Background: Gene expression profiling (GEP)-based prognostic signatures are being rapidly integrated into clinical decision making for systemic management of breast cancer patients. However, GEP remains relatively underdeveloped for locoregional risk assessment. Yet, locoregional recurrence (LRR), especially early after surgery, is associated with poor survival. Patients and methods: GEP was carried out on two independent luminal-like breast cancer cohorts of patients developing early (<5 years after surgery) or late (>5 years) LRR and used, by a training and testing approach, to build a gene signature able to intercept women at risk of developing early LRR. The GEP data of two in silico datasets and of a third independent cohort were used to explore its prognostic value. Results: Analysis of the first two cohorts led to the identification of three genes, CSTB, CCDC91 and ITGB1, whose expression, derived by principal component analysis, generated a three-gene signature significantly associated with early LRR in both cohorts (P value <0.001 and 0.005, respectively), overcoming the discriminatory capability of age, hormone receptor status and therapy. Remarkably, the integration of the signature with these clinical variables led to an area under the curve of 0.878 [95% confidence interval (CI) 0.810-0.945]. In in silico datasets we found that the three-gene signature retained its association, showing higher values in the early relapsed patients. Moreover, in the third additional cohort, the signature significantly associated with relapse-free survival (hazard ratio 1.56, 95% CI Conclusions: Our three-gene signature represents a new exploitable tool to aid treatment choice in patients with luminal-like breast cancer at risk of developing early recurrence.

Background: The advent of immune check point inhibitors (ICIs) has improved prognosis of various cancers. To better select responding patients (pts) and for a more accurate management of economic resources, biological and biochemical factors have been investigated. To date, no predictive biomarkers have been validated. The aim of this study is to identify manageable and routinely detectable parameters to use in clinical practice to select pts with higher change of response to ICIs. Methods: 271 consecutive metastatic solid tumor pts treated in our Institute from 2013 to 2017 with ICIs were evaluated for baseline LDH serum level, ECOG score, age, type of ICI, number of metastatic sites, histology and sex. A training and validation set were used to build and test models, respectively. Variables' effects were assessed through odds ratio estimates (OR) and area under the receive operating characteristic curves (AUC), from univariate and multivariate logistic regression models. The validated estimates were used to develop an Excel algorithm to calculate probabilities of response. Results: As best response, 55.4% of pts achieved disease control and 44.7% had progressive disease. On the training set, LDH, age and ECOG showed a significant OR (p:<.001, 0.009, 0.042, respectively) and were combined in a multivariate model with an AUC of 0.771 (95%CI: 0.701;0.842). These results were statistically validated on the validation set (AUC: 0.685, 95%CI: 0.569;0.801). By fitting the validated model on all pts, the 3 variables retained a significant OR and a satisfactory cross-validated AUC. Conclusions: We confirm, as reported in literature, that baseline LDH serum levels are inversely associated with response probability. It's reasonable to jointly consider age and ECOG, which give a significant contribution to model performance. The developed algorithm, once validated on an independent prospective series, might be a base to guide physicians in clinical practice to better plan ICI therapy tailored on pts characteristics. Legal entity responsible for the study: Fondazione IRCCS Istituto Nazionale Tumori. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

PURPOSE:The aim is discussing the origins of worsening of external eye condition (EEC) and of tear film (TF) instability after wear of silicone-hydrogel contact lenses (CLs) with hydrogen-peroxide (H2O2) care system.METHODS:EEC and TF stability were evaluated before and after 15days of wear combined with different care systems: (1) H2O2, (2) detergent solution and H2O2, (3) multipurpose solution (MPS), (4) H2O2 and artificial tears. In-vitro cell mortality tests were performed after 24h cell incubation with CLs treated with H2O2. Photon correlation spectroscopy (PCS) was carried out on tears of non-wearers and CL wearers who used MPS or H2O2 solution.RESULTS:Worsening of EEC was observed only for the group using H2O2 (group 1). In-vitro, cell mortality was found higher for worn CL than for unworn CLs. Worsening of TF stability was observed regardless of care system and also PCS results on tears of CL wearers were found different compared to non-wearers regardless of care system. The only observed remedy for tear instability of CL wearers was found to be the administration of artificial tears.CONCLUSIONS:Worsening of EEC of CL wearers using H2O2 is attributed to H2O2 scarce cleaning efficacy, which can be solved by adding a CL detergent solution. The origin of TF instability is found to be different. A remedy was found to be the administration of artificial tears, whose effect could be attributed either to the role of specific components or to rinsing and replacement of TF during wear.

Purpose Investigate late radiation damages after focal radiotherapy (RT) for childhood brain cancer in terms of neurocognitive outcome. Methods 45 retrospective children (age at RT:median = 6.2 years, range 1.1–22.5, age at valuations:median = 11.1 years, range 4.4–25.9) who received focal RT at our Institution with at least 3-years follow-up without relapse, were recruited to undergo cognitive, neuropsychological and psychological testing. Planning CT images were retrieved and patients’ brains were parceled in 116 regions of interest (ROIs) using the Tzourio-Mazoyer atlas [ [1] Tzourio-Mazoyer N et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 2002;15:273–89. Google Scholar ] and a dedicated home-made, multimodal, highly deformable registration framework specifically developed for the study. Mean RT dose value was collected for each ROI. The pattern of association between the categorized cognitive tests scores and RT dose was assessed in each ROI through the Kruskal Wallis test. Subsequently, the preliminary threshold of RT dose (optimal cut-off value) discriminating patients with and without neurocognitive changes (impaired/non-impaired patients), was selected by using a Receiver Operating Characteristic curve (ROC). Results The statistical analysis allowed us to identify the ROIs where mean dose values and cognitive tests results were significantly related. For the 29 ROIs showing the most significant associations, preliminary threshold dose values related to a specific cognitive or neuropsychological damage were obtained, ranging from 3.5 to 29.8 Gy. As an example, Figure1 shows the distributions of dose values in the ROI “Frontal_ Sup_Orb_ R” for patients with impaired/non-impaired performances in a specific cognitive test (Processing Speed Index, WISC III). Conclusions The preliminary analysis of the retrospective children suggested that the main aim (identify brain structures highly susceptible to radiation damages and the respective radiation dose thresholds) is achievable, justifying a prospective study currently open to children enrollment. Partially funded by AIRC. Investigate late radiation damages after focal radiotherapy (RT) for childhood brain cancer in terms of neurocognitive outcome. 45 retrospective children (age at RT:median = 6.2 years, range 1.1–22.5, age at valuations:median = 11.1 years, range 4.4–25.9) who received focal RT at our Institution with at least 3-years follow-up without relapse, were recruited to undergo cognitive, neuropsychological and psychological testing. Planning CT images were retrieved and patients’ brains were parceled in 116 regions of interest (ROIs) using the Tzourio-Mazoyer atlas [ [1] Tzourio-Mazoyer N et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 2002;15:273–89. Google Scholar ] and a dedicated home-made, multimodal, highly deformable registration framework specifically developed for the study. Mean RT dose value was collected for each ROI. The pattern of association between the categorized cognitive tests scores and RT dose was assessed in each ROI through the Kruskal Wallis test. Subsequently, the preliminary threshold of RT dose (optimal cut-off value) discriminating patients with and without neurocognitive changes (impaired/non-impaired patients), was selected by using a Receiver Operating Characteristic curve (ROC). The statistical analysis allowed us to identify the ROIs where mean dose values and cognitive tests results were significantly related. For the 29 ROIs showing the most significant associations, preliminary threshold dose values related to a specific cognitive or neuropsychological damage were obtained, ranging from 3.5 to 29.8 Gy. As an example, Figure1 shows the distributions of dose values in the ROI “Frontal_ Sup_Orb_ R” for patients with impaired/non-impaired performances in a specific cognitive test (Processing Speed Index, WISC III). The preliminary analysis of the retrospective children suggested that the main aim (identify brain structures highly susceptible to radiation damages and the respective radiation dose thresholds) is achievable, justifying a prospective study currently open to children enrollment. Partially funded by AIRC.

The introduction of a camera-based dose-reduction strategy in myocardial perfusion imaging (MPI) clinical setting entails the definition of objective and reproducible criteria for establishing the amount of activity to be injected.

This study aims to deepen the knowledge on tear film properties by the development of a protocol for analyses of Photon Correlation Spectroscopy (PCS) on human tears and by the comparison between PCS results obtained on tears of contact lens wearers and non-wearers. Tears (5μL) were collected by a glass capillary. The analyses provide the hydrodynamic diameter of tear components by analyzing intensity fluctuations in time of scattered light. PCS appears a promising technique for studying tear features and for shedding light on specific eye conditions, such as on the clinical effects of CL wear. In fact, statistical difference (p<0.001) was found between the measured mean hydrodynamic diameter of tear components of wearers and non-wearers, the resulting value significantly higher for CL wearers. The scenario does not substantially change after (25±5)min from the CL removal. The difference is attributed to changes in the interactions between tear constituents due to CL wear. In order to get deeper insights on the influence of CL wear on aggregation and structure of tear components, a preliminary Electron Spin Resonance (ESR) investigation was performed, monitoring Fe3+ species. ESR spectra on tears of both CL wearers and non-wearers showed the presence of intense signals, probably associated to iron (III) centers in proteins such as lactoferrin, and a weaker resonance attributable to Fe3+ species interacting with S-S bridges of lysozyme. Differences in ESR spectra between CL wearers and non-wearers were detected and tentatively ascribed to changes in coordination or in local environment of Fe3+ centers connected to aggregation phenomena induced by CL wear, which promote their interaction with other neighboring iron species.

Introduction Point-spread-function (PSF) modelling seem to be very attractive to obtain superior image quality in [F-18] FDG oncological studies, nonetheless it is known to significantly increase noise variability. Purpose To evaluate the impact of PSF/TF on noise structure of iterative reconstructed (IR) images. Materials and methods An anthropomorphic phantom with [F-18] FDG clinical concentrations was acquired on Biograph-mCT (Siemens) and Discovery690 (General Electric) PET/CT scanners. Overall, 96 datasets were obtained by varying reconstruction modalities (RM = IR, TF, PSF, TF+PSF), frame (128,256), equivalent iterations number (IT = 63,270), and Gaussian filter (GF = 2, 4, 6 mm). To limit noise correlation in PET imaging, 6 groups of concentric ROIs (r = 8;10;13;16;19 mm) were drawn on 3 slices at liver level. Fixing slice and ROI size, the signal variation was defined: SV% = 100∗SD/M, were SD,M are standard deviation, mean among the mean count values found for the ROIs, respectively. Results SV decreases with ROI size and GF, and increases with IT. Moreover, SV depends on RM, but in different ways on the two PET scanners. For Biograph-mCT, highest and lowest SV were observed for PSF and TF and for GF = 2, 4, 6 mm mean(range) values were: 7.8%(5.1–10.6), 5.7%(3.1–8.5), 4.5%(2.5–6.7) and 4.5%(2.7–6.4), 3.8%(2.4–5.4), 3.2(2.2–4.5), respectively. For Discovery690, highest and lowest SV were observed for PSF+TF and IR and for GF = 2, 4, 6 mm the mean(range) values were: 8.3%(6.8–10.5), 8.1%(6.7–10.2), 7.9%(6.6–9.7) and 5.1%(3.5–8.2), 4.5%(3.1–7.0), 4.2%(3.2–6.2), respectively. Same trends are observed for the range of SV values. Conclusions The PET scanners of this study showed different behaviors of SV in relation to RM. Increased SV could lead to degradation of precision in quantitative oncological studies with [F-18] FDG for monitoring treatment response.

Purpose Over the past decade, nuclear medicine experts have been seeking to minimize patient exposure to radiation in myocardial perfusion scintigraphy (MPS). This review describes the latest technological innovations in MPS, particularly with regard to dose reduction. Methods We searched in PubMed for original clinical papers in English, published after 2008, using the following research criteria: (dose) and ((reduction) or (reducing)) and ((myocardial) or (cardiac) or (heart)) and ((nuclear medicine) or (nuclear imaging) or (radionuclide) or (scintigraphy) or (SPET) or (SPECT)). Thereafter, recent reviews on the topic were considered and other relevant clinical papers were added to the results. Results Of 202 non-duplicate articles, 17 were included. To these, another eight papers cited in recent reviews were added. By optimizing the features of software, i.e., through algorithms for iterative reconstruction with resolution recovery (IRRs), and hardware, i.e., scanners and collimators, and by preferring, unless otherwise indicated, the use of stress-first imaging protocols, it has become possible to reduce the effective dose by at least 50% in stress/rest protocols, and by up to 89% in patients undergoing a diagnostic stress-only study with new technology. With today’s SPECT/CT systems, the use of a stress-first protocol can conveniently be performed, resulting in an overall dose reduction of about 35% if two-thirds of stress-first examinations were considered definitively normal. Conclusion Using innovative gamma cameras, collimators and software, as well as, unless otherwise indicated, stress-first imaging protocols, it has become possible to reduce significantly the effective dose in a high percentage of patients, even when X-ray CT scanning is performed for attenuation correction.

Comment on ‘Circulating cell-free miRNAs as biomarker for triple-negative breast cancer’—Methodological challenges in combining miRNAs as circulating biomarkers

AIMSince the efficacy of antibiotics in the management of cough from upper respiratory tract infections (URTI) is unclear, we conducted an observational study to evaluate the efficacy of antibiotic compared to symptomatic treatment in adults with productive cough from URTI in a real life setting.METHODSOne-hundred and 50 subjects presenting to five general practice ambulatories with productive cough due to URTI were included in the study. According to the physician judgment, patients were treated with either oral antibiotics (group A, 50 patients), a mucoactive syrup (sobrerol: group S, 50 patients) as symptomatic treatment, or both sobrerol and oral antibiotics (group SA, 50 patients). Cough severity was assessed daily with a diary, by means of a validated verbal category-descriptive (VCD) Scale.RESULTSIn every treatment group cough severity decreased over time (P<0.001); however, during the first week of treatment patients in groups S and SA experienced significantly lower VCD score values in comparison to Group A (P=0.045 and P=0.010, respectively). On the other hand, the VCD score was never significantly different between the two groups that received symptomatic treatment at any of the 4 weeks of the study, suggesting that the effect observed was due to the action of the mucoactive syrup.CONCLUSIONOur data confirm the lack of efficacy of antibiotics in the management of productive cough in URTI and suggest that symptomatic treatment should be preferred to antibiotics in acute cough from URTI.