Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin’s coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin’s coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and 84%, respectively, for CESM, and 87% and 60% for MRI. CESM and MRI lesion size measurements were highly correlated. CESM seems at least as reliable as MRI in assessing the response to NAC, and may be an alternative if MRI is contraindicated or its availability is limited.

In patients with head-neck cancer treated with IMRT, immobility of the upper part of the body during radiation is maintained by means of customised immobilisation devices. The main purpose of this study was to determine how the procedures for preparation of customised immobilisation systems and the patients characteristics influence the extent of setup errors. A longitudinal, prospective study involving 29 patients treated with IMRT. Data were collected before CT simulation and during all the treatment sessions (528 setup errors analysed overall); the correlation with possible risk factors for setup errors was explored using a linear mixed model. Setup errors were not influenced by the patient’s anxiety and pain. Temporary removal of the thermoplastic mask before carrying out the CT simulation shows statistically borderline, clinically relevant, increase of setup errors (+24.7%, 95% CI: −0.5% - 55.8%). Moreover, a unit increase of radiation therapists who model the customised thermoplastic mask is associated to a −18% (−29.2% - -4.9%) reduction of the errors. The setup error is influenced by the patient’s physical features; in particular, it increases both in patients in whom the treatment position is obtained with ‘Shoulder down’ (+27.9%, 2.2% - 59.7%) and in patients with ‘Scoliosis/kyphosis’ problems (+65.4%, 2.3% - 164.2%). Using a ‘Small size standard plus customized neck support device’ is associated to a −52.3% (−73.7% - -11.2%) reduction. The increase in number of radiation therapists encountered during the entire treatment cycle does not show associations. Increase in the body mass index is associated with a slight reduction in setup error by (−2.8%, −5% - -0.7%). The position of the patient obtained by forcing the shoulders downwards, clinically significant scoliosis or kyphosis and the reduction of the number of radiation therapists who model the thermoplastic mask are found to be statistically significant risk factors that can cause an increase in setup errors, while the use of ‘Small size’ neck support device and patient BMI can diminish them.

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.

Diffuse large-B cell lymphomas (DLBCL) and follicular lymphomas (FL) are the most represented subtypes among mature B-cell neoplasms and originate from malignant B lymphocytes. Methylation represents one of the major epigenetic mechanisms of gene regulation. Silent information regulator 1 (SIRT1) is a class III lysine-deacetylase playing several functions and considered to be a context-dependent tumor promoter. We present the quantitative methylation, gene expression and tissue distribution of SIRT1 and some key mediators related to lymphoma pathogenesis in B lymphocytes purified from biopsies of follicular hyperplasias, FL and DLBCL. SIRT1 mRNA levels are higher in FL than follicular hyperplasias and DLBCL. B cell lymphoma 6 (BCL6) positively correlates with SIRT1. SIRT1 promoter shows a methylation decrease in the order: follicular hyperplasia - FL - DLBCL. Kruppel-like factor 4 (KLF4), Death-associated protein kinase 1 (DAPK1) and Spastic Paraplegia 20 (SPG20) methylation increase significantly in FL and DLBCL compared to follicular hyperplasias. Gene expression of DAPK1 and SPG20 inversely correlates with their degree of methylation. Our findings evidence a positive correlation between SIRT1 and BCL6 expression increase in FL. SIRT1 methylation decreases in FL and DLBCL accordingly and this parallels the increase of KLF4, DAPK1 and SPG20 methylation.

Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3^neg CD56^pos, CD3^pos CD56^pos, and CD3^pos CD56^neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2D^pos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2D^pos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2D^pos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis.

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with ¹⁷⁷Lu or ⁹⁰Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation. A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of ¹⁷⁷Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code. The similarity analysis demonstrated the superiority of the deformable registrations (p < .001). Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [-19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [-67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL. Image based 3D dosimetry for ¹⁷⁷Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.