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Primary CNS involvement is very rare in Hodgkin lymphoma. Here we present two cases of spinal cord dissemination. Two women of 40 and 65 years of age presented symptoms of spinal cord injury; imaging showed an intramedullary mass in T10 and T2, respectively, without vertebral involvement and upper diaphragmatic lymph nodes. Lymph-node biopsy confirmed the diagnosis of classical Hodgkin lymphoma in both patients. The first patient received four cycles of chemotherapy (escalated BEACOPP and ABVD) with intrathecal therapy, and the second four cycles of doxorubicin, vinblastine, dacarbazine (AVD) and local irradiation after surgery decompression. Complete metabolic response was obtained at the end of treatment. After 5 and 7 years of follow-up respectively, neurological deficits persisted in both.Lymph-node infiltration is the most common presentation in Hodgkin lymphoma at diagnosis. Primary extranodal involvement is rare and spinal cord infiltration exceptional. Back pain, tingling and vesico-sphincter dysfunctions are the main symptoms. 18F-fluorodeoxyglucose (FDG) PET and MRI can detect the location and extension of neurological involvement. We present here two cases of tumoral myelitis and a review of the literature. Local treatment (surgery/radiotherapy) is often administered together with chemotherapy to optimize local control and to avoid long-term sequelae.

International audience; Abstract The cellular prion protein PrP C partners with caveolin-1 (CAV1) in neurodegenerative diseases but whether this interplay occurs in cancer has never been investigated. By leveraging patient and cell line datasets, we uncover a molecular link between PrP C and CAV1 across cancer. Using cell-based assays, we show that PrP C regulates the expression of and interacts with CAV1. PrP C additionally controls the expression of the amyloid precursor protein APP and of the Aβ generating enzyme BACE1, and regulates the levels of Aβ, whose accumulation is a central event in Alzheimer’s disease. We further identify DKK1 and DKK3, involved in both Alzheimer’s disease and cancer progression, as targets of the PrP C -dependent axis. Finally, we establish that antibody-mediated blocking of the Aβ-PrP C interaction delays the growth of prostate cancer cell line-derived xenografts and prevents the development of metastases. Our data additionally support an enrichment of the Aβ-PrP C -dependent pathway in the basal subtype of prostate cancer, associated with anti-hormonal therapy resistance, and in mesenchymal colon cancer, associated with poor prognosis. Thus, based on a parallel with neurodegenerative diseases, our results bring to light an Aβ-PrP C axis and support the potential of targeting this pathway in patients with selected subtypes of prostate and colon cancer.

The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.

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.

Purpose: The aims of this study were to assess the intraindividual performance of F-18-fluorocholine (FCH) and C-11-acetate (ACE) PET studies for restaging of recurrent prostate cancer (PCa), to correlate PET findings with long-term clinical and imaging follow-up, and to evaluate the impact of PET results on patient management.Methods: Thirty-three PCa patients relapsing after radical prostatectomy (n = 10, prostate-specific antigen [PSA]

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.

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

We report the case of a 56-year-old male with bilateral total knee prostheses suffering from bilateral knee pain mainly on the right side and referred for bone scintigraphy. The medical history of the patient revealed an opening wedge high tibial osteotomy performed nine years earlier, with insertion of two blocks of ceramic made of hydroxyapatite and tricalcium phosphate in a wedge configuration as synthetic bone substitutes. The porous structure of these implants is analogous to the architecture of cancellous bone and permits fibrovascular and bone ingrowth, promoting the healing process. Planar scintigraphy and SPECT/CT showed an intense uptake within those implants in the early phase as well as in the late phase of the bone scan. It also showed bilateral patellofemoral arthritis. A (99m)Tc-labeled antigranulocyte antibody scintigraphy was negative for infection or inflammation. Bilateral patellar resurfacing led to complete symptom regression, confirmed at 10 months follow-up. To the best of our knowledge, this scintigraphic pattern with such a high tracer uptake reflecting bone substitute osteointegration has not yet been published. This should be considered in patients with such bone replacement materials that are increasingly used, in order to avoid false diagnosis of inflammation or infection.

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.