Position emission tomography (PET)/CT is widely used for diagnosis, response monitoring and radiotherapy planning in a variety of oncologic, neurologic and inflammatory disorders. Its high diagnostic accuracy in localization and characterization of diverse pathological processes derives from the combination of high-resolution CT and molecular imaging provided by PET within a single examination allowing for a precise spatial allocation of tracer uptake. 1 Moreover, the combination of PET and CT allows for efficient CT based attenuation correction of PET images.

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Pulmonary infections are frequent complications in lung cancer and may worsen its outcome and survival. Inflammatory mediators are suspected to promote tumor growth in non-small-cell lung cancer (NSCLC). Hence, bacterial pathogens may affect lung cancer growth by activation of inflammatory signalling. Against this background, we investigated the effect of purified lipoteichoic acids (LTA) of Staphylococcus aureus (S. aureus) on cellular proliferation and liberation of interleukin (IL)-8 in the NSCLC cell lines A549 and H226. A549 as well as H226 cells constitutively expressed TLR-2 mRNA. Even in low concentrations, LTA induced a prominent increase in cellular proliferation of A549 cells as quantified by automatic cell counting. In parallel, metabolic activity of A549 cells was enhanced. The increase in proliferation was accompanied by an increase in IL-8 mRNA expression and a dose- and time-dependent release of IL-8. Cellular proliferation as well as the release of IL-8 was dependent on specific ligation of TLR-2. Interestingly, targeting IL-8 by neutralizing antibodies completely abolished the LTA-induced proliferation of A549 cells. The pro-proliferative effect of LTA could also be reproduced in the squamous NSCLC cell line H226. In summary, LTA of S. aureus induced proliferation of NSCLC cell lines of adeno- and squamous cell carcinoma origin. Ligation of TLR-2 followed by auto- or paracrine signalling by endogenously synthesized IL-8 is centrally involved in LTA-induced tumor cell proliferation. Therefore, pulmonary infections may exert a direct pro-proliferative effect on lung cancer growth.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-017-1980-4) contains supplementary material, which is available to authorized users.

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Purpose To assess the role of CT-texture analysis (CTTA) for differentiation of pancreatic ductal adenocarcinoma (PDAC) from pancreatic neuroendocrine neoplasm (PNEN) in the portal-venous phase as compared with visual assessment and tumor-to-pancreas attenuation ratios. Methods 53 patients (66.1 ± 8.6y) with PDAC and 42 patients (65.5 ± 12.2y) with PNEN who underwent contrast-enhanced CT for primary staging were evaluated. Volumes of interests (VOIs) were set in the tumor tissue at the portal-venous phase excluding adjacent structures. Based on pyradiomics library, 92 textural features were extracted including 1st, 2nd, and higher order features, and then compared between PNEN and PDAC. The visual assessment classified tumors into hypo-, iso-, or hyperdense to pancreas parenchyma or into homogeneous/heterogeneous. Additionally, attenuation ratios between the tumors and the non-involved pancreas were calculated. Results 8/92 (8.6%) highly significant (p < 0.005) discriminatory textural features between PDAC and PNEN were identified including the 1st order features “median,” “total energy,” “energy,” “10th percentile,” “90th percentile,” “minimum,” “maximum,” and the 2nd order feature “Gray-Level co-occurrence Matrix (GLCM) Informational Measure of Correlation (Imc2).” In PNEN, the higher order feature “GLSZM Small Area High Gray-Level Emphasis” proved significantly higher in G1 compared to G2/3 tumors (p < 0.05). The tumor/parenchyma ratios as well as the visual assessment into hypo-/iso-/hyperdense or homogeneous/heterogeneous did not significantly differ between PDAC and PNEN. Conclusions Our data indicate that CTTA is a feasible tool for differentiation of PNEN from PDAC and also of G1 from G2/3 PNEN in the portal-venous phase. Visual assessment and tumor-to-parenchyma ratios were not useful for discrimination.

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Background To investigate the association of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT with serologic tumor markers and inflammatory markers and the role as imaging predictors for overall survival. Methods A patient cohort with advanced melanoma undergoing 18F-FDG-PET/CT for planning metastasectomy between 04/2013 and 01/2015 was retrospectively included. The volumetric PET parameters whole-body MTV and whole-body TLG as well as the standard uptake value (SUV) peak were quantified using 50%-isocontour volumes of interests (VOIs) and then correlated with the serologic parameters lactate dehydrogenase (LDH), S-100 protein, c-reactive protein (CRP) and alkaline phosphatase (AP). PET parameters were dichotomized by their respective medians and correlated with overall survival (OS) after PET/CT. OS was compared between patients with or without metastases and increased or not-increased serologic parameters. Results One hundred seven patients (52 female; 65 ± 13.1yr.) were included. LDH was strongly associated with MTV (rP = 0.73, p <  0.001) and TLG (rP = 0.62, p <  0.001), and moderately associated with SUVpeak (rP = 0.55, p <  0.001). S-100 protein showed a moderate association with MTV (rP = 0.54, p <  0.001) and TLG (rP = 0.48, p <  0.001) and a weak association with SUVpeak (rP = 0.42, p <  0.001). A strong association was observed between CRP and MTV (rP = 0.66, p <  0.001) and a moderate to weak association between CRP and TLG (rP = 0.53, p <  0.001) and CRP and SUVpeak (rP = 0.45, p <  0.001). For differentiation between patients with or without metastases, receiver operating characteristic (ROC) analysis revealed a cut-off value of 198 U/l for serum LDH (AUC 0.81, sensitivity 0.80, specificity 0.72). Multivariate analysis for OS revealed that both MTV and TLG were strong independent prognostic factors. TLG, MTV and SUVpeak above patient median were accompanied with significantly reduced estimated OS compared to the PET parameters below patient median (e.g. TLG: 37.1 ± 3.2 months vs. 55.9 ± 2.5 months, p <  0.001). Correspondingly, both elevated serum LDH and S-100 protein were accompanied with significantly reduced OS (36.5 ± 4.9 months and 37.9 ± 4.4 months) compared to normal serum LDH (49.2 ± 2.4 months, p = 0.01) and normal S-100 protein (49.0 ± 2.5 months, p = 0.01). Conclusions Tumor volumetric parameters in 18F-FDG-PET/CT serve as prognostic imaging biomarkers in patients with advanced melanoma which are associated with established serologic tumor markers and inflammatory markers.

The goal of this study was to investigate the value of CT-textural features and volume-based PET parameters in comparison to serologic markers for response prediction in patients with diffuse large B-cell lymphoma (DLBCL) undergoing cluster of differentiation (CD19)-chimeric antigen receptor (CAR)-T cell therapy. We retrospectively analyzed the whole-body (WB)-metabolic tumor volume (MTV), the WB-total lesion glycolysis (TLG) and first order textural features derived from 18F-FDG-PET/CT, as well as serologic parameters (C-reactive protein [CRP] and lactate dehydrogenase [LDH], leucocytes) prior and after CAR-T cell therapy in 21 patients with DLBCL (57.7 ± 14.7 year; 7 female). Interleukin 6 (IL-6) and IL-2 receptor peaks were monitored after treatment onset and compared with patient outcome judged by follow-up 18F-FDG-PET/CT. In 12/21 patients (57%), complete remission (CR) was observed, whereas 9/21 patients (43%) showed partial remission (PR). At baseline, WB-MTV and WB-TLG were lower in patients achieving CR (35 ± 38 mL and 319 ± 362) compared to patients achieving PR (88 ± 110 mL and 1487 ± 2254; p < 0.05). The “entropy” proved lower (1.81 ± 0.09) and “uniformity” higher (0.33 ± 0.02) in patients with CR compared to PR (2.08 ± 0.22 and 0.28 ± 0.47; p < 0.05). Patients achieving CR had lower levels of CRP, LDH and leucocytes at baseline compared to patients achieving PR (p < 0.05). In the entire cohort, WB-MTV and WB-TLG decreased after therapy onset (p < 0.01) becoming not measurable in the CR-group. Leucocytes and CRP significantly dropped after therapy (p < 0.01). The IL-6 and IL-2R peaks after therapy were lower in patients with CR compared to PR (p > 0.05). In conclusion, volume-based PET parameters derived from PET/CT and CT-textural features have the potential to predict therapy response in patients with DLBCL undergoing CAR-T cell therapy.