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4D flow MRI allows the analysis of hemodynamic changes in the aorta caused by pathologies such as thoracic aortic aneurysms (TAA). For personalized management of TAA, new biomarkers are required to analyze the effect of fluid structure iteration which can be obtained from 4D flow MRI. However, the generation of these biomarkers requires prior 4D segmentation of the aorta.To develop an automatic deep learning model to segment the aorta in 4D from 4D flow MRI.Segmentation is addressed with a U-Net based segmentation model that treats each 4D flow MRI frame as an independent sample. Performance is measured with respect to Dice score (DS) and Hausdorff distance (HD). In addition, the maximum and minimum surface areas at the level of the ascending aorta are measured and compared with those obtained from cine-MRI.The segmentation performance was 0.90 ± 0.02 for the DS and the mean HD was 9.58 ± 4.36 mm. A correlation coefficient of r = 0.85 was obtained for the maximum surface and r = 0.86 for the minimum surface between the 4D flow MRI and cine-MRI.The proposed automatic approach of 4D aortic segmentation from 4D flow MRI seems to be accurate enough to contribute to the wider use of this imaging technique in the analysis of pathologies such as TAA.

Background Despite adequate neoadjuvant chemotherapy, TNBC remains poor prognosis. Non-responding patient have 25-40% risk of relapse at 5 years. pCR is therefore currently considered as a major goal in TNBC and new tools of early prediction of residual disease should be identified. TransTep is a phase 2 monocentric clinical trial which aims to identify transcriptomic profile of triple-negative cancer cells associated with early tumor chemoresistance, as identified by FDG PET after the first course of neoadjuvant chemotherapy. Twenty patients were included between January 2015 and October 2017, with stage II or III of the UICC classification (except stage T4d). All patients received neoadjuvant chemotherapy with anthracyclines and taxanes sequentially, none of them had a dose-dense chemotherapy. Six patients obtained metabolic response (Delta SUV < -30%) after one cycle of anthracycline. Methods Total RNA was extracted from biopsies (HES > 30%) and used to prepare libraries thanks to TruSeq RNA library Prep kit (Illumina) and sequenced on NextSeq500 device. Results Transcriptomic expression analysis between tumors before chemotherapy and tumors after one course of chemotherapy showed that tumors showing a significant decrease of their Delta SUV (←30%) had a much higher gene expression variation than tumors with a Delta SUV >-30%. These tumors presented, after one course of chemotherapy, a decrease of cell cycle, DNA replication and Fanconi anemia pathway related genes, while they harbored an increase of genes belonging to immunity related pathways such as natural killer cell mediated toxicity, TH17 cell differentiation, or chemokine signaling pathway. As patients had a surgery after neoadjuvant chemotherapy, we had Chevalier tumor response. As observed with FDG PET data, patients with a good response according to Chevalier (class 1) criteria presented a much higher transcriptomic modification after one course of chemotherapy. Patients with a little gene expression modification were classified as Chevalier 3. When we focused on pathways impacted by chemotherapy in tumors classified as Chevalier 1, we observed a significant decrease of cell cycle, DNA replication and DNA repair pathways related gene after one course of chemotherapy, whereas a high number of genes belonging to immunity related genes (NK cells, antigen processing and presentation, or chemokine signaling pathway) were increased. Conclusion Our results tend to indicate that transcriptomic tumor response after one course of chemotherapy could forecast final response to treatment. Moreover, it seems that one cycle of anthracycline-based chemotherapy is able to get hot some breast tumors, and that this tumor warming could be a marker of good response to the full treatment. In the following months, we will test whether transcriptomic could predict progression free survival and/or overall survival of patients. We will also look for the best early marker of response between PET FDG and tumor transcriptomic modifications. Based on these results, a new trial will be organized. A therapeutic adaptation depending on the transcriptomic or metabolic data will be proposed to increase pCR rate and prognosis of patients. Moreover, with years and therapeutic innovations, patient managment obviously evolves. This was recently the case with a new standard of care in triple negative breast cancer with combination of platinum salt and immunotherapy. Therefore, a new trial, similar to TRANSTEP, will be carried out with this new standard of care. Citation Format: Isabelle Desmoulins, David Chardin, Corentin Richard, Laurent Arnould, ALEXANDRE COCHET, Olivier Humbert, Romain Boidot. Transcriptomic modification induced by the first cycle of neoadjuvant chemotherapy impacts response to treatment in triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-23.

Coronary artery embolism (CAE) is a rare, non-atherosclerotic cause of acute myocardial infarction (MI). Atrial fibrillation (AF) is the most frequent cause of CAE, and can be associated with multiple embolisms, particularly in the brain.To characterize CAE-related myocardial injury, assess the proportion of cardiocerebral infarction and characterize brain injuries associated with dual embolism.In this prospective study, patients with CAE-associated MI underwent (1) cardiac magnetic resonance imaging (MRI) to assess the extent of infarct transmurality and myocardial necrosis size and (2) brain MRI to assess the proportion of simultaneous cardiocerebral infarction. We screened 1401 consecutive patients with de novo acute MI from January 2019 to June 2021. CAE was diagnosed based on clinical, angiographic and diagnostic imaging criteria.Overall, 29/1401 patients presented with CAE (2.1%), of whom 21 underwent cardiac and cerebral MRI. Of these, nine (43%) had an ischaemic stroke, and AF was the leading cause of CAE in 14 patients (67%). Multiple CAE were common at coronary angiography (33%). Four patients (19%) had left atrial appendage thrombus - 4/9 patients (44%) with a stroke but 0/12 patients without a stroke. On cardiac MRI, the median (interquartile range) number of segments with acute infarction was 3 (0-11) in patients with stroke and 3 (1-6) in those without. Most acute ischaemic strokes (78%) were localized in the superficial sylvian territory and only 2/21 patients (10%) had stroke sequelae.MI-related to CAE was associated with infarctions of average size but multiple locations. Systematic brain MRI revealed that 33% of cases were associated with a stroke, which was generally asymptomatic. Further studies are required to better characterize the pathophysiology, clinical course and prognostic value of CAE. Moreover, optimal management strategies remain to be determined.

Background: Invasive lobular carcinoma accounts for 10 to 15% of all breast cancers. The first objective of this retrospective study was to assess the diagnostic performance of FDG-PET/CT scanning in women previously treated for invasive lobular carcinoma with suspected first recurrence. The secondary objectives were to evaluate the impact of PET/CT in a change in treatment and its prognostic value on specific survival. Methods: Patients in whom a PET/CT scan was performed from January 2011 to July 2019 in our Cancer Research Center were enrolled. Recurrence was suspected based on clinical symptoms, abnormal findings on conventional imaging, and/or elevated tumor markers. The diagnosis of recurrence was established by the oncologist after integration of all clinical, biological, histological, imaging, and follow-up data. Prognostic factors of recurrence as predicted by PET were determined using univariate logistic regression. KI67, mitotic index, or grade of mitosis were tested. Survival curves were compared using the log-rank test. Sixty-four patients (mean age: 60.3; SD = 12.4 years) were enrolled. The average time from initial diagnosis of the primary tumor to suspicion of recurrence was 5.2 ± 4.1 years. Forty-eight patients (75%) were judged to have recurrence by the oncologist: 7 local and 41 metastatic, with mainly bone (n = 24), lymph node (n = 14) and liver (n = 10) metastases. Results: Sensitivity, specificity, and positive and negative predictive values of PET/CT to predict recurrence were, respectively: 87%, 87%, 95%, and 70%. SUVmax at recurrence sites was generally high (mean: 6.4; SD = 2.9). False negative PET/CT results occurred with local (n = 2), peritoneal (n = 2), meningeal (n = 1), or bladder (n = 1) recurrences. In 40 patients with available histopathological data from suspected sites of recurrence, 30 PET/CT were true positive. In four patients, primary lung (n = 1) or gastric (n = 1) tumors or lymphomas (n = 2) were found. The detection of a recurrence resulted in a change in treatment in 44/48 patients (92%). No association between recurrence predicted by PET and biological biomarkers was found. Median specific survival appears shorter in patients with metastatic recurrence versus patients with local or no recurrence on PET/CT (p = 0.067). Conclusions: FDG-PET/CT is an effective and reliable tool for the detection of invasive lobular carcinoma recurrence, although certain recurrence sites specific to this histological type can impair its diagnostic performance.

Purpose: To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC).Experimental Design: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (ΔSUVmax) were assessed using FDG-PET.Results: The pCR rate was 42%. High Ki-67 proliferation index (P = 0.016), negative EGFR status (P = 0.042), and high ΔSUVmax (P = 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P = 0.043) and high ΔSUVmax (OR, 7.1; P = 0.014) were independent predictors of pCR. Using a threshold at −50%, tumor ΔSUVmax predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low ΔSUVmax and positive EGFR status could predict non-pCR with an accuracy of 92%.Conclusions: It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials. Clin Cancer Res; 21(24); 5460–8. ©2015 AACR.

Supplementary Figure 1: Graphical display of changes in primary tumor SUVmax between baseline and interim 18F-FDG PET exams.

Resume Cette etude propose un retour d’experience sur les modalites de gestion et d’elimination des dechets contamines au Lutetium-177 (177Lu, Lu-177) instaurees dans le cadre des procedures de radiotherapie interne vectorisee au 177Lu-oxodotreotide (Lutathera®). Les traitements sont administres dans un box dedie du service de medecine nucleaire ou tous les dechets solides sont tries et collectes dans des contenants appropries. Des durees previsionnelles de stockage ont ete extrapolees a partir des resultats d’une campagne de mesures iteratives sur deux ans. Les effluents radioactifs des eviers chauds se deversent dans des cuves, dont l’activite volumique mesuree a la fermeture permet de calculer la duree d’entreposage avant vidange. L’activite du Lu-177 elimine par excretion renale dans les 6 heures qui suivent la fin de la perfusion du medicament radiopharmaceutique a ete evaluee a partir de l’analyse de prelevements urinaires. Les premieres mictions sont dirigees vers trois fosses tampons dont l’efficacite a ete estimee en comparant l’activite du Lu-177 qui entre dans le dispositif a celle qui en sort. Les resultats des controles semestriels, effectues par mesure en continu de l’activite volumique des effluents aux emissaires, ont permis d’evaluer la fraction de l’activite annuelle administree finalement rejetee dans les eaux usees et de definir des valeurs guides. L’impact des deversements radioactifs de l’etablissement sur l’exposition annuelle des travailleurs du reseau d’assainissement a ete quantifie avec l’outil de Calcul de l’Impact des Deversements Radioactifs dans les REseaux (CIDRRE) developpe par l’Institut de radioprotection et de surete nucleaire (IRSN).

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.

Background During anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction. The objective of the present study was to compare [18F]FDG and [123I]MIBG (metaiodobenzylguanidine) in a longitudinal study in a doxorubicin-induced cardiotoxicity rat model. Methods Male Wistar Han rats were intravenously administered 3 times at 10 days’ interval with saline or doxorubicin (5 mg/kg). [123I]MIBG SPECT/CT (single photon emission computed tomography-computed tomography) and simultaneous [18F]FDG PET (positron emission tomography)/7 Tesla cardiac MR (magnetic resonance) imaging acquisitions were performed at 24 h interval before first doxorubicin / saline injection and every 2 weeks during 6 weeks. At 6 weeks, the heart tissue was collected for histomorphometry measurements. Results At week 4, left ventricle (LV) end-diastolic volume was significantly reduced in the doxorubicin group. At week 6, the decreased LV end-diastolic volume was maintained, and LV end-systolic volume was increased resulting in a significant reduction of LV ejection fraction (47 ± 6% vs. 70 ± 3%). At weeks 4 and 6, but not at week 2, myocardial [18F]FDG uptake was decreased compared with the control group (respectively, 4.2 ± 0.5%ID/g and 9.2 ± 0.8%ID/g at week 6). Moreover, [18F]FDG cardiac uptake correlated with cardiac function impairment. In contrast, from week 2, a significant decrease of myocardial [123I]MIBG heart to mediastinum ratio was detected in the doxorubicin group and was maintained at weeks 4 and 6 with a 45.6% decrease at week 6. Conclusion This longitudinal study precises that after doxorubicin treatment, cardiac [123I]MIBG uptake is significantly reduced as early as 2 weeks followed by the decrease of the LV end-diastolic volume and [18F]FDG uptake at 4 weeks and finally by the increase of LV end-systolic volume and decrease of LV ejection fraction at 6 weeks. Cardiac innervation imaging should thus be considered as an early key feature of anthracycline cardiac toxicity.

Introduction Giant cell arteritis (GCA) is a frequent granulomatous vasculitis. In the diagnosis of large vessel GCA, FDG-PET/CT imaging has been recommended and its use has steadily increased. The objective of this prospective study was to evaluate the diagnostic performance of digital FDG-PET imaging with a head and neck dedicated protocol, especially to detect cranial arteries involvement, using different visual grading scores, and to assess the inter-reader agreement. Material and Methods FDG-PET/CT scans with a 10-min acquisition time on the head and neck were performed in patients suspected of having recent GCA. A score including 20 segments due to the inclusion of cranial segments and a score established only for the cranial segments were compared to the Total Vascular Score (TVS) established on 7 arterial segments. These scores were assessed by two nuclear medicine physicians on a blinded manner and, in case of disagreement, a consensus was established with a third nuclear medicine physician. Results GCA diagnosis was retained for 15 of the 52 patients included. Sensitivity and specificity of the 20-segment or the cranial scores were higher than those of TVS (sensitivity and specificity of 80% of 97% for both scores vs 73% and 89% for TVS, respectively). The inter-reader agreement was substantial in the 20-segment score (weighted kappa = 0.68) but better in the cranial segments than other segments. Conclusion This study shows the usefulness of grading scores able to highlight involvement of cranial arteries in GCA with a better inter-reader agreement in cranial segments than other segments.

Performing a cardiac CT scan before ablation provides a better understanding of the anatomical variations of the left atrium and pulmonary veins, as well as an analysis of coronary anatomy and the calcium score. The aim of the present study was to determine whether the CT characteristics of patients with unknown CAD have an impact on recurrence of AF. This monocentric retrospective study included patients with AF who had undergone cardiac CT prior to a single ablation. Among the 229 patients included in the study, 70 (30.5%) presented AF recurrence between 3 and 12 months after a single ablation. The prevalence of CAD confirmed by CT coronary angiogram and the coronary calcium score were similar in the two groups. Patients with recurrent atrial fibrillation had a significantly higher LAVI evaluated by CT scan than patients without recurrence. The ROC curve determined an optimal LAVI threshold of 49 mL/m2. In multivariate analysis, the LAVI measured by CT scan was independently associated with the risk of AF recurrence. Our study confirms that CAD is not a predictor of AF recurrence after a single ablation, unlike the LAVI. Further studies are necessary to re-evaluate the long-term conclusions of this work.

The availability of preclinical simultaneous PET/MR imaging systems has been increasing in recent years. Therefore, this technique is progressively moving from the hands of pure physicists towards those of scientists more involved in pharmacology and biology. Unfortunately, these combined scanners can be prone to artefacts and deviation of their characteristics under the influence of external factors or mutual interference between subsystems. This may compromise the image quality as well as the quantitative aspects of PET and MR data. Hence, quality assurance is crucial to avoid loss of animals and experiments. A possible risk to the acceptance of quality control by preclinical teams is that the complexity and duration of this quality control are increased by the addition of MR and PET tests. To avoid this issue, we have selected over the past 5 years, simple tests that can be easily and quickly performed each day before starting an animal PET/MR acquisition. These tests can be performed by the person in charge of the experiment even if this person has a limited expertise in instrumentation and performance evaluation. In addition to these daily tests, other tests are suggested for an advanced system follow-up at a lower frequency. In the present paper, the proposed tests are sorted by periodicity from daily to annual. Besides, we have selected test materials that are available at moderate cost either commercially or through 3D printing.

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.

Melanoma is a skin cancer at high risk of metastatic progression, hence associated with poorer prognosis. Imaging represents an essential tool to assess tumor stage, but also to monitor disease progression and therapy response. However, a single imaging technique cannot efficiently detect and characterize all metastases. Therefore, we evaluated the potential of simultaneous 18F-FDG PET/MR imaging in preclinical models of disseminated melanoma at different stages. Female Nude and SDRG rats were intravenously injected with CMEL 5 cells, originating from brain metastases of a human melanoma. On day (D) 60, 70, and 80 post-injection, Nude rats were imaged using brain T2-weighted (T2w) 7T MRI and whole-body simultaneous 18F-FDG (10-15 MBq) PET/MR. Furthermore, whole-body and brain T2w MR images were acquired using a 4.7T MRI on D20 and D34 post-injection in SDRG rats. Visual detection and quantitative analysis of lesions were performed on MRI or PET/MR images, and results were confronted with necropsy (melanin pigmented lesions) and gamma counting data. From D60 post-CMEL-5 cell injection, all Nude animals exhibited metastases in one to four different locations. Moreover, most of metastases locations found in clinical setting were detected in our experimental model using simultaneous 18F-FDG PET/MR imaging, even allowing the observation of brain lesions on T2w MR images. MRI further allowed precise contouring of each organ of interest to effectively identify bone, lung, adrenal and spleen metastases with enhanced 18F-FDG uptake. Additionally, PET image quantification in adrenals was consistent with gamma counting results. As anticipated, small lesions below PET spatial resolution limit (i.e. Citation Format: Alexandra Oudot, Peggy Provent, Alan Courteau, Nicolas Hoffmann, Melanie Guillemin, Jordan Longin, Sarah Belderbos, Bertrand Collin, Marc Hillairet de Boisferon, Alexandre Cochet, Cyril Berthet. Simultaneous 18F-FDG PET/MR imaging for metastases identification in a disseminated human preclinical melanoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2767.

Purpose: To evaluate the value of early FDG-PET (18F-Fluorodeoxyglucose-Positron Emission Tomography) metabolic criteria for prediction of pathologic complete response in axilla (pCRAx) after neoadjuvant chemotherapy (NAC) in breast cancer. Methods: Inclusion criteria were all T-stage breast cancers, non-metastatic, with initial lymph node involvement estimated by PET +/- lymph node biopsy, treated with NAC followed by surgery with axillary lymph node dissection (ALND), managed at the George-François Leclerc Cancer Center in Dijon, France, between 2009 and 2019. A PET was performed before and after the first course of chemotherapy (PET1 and PET2). pCRAx was defined as the absence of invasive cells in the nodes at the time of ALND (i.e. ypN0). The Sataloff classification was used as reference on each pathological report. Patients with a Sataloff NA classification (i.e. evidence of therapeutic effect, and no residual disease) and, if axillary involvement was proven at diagnosis, NB (i.e. no metastasis, no therapeutic effect) were considered as pCRAx. The PET metabolic criteria studied in the axilla were: - SUVmax (Standard Uptake Value) on PET1 and PET2 = fixation in the axillary voxel with the highest activity (kBq/mL)/(injected dose (kBq)/weight (g)) - ΔSUVmax (%) = metabolic response after the first course of NAC = 100 x (SUVmax1 - SUVmax2)/(SUVmax1). Univariate and multivariate analysis were performed to identify factors (clinical, pathologic, metabolic) that may be associated with pCRAx. Relationships between baseline TEP uptake and prognostic parameters were assessed using Receiver Operating Characteristic (ROC) curves. Results: Among 188 patients included, the rate of pathologically proven node involvement was 63.3% (n=119). The pCRAx rate was 45.7% (n=86/188) but varied according to tumor subtypes: 14.5% (n=9/62) of HR(Hormone Receptor)+/HER2-negative, 47.7% (n=21/44) of HR+/HER2-positive, 61.4% (n=27/44) of triple-negative (TN) and 76.3% (n=29/38) of HR-/HER2-positive. Factors significantly associated with pCRAx were by univariate analysis: HER2-positive (HR+ and HR-) and TN subtypes (p< 0.001), SBR (Scarff-Bloom-Richardson) grade (p=0.01), breast pCR (ypT0/is) (p< 0.001), SUVmax2 (p=0.01) and ΔSUVmax (p< 0.001). By multivariate analysis, it persisted the HR-/HER2-positive (p=0.02) and TN (p=0.02) subtypes and breast pCR (p< 0.001). In global population, a decrease in ΔSUVmax of 63% was the optimal threshold to predict pCRAx (Area Under the Curve AUC = 0.73) with a sensitivity (Se) of 51% and specificity (Sp) of 83%. ΔSUVmax remains the best performing parameter in TN (AUC = 0.72; Se at 52%; Sp at 88%). In HR-/HER2-positive patients, SUVmax2 appeared to be a better predictor of pCRAx than ΔSUVmax. A SUVmax2 value of 1.99 was the optimal threshold for predicting pCRAx (AUC = 0.72), yielding a Se of 66% and a Sp of 78%. None of the PET criteria predicted axillary response with sufficient accuracy for HR+ subtypes. Conclusion: PET alone does not appear to be sufficient to predict pCRAx. It seems necessary to use other parameters, whether clinical, biological or imaging, to discriminate responders from non-responders to NAC in order to adapt the subsequent surgical management. Citation Format: ELOISE MICHEL, FRANCOISE BELTJENS, ALEXANDRE COCHET, JEAN LOUIS ALBERINI, CHARLES COUTANT, CLEMENTINE JANKOWSKI. Utility of 18F-FDG PET/CT for the prediction of pathologic complete response in axilla to neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-11.

Purpose Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor outcome and limited therapeutic options. Imaging of IPF is limited to high-resolution computed tomography (HRCT) which is often not sufficient for a definite diagnosis and has a limited impact on therapeutic decision and patient management. Hypoxia of the lung is a significant feature of IPF but its role on disease progression remains elusive. Thus, the aim of our study was to evaluate hypoxia imaging with [18F]FMISO as a predictive biomarker of disease progression and therapy efficacy in preclinical models of lung fibrosis in comparison with [18F]FDG. Methods Eight-week-old C57/BL6 mice received an intratracheal administration of bleomycin (BLM) at day (D) 0 to initiate lung fibrosis. Mice received pirfenidone (300 mg/kg) or nintedanib (60 mg/kg) by daily gavage from D9 to D23. Mice underwent successive PET/CT imaging at several stages of the disease (baseline, D8/D9, D15/D16, D22/D23) with [18F]FDG and [18F]FMISO. Histological determination of the lung expression of HIF-1α and GLUT-1 was performed at D23. Results We demonstrate that mean lung density on CT as well as [18F]FDG and [18F]FMISO uptakes are upregulated in established lung fibrosis (1.4-, 2.6- and 3.2-fold increase respectively). At early stages, lung areas with [18F]FMISO uptake are still appearing normal on CT scans and correspond to areas which will deteriorate towards fibrotic lesions at later timepoints. Nintedanib and pirfenidone dramatically and rapidly decreased mean lung density on CT as well as [18F]FDG and [18F]FMISO lung uptakes (pirfenidone: 1.2-, 2.9- and 2.6-fold decrease; nintedanib: 1.2-, 2.3- and 2.5-fold decrease respectively). Early [18F]FMISO lung uptake was correlated with aggressive disease progression and better nintedanib efficacy. Conclusion [18F]FMISO PET imaging is a promising tool to early detect and monitor lung fibrosis progression and therapy efficacy.

Background 18F-fluorocholine positron emission tomography/computed tomography (F-choline PET/CT) is considered a cornerstone in the staging and restaging of patients with prostate cancer (PCa). The aim of this study was to retrospectively assess unusual uptakes in patients who underwent a F-choline PET/CT for the initial staging or for the restaging of a relapsing PCa. Methods Three hundred and sixty-eight PCa patients were staged or restaged using F-choline PET/CT. Unusual uptakes were defined as uptakes occurring outside the usual paths of diffusion of PCa or as uptake in bone with a clear morphological evidence of nonmetastatic lesion. Results We found unusual uptakes in 47/368 patients (12.8%). Among them, 41/47 presented with benign F-choline uptake, usually within lymph nodes, due to inflammatory processes (22/47). Other benign processes were found in: thyroid (3/47), adrenal gland (3/47), brain (2/47), liver (1/47), bowel (3/47), frontal sinus (1/47), lungs (4/47), parotid gland (1/47) and bone (1/47). The six remaining patients presented with a second cancer, including lymphoma (1/47), non-small cell lung cancer (4/47) and neuroendocrine tumor (1/47). Conclusions unusual uptakes on F-choline PET/CT are quite frequent and should be explored since they may correspond to non-PCa.

The occurrence of coronary artery embolism (CE) has been associated with various clinical conditions, including aortic and mitral prosthetic heart valve implantation, atrial fibrillation (AF), dilated cardiomyopathy, neoplasia, infective endocarditis, atrial septal defect, cardiac tumors, and hypercoagulable states. CE is also a rare cause of myocardial infarction (MI), with a prevalence of about 5%, a figure probably underestimated. The purpose of this article was to determine the current state of knowledge on acute coronary syndrome (ACS) related to CE. We thus performed a comprehensive structured literature search of the MEDLINE database for articles published between 1 January 1990 and 31 December 2021. The diagnosis of CE remains difficult despite the currently used Shibata classification, which is based on major criteria, including angiographic characteristics: globular filling defects, saddle thrombi or multiple filling defects and absence of atherosclerosis in the coronary arteries. Suspected or confirmed CE requires the identification of an etiology. There are only two published series on CE, including about 50 cases each. The three main causes in these series were: 1) atrial fibrillation (73% vs 28.3%), 2) cardiomyopathy (9.4% vs 25%) and 3) malignancy (9.6% vs 15.1%). Finally, 26.3% of the MI patients with CE had no identifiable cause of CE. When anatomically possible, analyzing the thrombus after thrombectomy may help. MI due to CE requires systematic assessment of other locations, i.e. multiple coronary and extracardiac locations. Simultaneous systemic embolization to the brain (67%), limbs (25%), kidneys (25%) or spleen (4%) is frequent, occurring in approximately 25% of CE-related MI. In the setting of acute MI, CE is associated with significant morbidity and mortality. Coronary artery thromboembolism is a rare, non-atherosclerotic, cause of ACS, and prospective studies are needed to evaluate a systematic diagnostic approach and personalized therapeutic strategies.

Objectives To investigate the performance of cranial PET/CT for the diagnosis of GCA. Methods All patients with a suspected diagnosis of GCA were prospectively enrolled in this study and had a digital PET/CT with evaluation of cranial arteries if they had not started glucocorticoids >72 h previously. The diagnosis of GCA was retained after at least 6 months of follow-up if no other diagnosis was considered by the clinician and the patient went into remission after at least 6 consecutive months of treatment. Cranial PET/CT was considered positive if at least one arterial segment showed hypermetabolism similar to or greater than liver uptake. Results For cranial PET/CT, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were 73.3%, 97.2%, 91.7% and 89.7%, respectively. For extracranial PET/CT, diagnostic performance was lower (Se = 66.7%, Sp = 80.6%, PPV = 58.8%, NPV = 85.3%). The combination of cranial and extracranial PET/CT improved overall sensitivity (Se = 80%) and NPV (NPV = 90.3%) while decreasing overall specificity (Sp = 77.8%) and PPV (PPV = 60%). Conclusion Cranial PET/CT can be easily combined with extracranial PET/CT with a limited increase in examination time. Combined cranial and extracranial PET/CT showed very high diagnostic accuracy for the diagnosis of GCA. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT05246540.

To assess whether data from pre-therapeutic multiparametric magnetic resonance imaging (mpMRI) combined with three-dimensional magnetic resonance spectroscopy (3D MRS) provide prognostic factors of biochemical relapse in patients with localized prostate cancer treated by external radiotherapy or brachytherapy.In our single institution observational retrospective study we included a cohort of 230 patients treated by external radiotherapy or brachytherapy who had an initial mpMRI with 3D MRS from January 2008 to December 2015 for newly diagnosed localized prostatic cancer, proven histologically. Three trained radiologists recorded tumor characteristics, MRI T-stage and metabolic abnormalities from 3D MRS data. Univariate and multivariate Cox analyzes explored the relationship between clinical and imaging variables to highlight prognostic factors for recurrence, using biochemical relapse as the primary endpoint.mpMRI data analysis allowed to reclassify 21.7% of the patients in a MRI National Comprehensive Cancer Network (NCCN) group higher than their initial clinical T-stage, but also to detect a lesion in 78% of the patients considered as clinically T1c. After a median of follow-up of 8.7 years (IQR, 6.6-10.1) following cancer diagnosis, 36 (16%) patients developed a biochemical relapse. The multivariate Cox analysis demonstrated the existence of 3 independent factors for prediction of biochemical recurrence: extracapsular extension (ECE) (HR =3.33; 95% CI: 1.93-5.73; P0.01), choline/citrate ratio in healthy tissue in the transition zone (TZ) (HR =2.96; 95% CI: 1.06-8.28; P=0.04) and the NCCN Magnetic Resonance Imaging classification (intermediate versus low-risk, HR =3.06; 95% CI: 1.13-8.30; P0.01).Combination of mpMRI and 3DMRS could aid in the prognostic stratification of localized prostate cancer treated by radiotherapy or brachytherapy, by combining accurate evaluation of tumor extension, and quantification of prostate metabolism.

Resume Objectif. Le but du Comite de cancerologie de l’Association francaise d’urologie est de proposer une mise a jour des recommandations dans la prise en charge du cancer de la prostate. Methodes. Une revue systematique (Medline) de la litterature de 2018 a 2020 a ete conduite par le CCAFU concernant les elements du diagnostic, les options de traitement et la surveillance du cancer de la prostate, en evaluant les references avec leur niveau de preuve. Resultats. Les recommandations precisent la genetique, l’epidemiologie et les moyens diagnostiques du cancer de la prostate, les notions de depistage et de detection precoce. L’imagerie par resonance magnetique (IRM), examen d’imagerie de reference du cancer localise, est recommandee avant la realisation de biopsies prostatiques. Les moyens therapeutiques sont detailles et recommandes en fonction des situations cliniques. La surveillance active est une option therapeutique de reference pour les tumeurs de faible risque evolutif. La radiotherapie de rattrapage precoce est recommandee en cas de recidive biologique postprostatectomie totale. La suppression androgenique (SAd) reste le traitement de fond au stade metastatique. Le docetaxel associe a la SAd ameliore la survie globale en premiere ligne du cancer de la prostate metastatique synchrone. Dans cette situation, l’association de la SAd a l’abiraterone est egalement un standard therapeutique quel que soit le volume tumoral. Les donnees recentes amenent a recommander la SAd a une hormonotherapie de nouvelle generation (apalutamide ou enzalutamide) chez les patients metastatiques synchrones ou metachrones, quel que soit le volume tumoral. Le traitement local du cancer de la prostate par radiotherapie ameliore la survie des patients oligometastatiques synchrones. Le traitement cible des metastases est en cours d’evaluation. Chez les patients presentant un cancer de la prostate resistant a la castration (CPRC), l’apport des nouvelles therapies qui ont emerge ces dernieres annees aide a mieux controler la progression tumorale et a ameliorer la survie. Conclusion. Cette actualisation des recommandations francaises doit contribuer a ameliorer la prise en charge des patients porteurs d’un cancer de la prostate.

Background The aim of this study was to compare the value of 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET/CT) with CGFL/Curie nomogram to predict a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor 2 (HER2)-positive breast cancer treated by trastuzumab. Methods Fifty-one women with HER2-positive breast cancer treated with trastuzumab plus taxane-based NAC, were retrospectively included from January 2005 to December 2015. For 18F-FDG PET/CT, the analyzed predictor was the maximum standardized uptake value of the primary tumor and axillary nodes after the first course of NAC (PET2.SUVmax). pCR was defined by no residual infiltrative tumor but in situ tumor was accepted. Accuracy of CGFL/Curie nomogram and PET2.SUVmax was evaluated measuring sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). For each predictor, receiver operating characteristic (ROC) curve was created. To evaluate the correlation between predictors, the Spearman coefficient was calculated. Combined prediction was evaluated testing predictor’s associations. Results For CGFL/Curie nomogram’s performances, Se, Sp, PPV and NPV were respectively: 76% (CI95%: 58-90%), 57% (CI95%: 43-66%), 55% (CI95%: 42-65), 77% (CI95%: 59-90%). For PET2.SUVmax’s performances, Se, Sp, PPV and NPV were respectively: 67% (CI95%: 48-81%), 77% (CI95%: 64-97%), 67% (CI95%: 48-82%), 77% (CI95%: 64-87%). ROC curves for these predictors were similar; the areas under the curve were 0.6 (CI95%: 0.56-0.64) for PET2.SUVmax and 0.55 (CI95%: 0.50-0.59) for CGFL/Curie nomogram. Spearman coefficient was 0.23. Combined prediction was more efficient with Se at 80%, VPN at 76%, Sp at 78% and VPP at 81 %. Conclusions CGFL/Curie nomogram and PET2.SUVmax were two efficient predictors of pCR in patients with HER2-positive breast cancer. Combined prediction has an improved accuracy. Citation Format: Laura Vincent, Clémentine Jankowski, Marion Cortet, Laurent Arnould, Sylvain Ladoire, Bruno Coudert, Isabelle Desmoulins, Céline Charron-Barra, Françoise Beltjens, Roman Rouzier, Fabien Reyal, Olivier Humbert, Alexandre Cochet, Charles Coutant. HER2-positive breast cancer: Combined 18F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after preoperative chemotherapy with trastuzumab [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-14.