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Objectives To investigate the diagnostic feasibility of a shortened breast PET/MRI protocol in breast cancer patients. Methods Altogether 90 women with newly diagnosed T1tumor-staged (T1ts) and T2tumor-staged (T2ts) breast cancer were included in this retrospective study. All underwent a dedicated comprehensive breast [18F]FDG-PET/MRI. List-mode PET data were retrospectively reconstructed with 20, 15, 10, and 5 min for each patient to simulate the effect of reduced PET acquisition times. The SUVmax/mean of all malign breast lesions was measured. Furthermore, breast PET data reconstructions were analyzed regarding image quality, lesion detectability, signal-to-noise ratio (SNR), and image noise (IN). The simultaneously acquired comprehensive MRI protocol was then shortened by retrospectively removing sequences from the protocol. Differences in malignant breast lesion detectability between the original and the fast breast MRI protocol were evaluated lesion-based. The 20-min PET reconstructions and the original MRI protocol served as reference. Results In all PET reconstructions, 127 congruent breast lesions could be detected. Group comparison and T1ts vs. T2ts subgroup comparison revealed no significant difference of subjective image quality between 20, 15, 10, and 5 min acquisition times. SNR of qualitative image evaluation revealed no significant difference between different PET acquisition times. A slight but significant increase of IN with decreasing PET acquisition times could be detected. Lesion SUVmax group comparison between all PET acquisition times revealed no significant differences. Lesion-based evaluation revealed no significant difference in breast lesion detectability between original and fast breast MRI protocols. Conclusions Breast [18F]FDG-PET/MRI protocols can be shortened from 20 to below 10 min without losing essential diagnostic information. Key Points • A highly accurate breast cancer evaluation is possible by the shortened breast [18F]FDG-PET/MRI examination protocol. • Significant time saving at breast [18F]FDG-PET/MRI protocol could increase patient satisfaction and patient throughput for breast cancer patients at PET/MRI.

Purpose: Evaluate the diagnostic potential of [18F]FDG-PET/MRI data compared with invasive acquired biomarkers in newly diagnosed early breast cancer (BC). Methods: Altogether 169 women with newly diagnosed BC were included. All underwent a breast- and whole-body [18F]FDG-PET/MRI for initial staging. A tumor-adapted volume of interest was placed in the primaries and defined bone regions on each standard uptake value (SUV)/apparent diffusion coefficient (ADC) dataset. Immunohistochemical markers, molecular subtype, tumor grading, and disseminated tumor cells (DTCs) of each patient were assessed after ultrasound-guided biopsy of the primaries and bone marrow (BM) aspiration. Correlation analysis and group comparisons were assessed. Results: A significant inverse correlation of estrogen-receptor (ER) expression and progesterone-receptor (PR) expression towards SUVmax was found (ER: r = 0.27, p < 0.01; PR: r = 0.19, p < 0.05). HER2-receptor expression showed no significant correlation towards SUV and ADC values. A significant positive correlation between Ki67 and SUVmax and SUVmean (r = 0.42 p < 0.01; r = 0.19 p < 0.05) was shown. Tumor grading significantly correlated with SUVmax and SUVmean (ρ = 0.36 and ρ = 0.39, both p’s < 0.01). There were no group differences between SUV/ADC values of DTC-positive/-negative patients. Conclusions: [18F]FDG-PET/MRI may give a first impression of BC-receptor status and BC-tumor biology during initial staging by measuring glucose metabolism but cannot distinguish between DTC-positive/-negative patients and replace biopsy.

Purpose: This study seeks to evaluate MR imaging morphological factors and other covariates that influence the presence of residual glandular tissue after risk-reducing mastectomy in patients with a familial predisposition. Methods: We analyzed women of a high-risk collective with pathogenic mutation (BRCA1 (n = 49), BRCA2 (n = 24), or further mutation (n = 9)). A total of 117 breasts were analyzed, 63 left and 54 right, from a cohort of 81 patients, who were on average 40 years old. The mean follow-up was 63 months (range 12–180 months, SD = 39.67). Retrospective analysis of MR imaging data from 2006–2022 of patients of a high-risk collective (all carriers of a pathogenic mutation) with contralateral (RRCM) or bilateral risk-reducing mastectomy (RRBM) was performed. In the image data the remaining skin flap thickness by distance measurements at eight equally distributed, clockwise points and the retromamillary area, as well as by volumetry of each breast, was elected. Residual glandular tissue was also volumetrized. In addition, patient-related covariates were recorded and their influence on postoperative residual glandular tissue and skin flap thickness was analyzed by uni- and multivariate regressions. Results: A significant association with postoperative residual glandular tissue was shown in multivariate analysis for the independent variables breast density, skin flap mean, and surgical method (all p-values < 0.01). A negatively significant association could be seen for the variables preoperative breast volume (p-values < 0.01) and surgeon experience (most p-values < 0.05&ndash

Objectives T o evaluate the value of multiparametric MRI (mpMRI) for the prediction of prostate cancer (PCA) aggressiveness. Methods In this single center cohort study, consecutive patients with histologically confirmed PCA were retrospectively enrolled. Four different ISUP grade groups (1, 2, 3, 4–5) were defined and fifty patients per group were included. Several clinical (age, PSA, PSAD, percentage of PCA infiltration) and mpMRI parameters (ADC value, signal increase on high b-value images, diameter, extraprostatic extension [EPE], cross-zonal growth) were evaluated and correlated within the four groups. Based on combined descriptors, MRI grading groups (mG1–mG3) were defined to predict PCA aggressiveness. Results In total, 200 patients (mean age 68 years, median PSA value 8.1 ng/ml) were analyzed. Between the four groups, statistically significant differences could be shown for age, PSA, PSAD, and for MRI parameters cross-zonal growth, high b-value signal increase, EPE, and ADC (p p p = 0.09). A mixed linear model demonstrated the strongest prediction of the respective ISUP grade group for the MRI grading system (p Conclusions MpMRI yields relevant pre-biopsy information about PCA aggressiveness. A combination of quantitative and qualitative parameters (MRI grading groups) provided the best prediction of the biopsy ISUP grade group and may improve clinical pathway and treatment planning, adding useful information beyond PI-RADS assessment category. Due to the high prevalence of higher grade PCA in patients within mG3, an early re-biopsy seems indicated in cases of negative or post-biopsy low-grade PCA. Key Points • MpMRI yields relevant pre-biopsy information about prostate cancer aggressiveness. • MRI grading in addition to PI-RADS classification seems to be helpful for a size independent early prediction of clinically significant PCA. • MRI grading groups may help urologists in clinical pathway and treatment planning, especially when to consider an early re-biopsy.

Purpose To compare CT, MRI, and [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET/MRI) for nodal status, regarding quantity and location of metastatic locoregional lymph nodes in patients with newly diagnosed breast cancer. Materials and methods One hundred eighty-two patients (mean age 52.7 ± 11.9 years) were included in this prospective double-center study. Patients underwent dedicated contrast-enhanced chest/abdomen/pelvis computed tomography (CT) and whole-body ([18F]-FDG PET/) magnet resonance imaging (MRI). Thoracal datasets were evaluated separately regarding quantity, lymph node station (axillary levels I–III, supraclavicular, internal mammary chain), and lesion character (benign vs. malign). Histopathology served as reference standard for patient-based analysis. Patient-based and lesion-based analyses were compared by a McNemar test. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for all three imaging modalities. Results On a patient-based analysis, PET/MRI correctly detected significantly more nodal positive patients than MRI (p p p p p = 0.015). Subgroup analysis for different lymph node stations showed that PET/MRI detected significantly more lymph node metastases than MRI and CT in each location (axillary levels I–III, supraclavicular, mammary internal chain). MRI was superior to CT only in axillary level I (p = 0.0291). Conclusion [18F]-FDG PET/MRI outperforms CT or MRI in detecting nodal involvement on a patient-based analysis and on a lesion-based analysis. Furthermore, PET/MRI was superior to CT or MRI in detecting lymph node metastases in all lymph node stations. Of all the tested imaging modalities, PET/MRI showed the highest sensitivity, whereas CT showed the lowest sensitivity, but was most specific.

Background: The aim of this study was to assess whether multiparametric 18F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification. Methods: A total of 73 female patients (mean age 49 years; range 27–77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model. Results: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2− group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets. Conclusion: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2− receptor status.

Locoregional therapy options for CCA are used, in particular, for non-resectable tumors and aim to reduce tumor viability or delay tumor growth and ultimately prolong overall survival. In addition to local ablative procedures such as radiofrequency- or microwave-ablation, transarterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), or selective internal radiotherapy (SIRT) play a major role. In particular, in combination with advances in molecular medicine and immunotherapy, there has been a further development in the therapy of primary malignant liver tumors in recent years. In this review, we analyze data from recent studies and examine the implications for therapy of CCA, particularly with regard to the combination of locoregional therapies with modern systemic therapies.

The aim of this study was to assess whether multiparametricA total of 73 female patients (mean age 49 years; range 27-77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneousThe best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2- group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets.

PET/MRI has been available since 2010, representing the newest of the hybrid imaging modalities. It combines functional as well as morphologic high-resolution MRI data with metabolic information from PET, providing image data sets with complementary information. Especially in the field of oncology, PET/MRI is a promising imaging modality with diverse applications. Since its introduction there has already been a large quantity of studies indicating a high diagnostic value of PET/MRI for whole-body cancer staging. The simultaneous acquisition of metabolic PET and MRI data is expected to have a major impact in the assessment of breast cancer due to the superior resolution of MRI in breast tissue compared to CT. While there is an ongoing debate if the added value of breast

To evaluate the impact of different metal artifact reduction algorithms on Hounsfield units (HU) and the standardized uptake value (SUV) in normal organs in patients with different metal implants.This study prospectively included 66 patients (mean age of 66.02 ± 13.1 years) with 87 different metal implants. CT image reconstructions were performed using weighted filtered back projection (WFBP) as the standard method, metal artifact reduction in image space (MARIS), and an iterative metal artifacts reduction (iMAR) algorithm for large implants. These datasets were used for PET attenuation correction. HU and SUV measurements were performed in nine predefined anatomical locations: liver, lower lung lobes, descending aorta, thoracic vertebral body, autochthonous back muscles, pectoral muscles, and internal jugular vein. Differences between HU and SUV measurements were compared using pairedNo significant differences were observed between reconstructed images using iMAR and WFBP concerning HU and SUV measurements in liver (HU:Metal artifact reduction algorithms such as iMAR do not alter the data information of normal organs not affected by artifacts.

To assess the diagnostic value of an additional late-phase PET/CT scan after urination as part ofThis retrospective trial included patients with BCR following radical prostatectomy, who underwent standard whole-body early-phase PET/CT performed 105 ± 45 min and an additional late-phase PET/CT performed 159 ± 13 min after injection ofWhole-body early-phase PET/CT detected 93 prostate cancer lesions in 33 patients. Late-phase PET/CT detected two additional lesions in two patients, both local recurrences. In total, there were 57 nodal, 28 bone, and 3 lung metastases, and 7 local recurrences. Between early- and late-phase PET/CT, lymph node metastases showed a significant increase of SUVmax from 14.5 ± 11.6 to 21.5 ± 17.6 (p = 0.00007), translating to a factor of + 1.6. Benign lymph nodes in the respective regions showed a significantly lower increase of SUVmax of 1.4 ± 0.5 to 1.7 ± 0.5 (p = 0.0014, factor of + 1.2). Local recurrences and bone metastases had a SUVmax on late-phase PET/CT that was + 1.7 and + 1.1 times higher than the SUVmax on early-phase PET/CT, respectively.In patients with BCR following radical prostatectomy, an additional abdomino-pelvic late-phase

Simple Summary In this study, we assessed the potential of simultaneously acquired 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and magnetic resonance imaging-derived quantitative imaging parameters to predict the tumor grade, metastatic status, and response to neoadjuvant therapy of primary soft-tissue sarcomas of the extremities. Based on the results of the present study, quantifications of the 18F-FDG PET uptake provide useful prognostic data for the evaluation of histopathological response to neoadjuvant treatment as well as the aggressiveness of high-risk sarcomas, whereas no correlation between the different outcome variables and the results for tumor size and diffusion-weighted imaging-derived apparent diffusion coefficient values was found. Accordingly, measurements of the metabolic activity of primary and untreated soft-tissue sarcomas could non-invasively deliver relevant information, that may be used for treatment planning and risk-stratification of sarcoma patients in a pretherapeutic setting. Abstract Background: To evaluate the potential of simultaneously acquired 18F-FDG PET- and MR-derived quantitative imaging data sets of primary soft-tissue sarcomas for the prediction of neoadjuvant treatment response, the metastatic status and tumor grade. Methods: A total of 52 patients with a high-risk soft-tissue sarcoma underwent a 18F-FDG PET/MR examination within one week before the start of neoadjuvant treatment. For each patient, the maximum tumor size, metabolic activity (SUVs), and diffusion-restriction (ADC values) of the tumor manifestations were determined. A Mann–Whitney-U test was used, and ROC analysis was performed to evaluate the potential to predict histopathological treatment response, the metastatic status or tumor grade. The results from the histopathological analysis served as reference standard. Results: Soft-tissue sarcomas with a histopathological treatment response revealed a significantly higher metabolic activity than tumors in the non-responder group. In addition, grade 3 tumors showed a significant higher 18F-FDG uptake than grade 2 tumors. Furthermore, no significant correlation between the different outcome variables and tumor size or calculated ADC-values could be identified. Conclusion: Measurements of the metabolic activity of primary and untreated soft-tissue sarcomas could non-invasively deliver relevant information that may be used for treatment planning and risk-stratification of high-risk sarcoma patients in a pretherapeutic setting.

Background: This study investigated the performance of simultaneous 18F-FDG PET/MRI of the breast as a platform for comprehensive radiomics analysis for breast cancer subtype analysis, hormone receptor status, proliferation rate and lymphonodular and distant metastatic spread. Methods: One hundred and twenty-four patients underwent simultaneous 18F-FDG PET/MRI. Breast tumors were segmented and radiomic features were extracted utilizing CERR software following the IBSI guidelines. LASSO regression was employed to select the most important radiomics features prior to model development. Five-fold cross validation was then utilized alongside support vector machines, resulting in predictive models for various combinations of imaging data series. Results: The highest AUC and accuracy for differentiation between luminal A and B was achieved by all MR sequences (AUC 0.98, accuracy 97.3). The best results in AUC for prediction of hormone receptor status and proliferation rate were found based on all MR and PET data (ER AUC 0.87, PR AUC 0.88, Ki-67 AUC 0.997). PET provided the best determination of grading (AUC 0.71), while all MR and PET analyses yielded the best results for lymphonodular and distant metastatic spread (0.81 and 0.99, respectively). Conclusion: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for breast cancer phenotyping and tumor decoding, utilizing the perks of simultaneously acquired morphologic, functional and metabolic data.

Purpose To compare CT, MRI, and [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET/MRI) for nodal status, regarding quantity and location of metastatic locoregional lymph nodes in patients with newly diagnosed breast cancer. Materials and methods One hundred eighty-two patients (mean age 52.7 ± 11.9 years) were included in this prospective double-center study. Patients underwent dedicated contrast-enhanced chest/abdomen/pelvis computed tomography (CT) and whole-body ([18F]-FDG PET/) magnet resonance imaging (MRI). Thoracal datasets were evaluated separately regarding quantity, lymph node station (axillary levels I–III, supraclavicular, internal mammary chain), and lesion character (benign vs. malign). Histopathology served as reference standard for patient-based analysis. Patient-based and lesion-based analyses were compared by a McNemar test. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for all three imaging modalities. Results On a patient-based analysis, PET/MRI correctly detected significantly more nodal positive patients than MRI (p

Purpose: The evaluation of the clinical relevance of missed lung nodules at initial staging of breast cancer patients in [18F]FDG-PET/MRI compared with CT. Methods: A total of 152 patients underwent an initial whole-body [18F]FDG-PET/MRI and a thoracoabdominal CT for staging. Presence, size, shape and location for each lung nodule in [18F]FDG-PET/MRI was noted. The reference standard was established by taking initial CT and follow-up imaging into account (a two-step approach) to identify clinically-relevant lung nodules. Patient-based and lesion-based data analysis was performed. Results: No patient with clinically-relevant lung nodules was missed on a patient-based analysis with MRI VIBE, while 1/84 females was missed with MRI HASTE (1%). Lesion-based analysis revealed 4/96 (4%, VIBE) and 8/138 (6%, HASTE) missed clinically-relevant lung nodules. The average size of missed lung nodules was 3.2 mm ± 1.2 mm (VIBE) and 3.6 mm ± 1.4 mm (HASTE) and the predominant location was in the left lower quadrant and close to the hilum. Conclusion: All patients with newly-diagnosed breast cancer and clinically-relevant lung nodules were detected at initial [18F]FDG-PET/MRI staging. However, due to the lower sensitivity in detecting lung nodules, a small proportion of clinically-relevant lung nodules were missed. Thus, supplemental low-dose chest CT after neoadjuvant therapy should be considered for backup.

The purpose of this study was to compare breast MRI, thoracic MRI, thoracic (18)F-FDG PET/MRI, and axillary sonography for the detection of axillary lymph node metastases in women with newly diagnosed breast cancer. Methods: This prospective double-center study included patients with newly diagnosed breast cancer between March 2018 and December 2019. Patients underwent thoracic ((18)F-FDG PET/)MRI, axillary sonography, and dedicated prone breast MRI. Datasets were evaluated separately regarding nodal status (nodal-positive vs. nodal-negative). Histopathology served as the reference standard in all patients. The diagnostic performance of breast MRI, thoracic MRI, thoracic PET/MRI, and axillary sonography in detecting nodal-positive patients was tested by creating receiver-operating-characteristic curves (ROC) with a calculated area under the curve (AUC). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all 4 modalities. A McNemar test was used to assess differences. Results: In total, 112 female patients (mean age, 53.04 ± 12.6 y) were evaluated. Thoracic PET/MRI showed the highest AUC, with a value of 0.892. The AUCs for breast MRI, thoracic MRI, and sonography were 0.782, 0.814, and 0.834, respectively. Differences between thoracic PET/MRI and axillary sonography, thoracic MRI, and breast MRI were statistically significant (PET/MRI vs. axillary sonography, P = 0.01; PET/MRI vs. thoracic MRI, P = 0.02; PET/MRI vs. breast MRI, P = 0.03). PET/MRI showed the highest sensitivity (81.8% [36/44]; 95% CI, 67.29%–91.81%), whereas axillary sonography had the highest specificity (98.5% [65/66]; 95% CI, 91.84%–99.96%). Conclusion: (18)F-FDG PET/MRI outperforms axillary sonography, breast MRI, and thoracic MRI in determining the axillary lymph node status. In a clinical setting, the combination of (18)F-FDG PET/MRI and axillary sonography might be considered to provide even greater accuracy in diagnosis.

PURPOSE The aim of this study was to correlate prognostically relevant immunohistochemical parameters of breast cancer with simultaneously acquired SUVs and apparent diffusion coefficient (ADC) values derived from hybrid breast PET/MRI. PATIENTS AND METHODS Fifty-six women with newly diagnosed, therapy-naive, histologically proven breast cancer (mean age, 54.1 ± 12.0 years) underwent dedicated prone 18F-FDG breast PET/MRI. Diffusion-weighted imaging (b-values: 0, 500, 1000 s/mm2) was performed simultaneously with the PET acquisition. A region of interest encompassing the entire primary tumor on each patient's PET/MRI scan was used to determine the glucose metabolism represented by maximum and mean SUV as well as into corresponding ADC maps to assess tumor cellularity represented by mean and minimum ADC values. Histopathological tumor grading and prognostically relevant immunohistochemical markers, that is, Ki67, progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 (HER2), were assessed. Pearson correlation coefficients were calculated to compare SUV and ADC values as well as the immunohistochemically markers and molecular subtype. For the comparison with the tumor grading, a Wilcoxon test was used. RESULTS A significant inverse correlation between SUV and ADC values derived from breast PET/MRI (r = -0.49 for SUVmean vs ADCmean; r = -0.43 for SUVmax vs ADCmin; both P's < 0.001) was found. Tumor grading and Ki67 both showed a positive correlation with SUVmean from breast PET/MRI (r = 0.37 and r = 0.32, P < 0.01). For immunohistochemical markers, HER2 showed an inverse correlation with ADC values from breast PET/MRI (r = -0.35, P < 0.01). Molecular subtypes significantly correlate with SUVmax and SUVmean (r = 0.52 and r = 0.42, both P's < 0.05). In addition, estrogen receptor expression showed an inverse correlation with SUVmax and SUVmean from breast PET/MRI (r = -0.45 and r = -0.42, P < 0.001). CONCLUSIONS The present data show a correlation between increased glucose metabolism, cellularity, tumor grading, estrogen and HER2 expression, as well as molecular subtype of breast cancer primaries. Hence, simultaneous 18F-FDG PET and diffusion-weighted imaging from hybrid breast PET/MRI may serve as a predictive tool for identifying high-risk breast cancer patients in initial staging and guide-targeted therapy.

Purpose: To compare breast magnetic resonance imaging (MRI), thoracal MRI, thoracal 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/MRI and axillary sonography for the detection of axillary lymph node metastases in women with newly diagnosed breast cancer. Materials and Methods: This prospective double-center study included patients with newly diagnosed breast cancer between March 2018 and December 2019. Patients underwent thoracal (18F-FDG PET/)MRI, axillary sonography, and dedicated prone breast MRI. Datasets were evaluated separately regarding nodal status (nodal+ vs. nodal-). Histopathology served as reference standard in all patients. The diagnostic performance of breast MRI, thoracal MRI, thoracal PET/MRI and axillary sonography in detecting nodal positive patients was tested by creating receiver-operating-characteristic curves (ROC) with a calculated area under the curve (AUC). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all four modalities. A McNemar test was used to assess differences. Results: 112 female patients (mean age 53.04 ± 12.6 years) were evaluated. Thoracal PET/MRI showed the highest ROC-AUC with a value of 0.892. The AUC for breast MRI, thoracal MRI and sonography were 0.782, 0.814 and 0.834, respectively. Differences between thoracal PET/MRI and axillary sonography, thoracal MRI and breast MRI were statistically significant (PET/MRI vs. axillary sonography, P = 0.01; PET/MRI vs. thoracal MRI, P = 0.02; PET/MRI vs. breast MRI, P = 0.03). PET/MRI showed the highest sensitivity (81.8%, 36/44) (95%-CI: 67.29-91.81%) while axillary sonography had the highest specificity (98.5%, 65/66), 95%-CI: 91.84-99.96%). Conclusion:18F-FDG PET/MRI outperforms axillary sonography, breast MRI and thoracal MRI in determining the axillary lymph node status. In a clinical setting, the combination of 18F-FDG PET/MRI and axillary sonography might be considered to provide even more accuracy in diagnosis.

Objectives To compare prostate specific membrane antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) and computed tomography (CT) alone for the detection of biochemical recurrence of prostate cancer (PCa) and effect on treatment. Methods This retrospective study included 59 patients with recently recorded biochemical recurrence of PCa (mean PSA 1.96 ± 1.64 ng/mL) after radical prostatectomy. Patients received PET/CT with either 68Ga-PSMA-11 (n = 36) or 18F-PSMA-1007 (n = 23). PET/CT and CT images were evaluated separately in regard to PCa lesion count, type, and localisation by two physicians. Histopathology, follow-up imaging and PSA levels after salvage irradiation served as reference standard. A McNemar test was used to compare detection rates. Changes in therapeutic approaches based on staging differences between CT alone and PET/CT were assessed in a virtual multidisciplinary tumour board. Results There were 142 lesions in 50 of 59 patients. PSMA PET/CT detected 141 lesions (99.3 %) in 50 patients (84.7 %), while CT detected 72 lesions (50.7 %) in 29 patients (49.2 %). A significantly higher detection rate of PSMA PET/CT was observed on a lesion-based analysis (p Conclusion PSMA PET/CT is superior to CT alone in detecting biochemical recurrence in PCa patients after radical prostatectomy and offered additional therapeutic options in a substantial number of patients.

Despite surgery or chemo radiotherapy the five-year survival rate of esophageal carcinoma (eSCC) patients remains around 15% indicating the need for new therapy regimes. Recently the role of the tumor microenvironment has been recognized as an important determinant of radiation responses. Here we investigate the influence of stromal fibroblasts (hF) on radiation induced tumor cell death. To evaluate functional consequences of ionizing radiation hF and eSCC cells were either cultured separately and irradiated (2Gy) or co-cultured after irradiation to investigate radiation dependent tumor-stroma interactions. Subsequently cells were monitored by time-lapse microscopy and cell death was assessed visually as well as by PARP cleavage, live cell staining with Hoechst33342/propidium iodide and quantification of sub-G1 cell cycle. The rate of cell death was barely altered in monocultures. Of note significantly increased cell death of eSCC was observed in co-culture with irradiated hF compared to co-cultures with mock-irradiated fibroblasts (16.10±4.25 fold of control). Microscopic evaluation of co-cultures revealed that hF and cancer cells are connected via tunnelling nanotubes (TNT). Furthermore, TNT formation was found to be dependent on the extracellular matrix component hyaluronan. eSCC cell death was prevented by pharmacological inhibition of TNT formation by cytochalasin B as well as inhibition of hyaluronan by 4-MU. As TNTs are known to mediate intercellular protein or mitochondrial transfer we investigated which stromal proteins are shuttled into eSCC cells by trans-SILAC experiments. For this purpose the proteome of fibroblasts was labeled with heavy amino acids. After co-culturing hF and eSCC were separated by FACS-sorting and labeled stromal proteins were identified in the cancer cells by mass spectrometry. Four consistently shuttled proteins were identified in the cancer cells, which were exclusively transferred after irradiation of both cell lines. Knock-down experiments of these proteins in hF were performed and SHANK1, which is not expressed in eSCC cells, was found to be responsible for the hF induced cell death of eSCC cells in response to radiation. In conclusion, by usage of a novel trans-SILAC approach, we provide evidence that in response to ionizing radiation stromal hF transfer SHANK1 to eSCC cells, thereby inducing cellular death. SHANK1 might therefore serve as potential new pharmacological target to sensitize cancer cells to radiation therapy. Citation Format: Katharina Röck, Alexandra Schütze, Janna Morawitz, Verena Jendrossek, Klaus Pantel, Jens W. Fischer. Deadly fuel: Fibroblasts mediate cancer cell death through tunneling nanotubes in response to ionizing radiation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1649.