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Purpose: The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). Methods: 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Results: Spearman's coefficients between SUV and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV and TLG predicted the pathological response ( P = 0.0021 and P = 0.02 respectively); TFs didn't ( P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). Conclusions: The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV and TLG were able to predict response to NAC, TFs failed. [ABSTRACT FROM AUTHOR]

Background: This study investigated the value of some clinicopathological parameters and 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) indices, including textural features, to predict event-free survival (EFS) in estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) locally advanced breast cancer (BC) patients.Methods: FDG-PET/CT indices and clinicopathological parameters were assessed before neoadjuvant chemotherapy (NAC). After completion of chemotherapy, all patients had breast surgery with axillary lymph node dissection, followed by radiation therapy and endocrine therapy for 5 years. EFS was estimated using the Kaplan-Meier method. A Cox proportional hazard regression model was used for multivariate analysis.Results: One hundred forty-three consecutive patients with stage II-III ER+/HER2- BC and without distant metastases at baseline PET were included. High standardized uptake values (SUVs), were associated with shorter EFS (HR = 3.51, P < 0.01 for SUVmax; HR = 2.76, P = 0.02 for SUVmean; and HR = 4.40 P < 0.01 for SUVpeak). Metabolically active tumor volume (MATV, HR = 3.47, P < 0.01) and total lesion glycolysis (TLG, HR = 3.10, P < 0.01) were also predictive of EFS. Homogeneity was not predictive (HR = 2.27, P = 0.07) and entropy had weak prediction (HR = 2.89, P = 0.02). Among clinicopathological parameters, EFS was shorter in progesterone receptor (PR)-negative tumor (vs. PR-positive tumor; HR = 3.25, P < 0.01); histology was predictive of EFS (lobular vs. ductal invasive carcinoma; HR = 3.74, P = 0.01) but not tumor grade (grade 3 vs. grade 1-2; HR = 1.64, P = 0.32). Pathological complete response after NAC was not correlated to the risk of relapse. Three parameters remained significantly associated with EFS in multivariate analysis. MATV (HR = 1.01, P < 0.01), progesterone receptor expression (HR = 2.90, P = 0.03) and tumor histology (HR = 3.80, P = 0.02).Conclusions: Baseline PET parameters measured before neoadjuvant treatment have prognostic values in ER+/HER2- locally advanced breast cancer patients. After multivariate analysis, metabolically active tumor volume remains significant while textural analysis of PET images is not of added value. Considering histopathological parameters, our study shows that patients with PR-negative or lobular invasive tumor have poorer prognosis than patients with PR-positive or ductal carcinoma, respectively. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this retrospective study was to determine if some features of baseline F-FDG PET images, including volume and heterogeneity, reflect clinical, histological or immunohistochemical characteristics in patients with stage II or III breast cancer (BC). Methods: Included in the present retrospective analysis were 171 prospectively recruited patients with stage II/III BC treated consecutively at Saint-Louis hospital. Primary tumour volumes were semiautomatically delineated on pretreatment F-FDG PET images. The parameters extracted included SUV, SUV, metabolically active tumour volume (MATV), total lesion glycolysis (TLG) and heterogeneity quantified using the area under the curve of the cumulative histogram and textural features. Associations between clinical/histopathological characteristics and F-FDG PET features were assessed using one-way analysis of variance. Areas under the ROC curves (AUC) were used to quantify the discriminative power of the features significantly associated with clinical/histopathological characteristics. Results: T3 tumours (>5 cm) exhibited higher textural heterogeneity in F-FDG uptake than T2 tumours (AUC <0.75), whereas there were no significant differences in SUV and SUV. Invasive ductal carcinoma showed higher SUV values than invasive lobular carcinoma ( p = 0.008) but MATV, TLG and textural features were not discriminative. Grade 3 tumours had higher FDG uptake (AUC 0.779 for SUV and 0.694 for TLG), and exhibited slightly higher regional heterogeneity (AUC 0.624). Hormone receptor-negative tumours had higher SUV values than oestrogen receptor-positive (ER-positive) and progesterone receptor-positive tumours, while heterogeneity patterns showed only low-level variation according to hormone receptor expression. HER-2 status was not associated with any of the image features. Finally, SUV, SUV and TLG significantly differed among the three phenotype subgroups (HER2-positive, triple-negative and ER-positive/HER2-negative BCs), but MATV and heterogeneity metrics were not discriminative. Conclusion: SUV parameters, MATV and textural features showed limited correlations with clinical and histopathological features. The three main BC subgroups differed in terms of SUVs and TLG but not in terms of MATV and heterogeneity. None of the PET-derived metrics offered high discriminative power. [ABSTRACT FROM AUTHOR]

Background This study prospectively evaluated the yield of fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET-CT) in patients with clinical stages II and III breast cancer and the impact of PET-CT results on prognosis. Methods In the course of 71 months, 254 consecutive patients with clinical stages II and III breast cancer (based on clinical examination, mammography, breast magnetic resonance imaging, and Iocoregional ultrasonography) underwent 18FDG-PET-CT.The yield was assessed in the whole population and for each American Joint Committee on Cancer subgroup. The prognostic impact of PET-CT findings was analyzed. Tests of statistical significance were two-sided. Results 18FDG-PET-CT changed the clinical stage in 77 of 254 patients (30.3%; 95% confidence interval [CI] = 25.0% to 36.2%). It showed unsuspected N3 disease (infraclavicular, supraclavicular, or internal mammary nodes) in 40 patients and distant metastases in 53. PET-CT revealed distant metastases in 2.3% (1 of 44) of clinical stage IIA, 10.7% (6 of 56) of stage liB, 17.5% (11 of 63) of stage IIA, 36.5% (27 of 74) of stage IIIB, and 47.1% (8 of 17) of stage IIIC patients. Among 189 patients with clinical stage IBM or higher disease and adequate follow-up, disease-specific survival was statistically significantly shorter in the 47 patients scored M1 on 18SFDG-PET-CT in comparison with those scored M0, with a three-year disease-specific survival of 57% vs 88% (P < .001). In multivariable analysis, only distant disease on PET-CT and triple-negative phenotype were statistically significant prognostic factors.The relative risk of death was 26.60 (95% CI = 6.60 to 102.62) for M1 vs M0 patients. Conclusions The yield of 18SFDG-PET-CT appeared substantial in patients with clinical stage IIB or higher breast cancer. In these patients, 18SFDG-PET-CT provided powerful prognostic stratification. [ABSTRACT FROM AUTHOR]

Phosphatidylserin exposure on cell surfaces occurs early during apoptosis and is detected in vivo by using 99mTc-annexin-V (ANX). Cardiomyocyte membrane disruption is detected in vivo by using 111In-antimyosin-antibodies (AM). We aimed to determine if ANX and AM allow evaluation of the time-course of these two distinct cell death events after myocardial ischemia-reperfusion. Coronary tying (20 min) followed by reperfusion (IR) was performed in 31 rats. Twelve of the rats were injected with ANX, 11 with AM, and eight with both tracers. Myocardial uptake of tracers was studied 1–2 h, 4 h, or 24 h after IR by scintigraphy (ANX, n = 14) and autoradiography (all cases), and compared to histology and Apostain staining. Scintigraphy was positive in all rats 2 h after IR and in three of five rats at 24 h. On autoradiography, ANX activity was intense in myocardial lesions as early as 1 h post-IR, whereas AM activity was mild at 2 h then increased at 4 h post-IR. ANX and AM uptakes evolved from mid-myocardium to endocardial and epicardial regions from 2 h to 24 h post-IR. Apostain staining was significant in myocardial lesions ( p < 106 compared to six sham-operated rats). On histology, myocardial lesion was characterized by interstitial oedema, myocytes necrosis, and dramatic thinning at 24 h. These data suggest that ANX and AM allow temporal and regional evaluations of PS exposure and membrane disruption, respectively, during myocytes death after 20-min myocardial ischemia followed by reperfusion. Also, (i) apoptosis starts very early in injured myocardium, (ii) myocyte necrosis occurs later (3–4 h post-reperfusion), and (iii) most dead cells are removed from mid-myocardium between 6 h and 24 h after reperfusion. [ABSTRACT FROM AUTHOR]

Objective: Transplantation of skeletal myogenic precursor cells (mpc) into the myocardium using a non-surgical procedure. Methods: Closed-chest mpc transplantation was assessed in pigs using the NOGA-Biosense® device allowing both electromechanical mapping of the left ventricle (LV), and guided mpc injections through endocardium. Results: We successively established that: (1) adequate preimplantation handling of mpc can be achieved when mpc are kept in 0.1% serum albumin-containing medium until implantation; (2) mpc are neither retained nor destroyed in the catheter or the needle and their passage does not affect their survival, growth and differentiation; (3) large numbers of autologous mpc can be actually transplanted in the LV myocardium by transendocardial route, as assessed by post-mortem examination of pigs injected with iron-loaded mpc; (4) cell injection into the myocardium does not induce conspicuous cell mortality since more than 80% of mpc recovered from LV tissue are alive 15 min after injection; (5) mpc injections can be guided into circumscribed LV targets such as infarcted areas, as assessed by comparison of map injection sites with location of iron-loaded mpc at post-mortem examination of LV myocardium. Conclusion: This new approach may pave the way for a large spectrum of cell therapies targeting myocardial diseases. [Copyright &y& Elsevier]