Bas B. Koolen

FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative, but not in HER2-positive breast cancer

BACKGROUND Response monitoring with MRI during neoadjuvant chemotherapy (NAC) in breast cancer is promising, but knowledge of breast cancer subtype is essential. The aim of the present study was to evaluate the relevance of breast cancer subtypes for monitoring of therapy response during NAC with 18F-FDG PET/CT. METHODS Evaluation included 98 women with stages II and III breast cancer. PET/CTs were performed before and after six or eight weeks of NAC. FDG uptake was quantified using maximum standardized uptake values (SUVmax). Tumors were divided into three subtypes: HER2-positive, ER-positive/HER2-negative, and triple negative. Tumor response at surgery was assessed dichotomously (presence or absence of residual disease) and ordinally (breast response index, representing relative change in tumor stage). Multivariate regression and receiver operating characteristic (ROC) analyses were employed to determine associations with pathological response. RESULTS A (near) complete pathological response was seen in 19 (76%) of 25 HER2-positive, 7 (16%) of 45 ER-positive/HER2-negative, and 20 (71%) of 28 triple negative tumors. Multivariate regression of pathological response indicated a significant interaction between change in FDG uptake and breast cancer subtype. The area under the ROC curve was 0.35 (0.12-0.64) for HER2-positive, 0.90 (0.76-1.00) for ER-positive/HER2-negative, and 0.96 (0.86-1.00) for triple negative tumors. We found no association between age, stage, histology, or baseline SUVmax and pathological response. CONCLUSION Response monitoring with PET/CT during NAC in breast cancer seems feasible, but is dependent on the breast cancer subtype. PET/CT may predict response in ER-positive/HER2-negative and triple negative tumors, but seems less accurate in HER2-positive tumors.

Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET

Positron emission tomography (PET), with or without integrated computed tomography (CT), using 18F-fluorodeoxyglucose (FDG) is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

Accuracy of 18F-FDG PET/CT for primary tumor visualization and staging in T1 breast cancer

Abstract Background. The aim of this study was to assess the accuracy of 18F-FDG PET/CT in T1 breast cancer regarding visualization of the primary tumor and the detection of locoregional and distant metastases. Methods. Sixty-two women with invasive T1 breast cancer underwent a PET/CT. Image acquisition of the thorax was done in prone position with hanging breasts, followed by whole-body scanning in supine position. Primary tumor FDG uptake was evaluated and compared with clinical and histopathological characteristics. Presence of locoregional and distant metastases was assessed and compared with conventional imaging procedures. Results. The primary tumor was visible with PET/CT in 54 (87%) of 62 patients, increasing from 59% (10/17) in tumors ≤ 10 mm to 98% (44/45) in tumors over 10 mm. All triple negative and HER2-positive tumors and 40/48 (83%) ER-positive/HER2-negative tumors were visualized. Sensitivity and specificity of PET/CT in the detection of axillary metastases were 73% and 100%, respectively. PET/CT depicted periclavicular nodes in two patients. Of 12 distant lesions, one was confirmed to be a lung metastasis, three were false positive, and eight were new primary proliferative lesions. Conclusion. Using optimal imaging acquisition, the majority of T1 breast carcinomas can be visualized with PET/CT. Specificity in the detection of axillary metastases is excellent, but sensitivity appears to be limited. Additional whole body imaging has a low yield in this specific patient group.

FDG-avid sclerotic bone metastases in breast cancer patients : a PET/CT case series

Distant metastases from breast cancer most frequently occur in the skeleton. Although 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), with or without computed tomography (CT), is superior to bone scintigraphy for the detection of osteolytic bone metastases, it has been reported that sclerotic bone metastases frequently show no or only a low degree of FDG uptake on PET and PET/CT. Since both lytic and sclerotic metastases can occur in breast cancer patients, bone scintigraphy may remain of additional value in these patients. In this case series, we describe four breast cancer patients in whom FDG PET/CT has clearly visualized sclerotic bone metastases because of increased FDG uptake. Not so much the type of metastasis (sclerotic or lytic), but possibly the characteristics of the primary tumor or treatments prior to the FDG PET/CT scan might influence the degree of FDG uptake of bone metastases. The ability to detect sclerotic bone metastases based on increased FDG uptake supports the use of FDG PET/CT as a staging procedure in breast cancer patients, but knowledge of factors determining the visibility of bone metastases with FDG PET/CT is crucial.

Evaluating heterogeneity of primary tumor (18)F-FDG uptake in breast cancer with a dedicated breast PET (MAMMI): a feasibility study based on correlation with PET/CT.

PurposeThe aim of the study was to evaluate the heterogeneity of primary tumor 18F-fluorodeoxyglucose (18F-FDG) uptake in breast cancer patients using a dedicated breast PET. Patients and methodsA positron emission tomography/computed tomography (PET/CT) of the thorax was performed 60 min after administration of 180–240 MBq of 18F-FDG in patients with breast cancer. Subsequently, 110 min after injection, a scan was taken with a dedicated high-resolution breast PET [MAMmography with Molecular Imaging (MAMMI)]. Both procedures were performed with the patients in the prone position. Four-point scores were used to compare the intensity (0: none; 1: mild; 2: moderate; 3: high) and heterogeneity (0: none; 1: mild; 2: moderate; 3: high) of 18F-FDG uptake between PET/CT and MAMMI images. ResultsThirty-five patients in whom the primary tumor was visualized on both scans were included in this analysis. The mean primary tumor size was 35.1 mm (range 10–108 mm). The mean intensity score was similar on both devices (2.4 for PET/CT and 2.3 for MAMMI; P=0.439), but the mean heterogeneity score on MAMMI images was significantly higher (PET/CT 1.9 vs. MAMMI 2.3; P=0.005). MAMMI showed a higher heterogeneity score in 11 (31%) of 35 patients, especially in tumors with moderate or high intensity. Significantly higher heterogeneity scores on both PET/CT and MAMMI were seen in large tumors (P=0.005 and 0.014, respectively) and in tumors with high intensity scores (P=0.012 and P<0.001, respectively). ConclusionHeterogeneous tumor 18F-FDG uptake in breast cancer is frequently observed, particularly in large tumors with intense 18F-FDG uptake. It is more often seen on MAMMI PET than on conventional PET/CT. Although the observed heterogeneity should be proven histopathologically, this finding offers a rationale for 18F-FDG-guided biopsies.

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.

Combined PET–CT and axillary lymph node marking with radioactive iodine seeds (MARI procedure) for tailored axillary treatment in node‐positive breast cancer after neoadjuvant therapy

The treatment of axillary lymph node metastases after neoadjuvant systemic therapy (NST) remains debatable and axillary lymph node dissection (ALND) is still the standard of care. Marking axillary lymph nodes with radioactive iodine seeds (MARI procedure) is accurate in restaging the axilla after NST (false‐negative rate 7 per cent). Here, the potential of tailored axillary treatment, determined by combining the results of PET–CT before NST with those of the MARI procedure after NST, was analysed.

Does the pretreatment tumor sampling location correspond with metabolic activity on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy?

PURPOSE To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II-III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling. METHODS A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥ 2 cm and a relative difference in SUV ≥ 25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed. RESULTS Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p = 0.028), diffuse (non-mass) and multifocal tumors on MRI (p = 0.001), diffuse and multifocal tumors on PET/CT (p<0.001), tumors >3 cm (p<0.001), and lobular carcinomas (p<0.001). No association was found with other features. CONCLUSION Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II-III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3 cm, lobular carcinomas, and diffuse and multifocal tumors.

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

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.