Suzana C Teixeira

Evaluation of a Hanging-Breast PET System for Primary Tumor Visualization in Patients With Stage I-III Breast Cancer: Comparison With Standard PET/CT

OBJECTIVE The purposes of this study were to evaluate the performance of a mammography with molecular imaging PET (MAMMI-PET) system for breast imaging in the hanging-breast position for the visualization of primary breast cancer lesions and to compare this method with whole-body PET/CT. SUBJECTS AND METHODS Between March 2011 and March 2014, a prospective evaluation included women with one or more histologically confirmed primary breast cancer lesions (index lesions). After injection of 180-240 MBq of (18)F-FDG, whole-body PET/CT and MAMMI-PET acquisitions were performed, index lesions were scored 0, 1, or 2 for FDG uptake relative to background. Detection and FDG uptake were compared by breast length, maximal tumor diameter, affected breast quadrants, tumor grade, and histologic and immunologic sub-types. Finally, the two PET modalities were compared for detection of index lesions. RESULTS For 234 index lesions (diameter, 5-170 mm), the overall sensitivity was 88.9% for MAMMI-PET and 91% for PET/CT (p = 0.61). Twenty-three (9.8%) index lesions located too close to the pectoral muscle were missed with MAMMI-PET, and 20 index lesions were missed with PET/CT. Lesion visibility on MAMMI-PET images was influenced by tumor grade (p = 0.034) but not by cancer subtype (p = 0.65). CONCLUSION Although in an overall evaluation MAMMI-PET was not superior to PET/CT, MAMMI-PET does have higher sensitivity for primary breast cancer lesions within the scanning range of the device. Optimization of the positioning device may increase visualization of the most dorsal lesions.

Additional Prone 18F-FDG PET/CT Acquisition to Improve the Visualization of the Primary Tumor and Regional Lymph Node Metastases in Stage II/III Breast Cancer.

Purpose To prospectively compare prone and supine acquired 18F-FDG PET/CT for visualization of primary tumors and regional lymph nodes in stage II/III breast cancer patients. Materials and Methods One hundred ninety-eight patients were included consecutively from August 2010 to April 2012. One hour after administration of 180-240 MBq 18F-FDG, PET/CT images of the thorax were firstly acquired in prone position. Subsequently, a standard PET/CT in supine position from skull base to thighs was made. Both sets of images were tested in a univariate and a multivariate analysis for the number of lesions per breast or lymph node (LN) region and anatomical mismatch between PET and CT images. Results Images in prone position showed less compression of breast tissue, more primary tumor (PT) multifocality (P < 0.001) and more avid axillary LNs (P < 0.001) compared with supine position. Anatomical mismatch of the axillary LN metastases was found more often on supine PET/CT images compared with prone (P = 0.004). Prone images showed a smaller PT functional volume compared with supine position (P < 0.001). Conclusions Prone position PET/CT improved the visualization of PT multifocality and the number of detected axillary lymph nodes. Therefore, it is a valuable addition to standard supine PET/CT in the protocol for locoregional assessment in stage II/III breast cancer patients.

A novel semi-robotized device for high-precision (18)F-FDG-guided breast cancer biopsy.

PURPOSE To assess the 3D geometric sampling accuracy of a new PET-guided system for breast cancer biopsy (BCB) from areas within the tumour with high 18F-FDG uptake. MATERIALS AND METHODS In the context of the European Union project MammoCare, a prototype semi-robotic stereotactic prototype BCB-device was incorporated into a dedicated high resolution PET-detector for breast imaging. The system consists of 2 stacked rings, each containing 12 plane detectors, forming a dodecagon with a 186mm aperture for 3D reconstruction (1mm3 voxel). A vacuum-assisted biopsy needle attached to a robot-controlled arm was used. To test the accuracy of needle placement, the needle tip was labelled with 18F-FDG and positioned at 78 target coordinates distributed over a 35mm×24mm×28mm volume within the PET-detector field-of-view. At each position images were acquired from which the needle positioning accuracy was calculated. Additionally, phantom-based biopsy proofs, as well as MammoCare images of 5 breast cancer patients, were evaluated for the 3D automated locating of 18F-FDG uptake areas within the tumour. RESULTS Needle positioning tests revealed an average accuracy of 0.5mm (range 0-1mm), 0.6mm (range 0-2mm), and 0.4mm (range 0-2mm) for the x/y/z-axes, respectively. Furthermore, the MammoCare system was able to visualize and locate small (<10mm) regions with high 18F-FDG uptake within the tumour suitable for PET-guided biopsy after being located by the 3D automated application. CONCLUSIONS Accuracy testing demonstrated high-precision of this semi-automatic 3D PET-guided system for breast cancer core needle biopsy. Its clinical feasibility evaluation in breast cancer patients scheduled for neo-adjuvant chemotherapy will follow.

Cost-Effectiveness of 18f-Fdg Pet/Ct for Screening Distant Metastasis in Stage Ii/Iii Breast Cancer Patients of the UK, the United States and the Netherlands

Objectives: 18F-FDG-PET/CT is accurate in detecting distant metastases (DM) in breast cancer patients scheduled for neoadjuvant chemotherapy. If DMs are screen-detected in an early phase, morbidity and mortality may be reduced. Because 18F-FDG-PET/CT comes at a significant cost, we compared its expected cost-effectiveness in stage II/III breast cancer patients of the UK, the US and the Netherlands (NL) vs. the gold-standard (X-thorax/liver sonography/bone scan (UK/NL) and CT-thorax-abdomen/bone scan (US)). Methods: A time-dependent Markov model compared expected Life Year (LY) and cost/Quality-adjusted Life Year (QALY) gained in four breast cancer subtypes (ER-/HER2+;ER+/HER2+;ER-/HER2-;ER+/HER2-) over a 5-year time horizon from a hospital perspective. Sensitivity and specificity of imaging and type of systemic and local treatments were derived from the Netherlands Cancer Institute. Epidemiological, survival and utility data were estimated from literature or informed by expert assumptions. Costs (2013) were derived from national tariffs (UK and NL), and from the Centres for Medicaid and Medicare Services (US). Results: 18F-FDG-PET/CT is more sensitive (53% vs. 15%) and specific (97% vs. 94%) than the gold-standard. LYs and QALYs gained were similar across subtypes, ranging from 0.025 to 0.027 and 0.0037 to 0.0044 respectively. In all countries, ER+HER2+ was the least and ER+HER2- the most costly group. 18F-FDG-PET/CT is expected to be cost-effective in the NL and the US (with highest ICERs of €165/QALY in ER+/HER2+ and

Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

750 in ER-HER2+), with probabilities of cost-effectiveness ranging from 46-52% and 62-72% respectively, but not in the UK, with a 66-75% probability, depending on tumor subtype. Conclusions: Using 18F-FDG-PET/CT for DM screening in stage II/III breast cancer is expected to result in incremental QALY gains in all subtypes and countries. Due to costs differences between countries, 18F-FDG-PET/CT is expected to be cost-effective in the US and the NL, but not in the UK.

Additional value of 18 F-FDG PET/CT response evaluation in axillary nodes during neoadjuvant therapy for triple-negative and HER2-positive breast cancer

Purpose To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. Materials and methods In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and 18F-FDG-PET/CT were acquired before and during NAC. Baseline pathology was assessed from tumor biopsy. Tumors were stratified into HER2-positive, ER-positive/HER2-negative (ER-positive), and ER-negative/PR-negative/HER2-negative (triple-negative) subtypes, and treated according to subtype. Primary endpoint was pathological complete response (pCRmic) defined as no or only small numbers of scattered invasive tumor cells. We evaluated imaging scenarios using MRI only, PET/CT only, and combinations. Results pCRmic was found in 35/46 (76.1%) of HER2-positive, 11/87 (12.6%) of ER-positive, and 31/55 (56.4%) of triple-negative tumors. For HER2-positive tumors, MRI yielded the strongest predictor (AUC: 0.735; sensitivity 36.2%), outperforming PET/CT (AUC: 0.543; p = 0.04), and with comparable results to combined imaging (AUC: 0.708; p = 0.213). In ER-positive tumors, the combination of MRI and PET/CT was slightly superior (AUC: 0.818; sensitivity 55.8%) over MRI alone (AUC: 0.742; p = 0.117) and PET/CT alone (AUC: 0.791). However, even though relatively large numbers of ER-positive tumor patients were included, no significant differences were yet found. For triple-negative tumors, MRI (AUC: 0.855; sensitivity 45.4%), PET/CT (AUC: 0.844; p = 0.220) and combined imaging (AUC: 0.868; p = 0.213) yielded comparable results. Conclusions For HER2-positive tumors, MRI shows significant advantage over PET/CT. For triple-negative tumors, comparable results were seen for MRI, PET/CT and combined imaging. For ER-positive tumors, combining MRI with PET/CT may result in optimal response monitoring, although not yet significantly.

Dedicated breast PET (MAMMI-PET) in daily clinical practice: implications for radiation safety of nuclear medicine personnel

Background18F-FDG PET/CT can monitor metabolic activity in early breast cancer during neoadjuvant systemic therapy (NST), but it is unknown if the metabolic breast and axillary response differ. We evaluated the correlation between metabolic breast and axillary response at various time points during NST. Furthermore, we analysed if the combined metabolic response improves pathologic complete response (pCR) prediction compared to using the metabolic breast response alone.Methods18F-FDG PET/CT was performed at baseline (PET1), 2–3 weeks (PET2), and 6–8 weeks (PET3) of NST in patients with triple-negative (TN) and HER2-positive node-positive breast cancer. SUVmax and ∆SUVmax were determined separately for breast and axilla. Spearman’s correlation coefficients (r) between both localisations were calculated. The accuracy of pCR total (ypT0/is,ypN0) prediction using the metabolic response in breast, axilla or both was examined using logistic regression analysis.ResultsHundred-five patients were included: 45 TN and 60 HER2-positive tumours. The metabolic response in breast and axilla correlated moderately in TN tumours (r = 0.57) using ∆SUVmax between PET1-PET3 and poorly in HER2-positive tumours (r = 0.49) using SUVmax at PET2. In TN tumours, metabolic breast response predicted pCR well without improvement after adding axillary response (c-index 0.82 versus 0.85, p = 0.63). In HER2-positive tumours, metabolic breast response predicted pCR poorly with improvement after adding axillary response (c-index 0.64 versus 0.72, p = 0.06).Conclusions18F-FDG PET/CT response during NST differs between breast and axilla. In TN tumours, pCR total prediction can be made independent of metabolic axillary response. In HER2-positive tumours, axillary response may improve pCR total prediction. These findings may help guide PET/CT-response-based changes during NST.Trial registrationNTR NTR1797. Registered 29 May 2009, retrospectively registered.

Abstract P1-02-02: Locoregional assessment by FDG PET/CT in stage II/III breast cancer patients: A multivariate analysis

Aim. A dedicated breast PET (MAMMI-PET) for prone position imaging was recently introduced for better visualization of small breast cancer lesions. The aim of the present study was to evaluate radiation safety for nuclear medicine technologists (NMTs) for additional MAMMI-PET imaging using daily practice standards. Methods. Five patients who underwent PET/CT before pre-operative systemic treatment (PST) or radiotherapy and gave informed consent for an additional MAMMI-PET scan between September and November of 2013 were included in this study. The additional scan was acquired between 90 and 120 min after injection of either 180 or 240 MBq 18F-FDG, depending on body mass index. Radiation doses were measured using a dose rate monitor (DRM) before acquisition and NMTs wore electronic personal μSv dosimeters (EPD) during patient related proceedings. Results. Using the results of the DRM to predict the radiation dose at 1 m we found on average an increased expected dose during the PET/CT scan (4.4 μSv) compared to the MAMMI-PET scan (2.2 μSv). As a consequence of safety measures during PET/CT, the EPD showed a radiation dose of <1 μSv per PET/CT acquisition, but a mean of 0.6 μSv per MAMMI-PET acquisition. Conclusions. The additional radiation dose for NMTs following possible implementation of a MAMMI-PET acquisition after PET/CT is expected to remain within levels marked by national and international legislations. Further reduction of this dose may be established with additional safety measurements.

Contribution of SPECT/CT for sentinel node localization in patients with ipsilateral breast cancer relapse

Aim : Previously we demonstrated the additional value of PET/CT in prone position for breast cancer detection. The purpose of the present study was to evaluate, with a multivariate analysis, the factors influencing detection and quantification of FDG–avid primary tumors (PT) and regional lymph node metastases (LN) detected with PET/CT in patients with stage II/III breast cancer. Materials and methods : From August 2010 to April 2012 we included 198 patients (mean 51 yr, range 26–82), with stage II/III breast cancer. A dose of 18F–FDG between 180–240 MBq, was administered intravenously. After 60±10 minutes a PET/CT of the thorax in prone position was acquired, scanning 3.00 min per bed position and reconstructed in high–resolution using 2x2x2 mm voxels and 2 mm CT slice thickness. Subsequently, a standard PET/CT was performed in supine position from skull base to thighs, scanning 1.30 min per bed position and using a standard reconstruction with 4x4x4 mm voxels, a standard 5mm CT slice reconstruction and an extra 2 mm CT slice reconstruction. On all PET/CT images we quantitatively assessed the SUVmax of FDG–avid PTs and LNs. We qualitatively assessed tumor multifocality, PT visibility, LN detection in defined regions and the occurrence of anatomical mismatch between PET and CT. The obtained results were then evaluated with a multivariate analysis for scanning position, patient age, breast size, tumor volume, number of FDG–avid lesions, lymph node location and anatomical mismatch between PET and CT. Results: Prone position imaging positively influenced the visualization of tumor multifocality (p A higher SUVmax of the primary tumor was found solely with increased tumor volume (p=0.001) or breast size (p Conclusion: Prone position for PET/CT influences the visualization of primary tumor multifocality and the number of FDG avid loco-regional lymph nodes. Tumor FDG-uptake appears to be most influenced by tumor volume and breast size. Both results can be important for adequate staging and subsequent breast cancer treatment. Citation Format: Suzana C Teixeira, Bas B Koolen, Wouter V Vogel, Marcel P Stokkel, Marie-Jeanne Vrancken-Peeters, Vincent van der Noort, Emiel J Th Rutgers, Renato A Valdes-Olmos. Locoregional assessment by FDG PET/CT in stage II/III breast cancer patients: A multivariate analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-02.