MRI texture features are generally considered to be sensitive to variations in signal-to-noise ratio and spatial resolution, which represents an obstacle for the widespread clinical application of texture-based pattern discrimination with MRI. This study investigates the sensitivity of texture features of different categories (co-occurrence matrix, run-length matrix, absolute gradient, autoregressive model, and wavelet transform) to variations in the number of acquisitions (NAs), repetition time (TR), echo time (TE), and sampling bandwidth (SBW) at different spatial resolutions. Special emphasis was placed on the influence of MRI protocol heterogeneity and implications for the results of pattern discrimination. Experiments were performed using two polystyrene spheres and agar gel phantoms with different nodular patterns. T2-weighted multislice multiecho images were obtained using a 3.0 T scanner equipped with a microimaging gradient insert coil. Linear discriminant analysis and k nearest neighbor classification were used for texture-based pattern discrimination. Results show that texture features of all categories are increasingly sensitive to acquisition parameter variations with increasing spatial resolution. Nevertheless, as long as the spatial resolution is sufficiently high, variations in NA, TR, TE, and SBW have little effect on the results of pattern discrimination. Texture features derived from the co-occurrence matrix are superior to features of other categories because they enable discrimination of different patterns close to the resolution limits for the smallest structures of physical texture even for datasets that are heterogeneous with regard to different acquisition parameters, including spatial resolution.

SummaryBackgroundPatients with refractory or relapsed haematological malignancies have few treatment options and short survival times. Identification of effective therapies with genomic-based precision medicine is hampered by intratumour heterogeneity and incomplete understanding of the contribution of various mutations within specific cancer phenotypes. Ex-vivo drug-response profiling in patient biopsies might aid effective treatment identification; however, proof of its clinical utility is limited.MethodsWe investigated the feasibility and clinical impact of multiparametric, single-cell, drug-response profiling in patient biopsies by immunofluorescence, automated microscopy, and image analysis, an approach we call pharmacoscopy. First, the ability of pharmacoscopy to separate responders from non-responders was evaluated retrospectively for a cohort of 20 newly diagnosed and previously untreated patients with acute myeloid leukaemia. Next, 48 patients with aggressive haematological malignancies were prospectively evaluated for pharmacoscopy-guided treatment, of whom 17 could receive the treatment. The primary endpoint was progression-free survival in pharmacoscopy-treated patients, as compared with their own progression-free survival for the most recent regimen on which they had progressive disease. This trial is ongoing and registered with ClinicalTrials.gov, number NCT03096821.FindingsPharmacoscopy retrospectively predicted the clinical response of 20 acute myeloid leukaemia patients to initial therapy with 88·1% accuracy. In this interim analysis, 15 (88%) of 17 patients receiving pharmacoscopy-guided treatment had an overall response compared with four (24%) of 17 patients with their most recent regimen (odds ratio 24·38 [95% CI 3·99–125·4], p=0·0013). 12 (71%) of 17 patients had a progression-free survival ratio of 1·3 or higher, and median progression-free survival increased by four times, from 5·7 (95% CI 4·1–12·1) weeks to 22·6 (7·4–34·0) weeks (hazard ratio 3·14 [95% CI 1·37–7·22], p=0·0075).InterpretationRoutine clinical integration of pharmacoscopy for treatment selection is technically feasible, and led to improved treatment of patients with aggressive refractory haematological malignancies in an initial patient cohort, warranting further investigation.FundingAustrian Academy of Sciences; European Research Council; Austrian Science Fund; Austrian Federal Ministry of Science, Research and Economy; National Foundation for Research, Technology and Development; Anniversary Fund of the Austrian National Bank; MPN Research Foundation; European Molecular Biology Organization; and Swiss National Science Foundation.

ObjectiveTumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.MethodsWe evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient’s outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.ResultsMuscle attenuation (MA)—a well established BCM parameter—is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA—reflecting a state of cachexia—is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively).ConclusionMA—ascertained by routine pre-operative CT—is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

In melanoma, therapies with inhibitors to oncogenic BRAFV600E are highly effective but responses are often short-lived due to the emergence of drug-resistant tumor subpopulations. We describe here a mechanism of acquired drug resistance through the tumor microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce the growth factor FGF-2, which activates tumor-infiltrating B cells to produce the growth factor IGF-1. B-cell-derived IGF-1 is critical for resistance of melanomas to BRAF and MEK inhibitors due to emergence of heterogeneous subpopulations and activation of FGFR-3. Consistently, resistance of melanomas to BRAF and/or MEK inhibitors is associated with increased CD20 and IGF-1 transcript levels in tumors and IGF-1 expression in tumor-associated B cells. Furthermore, first clinical data from a pilot trial in therapy-resistant metastatic melanoma patients show anti-tumor activity through B-cell depletion by anti-CD20 antibody. Our findings establish a mechanism of acquired therapy resistance through tumor-associated B cells with important clinical implications.

Because of its higher soft-tissue contrast, whole-body integrated PET/MR offers potential advantages over PET/CT for evaluation of bone lesions. However, unlike PET/CT, PET/MR ignores the contribution of cortical bone in the attenuation map. Thus, the aims of this study were to evaluate the diagnostic performance of wholebody integrated 18 F-FDG PET/MR specifically for bone lesions and to analyze differences in standardized uptake value (SUV) quantification between PET/MR and PET/CT. Methods: One hundred nineteen patients with 18 F-FDG-avid primary malignancies underwent a single-injection, dual-imaging protocol using 18 F-FDG on a PET/ CT scanner and a subsequent PET/MR scan with a T1-weighted volumetric interpolated breath-hold examination (VIBE) Dixon sequence for attenuation correction and an unenhanced coronal T1-weighted turbo spin-echo (TSE) sequence for bone analysis. Three sets of images (CT with PET [from PET/CT; set A], T1-weighted VIBE Dixon with PET [set B], and T1-weighted TSE with PET [both from PET/MR; set C]) were analyzed. Two readers rated every lesion using a 4-point scale for lesion conspicuity on PET, a 4-point scale for anatomic allocation of PET-positive lesions, and a 5-point scale for the nature of every lesion based on its appearance on morphologic imaging and uptake on PET. For all lesions and for representative regions of normal bone, SUV analysis was performed for PET/ MR and PET/CT. Results: In total, 98 bone lesions were identified in 33 of 119 patients, and 630 regions of normal bone were analyzed. Visual lesion conspicuity on PET was comparable for PET/CT (mean rating, 2.82 6 0.45) and PET/MR (2.75 6 0.51; P 5 0.3095). Anatomic delineation and allocation of suggestive lesions was significantly superior with T1-weighted TSE MRI (mean rating, 2.84 6 0.42) compared with CT (2.57 6 0.54, P 5 0.0001) or T1-weighted VIBE Dixon MRI (2.57 6 0.54, P 5 0.0002). No significant difference in correct classification of malignant bone lesions was found among sets A (85/90), B (84/90), and C (86/90). For bone lesions and regions of normal bone, a highly significant correlation existed between the mean SUVs for PET/MR and PET/CT (R 5 0.950 and 0.917, respectively, each P , 0.001). However, substantially lower mean SUVs were found for PET/MR than for PET/CT both for bone lesions (12.4% 6 15.5%) and for regions of normal bone (30.1% 6 27.5%). Conclusion: Compared with PET/CT, fully integrated whole-body 18 F-FDG PET/MR is technically and clinically robust for evaluation of bone lesions despite differences in attenuation correction. PET/MR, including diagnostic T1-weighted TSE sequences, was superior to PET/CT for anatomic delineation and allocation of bone lesions. This finding might be of clinical relevance in selected cases-for example, primary bone tumors, early bone marrow infiltration, and tumors with low uptake on PET. Thus, a diagnostic T1-weighted TSE sequence is recommended as a routine protocol for oncologic PET/MR.