: Twenty-seven subjects were investigated for neuro-degenerative dementia associated with parkinsonism of variable severity by FDG-PET and DaTSCAN SPECT. They were grouped according to the clinically established diagnosis, including probable Alzheimer disease (5 subjects), corticobasal degeneration (6 subjects), Lewy body dementia (8 subjects), frontotemporal dementia (4 subjects), and Parkinson disease with dementia (4 subjects). Normalized FDG uptake and DAT uptake ratios were obtained by the BRASS software. We used a discriminant analysis with a stepwise method and a leave-one-out cross-validation.Results: With the use of regional values of normalized FDG uptake, 85.2% and 55.6% of the patients were correctly classified by the discriminant analysis and the cross-validation, respectively. When DAT alone was considered, the results were 59.3% and 51.9%, whereas the combination of both DAT and normalized FDG uptake yielded 100% and 88.9% of accurate classifications.Conclusions: This automated analysis approach shows that the information provided by normalized FDG uptake and DAT is not redundant for the differential diagnosis of dementia and that taking into account both normalized FDG uptake and DAT uptake allows a better classification of individual patients. These results further support the usefulness of both modalities in the clinical workup of dementia.

A 70-year-old male patient underwent an Fluorodeoxyglucose-positron emission tomography-computed tomography for staging of a left parahilar lung neoplasm found during work-up for fatigue and asthenia. The scan demonstrated a hypermetabolic lung tumor, a hypermetabolic pleural effusion and 4 hypermetabolic bilateral soft tissue lesions of the chest wall corresponding to 4 elastofibroma dorsi. Initially, the oncologic disease was classified as stage IV because of the hypermetabolic pleural effusion. A transbronchial biopsy showed squamous cell carcinoma and the cytology of the pleural effusion revealed no malignant cells. As the other 4 hypermetabolic thoracic wall lesions were correctly diagnosed as benign despite their unusual presentation, the patient underwent surgery by left pneumonectomy and mediastinal lymphadenectomy. The lymph node involvement required adjuvant chemotherapy. Diagnostic confidence of the benignity of the hypermetabolic chest wall lesions allowed a more aggressive treatment with a better outcome after a malignant pleural effusion was excluded.