SUVmax to tumor perimeter distance: a robust radiomics prognostic biomarker in resectable non-small cell lung cancer patients.

OBJECTIVE: The purpose of this study was to evaluate the prognostic value of novel geometric variables obtained from pre-treatment [18F]FDG PET/CT with respect to classical ones in patients with non-small cell lung cancer (NSCLC). METHODS: Retrospective study including stage I-III NSCLC patients with baseline [18F]FDG PET/CT. Clinical, histopathologic, and metabolic parameters were obtained. After tumor segmentation, SUV and volume-based variables, global texture, sphericity, and two novel parameters, normalized SUVpeak to centroid distance (nSCD) and normalized SUVmax to perimeter distance (nSPD), were obtained. Early recurrence (ER) and short-term mortality (STM) were used as end points. Univariate logistic regression and multivariate logistic regression with respect to ER and STM were performed. RESULTS: A cohort of 173 patients was selected. ER was detected in 49/104 of patients with recurrent disease. Additionally, 100 patients died and 53 had STM. Age, pathologic lymphovascular invasion, lymph nodal infiltration, TNM stage, nSCD, and nSPD were associated with ER, although only age (aOR = 1.06, p = 0.002), pathologic lymphovascular invasion (aOR = 3.40, p = 0.022), and nSPD (aOR = 0.02, p = 0.018) were significant independent predictors of ER in multivariate analysis. Age, lymph nodal infiltration, TNM stage, nSCD, and nSPD were predictors of STM. Age (aOR = 1.05, p = 0.006), lymph nodal infiltration (aOR = 2.72, p = 0.005), and nSPD (aOR = 0.03, p = 0.022) were significantly associated with STM in multivariate analysis. Coefficient of variation (COV) and SUVmean/SUVmax ratio did not show significant predictive value with respect to ER or STM. CONCLUSION: The geometric variables, nSCD and nSPD, are robust biomarkers of the poorest outcome prediction of patients with NSCLC with respect to classical PET variables. KEY POINTS: • In NSCLC patients, it is crucial to find prognostic parameters since TNM system alone cannot explain the variation in lung cancer survival. • Age, lymphovascular invasion, lymph nodal infiltration, and metabolic geometrical parameters were useful as prognostic parameters. • The displacement grade of the highest point of metabolic activity towards the periphery assessed by geometric variables obtained from [18F]FDG PET/CT was a robust biomarker of the poorest outcome prediction of patients with NSCLC.

Segmentation in Non-Small Cell Lung Tumors Using 18F-FDG PET/CT: Tips and Rules.

The assessment of tumor parameters derived from F-FDG PET/CT in oncology provides valuable information in non-small cell lung cancer. A proper segmentation should delineate tumor with high accuracy, being the most important step to measure metabolic parameters. However, there is still no consensus about the optimal methodology. Additionally, some clinical conditions inherently tied to tumor and imaging can limit the proper tumor delineation. We present some practical cases that represent different aspects to consider during segmentation of primary non-small cell lung cancer by using F-FDG-PET/CT and some possible solutions to tackle with the most common limitations in clinical practice.

18F-choline PET/computed tomography and clinical parameters in the detection of significant prostate cancer in patients with increased prostate-specific antigen levels and previous negative biopsies.

OBJECTIVES: The aim of this study is to assess the value of the F-choline PET/computed tomography (CT) in predicting significant prostate cancer (sPCa) in patients with persistently increased prostate-specific antigen (PSA) levels and previous negative biopsies. To study the possible predictive added value of F-choline PET/CT to clinical variables and biomarkers derived from PSA in detecting sPCa. METHODS: We evaluated patients who underwent F-choline PET/CT because of ongoing suspicion of prostate cancer (PCa) due to elevated PSA levels (4-20 ng/mL) and at least one previous negative or no conclusive prostate biopsy for PCa. Age, PSA, free PSA, free/total PSA ratio, PSA velocity, PSA doubling time, PSA density and score risk were obtained. F-choline PET/CT was classified as negative/positive (PET-categorical). Additionally, we subclassified F-choline PET/CT according to the radiotracer uptake patterns (PET-pattern). The reference standard was the histological confirmation. Accuracy of PET/CT was evaluated. Univariate and multivariate logistic regression analyses were performed for metabolic and clinical variables. RESULTS: A total of 78 patients were included in our study, 23 had PCa (15 with sPCa). The PET pattern showed the highest accuracy and was the most powerful predictor of sPCa. In this research, the prediction of sPCa was improved combining PET pattern and score risk. CONCLUSION: F-choline PET/CT is a potential tool for predicting sPCa in patients with persistently increased PSA levels and previous negative biopsies, and also it could improve the performance of score risk in predicting sPCa.

Value of [18F]FDG-PET/CT and CA125, serum levels and kinetic parameters, in early detection of ovarian cancer recurrence: Influence of histological subtypes and tumor stages.

To assess the diagnostic accuracy of CA125, its kinetic values and positron emission tomography/computed tomography with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG-PET/CT), in relation with tumor characteristics for suspected recurrence of ovarian cancer. To evaluate the performance of CA125-related parameters as a selection criteria to perform a [F]FDG-PET/CT.A retrospective analysis of 69 [F]FDG-PET/CT for suspected recurrence of ovarian cancer was performed. All patients had 2 measurements of CA125, before PET/CT, to calculate kinetic values, as CA125vel (CA125vel = [CA125a - CA125b]/time) and CA125dt (CA125dt = [log2 × time]/[logCA125a - CA125b]). Maximum standard uptake value (SUVmax) was calculated. The diagnostic accuracy was calculated for all the variables and the optimal cut-off value of each of them by the receiver-operating characteristics (ROC) analysis. All the tests were compared with tumor characteristics and clinical-radiological evolution during follow-up of at least 6 months.Fifty-five cases were diagnosed of recurrence (11 with CA125 <35 U/mL), while 14 showed no disease (11 with CA125 < 35 U/mL). All of them were correctly cataloged by PET/CT. CA125, CA125vel, and SUVmax showed higher levels in recurrent patients (mean 129.54 U/mL, 24.58 U/mL per mo, and 8.69 g/mL, respectively) than in nonrecurrent (mean 20.35 U/mL, 0.60 U/mL per mo, and 0.64 g/mL, respectively). No statistical differences in CA125dt were found. Patients with recurrence of high-grade serous carcinoma (HGSC) showed higher CA125 and CA125vel, without differences in the rest of subtypes and International Federation of Gynecology and Obstetrics stages. The ROC analyses for CA125, CA125vel, and CA125dt showed an area under the curve (AUC) of 0.873 (95% confidence interval [CI] 0.77-0.969), 0.903 (95% CI 0.813-0.994), and 0.727 (95% CI 0.542-0.913), respectively, with an optimal cut-off point of 23.95 U/mL, 4.49 U/mL per mo, and 3.36 months, respectively, while for the SUVmax the AUC was of 0.982 (95% CI 0.948-1.000), and the cut-off point of 2. Multivariate regression analysis identified CA125 and CA125vel as predictors of recurrence.[F]FDG-PET/CT is more accurate than the parameters obtained from the CA125 to detect early recurrence. CA125vel is the most suitable parameter, mainly in HGSC. Levels of CA125vel ≥ 4.49 U/mL per mo facilitate earlier detection by the execution of a [F]FDG-PET/CT. The calculation of these parameters is independent of tumor stage at diagnosis.

Do clinical and laboratory variables have any impact on the diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin?

OBJECTIVE: To assess the influence of clinical features and laboratory test results on the determination of fever of unknown origin (FUO) by means of 18F-FDG PET/CT. METHODS: Retrospective and longitudinal analysis, including all the PET/CT studies requested for FUO. Reference standard was established by serology, cultures or biopsy with other laboratory tests or clinical follow-up when necessary. Clinical variables, inflammation markers, protein analysis, serology and culture results close to the PET scan were obtained. The final diagnosis was classified into three groups attending to the etiology; group 1: infection or neoplasm, group 2: vasculitis, autoimmune disease or non-infectious inflammatory disease and group 3: auto-limited fever or persistent fever without diagnosis. PET/CT scans were classified as positive or negative and helpful or not in the diagnosis of the fever origin. The effect of clinical features and laboratory variables on the PET/CT results was analyzed. RESULTS: Sixty-seven patients were evaluated. The final diagnosis was: Group 1 (25), Group 2 (20) and Group 3 (22). 89.6% of patients had a positive inflammation marker, 28.4% proteinogram alterations and 20.9% positive cultures. PET/CT was positive in 52/67 patients. PET/CT helped in the establishment of the fever origin in 35 cases and was especially helpful in groups 1 and 2. Sensitivity, specificity and accuracy of PET/CT were: 84, 31 and 61%. PET results shown significant relations with the final diagnosis (p = 0.035) and culture results (p = 0.037). No significant relations were observed with the rest of clinical or laboratory variables. CONCLUSIONS: 18F-FDG PET/CT had a high sensitivity but a low specificity in the diagnosis of the fever origin, probably due to the high rate of diffuse and auto-limited aetiologies. Patients who are most likely to benefit from the PET/CT study would be those with several positive inflammation markers, reflecting a higher pre-test probability of active disease.

18F-Fluorocholine PET/CT, Brain MRI, and 5-Aminolevulinic Acid for the Assessment of Tumor Resection in High-Grade Glioma.

High-grade glioma is a very aggressive and infiltrative tumor in which complete resection is a chance for a better outcome. We present the case of a 57-year-old man with a brain lesion suggestive of high-grade glioma. Brain MRI and F-fluorocholine PET/CT were performed previously to plan the surgery. Surgery was microscope assisted after the administration of 5-aminolevulinic acid. Postsurgery brain MRI and PET were blind evaluated to the surgery results and reported as probably gross total resection.

Metabolic Tumor Burden Assessed by Dual Time Point [18F]FDG PET/CT in Locally Advanced Breast Cancer: Relation with Tumor Biology.

PURPOSE: The aim of the study was to investigate the influence of dual time point 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) on the standard uptake value (SUV) and volume-based metabolic variables of breast lesions and their relation with biological characteristics and molecular phenotypes. PROCEDURES: Retrospective analysis including 67 patients with locally advanced breast cancer (LABC). All patients underwent a dual time point [18F]FDG PET/CT, 1 h (PET-1) and 3 h (PET-2) after [18F]FDG administration. Tumors were segmented following a three-dimensional methodology. Semiquantitative metabolic variables (SUVmax, SUVmean, and SUVpeak) and volume-based variables (metabolic tumor volume, MTV, and total lesion glycolysis, TLG) were obtained. Biologic prognostic parameters, such as the hormone receptors status, p53, HER2 expression, proliferation rate (Ki-67), and grading were obtained. Molecular phenotypes and risk-classification [low: luminal A, intermediate: luminal B HER2 (-) or luminal B HER2 (+), and high: HER2 pure or triple negative] were established. Relations between clinical and biological variables with the metabolic parameters were studied. The relevance of each metabolic variable in the prediction of phenotype risk was assessed using a multivariate analysis. RESULTS: SUV-based variables and TLG obtained in the PET-1 and PET-2 showed high and significant correlations between them. MTV and SUV variables (SUVmax, SUVmean, and SUVpeak) where only marginally correlated. Significant differences were found between mean SUV variables and TLG obtained in PET-1 and PET-2. High and significant associations were found between metabolic variables obtained in PET-1 and their homonymous in PET-2. Based on that, only relations of PET-1 variables with biological tumor characteristics were explored. SUV variables showed associations with hormone receptors status (p < 0.001 and p = 0.001 for estrogen and progesterone receptor, respectively) and risk-classification according to phenotype (SUVmax, p = 0.003; SUVmean, p = 0.004; SUVpeak, p = 0.003). As to volume-based variables, only TLG showed association with hormone receptors status (estrogen, p < 0.001; progesterone, p = 0.031), risk-classification (p = 0.007), and grade (p = 0.036). Hormone receptor negative tumors, high-grade tumors, and high-risk phenotypes showed higher TLG values. No association was found between the metabolic variables and Ki-67, HER2, or p53 expression. CONCLUSION: Statistical differences were found between mean SUV-based variables and TLG obtained in the dual time point PET/CT. Most of PET-derived parameters showed high association with molecular factors of breast cancer. However, dual time point PET/CT did not offer any added value to the single PET acquisition with respect to the relations with biological variables, based on PET-1 SUV, and volume-based variables were predictors of those obtained in PET-2.

Prognostic Role of Early and End-of-Neoadjuvant Treatment 18F-FDG PET/CT in Patients With Breast Cancer.

AIM: To determine the use of early and final treatment F-FDG PET/CT in the prediction of response to neoadjuvant chemotherapy (NAC) and its role in the prognosis of patients with locally advanced breast cancer (LABC). METHODS: One hundred thirty-two patients underwent a baseline FDG PET/CT (PET-1) after the second course of chemotherapy (PET-2) and after the last course (PET-3). Breast tumors were categorized into molecular phenotypes and risk categories according to the biological prognostic factors obtained by immunohistochemistry. PET/CT scans were semiquantitatively evaluated, obtaining the Δ% SUV1-2 and SUV1-3 in primary tumor and axillary lymph nodes to establish response groups attending to EORTC criteria. Moreover, a binary assessment was obtained classifying the studies as positive or negative. Histopathological response was obtained in breast and lymph node specimens. Overall survival (OS) and disease-free survival (DFS) were obtained after the follow-up. ROC analysis was performed to determine a cutoff value of Δ% SUV1-2 and SUV1-3 for the prediction of response and prognosis. Relations between phenotypes, metabolic behavior, final histopathological response, OS, and DFS were evaluated. RESULTS: In binary analysis, only PET-3 was able to predict histopathological response in lymph nodes. The cutoff values of %Δ SUV1-2 and %Δ SUV1-3 with the best sensitivity and specificity in the prediction of response in breast tumor were 62% (Se: 70% and Sp: 69%) and 84% (Se: 70% and Sp: 88%). A %ΔSUV1-3 of 74% in breast tumor was a predictor of DFS (AUC = 0.647; P = 0.037, Se: 52% and Sp: 66%). Kaplan-Meier analysis revealed significant relations between the binary lymph node assessment of PET-3 with OS (P = 0.016, χ = 5.78) and DFS (P = 0.003, χ = 9.10). CONCLUSIONS: End-of-treatment F-FDG PET/CT was a predictor of lymph node response and prognosis. Most of metabolic response variables related to histopathological response showed association with the prognosis.

(18)F-FDG-PET/CT in the assessment of pulmonary solitary nodules: comparison of different analysis methods and risk variables in the prediction of malignancy.

OBJECTIVE: To compare the diagnostic performance of different metabolical, morphological and clinical criteria for correct presurgical classification of the solitary pulmonary nodule (SPN). METHODS: Fifty-five patients, with SPN were retrospectively analyzed. All patients underwent preoperative (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). Maximum diameter in CT, maximum standard uptake value (SUVmax), histopathologic result, age, smoking history and gender were obtained. Different criteria were established to classify a SPN as malignant: (I) visually detectable metabolism, (II) SUVmax >2.5 regardless of SPN diameter, (III) SUVmax threshold depending of SPN diameter, and (IV) ratio SUVmax/diameter greater than 1. For each criterion, statistical diagnostic parameters were obtained. Receiver operating characteristic (ROC) analysis was performed to select the best diagnostic SUVmax and SUVmax/diameter cutoff. Additionally, a predictive model of malignancy of the SPN was derived by multivariate logistic regression. RESULTS: Fifteen SPN (27.3%) were benign and 40 (72.7%) malignant. The mean values ± standard deviation (SD) of SPN diameter and SUVmax were 1.93±0.57 cm and 3.93±2.67 respectively. Sensitivity (Se) and specificity (Sp) of the different diagnostic criteria were (I): 97.5% and 13.1%; (II) 67.5% and 53.3%; (III) 70% and 53.3%; and (IV) 85% and 33.3%, respectively. The SUVmax cut-off value with the best diagnostic performance was 1.95 (Se: 80%; Sp: 53.3%). The predictive model had a Se of 87.5% and Sp of 46.7%. The SUVmax was independent variables to predict malignancy. CONCLUSIONS: The assessment by semiquantitative methods did not improve the Se of visual analysis. The limited Sp was independent on the method used. However, the predictive model combining SUVmax and age was the best diagnostic approach.

Comparison of different predictive tools of axillary status in breast cancer with micrometastatic sentinel node.

AIM: To compare the performance of six different nomograms and one score in the prediction of non-sentinel lymph node status in a subset of women with breast cancer and micrometastatic sentinel nodes (SN). MATERIAL AND METHODS: Twenty-five patients were included in the study. Five different nomograms not specifically designed for micrometastatic SN, one recently published nomogram specially developed for this type of patients and one score were analyzed, and the corresponding receiver operating characteristic curves were obtained. The area under the curve (AUC) was calculated, as well as the false negative and false positive results and their corresponding rates (FNR and FPR) for a cutoff of ≤10% or ≤4 points. RESULTS: The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram showed the best performance in this low-risk group of patients (AUC 0.900, FPR 64%, FNR 0%), followed by the French nomogram. CONCLUSIONS: The MSKCC nomogram seems to have the highest accuracy in the identification of patients with low risk of further axillary disease in the subgroup of women with micrometastatic SN.

¹8F-FDG PET/contrast enhanced CT in the standard surveillance of high risk colorectal cancer patients.

OBJECTIVE: To assess the accuracy of FDG-PET/contrast enhanced CT (FDG-PET/ceCT) in the detection of unsuspected recurrence of colorectal cancer (CRC) in patients with high risk of relapse. METHODS: Thirty-three patients (14 females and 19 males, mean age: 62, range: 41-78), with CRC in complete remission, were prospectively included. All patients underwent FDG-PET/ceCT (58 studies). FDG-PET/ceCT was requested in the surveillance setting, and performed following a standardized protocol. A portal venous phase CT scan was performed after the injection of iodinated contrast agent. An individual and combined assessment of both techniques (PET and ceCT) was performed. Concordant and discordant findings of PET, ceCT and FDG-PET/ceCT were compared in a patient-based and a lesion-based analysis. The final diagnosis, recurrence or disease free status (DFS), were established by histopathology or clinical/radiological follow-up of at least 6 months. RESULTS: Seven out of 33 patients had a confirmed recurrence and the rest of patients had a DFS. In a patient-based analysis the sensitivity and specificity of PET, ceCT and PET/ceCT was of 86% and 88%, 86% and 92%, 86% and 85%, respectively. Attending to the lesion-based analysis, the sensitivity for PET, ceCT and PET/ceCT was of 56%, 71% and 97%, respectively. Both techniques showed a good concordance in the establishment of the final patient status. However, on a lesion-based analysis, no concordance was observed between them. CONCLUSION: PET and ceCT seem to have similar value in the detection of unsuspected recurrence of CRC in a patient-based analysis. However, the combined assessment of PET/ceCT improves the accuracy in the lesion-based analysis.

Heterogeneity in [18F]fluorodeoxyglucose positron emission tomography/computed tomography of non-small cell lung carcinoma and its relationship to metabolic parameters and pathologic staging.

To investigate the relationships between tumor heterogeneity, assessed by texture analysis of [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) images, metabolic parameters, and pathologic staging in patients with non-small cell lung carcinoma (NSCLC). A retrospective analysis of 38 patients with histologically confirmed NSCLC who underwent staging FDG-PET/computed tomography was performed. Tumor images were segmented using a standardized uptake value (SUV) cutoff of 2.5. Five textural features, related to the heterogeneity of gray-level distribution, were computed (energy, entropy, contrast, homogeneity, and correlation). Additionally, metabolic parameters such as SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), as well as pathologic staging, histologic subtype, and tumor diameter, were obtained. Finally, a correlation analysis was carried out. Of 38 tumors, 63.2% were epidermoid and 36.8% were adenocarcinomas. The mean ± standard deviation values of MTV and TLG were 30.47 ± 25.17 mL and 197.81 ± 251.11 g, respectively. There was a positive relationship of all metabolic parameters (SUVmax, SUVmean, MTV, and TLG) with entropy, correlation, and homogeneity and a negative relationship with energy and contrast. The T component of the pathologic TNM staging (pT) was similarly correlated with these textural parameters. Textural features associated with tumor heterogeneity were shown to be related to global metabolic parameters and pathologic staging.

Early and delayed prediction of axillary lymph node neoadjuvant response by (18)F-FDG PET/CT in patients with locally advanced breast cancer.

PURPOSE: To determine the utility of (18)F-FDG (FDG) PET/CT performed in an early and delayed phase during neoadjuvant chemotherapy in the prediction of lymph node histopathological response in patients with locally advanced breast cancer. METHODS: FDG PET/CT studies performed in 76 patients (mean age 53 years) at baseline (PET-1), after the second course of chemotherapy (PET-2) and after the last course of chemotherapy (PET-3) were prospectively analysed. Inclusion criteria were lymph node involvement detected by PET/CT and non-sentinel node biopsy before or after the baseline PET/CT scan. Following the recommendations of the 12th International Breast Conference (St. Gallen), the patients were divided into five subgroups in relation to biological prognostic factors by immunohistochemistry. For diagnosis visual and semiquantitative analyses was performed. Absence of detectable lymph node uptake on the PET-2 or PET-3 scan with respect to the PET-1 scan was considered metabolic complete response (mCR). Lymph nodes were histopathologically classified according the lymph node regression grade and in response groups as pathological complete response (pCR) or not pCR (type A/D or B/C of the Smith grading system, respectively). ROC analysis was performed to determine a cut-off value of Δ% SUV1-2 and SUV1-3 for prediction of nodal status after chemotherapy. An association between mCR and pCR was found (Cohen's kappa analysis), and associations between phenotypes and metabolic behaviour and the final histopathological status were also found. RESULTS: Lymph node pCR was seen in 34 patients. The sensitivity, specificity, and positive and negative predictive values of PET-2 and PET-3 in establishing the final status of the axilla after chemotherapy were 52 %, 45 %, 50 % and 47 %, and 33 %, 84 %, 67 % and 56 %, respectively. No significant relationship was observed between mCR on PET-2 and PET-3 and pCR (p = 0.31 and 0.99, respectively). Lymph node metabolism on PET-1 was not able to predict the final histopathological status, whereas basal carcinomas showed a higher rate of pCR (70.6 %) than the other groups (p = 0.03). CONCLUSION: FDG PET/CT seems to have limitations in both the early and delayed evaluation of lymph node status after chemotherapy, with reduced predictive values.

Heterogeneity in [¹8F]fluorodeoxyglucose positron emission tomography/computed tomography of non-small cell lung carcinoma and its relationship to metabolic parameters and pathologic staging.

To investigate the relationships between tumor heterogeneity, assessed by texture analysis of [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) images, metabolic parameters, and pathologic staging in patients with non-small cell lung carcinoma (NSCLC). A retrospective analysis of 38 patients with histologically confirmed NSCLC who underwent staging FDG-PET/computed tomography was performed. Tumor images were segmented using a standardized uptake value (SUV) cutoff of 2.5. Five textural features, related to the heterogeneity of gray-level distribution, were computed (energy, entropy, contrast, homogeneity, and correlation). Additionally, metabolic parameters such as SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), as well as pathologic staging, histologic subtype, and tumor diameter, were obtained. Finally, a correlation analysis was carried out. Of 38 tumors, 63.2% were epidermoid and 36.8% were adenocarcinomas. The mean ± standard deviation values of MTV and TLG were 30.47 ± 25.17 mL and 197.81 ± 251.11 g, respectively. There was a positive relationship of all metabolic parameters (SUVmax, SUVmean, MTV, and TLG) with entropy, correlation, and homogeneity and a negative relationship with energy and contrast. The T component of the pathologic TNM staging (pT) was similarly correlated with these textural parameters. Textural features associated with tumor heterogeneity were shown to be related to global metabolic parameters and pathologic staging.

Semi-quantitative lymph node assessment of (18)F-FDG PET/CT in locally advanced breast cancer: correlation with biological prognostic factors.

PURPOSE: The aim of this study was to analyse the correlation between dual-time-point (18)F-2-deoxy-2-fluoro-D-glucose (FDG) uptakes in lymph nodes assessed by positron emission tomography (PET)/CT and histopathological and immunohistochemical prognostic factors. METHODS: Seventy-five women with locally advanced breast cancer were prospectively evaluated. PET/CT was requested in the initial staging previous to adjuvant chemotherapy (multicentre study). All of the patients underwent (18)F-FDG PET/CT with a dual-time-point acquisition. Both examinations were evaluated qualitatively and semi-quantitatively with calculation of maximum standardized uptake values (SUV(max)) in PET-1 (SUV-1) and in PET-2 (SUV-2) and the percentage variation of the SUV or retention index (RI) between PET-1 and PET-2 in lymph nodes with the greater (18)F-FDG uptake. The biological prognostic parameters such as the steroid receptor status, p53 and HER2 expression, proliferation rate (Ki-67) and grading were determined from tissue of the primary tumour. Metabolic and biological parameters were correlated using Spearman's rank-order correlation coefficient and Mann-Whitney U and Kruskal-Wallis tests. RESULTS: Negative receptor status was correlated with higher SUV-1, SUV-2 and RI in lymph nodes. The results were significant for progesterone receptor status. p53 over-expression and triple-negative status were associated with greater semi-quantitative parameters in lymph nodes. Higher tumoural grades were related with greater semi-quantitative parameters (p > 0.05). CONCLUSION: Biological factors of bad prognosis were correlated with higher semi-quantitative metabolic values in lymph nodes. Therefore these results appear to reveal biological significance of lymph node (18)F-FDG accumulation.